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Sample records for 28-day cycle patients

  1. The combined oral contraceptive pill and the assumed 28-day cycle.

    PubMed

    Dowse, M St Leger; Gunby, A; Moncad, R; Fife, C; Smerdon, G; Bryson, P

    2007-07-01

    Some studies involving women taking the combined oral contraceptive pill (COCP) have on occasion assumed the COCP group to have a rigid 28-day pharmaceutically driven cycle. Anecdotal evidence suggests otherwise, with many women adjusting their COCP usage to alter the time between break-through bleeds for sporting and social reasons. A prospective field study involving 533 scuba diving females allowed all menstrual cycle lengths (COCP and non-COCP) to be observed for up to three consecutive years (St Leger Dowse et al. 2006). A total of 29% of women were COCP users who reported 3,241 cycles. Of these cycles, only 42% had a rigid 28-day cycle, with the remainder varying in length from 21 to 60 days. When performing studies involving the menstrual cycle, it should not be assumed that COCP users have a rigid confirmed 28-day cycle and careful consideration should be given to data collection and analysis. The effects of differing data interpretations are shown.

  2. Incremental effects of 28 days of beta-alanine supplementation on high-intensity cycling performance and blood lactate in masters female cyclists.

    PubMed

    Glenn, J M; Gray, M; Stewart, R; Moyen, N E; Kavouras, S A; DiBrezzo, R; Turner, R; Baum, J

    2015-12-01

    Within the aging population, there exists a subset of individuals termed masters athletes (MA). As masters-level competition increases in popularity, MA must find methods to enhance individual athletic performance. Longitudinal beta-alanine (BA) supplementation is suggested to enhance physical capability during exercise; however, these effects have not been evaluated in MA. To examine the longitudinal effects of BA on time to exhaustion (TTE), total work completed (TWC), and lactate clearance in female MA cyclists. Twenty-two female MA (age = 53.3 ± 1.0) participated in this double-blind design. Subjects were randomly assigned to BA (n = 11; 800 mg BA + 8 g dextrose) or placebo (PLA; n = 11; 8 g dextrose) groups and supplemented 4 doses/day over 28 days. Every 7 days, subjects completed a cycling TTE at 120% VO2max, and TWC was calculated. Blood lactate was measured at baseline, immediate post, and 20-min post each TTE. No significant differences existed between groups for any variable at baseline (p > 0.05). After 28 days supplementation, BA had greater TTE (23 vs 1% change) and TWC (21 vs 2% change) than PLA (p < 0.05). Following the 20-min TTE recovery, lactate was 24% lower in BA compared to PLA (4.35 vs. 5.76 mmol/L, respectively). No differences existed for variables during intermittent weeks. 28 days of BA supplementation increased cycling performance via an enhanced time to exhaustion and total work completed with associated lactate clearance during passive rest in female MA.

  3. Incremental effects of 28 days of beta-alanine supplementation on high-intensity cycling performance and blood lactate in masters female cyclists.

    PubMed

    Glenn, J M; Gray, M; Stewart, R; Moyen, N E; Kavouras, S A; DiBrezzo, R; Turner, R; Baum, J

    2015-12-01

    Within the aging population, there exists a subset of individuals termed masters athletes (MA). As masters-level competition increases in popularity, MA must find methods to enhance individual athletic performance. Longitudinal beta-alanine (BA) supplementation is suggested to enhance physical capability during exercise; however, these effects have not been evaluated in MA. To examine the longitudinal effects of BA on time to exhaustion (TTE), total work completed (TWC), and lactate clearance in female MA cyclists. Twenty-two female MA (age = 53.3 ± 1.0) participated in this double-blind design. Subjects were randomly assigned to BA (n = 11; 800 mg BA + 8 g dextrose) or placebo (PLA; n = 11; 8 g dextrose) groups and supplemented 4 doses/day over 28 days. Every 7 days, subjects completed a cycling TTE at 120% VO2max, and TWC was calculated. Blood lactate was measured at baseline, immediate post, and 20-min post each TTE. No significant differences existed between groups for any variable at baseline (p > 0.05). After 28 days supplementation, BA had greater TTE (23 vs 1% change) and TWC (21 vs 2% change) than PLA (p < 0.05). Following the 20-min TTE recovery, lactate was 24% lower in BA compared to PLA (4.35 vs. 5.76 mmol/L, respectively). No differences existed for variables during intermittent weeks. 28 days of BA supplementation increased cycling performance via an enhanced time to exhaustion and total work completed with associated lactate clearance during passive rest in female MA. PMID:26255281

  4. Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

    PubMed

    Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-01

    Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

  5. Hypoalbuminemia, Low Base Excess Values, and Tachypnea Predict 28-Day Mortality in Severe Sepsis and Septic Shock Patients in the Emergency Department

    PubMed Central

    Seo, Min Ho; Choa, Minhong; You, Je Sung; Lee, Hye Sun; Hong, Jung Hwa; Chung, Sung Phil; Park, Incheol

    2016-01-01

    Purpose The objective of this study was to develop a new nomogram that can predict 28-day mortality in severe sepsis and/or septic shock patients using a combination of several biomarkers that are inexpensive and readily available in most emergency departments, with and without scoring systems. Materials and Methods We enrolled 561 patients who were admitted to an emergency department (ED) and received early goal-directed therapy for severe sepsis or septic shock. We collected demographic data, initial vital signs, and laboratory data sampled at the time of ED admission. Patients were randomly assigned to a training set or validation set. For the training set, we generated models using independent variables associated with 28-day mortality by multivariate analysis, and developed a new nomogram for the prediction of 28-day mortality. Thereafter, the diagnostic accuracy of the nomogram was tested using the validation set. Results The prediction model that included albumin, base excess, and respiratory rate demonstrated the largest area under the receiver operating characteristic curve (AUC) value of 0.8173 [95% confidence interval (CI), 0.7605–0.8741]. The logistic analysis revealed that a conventional scoring system was not associated with 28-day mortality. In the validation set, the discrimination of a newly developed nomogram was also good, with an AUC value of 0.7537 (95% CI, 0.6563–0.8512). Conclusion Our new nomogram is valuable in predicting the 28-day mortality of patients with severe sepsis and/or septic shock in the emergency department. Moreover, our readily available nomogram is superior to conventional scoring systems in predicting mortality. PMID:27593863

  6. The Diet of Inmates: An Analysis of a 28-Day Cycle Menu Used in a Large County Jail in the State of Georgia.

    PubMed

    Cook, Emma A; Lee, Yee Ming; White, B Douglas; Gropper, Sareen S

    2015-10-01

    Given the many well-documented relationships between diet and health, growing medical care expenses for those incarcerated, and limited information on foods served in correctional facilities, this study examined the nutritional adequacy of a 28-day cycle menu used in a large county jail in Georgia. When compared with Dietary Reference Intakes, provisions of energy (female inmates only), sodium, saturated fat, and cholesterol exceeded recommendations. Magnesium, potassium, and vitamins A, D, and E met less than two thirds of recommendations. Compared with MyPlate recommendations, grains were overrepresented, while vegetables, fruits, and dairy were underrepresented in the menu. Small menu changes could improve the menu's nutrient content and potentially increase inmates' health and well-being. PMID:26276135

  7. Prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction based on gender in Isfahan, Iran (2000-2009)

    PubMed Central

    Mohammadian, Mahdi; Hosseini, Shidokht; Salehiniya, Hamid; Sadeghi, Masoumeh; Sarrafzadegan, Nizal; Roohafza, Hamid Reza; Khazaei, Salman; Soltani, Shahin; Sarrafkia, Ali; Golshahi, Jafar; Mohammadian-Hafshejani, Abdollah

    2015-01-01

    BACKGROUND Determinant prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction (AMI) based on gender in teen year’s period in Isfahan, Iran, was the aim of this study. METHODS This study is a prospective hospital-based study that consisted, all patients with AMI admitted to all hospitals (private and universal hospitals) in Isfahan and Najafabad (Iran) during 2000-2009. To determinant the prognostic factors of 28 days survival rate in patients based on gender, analysis conducted separately for male and female. In analysis, we use of t-test, log Rank tests, Kaplan-Meier method, and univariate and multivariate Cox regression model. RESULTS Short-term (28 days) survival rate was 92.5% in male and 86.7% in female (P < 0.001). The adjusted hazard ratio (HR) of death for age group 80 years and older was 12.7 [95% confidence interval (CI): 5.14-31.3] in male and 8.78 (95% CI: 1.2-63.1) in female. HR for acute transmural MI of the unspecified site in male was 8.9 (95% CI: 4.68-16.97) and in female 9.33 (95% CI: 4.42-19.7). HR for receive of streptokinase in male was 1.11 (95% CI: 0.94-1.31) and in female was 0.69 (95% CI: 0.56-0.84). CONCLUSION Short-term survival rate in male was a higher than female. In male age, anatomic location of MI and hospital status and in female streptokinase use and anatomic location of MI was the most important prognostic factors of survival in-patient with AMI in Isfahan. PMID:26862341

  8. Diurnal and menstrual cycles in body temperature are regulated differently: a 28-day ambulatory study in healthy women with thermal discomfort of cold extremities and controls.

    PubMed

    Kräuchi, Kurt; Konieczka, Katarzyna; Roescheisen-Weich, Corina; Gompper, Britta; Hauenstein, Daniela; Schoetzau, Andreas; Fraenkl, Stephan; Flammer, Josef

    2014-02-01

    Diurnal cycle variations in body-heat loss and heat production, and their resulting core body temperature (CBT), are relatively well investigated; however, little is known about their variations across the menstrual cycle under ambulatory conditions. The main purpose of this study was to determine whether menstrual cycle variations in distal and proximal skin temperatures exhibit similar patterns to those of diurnal variations, with lower internal heat conductance when CBT is high, i.e. during the luteal phase. Furthermore, we tested these relationships in two groups of women, with and without thermal discomfort of cold extremities (TDCE). In total, 19 healthy eumenorrheic women with regular menstrual cycles (28-32 days), 9 with habitual TDCE (ages 29 ± 1.5 year; BMI 20.1 ± 0.4) and 10 controls without these symptoms (CON: aged 27 ± 0.8 year; BMI 22.7 ± 0.6; p < 0.004 different to TDCE) took part in the study. Twenty-eight days continuous ambulatory skin temperature measurements of distal (mean of hands and feet) and proximal (mean of sternum and infraclavicular regions) skin regions, thighs, and calves were carried out under real-life, ambulatory conditions (i-Buttons® skin probes, sampling rate: 2.5 min). The distal minus proximal skin temperature gradient (DPG) provided a valuable measure for heat redistribution from the core to the shell, and, hence, for internal heat conduction. Additionally, basal body temperature was measured sublingually directly after waking up in bed. Mean diurnal amplitudes in skin temperatures increased from proximal to distal skin regions and the 24-h mean values were inversely related. TDCE compared to CON showed significantly lower hand skin temperatures and DPG during daytime. However, menstrual cycle phase did not modify these diurnal patterns, indicating that menstrual and diurnal cycle variations in skin temperatures reveal additive effects. Most striking was the finding that all measured skin

  9. Biochemical observation during 28 days of space flight

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Kambaut, P. C.

    1975-01-01

    With the completion of the 28-day flight of Skylab 2, the sum of biochemical data on human reaction to the weightless environment was significantly extended both quantitatively and qualitatively. The biochemical studies were divided into two broad categories. One group included the more routine blood studies similar to those used in everyday medical practice. The second category encompassed those analyses used to investigate more thoroughly the endocrinological and fluid changes first seen in the crewmembers following the Gemini, Apollo, and Soviet missions. Significant biochemical changes were observed that varied in magnitude and direction, but all disappeared shortly after return to earth. Most of changes indicate successful adaptation by the body to the combined stresses of weightlessness. Results of the biochemical observation are presented in the form of data tables and graphs.

  10. Novel three dimensional human endocervix cultures respond to 28-day hormone treatment.

    PubMed

    Arslan, Sevim Yildiz; Yu, Yanni; Burdette, Joanne E; Pavone, Mary Ellen; Hope, Thomas J; Woodruff, Teresa K; Kim, J Julie

    2015-04-01

    The endocervix has both anatomical and biological functions that participate in the delicate balance between tolerance necessary for conception and protection from pathogens. Our goal was to develop a robust 3-dimensional (3D) endocervix model that was a reliable representation of the in vivo tissues and to identify the physiological responses to changing levels of steroid hormones during a 28-day time period. Human endocervical cells were grown on polystyrene scaffolds, and the morphologic and hormonal responses of cultured cells were assessed in response to fluctuating levels of estradiol (E2) or progesterone (P4). Morphologically, the 3D cultures were composed of a mixed population of cells, including epithelial and stromal cells. Treatment with E2 and P4 (d 28) increased cell growth and proliferation as compared with no treatment control. Cells expressed estrogen receptor and P4 receptor and produced both neutral and acidic mucins, including Mucin 16. In addition, a 45-plex Luminex assay identified numerous factors secreted and regulated by hormones. Specifically, IL-1β and leukemia inhibitory factor significantly decreased in the presence of E2 and P4 as compared with the no hormone control at day 26. Cotreatment with RU486 (mifepristone) attenuated the inhibition of IL-1β and leukemia inhibitory factor secretion. In summary, a robust, novel 3D endocervical culture was developed, and physiologic responses to the menstrual cycle mimic of E2 and P4 levels for a period of 28 days were identified.

  11. Aortic Coarctation 28 Days after an Arterial Switch Operation in a Neonate

    PubMed Central

    Okamura, Toru; Higaki, Takashi; Okura, Masahiro; Kojima, Ai; Uchita, Shunji; Izutani, Hironori

    2016-01-01

    Aortic coarctation rarely occurs after an arterial switch operation for D-transposition of the great arteries with intact ventricular septum. We report the case of a neonate patient in whom aortic coarctation developed 28 days after an uncomplicated arterial switch operation. Preoperatively, the aorta was noted to have an irregular shape, but there was no pressure gradient across the lesion. The patient underwent successful reoperation to correct the coarctation. We hope that our report raises awareness of a rare early complication after arterial switch operation with intact ventricular septum, and the need to carefully monitor the aortic isthmus in patients who have aortic irregularities, even in the absence of a pressure gradient. PMID:27547151

  12. Tamarind seed polysaccharide: a 28-day dietary study in Sprague-Dawley rats.

    PubMed

    Heimbach, James T; Egawa, Hiroshi; Marone, Palma Ann; Bauter, Mark R; Kennepohl, Elke

    2013-01-01

    Forty male and 40 female Crl:SD® CD® IGS rats were fed diets containing 0, 40,000, 80,000, or 120,000 ppm tamarind seed polysaccharide (equivalent to 3450.8, 6738.9, or 10 597.1 mg/kg bw/day and 3602.1, 7190.1, or 10,690.7 mg/kg bw/day for males and females, respectively) for 28 days. Animals were observed for adverse clinical signs, body weight, feed consumption, hematology and clinical chemistry parameters, urinalysis values were recorded, and at the end of the study the rats underwent a full necropsy. Functional Observational Battery (FOB) and Motor Activity (MA) tests were performed on all animals. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption and food efficiency, FOB or MA findings associated with the administration of tamarind seed polysaccharide. Initial statistically significant decreases in body weight gain and food consumption resolved after the first week and were considered the result of reduced palatability. There were no adverse changes in hematology, coagulation, clinical chemistry or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, estrus cycle, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study and based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for tamarind seed polysaccharide in the diet was the highest concentration tested of 120,000 ppm (equivalent to 10,597 mg/kg bw/day and 10,691 mg/kg bw/day for male and female rats, respectively).

  13. Tamarind seed polysaccharide: a 28-day dietary study in Sprague-Dawley rats.

    PubMed

    Heimbach, James T; Egawa, Hiroshi; Marone, Palma Ann; Bauter, Mark R; Kennepohl, Elke

    2013-01-01

    Forty male and 40 female Crl:SD® CD® IGS rats were fed diets containing 0, 40,000, 80,000, or 120,000 ppm tamarind seed polysaccharide (equivalent to 3450.8, 6738.9, or 10 597.1 mg/kg bw/day and 3602.1, 7190.1, or 10,690.7 mg/kg bw/day for males and females, respectively) for 28 days. Animals were observed for adverse clinical signs, body weight, feed consumption, hematology and clinical chemistry parameters, urinalysis values were recorded, and at the end of the study the rats underwent a full necropsy. Functional Observational Battery (FOB) and Motor Activity (MA) tests were performed on all animals. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption and food efficiency, FOB or MA findings associated with the administration of tamarind seed polysaccharide. Initial statistically significant decreases in body weight gain and food consumption resolved after the first week and were considered the result of reduced palatability. There were no adverse changes in hematology, coagulation, clinical chemistry or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, estrus cycle, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study and based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for tamarind seed polysaccharide in the diet was the highest concentration tested of 120,000 ppm (equivalent to 10,597 mg/kg bw/day and 10,691 mg/kg bw/day for male and female rats, respectively). PMID:23616144

  14. The Return Home: Transitioning from a 28-Day Remote Outdoor Education Programme

    ERIC Educational Resources Information Center

    McNatty, Shannon

    2016-01-01

    This article addresses the challenges for students transitioning from the remote Te Kahu (pseudonym) outdoor education programme back into their home and school city environments. Students must develop methods of coping and readjust to society to continue the personal growth and process the learning affected through the 28-day programme. The…

  15. In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.

    PubMed

    Kim, Jin Sik; Sung, Jae Hyuck; Choi, Byung Gil; Ryu, Hyeon Yeol; Song, Kyung Seuk; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Lee, Gun Ho; Jeon, Kisoo; Ahn, Kang Ho; Yu, Il Je

    2014-03-01

    Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96 mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H2O2 levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats showed no changes in the H2O2 levels. The inflammatory cytokine levels in the

  16. Trends of 28 days case fatality rate after first acute myocardial infarction in Isfahan, Iran, from 2000 to 2009

    PubMed Central

    Mohammadian, Mahdi; Hosseini, Shidokht; Sadeghi, Masoumeh; Sarrafzadegan, Nizal; Salehiniya, Hamid; Roohafza, Hamidreza; Khazaei, Salman; Mohammadian-Hafshejani, Abdollah

    2015-01-01

    BACKGROUND The purpose of the present study was the analysis of the trends in case fatality rate of acute myocardial infarction (AMI) in Isfahan, Iran. This analysis was performed based on gender, age groups, and type of AMI according to the International Classification of Diseases, version 10, during 2000-2009. METHODS Disregarding the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA), this cohort study considered all AMI events registered between 2000 and 2009 in 13 hospitals in Isfahan. All patients were followed for 28 days. In order to assess the case fatality rate, the Kaplan-Meier analysis, and to compare survival rate, log-rank test were used. Using the Cox regression model, 28 days case fatality hazard ratio (HR) was calculated. RESULTS In total, 12,900 patients with first AMI were entered into the study. Among them, 9307 (72.10%) were men and 3593 (27.90%) women. The mean age in all patients increased from 61.36 ± 12.19 in 2000-2001 to 62.15 ± 12.74 in 2008-2009, (P = 0.0070); in women, from 65.38 ± 10.95 to 67.15 ± 11.72 (P = 0.0200), and in men, from 59.75 ± 12.29 to 59.84 ± 12.54 (P = 0.0170),. In addition, the 28 days case fatality rate in 2000-2009 had a steady descending trend. Thus, it decreased from 11.20% in 2000-2001 to 07.90% in 2008-2009; in men, from 09.20% to 06.70%, and in women, from 16.10% to 10.90%. During the study, HR of case fatality rate in 2000-2001 declined; therefore, in 2002-2003, it was 0.93 [95% confidence interval (CI) = 0.77-1.11], in 2004-2005, 0.88 (95% CI = 0.73-1.04), in 2006-2007, 0.67 (95% CI = 0.56-0.82), and in 2008-2009, 0.69 (95% CI = 0.56-0.82). CONCLUSION In Isfahan, a reduction was observable in the trend of case fatality rate in both genders and all age groups. Thus, there was a 29.46% reduction in case fatality rate (27.17% in men, 32.29% in women) during the study period. PMID:26478731

  17. Evaluation of spontaneous baroreflex response after 28 days head down tilt bedrest

    NASA Astrophysics Data System (ADS)

    Hughson, R. L.; Yamamoto, Y.; Butler, G. C.; Güell, A.; Gharib, C.

    The spontaneous baroreflex response was evaluated during supine rest and head up tilt (60°) before and immediately after a 28 day 6° HDT bedrest in 6 healthy adult men (age 30-42 years). Sequences of 3 or more beats where RR-interval and systolic blood pressure changed in the same direction were used to evaluate baroreflex response slope (BRS). Prior to bedrest, the mean BRS and RR-interval were 18.0 ± 3.9 ms/mm Hg and 926 ± 61 ms at rest and 10.5 ± 2.5 ms/mm Hg and 772 ± 63 ms during the first 10 min of 60° tilt. Following bedrest, these values changed to 15.6 ± 2.7 ms/mm Hg and 780 ± 53 ms at rest, and to 6.5 ± 1.2 ms/mm Hg and 636 ± 44 ms during tilt. Thus, (1) the spontaneous baroreflex can be evaluated in human subjects during experiments of orthostatic stress; (2) the baroreflex slope was reduced on going from supine to the head up tilt position; and (3) 28 days of bedrest reduced the spontaneous baroreflex slope.

  18. Mineral and nitrogen balance study - Results of metabolic observations on Skylab II 28-day orbital mission

    NASA Technical Reports Server (NTRS)

    Whedon, G. D.; Lutwak, L.; Reid, J.; Rambaut, P.; Whittle, M.; Smith, M.; Leach, C.

    1975-01-01

    The prediction that various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various balance-study observations of long-term immobilized or inactive bed rest. The three astronauts of Skylab II consumed a planned dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, 28 days inflight, and 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative nitrogen and phosphorus balances inflight indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations of calcium, phosphorus, and nitrogen loss, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur in the planed Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration.

  19. Evaluation of toxicity to triclosan in rats following 28 days of exposure to aerosol inhalation.

    PubMed

    Yang, Young-Su; Kwon, Jung-Taek; Shim, Ilseob; Kim, Hyun-Mi; Kim, Pilje; Kim, Jong-Choon; Lee, Kyuhong

    2015-03-01

    The present study was conducted to investigate the potential subchronic toxicity of triclosan (TCS) in rats following 28 days of exposure by repeated inhalation. Four groups of six rats of each sex were exposed to TCS-containing aerosols by nose-only inhalation of 0, 0.04, 0.13, or 0.40 mg/L for 6 h/day, 5 days/week over a 28-day period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. At 0.40 mg/L, rats of both sexes exhibited an increase in the incidence of postdosing salivation and a decrease in body weight. Histopathological alterations were found in the nasal septum and larynx. There were no treatment-related effects in rats of either sex at ⩽0.13 mg/L. Under the present experimental conditions, the target organs in rats were determined to be the nasal cavity and larynx. The no-observed-adverse-effect concentration in rats was determined to be 0.13 mg/L.

  20. 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

    PubMed

    Kim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il Je

    2016-09-01

    Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung

  1. 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

    PubMed

    Kim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il Je

    2016-09-01

    Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung

  2. Your Menstrual Cycle

    MedlinePlus

    ... during your menstrual cycle What happens during your menstrual cycle The menstrual cycle includes not just your period, but the rise ... tool is based on a sample 28-day menstrual cycle, but every woman is different in how long ...

  3. Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

    PubMed Central

    Clarke, Kieran; Tchabanenko, Kirill; Pawlosky, Robert; Carter, Emma; Knight, Nicholas S.; Murray, Andrew J.; Cochlin, Lowri E.; King, M. Todd; Wong, Andrea W.; Roberts, Ashley; Robertson, Jeremy; Veech, Richard L.

    2013-01-01

    (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester) has been developed as an oral source of ketones, which may be utilized for energy. In a 28-day toxicity study, Crl:WI (Wistar) rats received diets containing, as 30% of the calories, ketone monoester (12 and 15 g/kg body weight/day for male and female rats, respectively). Control groups received either carbohydrate- or fat-based diets. Rats in the test group consumed less feed and gained less weight than control animals; similar findings have been documented in studies of ketogenic diets. Between-group differences were noted in selected hematology, coagulation, and serum chemistry parameters; however, values were within normal physiological ranges and/or were not accompanied by other changes indicative of toxicity. Upon gross and microscopic evaluation, there were no findings associated with the ketone monoester. In a developmental toxicity study, pregnant Crl:WI (Han) rats were administered 2 g/kg body weight/day ketone monoester or water (control) via gavage on days 6 through 20 of gestation. No Caesarean-sectioning or litter parameters were affected by the test article. The overall incidence of fetal alterations was higher in the test group; however, there were no specific alterations attributable to the test substance. The results of these studies support the safety of ketone monoester. PMID:22504461

  4. ANALYTICAL RESULTS OF MOX COLEMANITE CONCRETE SAMPLE POURED JULY 25, 2012 - CURED 28 DAYS

    SciTech Connect

    Cozzi, A. D.; Best, D. R.; Reigel, M. M.

    2012-09-18

    The Mixed Oxide Fuel Fabrication Facility (MFFF) will use Colemanite bearing concrete neutron absorber panels credited with attenuating neutron flux in the criticality design analyses and shielding operators from radiation. The Savannah River National Laboratory is tasked with measuring the total density, partial hydrogen density, and partial boron density of the colemanite concrete. Samples 8.1.2, 8.2.2, 8.3.2, and 8.4.2 were received on 8/1/2012 and analyzed after curing for 28 days. The average total density measured by the ASTM method C 642 was 2.09 g/cm{sup 3}, within the lower bound of 1.88 g/cm{sup 3}. The average partial hydrogen density was 7.48E-02 g/cm{sup 3} as measured using method ASTM E 1311 and met the lower bound of 6.04E-02 g/cm{sup 3}. The average measured partial boron density was 1.71E-01 g/cm{sup 3} which met the lower bound of 1.65E-01 g/cm{sup 3} measured by the ASTM C 1301 method.

  5. Physiological effects following administration of Citrus aurantium for 28 days in rats

    SciTech Connect

    Hansen, Deborah K.; Pellicore, Linda S.

    2012-06-15

    Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. Method: Female Sprague–Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.

  6. 5-Day repeated inhalation and 28-day post-exposure study of graphene.

    PubMed

    Shin, Jae Hoon; Han, Sung Gu; Kim, Jin Kwon; Kim, Boo Wook; Hwang, Joo Hwan; Lee, Jong Seong; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Keun Soo; Lee, Heon Sang; Song, Nam Woong; Ahn, Kangho; Yu, Il Je

    2015-01-01

    Graphene has recently been attracting increasing attention due to its unique electronic and chemical properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats. A total of three groups (20 rats per group) were compared: (1) control (ambient air), (2) low concentration (0.68 ± 0.14 mg/m(3) graphene) and (3) high concentration (3.86 ± 0.94 mg/m(3) graphene). The rats were exposed to graphene for 6 h/day for 5 days, followed by recovery for 1, 3, 7 or 28 days. The bioaccumulation and macrophage ingestion of the graphene were evaluated in the rat lungs. The exposure to graphene did not change the body weights or organ weights of the rats after the 5-day exposure and during the recovery period. No statistically significant difference was observed in the levels of lactate dehydrogenase, protein and albumin between the exposed and control groups. However, graphene ingestion by alveolar macrophages was observed in the exposed groups. Therefore, these results suggest that the 5-day repeated exposure to graphene only had a minimal toxic effect at the concentrations and time points used in this study.

  7. Dietary Lysine Responses of Male Broilers From 14 to 28 Days of Age Subjected to Different Environmental Conditions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary amino acid requirements are influenced by environmental conditions. Two experiments examined growth responses of Ross × Ross TP 16 male broilers fed diets varying in digestible (dig) Lys concentrations from 14 to 28 days of age under different environmental conditions. Experiment 1 was condu...

  8. Supra-nutritional vitamin E supplementation for 28 days before slaughter maximises muscle vitamin E concentration in finisher pigs.

    PubMed

    Kim, J C; Jose, C G; Trezona, M; Moore, K L; Pluske, J R; Mullan, B P

    2015-12-01

    A 4 × 3 factorial experiment (n=8 pigs per treatment combination) was conducted with 96 female Landrace × Large White pigs to examine the required level of dietary vitamin E and optimum feeding duration before slaughter to maximise muscle vitamin E content in the Longissimus thoracis et lumborum (LTL) muscle. The respective factors were four dietary levels of vitamin E (supplemented as dl-α-tocopheryl acetate; 35, 300, 500, and 700 IU/kg) and three feeding durations (14, 28 and 42 days before slaughter). Vitamin E concentration in the LTL was maximised at 6 mg/kg, which was achieved by feeding a 700 IU vitamin E diet for 28 days before slaughter (P<0.001). There was no further increase in the vitamin E content of the LTL by feeding the high vitamin E diet more than 28 days before slaughter. PMID:26313847

  9. 29 CFR 553.230 - Maximum hours standards for work periods of 7 to 28 days-section 7(k).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Maximum hours standards for work periods of 7 to 28 days... Fire protection Law enforcement 28 212 171 27 204 165 26 197 159 25 189 153 24 182 147 23 174 141 22 167 134 21 159 128 20 151 122 19 144 116 18 136 110 17 129 104 16 121 98 15 114 92 14 106 86 13 98...

  10. 29 CFR 553.230 - Maximum hours standards for work periods of 7 to 28 days-section 7(k).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Maximum hours standards for work periods of 7 to 28 days... Fire protection Law enforcement 28 212 171 27 204 165 26 197 159 25 189 153 24 182 147 23 174 141 22 167 134 21 159 128 20 151 122 19 144 116 18 136 110 17 129 104 16 121 98 15 114 92 14 106 86 13 98...

  11. 29 CFR 553.230 - Maximum hours standards for work periods of 7 to 28 days-section 7(k).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Maximum hours standards for work periods of 7 to 28 days... Fire protection Law enforcement 28 212 171 27 204 165 26 197 159 25 189 153 24 182 147 23 174 141 22 167 134 21 159 128 20 151 122 19 144 116 18 136 110 17 129 104 16 121 98 15 114 92 14 106 86 13 98...

  12. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol

    SciTech Connect

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Takeyoshi, Masahiro; Imatanaka, Nobuya; Itahashi, Megu; Murakami, Tomoaki; Shibutani, Makoto

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200 mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc{sup +} neurons at 1000 ppm and Fos{sup +} neurons at ≥ 300 ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure. - Highlights: • Neuronal toxicity parameters after 28-day glycidol treatment were examined in rats. • Region-specific global gene expression profiling was conducted in brain regions. • Cortical tissues downregulated genes on axonogenesis and synaptic transmission. • Cortical tissues

  13. 17alpha-methyltestosterone: 28-day oral toxicity study in the rat based on the "Enhanced OECD Test Guideline 407" to detect endocrine effects.

    PubMed

    Wason, Sheila; Pohlmeyer-Esch, Gabriele; Pallen, Catherine; Palazzi, Xavier; Espuña, Gemma; Bars, Remi

    2003-11-01

    A 28-day oral gavage toxicity study in the rat with 17alpha-methyltestosterone was conducted as part of the international validation exercise on the modified Enhanced OECD Test Guideline 407 (Organisation for Economic Co-operation and Development, Paris). Special emphasis was placed on the endocrine mediated effects exerted by 17alpha-methyltestosterone, a potent androgen agonist. The test compound was administered daily by oral gavage for at least 28 days to groups of 7-week-old-Wistar rats. Dose levels were 0, 10, 40 and 200 mg/kg body weight per day for males and 0, 10, 100 and 600 mg/kg body weight per day for females. In addition, and outside the remit of the enhanced protocol, testosterone levels in males, oestradiol levels in females and luteinizing hormone (LH) levels in both sexes were measured, to provide a broader profile on the hormonally mediated effects of 17alpha-methyltestosterone. Furthermore, stage-specific quantification of Terminal deoxynucleotidyl transferase-mediated dUTP Nick-End Labeling (TUNEL)-labeled germ cells (apoptotic germ cells) in the seminiferous tubules was also performed, in an effort to demonstrate the precise stages in the spermatogenic cycle 17alpha-methyltestosterone exerts its effect. In this study, the most critical additional parameters contained in the Enhanced OECD Test Guideline 407 for the detection of endocrine disruption were considered to be the histopathological assessment and organ weight data of endocrine-related tissues. Beyond the scope of this validation exercise, an increase in apoptosis in specific germ cell types was detected using the TUNEL assay in male rats treated at 200 and 40 mg/kg.

  14. Effects of 28-Day Beta-Alanine Supplementation on Isokinetic Exercise Performance and Body Composition in Female Masters Athletes.

    PubMed

    Glenn, Jordan M; Gray, Michelle; Stewart, Rodger W; Moyen, Nicole E; Kavouras, Stavros A; DiBrezzo, Ro; Turner, Ronna; Baum, Jamie I; Stone, Matthew S

    2016-01-01

    Beta-alanine (BA) supplementation increases exercise performance due to increases in the intramuscular lactate buffer, carnosine. Females are more sensitive to these increases and results are further pronounced in trained individuals. Baseline intramuscular carnosine levels also naturally decrease with age; therefore, trained older females may experience augmented benefits from BA supplementation. However, the ability of BA to increase lower-body isokinetic strength (ISO) in female masters athletes (MA) is unknown. The purpose of this study was to examine the longitudinal effects of BA supplementation on ISO, handgrip strength (HG), and body composition in female MA cyclists. Twenty-two subjects participated in this double-blind randomized study. Subjects were randomized into 2 groups (placebo [PLA] = 8 g dextrose; BA = 800 mg + 8 g dextrose) and supplemented 4 times per day for 28 days. ISO, HG, and body composition were evaluated at baseline and at the same day/time each week over the 28-day intervention. No differences existed between groups at baseline or at the 7, 14, and 21 days time points for any variables (p > 0.05). When evaluating ISO (isokinetic) after 28 days, total work performed during the final third of the assessment (24.0 vs. -16.8% change) in flexion and average peak torque (5.4 vs. 2.9% change) in extension were significantly increased from baseline in BA compared with PLA (p ≤ 0.05). No differences existed for HG or body composition after supplementation. Twenty-eight days of BA supplementation increased peak torque and work completed, indicating BA improves lower-body exercise performance in female MA.

  15. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

    PubMed

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-06-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

  16. Effects of 28 days silicon dioxide aerosol exposure on respiratory parameters, blood biochemical variables and lung histopathology in rats.

    PubMed

    Deb, Utsab; Lomash, Vinay; Raghuvanshi, Suchita; Pant, S C; Vijayaraghavan, R

    2012-11-01

    Inhalation toxicity of silicon dioxide aerosol (150, 300 mg/m(3)) daily over a period of 28 days was carried out in rats. The changes in respiratory variables during the period of exposure were monitored using a computer programme that recognizes the modifications of the breathing pattern. Exposure to the aerosol caused a time dependent decrease in tidal volume, with an increase in respiratory frequency compared to the control. Biochemical variables and histopathological observation were noted at 28th day following the start of exposure. Biochemical markers of silica induced lung injury like plasma alkaline phosphatase, lactate dehydrogenase and angiotensine converting enzyme activities increased in a concentration dependent manner compared to control. Increase in the plasma enzymatic activities indicates endothelial lung damage, increased lung membrane permeability. Histopathological observation of the lungs confirmed concentration dependent granulomatous inflammation, fibrosis and proteinacious degeneration. Aggregates of mononuclear cells with entrapped silica particles circumscribed by fibroblast were observed in 300 mg/m(3) silica aerosol exposed group at higher magnification. Decrease in tidal volume and increase in respiratory frequency might be due to the thickening of the alveolar wall leading to a decreased alveolar volume and lowered elasticity of the lung tissue. The trends in histological and biochemical data are in conformity with the respiratory data in the present study. This study reports for the first time, the changes in respiratory variables during silica aerosol exposure over a period of 28 days.

  17. Inhibition of prolactin with bromocriptine for 28days increases blood-brain barrier permeability in the rat.

    PubMed

    Rosas-Hernandez, H; Ramirez, M; Ramirez-Lee, M A; Ali, S F; Gonzalez, C

    2015-08-20

    The blood-brain barrier (BBB) is necessary for the proper function of the brain. Its maintenance is regulated by endogenous factors. Recent evidences suggest prolactin (PRL) regulates the BBB properties in vitro, nevertheless no evidence of these effects have been reported in vivo. The aim of this study was to evaluate the role of PRL in the maintenance of the BBB in the rat. Male Wistar rats were treated with Bromocriptine (Bromo) to inhibit PRL production for 28days in the absence or presence of lipopolysaccharide (LPS). BBB permeability was evaluated through the Evans Blue dye and fluorescein-dextran extravasation as well as through edema formation. The expression of claudin-5, occludin, glial fibrillary acidic protein (GFAP) and the PRL receptor (PRLR) was evaluated through western blot. Bromo reduced the physiological levels of PRL at 28days. At the same time, Bromo increased BBB permeability and edema formation associated with a decrement in claudin-5 and occludin and potentiated the increase in BBB permeability induced by LPS. However, no neuroinflammation was detected, since the expression of GFAP was unchanged, as well as the expression of the PRLR. These data provide the first evidence that inhibition of PRL with Bromo affects the maintenance of the BBB through modulating the expression of tight junction proteins in vivo.

  18. Safety assessment of EPA-rich triglyceride oil produced from yeast: genotoxicity and 28-day oral toxicity in rats.

    PubMed

    Belcher, Leigh A; MacKenzie, Susan A; Donner, Maria; Sykes, Greg P; Frame, Steven R; Gillies, Peter J

    2011-02-01

    The 28-day repeat-dose oral and genetic toxicity of eicosapentaenoic acid triglyceride oil (EPA oil) produced from genetically modified Yarrowia lipolytica yeast were assessed. Groups of rats received 0 (olive oil), 940, 1880, or 2820 mg EPA oil/kg/day, or fish oil (sardine/anchovy source) by oral gavage. Lower total serum cholesterol was seen in all EPA and fish oil groups. Liver weights were increased in the medium and high-dose EPA (male only), and fish oil groups but were considered non-adverse physiologically adaptive responses. Increased thyroid follicular cell hypertrophy was observed in male high-dose EPA and fish oil groups, and was considered to be an adaptive response to high levels of polyunsaturated fatty acids. No adverse test substance-related effects were observed on body weight, nutritional, or other clinical or anatomic pathology parameters. The oil was not mutagenic in the in vitro Ames or mouse lymphoma assay, and was not clastogenic in the in vivo mouse micronucleus test. In conclusion, exposure for 28 days to EPA oil derived from yeast did not produce adverse effects at doses up to 2820 mg/kg/day and was not genotoxic. The safety profile of the EPA oil in these tests was comparable to a commercial fish oil.

  19. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    PubMed Central

    2012-01-01

    Background Nuna Kadugu (NK), a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose) were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats. There were no delayed effects

  20. Utility of models to predict 28-day or 30-day unplanned hospital readmissions: an updated systematic review

    PubMed Central

    Zhou, Huaqiong; Della, Phillip R; Roberts, Pamela; Goh, Louise; Dhaliwal, Satvinder S

    2016-01-01

    Objective To update previous systematic review of predictive models for 28-day or 30-day unplanned hospital readmissions. Design Systematic review. Setting/data source CINAHL, Embase, MEDLINE from 2011 to 2015. Participants All studies of 28-day and 30-day readmission predictive model. Outcome measures Characteristics of the included studies, performance of the identified predictive models and key predictive variables included in the models. Results Of 7310 records, a total of 60 studies with 73 unique predictive models met the inclusion criteria. The utilisation outcome of the models included all-cause readmissions, cardiovascular disease including pneumonia, medical conditions, surgical conditions and mental health condition-related readmissions. Overall, a wide-range C-statistic was reported in 56/60 studies (0.21–0.88). 11 of 13 predictive models for medical condition-related readmissions were found to have consistent moderate discrimination ability (C-statistic ≥0.7). Only two models were designed for the potentially preventable/avoidable readmissions and had C-statistic >0.8. The variables ‘comorbidities’, ‘length of stay’ and ‘previous admissions’ were frequently cited across 73 models. The variables ‘laboratory tests’ and ‘medication’ had more weight in the models for cardiovascular disease and medical condition-related readmissions. Conclusions The predictive models which focused on general medical condition-related unplanned hospital readmissions reported moderate discriminative ability. Two models for potentially preventable/avoidable readmissions showed high discriminative ability. This updated systematic review, however, found inconsistent performance across the included unique 73 risk predictive models. It is critical to define clearly the utilisation outcomes and the type of accessible data source before the selection of the predictive model. Rigorous validation of the predictive models with moderate-to-high discriminative

  1. Comparison of methionine sources around requirement levels using a methionine efficacy method in 0 to 28 day old broilers.

    PubMed

    Agostini, P S; Dalibard, P; Mercier, Y; Van der Aar, P; Van der Klis, J D

    2016-03-01

    The addition of methionine in the poultry feed industry is still facing the relative efficacy dilemma between DL-methionine (DLM) and hydroxy-methionine (HMTBA). The aim of this study was to compare the effect of dietary DLM and HMTBA on broiler performance at different levels of total sulfur amino acids (TSAA). The treatments consisted of a basal diet without methionine addition, and 4 increasing methionine doses for both sources resulting in TSAA/Lysine ratios from 0.62 to 0.73 in the starter phase and 0.59 to 0.82 in the grower phase. The comparison of product performance was performed by three-way ANOVA analysis and by methionine efficacy calculation as an alternative method of comparison. Growth results obtained during the starter phase with the different methionine supplementations did not show significant growth responses to TSAA levels, indicating a lower methionine requirement in the starter phase than currently assumed. However, a significant methionine dose effect was obtained for the period 10 to 28 day of age and for the entire growth period of 0 to 28 day of age. Excepting a significant gender effect, the statistical analysis did not allow for the discrimination of methionine sources, and no interaction between source and dose level was observed up to 28 days of age. A significant interaction between source and dose level was observed for methionine efficacy for the grower phase, and the total growth period showed better HMTBA efficacy at higher TSAA value. The exponential model fitted to each methionine source for body weight response depending on methionine intake or for feed conversion ratio (FCR) depending on methionine doses did not allow the methionine sources to be distinguished. Altogether, these results conclude that methionine sources lead to similar performances response when compared at TSAA values around the broiler requirement level. These results also showed that at TSAA values above requirement, HMTBA had a better methionine efficacy

  2. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol.

    PubMed

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Takeyoshi, Masahiro; Imatanaka, Nobuya; Itahashi, Megu; Murakami, Tomoaki; Shibutani, Makoto

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc(+) neurons at 1000ppm and Fos(+) neurons at ≥300ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure.

  3. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    PubMed Central

    2011-01-01

    Background The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials. Results AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG) staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM), nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver. Conclusions The results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver granules containing

  4. 28 day modulation of global lightning activity and its relation to tropical cloud coverage and solar activity

    NASA Astrophysics Data System (ADS)

    Sato, M.; Takahashi, Y.; Fukunishi, H.

    2005-12-01

    In order to investigate characteristics of global lightning activity changes, we analyzed Schumann resonance (SR) spectral intensity variation using 1-100 Hz ELF magnetic field waveform data obtained at Syowa station (69.0°S, 39.6°E) for the period between February 2000 and January 2003. We calculated dynamic spectra of ELF data with the fast Fourier transform (FFT) method and extracted spectral powers at the first three resonance modes (8, 14, 20 Hz) as a function of day. Then, we calculated a power spectrum of the SR spectral intensity variation. It is found that there are steep peaks at 28 and 11, and multiple peaks around ~4-6 days. Though it is suggested that the ~10 and ~5 day periodicities are highly associated with planetary wave activity in the tropical region, clear evidence for the presence of the 28 day periodicity over three years has been found for the first time in this study. As a next step, we analyzed the composite infrared cloud images to examine the relationship between the SR spectral intensity variation and the variation of the tropical cloud coverage. From the cross-spectral analysis between these variations it is found that the cross spectrum showed a steep peak at the 24 day period and that the phase histogram showed the clear anti-phase relation. The discovered anti-phase relation may be best explained by the decrease of lightning activity, driven by the decrease of the heat flux and the convective available potential energy (CAPE) needed to induce thunderstorms. Further, we performed dynamic cross-spectral analysis between the SR spectral intensity variation and solar and geomagnetic activity parameters such as F10.7 index, sunspot number, Kp index , Dst index, cosmic ray flux, and relativistic electron and ion fluxes measured by the GOES-8 satellite. Though the cross-spectrum peaks in the period range from 20 to 30 day, the coherence values in this period range are estimated to be less than 0.6. In addition, there is no clear one

  5. Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats.

    PubMed

    Cariddi, L N; Escobar, F M; Sabini, M C; Campra, N A; Bagnis, G; Decote-Ricardo, D; Freire-de-Lima, C G; Mañas, F; Sabini, L I; Dalcero, A M

    2016-04-01

    The present study aimed to characterize the chlorogenic acid (ChlA) capacity to reverse the toxic effects induced by ochratoxin A (OTA) in a subacute toxicity test in rats. Male Wistar rats were fed orally by gavage for 28 days with OTA (0.4mg/kg bw/day), ChlA (5mg/kg bw/day) or the combination OTA (0.4mg/kg bw/day)+ChlA (5mg/kg bw/day). No deaths, no decrease in feed intake or body weight in any experimental group were recorded. The negative control group and the animals treated with ChlA alone showed no changes in any parameters evaluated. In OTA-treated group significant changes such as decrease in urine volume, proteinuria, occult blood, increase in serum creatinine values; decrease in absolute and relative kidney weight and characteristics histopathological lesions that indicated kidney damage were observed. However, limited effect on oxidative stress parameters were detected in kidneys of OTA-treated group. Animals treated with the combination OTA+ChlA were showed as negative control group in the evaluation of several parameters of toxicity. In conclusion, ChlA, at given concentration, improved biochemical parameters altered in urine and serum and pathological damages in kidneys induced by OTA exposure, showing a good protective activity, but not by an apparent antioxidant mechanism.

  6. Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats.

    PubMed

    Cariddi, L N; Escobar, F M; Sabini, M C; Campra, N A; Bagnis, G; Decote-Ricardo, D; Freire-de-Lima, C G; Mañas, F; Sabini, L I; Dalcero, A M

    2016-04-01

    The present study aimed to characterize the chlorogenic acid (ChlA) capacity to reverse the toxic effects induced by ochratoxin A (OTA) in a subacute toxicity test in rats. Male Wistar rats were fed orally by gavage for 28 days with OTA (0.4mg/kg bw/day), ChlA (5mg/kg bw/day) or the combination OTA (0.4mg/kg bw/day)+ChlA (5mg/kg bw/day). No deaths, no decrease in feed intake or body weight in any experimental group were recorded. The negative control group and the animals treated with ChlA alone showed no changes in any parameters evaluated. In OTA-treated group significant changes such as decrease in urine volume, proteinuria, occult blood, increase in serum creatinine values; decrease in absolute and relative kidney weight and characteristics histopathological lesions that indicated kidney damage were observed. However, limited effect on oxidative stress parameters were detected in kidneys of OTA-treated group. Animals treated with the combination OTA+ChlA were showed as negative control group in the evaluation of several parameters of toxicity. In conclusion, ChlA, at given concentration, improved biochemical parameters altered in urine and serum and pathological damages in kidneys induced by OTA exposure, showing a good protective activity, but not by an apparent antioxidant mechanism. PMID:26987112

  7. Assessing sediment toxicity from navigational pools of the Upper Mississippi River using a 28-day Hyalella azteca test

    USGS Publications Warehouse

    Kemble, N.E.; Brunson, E.L.; Canfield, T.J.; Dwyer, F.J.; Ingersoll, C.G.

    1998-01-01

    To assess the extent of sediment contamination in the Upper Mississippi River (UMR) system after the flood of 1993, sediment samples were collected from 24 of the 26 navigational pools in the river and from one site in the Saint Croix River in the summer of 1994. Whole-sediment tests were conducted with the amphipod Hyalella azteca for 28 days measuring the effects on survival, growth, and sexual maturation. Amphipod survival was significantly reduced in only one sediment (13B) relative to the control and reference sediments. Body length of amphipods was significantly reduced relative to the control and reference sediments in only one sample (26C). Sexual maturation was not significantly reduced in any treatment when compared to the control and reference sediments. No significant correlations were observed between survival, growth, and maturation to either the physical or chemical characteristics of the sediment samples from the river. When highly reliable effect range medians (ERMs) were used to evaluate sediment chemistry, 47 of 49 (96%) of the samples were correctly classified as nontoxic. These results indicate that sediment samples from the Upper Mississippi River are relatively uncontaminated compared to other areas of known contamination in the United States.

  8. Psychomotor performance during a 28 day head-down tilt with and without lower body negative pressure

    NASA Astrophysics Data System (ADS)

    Traon, A. Pavy-le; de Feneyrols, A. Rous; Cornac, A.; Abdeseelam, R.; N'uygen, D.; Lazerges, M.; Güell, A.; Bes, A.

    Several factors may affect psychomotor performance in space: sensory-motor changes, sleep disturbances, psychological modifications induced by the social isolation and confinement. However, psychomotor performance is difficult to assess. A battery of standardized and computerized tests, so-called "Automated Portable Test System" (APTS) was devised to ascertain the cognitive, perceptive and motor abilities and their possible fluctuations according to environmental effects. Antiorthostatic bedrest, often used to simulate weightlessness, (particularly cardiovascular modifications) also constitutes a situation of social confinement and isolation. During two bedrest experiments (with head-down tilt of -6°) of 28 days each, we intended to assess psychomotor performance of 6 males so as to determine whether: —on the one hand, it could be altered by remaining in decubitus; —on the other, the Lower Body Negative Pressure sessions, designed to prevent orthostatic intolerance back on Earth, could improve the performance. To accomplish this, part of the APTS tests as well as an automated perceptive attention test were performed. No downgrading of psychomotor performance was observed. On the contrary, the tasks were more accurately performed over time. In order to assess the experimental conditions on the acquisition phase, the learning curves were modelled. A beneficial effect of the LBNP sessions on simple tests involving the visual-motor coordination and attention faculties can only be regarded as a mere trend. Methods used in this experiment are also discussed.

  9. Toxicological assessment of β-(1-->6)-glucan (lasiodiplodan) in mice during a 28-day feeding study by gavage.

    PubMed

    Túrmina, Janaína A; Carraro, Emerson; Alves da Cunha, Mário A; Dekker, Robert F H; Barbosa, Aneli M; Dos Santos, Fábio Seidel; Silva, Luiz A; Malfatti, Carlos R M

    2012-01-01

    Studies evaluating the toxicity caused by fungal exopolysaccharides of the β-(1-->6)-D-glucan type are rare. In this study, the toxicological effects of sub-chronic treatments with lasiodiplodan (β-(1-->6)-D-glucan from Lasiodiplodia theobromae MMPI) were evaluated in mice through the assessment of biochemical, hematological, and histopathological alterations. Thirty-two mice (16 male, 16 female) were used in this study divided in two groups; one group received lasiodiplodan (50 mg/kg body weight) daily for 28 days via gavage, and another (control group) received saline during the same period. Blood samples were collected via cardiac puncture for hematological and biochemical analyses. Liver, heart, kidney, and spleen were collected for histopathological analysis. Statistical analysis was performed through one-way analysis of variance and only p < 0.05 F-values were presented. Significant reduction in blood glucose in the male group (35%; p < 0.01), transaminases activity in both sexes (AST and ALT; ~35%; p < 0.05), and urea (20%; p < 0.01) in the female group was observed with the lasiodiplodan treatment. The results showed that sub-chronic treatments with lasiodiplodan did not generate hematological and histopathological alterations leading to signs of toxicity in healthy mice, independent of gender. PMID:23208465

  10. Neuropsychiatric manifestations in late-onset urea cycle disorder patients.

    PubMed

    Serrano, Mercedes; Martins, Cecilia; Pérez-Dueñas, Belén; Gómez-López, Lilian; Murgui, Empar; Fons, Carmen; García-Cazorla, Angels; Artuch, Rafael; Jara, Fernando; Arranz, José A; Häberle, Johannes; Briones, Paz; Campistol, Jaume; Pineda, Mercedes; Vilaseca, Maria A

    2010-03-01

    Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late-onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation, attention-deficit hyperactivity disorder [ADHD], language disorder, and delirium). Generally, these clinical pictures did not benefit from pharmacological treatment. Conversely, dietary treatment improved the symptoms. Regarding biochemical data, 2 patients showed normal ammonium but high glutamine levels. This study highlights the fact that neuropsychiatric/neurodevelopmental findings are common among the initial symptomatology of late-onset urea cycle disorders. The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder.

  11. Improving the revenue cycle by taking the patient's perspective.

    PubMed

    Langford, April; Dye, Lyda; Moresco, Jessica; Riefner, Donald C

    2010-09-01

    UPMC revenue cycle operations analyzed front-end processes to improve them, thereby also improving the patient experience. UPMC focused on scheduling, eligibility/insurance verification, and financial counseling to develop an integrated work flow ensuring data integrity and expediting account resolution. Automating the processes increased efficiency and reduced errors, while improving patient satisfaction.

  12. Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study.

    PubMed

    Pan, Chih-Hong; Chuang, Kai-Jen; Chen, Jen-Kun; Hsiao, Ta-Chih; Lai, Ching-Huang; Jones, Tim P; BéruBé, Kelly A; Hong, Gui-Bing; Ho, Kin-Fai; Chuang, Hsiao-Chi

    2015-01-01

    Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP. PMID:26251593

  13. Toxicological evaluation of isopropylparaben and isobutylparaben mixture in Sprague-Dawley rats following 28 days of dermal exposure.

    PubMed

    Kim, Min Ji; Kwack, Seung Jun; Lim, Seong Kwang; Kim, Yeon Joo; Roh, Tae Hyun; Choi, Seul Min; Kim, Hyung Sik; Lee, Byung Mu

    2015-11-01

    The alkyl esters of p-hydroxybenzoic acid (Parabens) have been of concern due to their probable endocrine disrupting property especially in baby consumer products. The safety of parabens for use as a preservative in cosmetics has come into controversy, and thus consumer demand for paraben-free products is ever increasing. Thus, more comprehensive studies are needed to conclusively determine the safety of the multiple prolonged exposure to parabens with cosmetic ingredients. This study was conducted to investigate the potential repeated 28 days dermal toxicity (50, 100, 300, or 600 mg/kg bw/day) of isopropylparaben (IPP), isobutylparaben (IBP), or the mixture of IPP and IBP in rats. There were no significant changes in body and organ weights in any group. However, histopathological examinations showed that weak or moderate skin damages were observed in female rats by macroscopic and microscopic evaluations. In female rats, no observed adverse effect levels (NOAELs) of IPP with no skin lesion and IBP for skin hyperkeratosis, were estimated to be 600 mg/kg bw/day, and 50 mg/kg bw/day, respectively. With regard skin hyperkeratosis, the lowest observed adverse effect level (LOAEL) of the mixture of IPP and IBP was estimated to be 50 mg/kg bw/day. Analysis of six serum hormones (estrogen, testosterone, insulin, T3, TSH, or FSH) in animals showed that only FSH was dose-dependently decreased in the mixture groups of 100 mg/kg bw/day or higher. These data suggest that the mixture of IPP and IBP showed a synergistic dermal toxicity in rats and should be considered for future use in consumer products.

  14. Correlation analysis of hypothalamic mRNA levels of appetite regulatory neuropeptides and several metabolic parameters in 28-day-old layer chickens.

    PubMed

    Honda, Kazuhisa; Saneyasu, Takaoki; Aoki, Koji; Shimatani, Tomohiko; Yamaguchi, Takuya; Kamisoyama, Hiroshi

    2015-05-01

    Various lines of evidence suggest that appetite-related neuropeptides in the hypothalamus are regulated by adiposity signals such as leptin and insulin in mammals. In the present study, we examined age-dependent changes in the weight of abdominal fat and hypothalamic mRNA levels of neuropeptide Y (NPY, an orexigenic neuropeptide) and proopiomelanocortin (POMC, a precursor of anorexigenic neuropeptides) in growing chickens at 7, 14, 21 and 28 days of age. Hypothalamic NPY mRNA levels were significantly (P < 0.05) decreased after 14 days of age, whereas hypothalamic POMC mRNA levels were significantly (P < 0.05) increased at 28 days of age. The percentage of abdominal fat was significantly increased after 14 days of age in chickens. We next examined the correlation of hypothalamic NPY and POMC mRNA levels and several parameters at 28 days of age. There were no significant correlations between hypothalamic mRNA levels of NPY or POMC and the percentage of abdominal fat. These findings suggest that the gene expressions of NPY and POMC do not depend on adiposity in chickens, at least in 28-day-old layer chickens.

  15. FES-cycling training in spinal cord injured patients.

    PubMed

    Mazzoleni, S; Stampacchia, G; Gerini, A; Tombini, T; Carrozza, M C

    2013-01-01

    Among the objectives of spinal cord injury (SCI) rehabilitation, (i) prevention of bony, muscular and joint trophism and (ii) limitation of spastic hypertone represent important goals to be achieved. The aim of this study is to use functional electrical stimulation (FES) to activate pedaling on cycle-ergometer and analyse effects of this technique for a rehabilitation training in SCI persons. Five spinal cord injured subjects were recruited and underwent a two months FES-cycling training. Our results show an increase of thigh muscular area and endurance after the FES-cycling training, without any increase of spasticity. This approach, which is being validated on a larger pool of patients, represents a potential tool for improving the rehabilitation outcome of complete and incomplete SCI persons.

  16. Nutritional management of patients with urea cycle disorders.

    PubMed

    Singh, R H

    2007-11-01

    The nutritional management of patients with urea cycle disorders (UCDs) involves restriction of dietary protein along with provision of adequate protein-free energy, essential amino acid supplements, and vitamins and minerals in combination with nitrogen-scavenging drugs. The present paper discusses nutrition therapy for a range of circumstances: during an acute hyperammonaemic episode and at hospital discharge; before, during, and after surgery; and for lifelong chronic management of UCDs.

  17. Acute and 28-day sub-acute oral toxicity evaluation of two dietary bamboo charcoal powders in Sprague-Dawley rats.

    PubMed

    Jia, Zhen-chao; Luo, Sha; Zhong, Yu-ting; Li, Xiao; Chen, Jin-yao; Zhang, Li-shi

    2015-04-01

    No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders (BCP1 and BCP2). The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley (SD) rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose (LD50) of BCP for both male and female rats is more than 11.24 g/kg body weight and the no-observed-adverse-effect level (NOAEL) is >11.24 g/kg body weight for 28 days.

  18. Glycidol induces axonopathy and aberrations of hippocampal neurogenesis affecting late-stage differentiation by exposure to rats in a framework of 28-day toxicity study.

    PubMed

    Akane, Hirotoshi; Shiraki, Ayako; Imatanaka, Nobuya; Akahori, Yumi; Itahashi, Megu; Abe, Hajime; Shibutani, Makoto

    2014-01-30

    Developmental exposure to glycidol induces aberrations of late-stage neurogenesis in the hippocampal dentate gyrus of rat offspring, whereas maternal animals develop axonopathy. To investigate the possibility whether similar effects on adult neurogenesis could be induced by exposure in a framework of 28-day toxicity study, glycidol was orally administered to 5-week-old male Sprague-Dawley rats by gavage at 0, 30 or 200 mg/kg for 28 days. At 200 mg/kg, animals revealed progressively worsening gait abnormalities as well as histopathological and immunohistochemical changes suggestive of axonal injury as evidenced by generation of neurofilament-L(+) spheroids in the cerebellar granule layer and dorsal funiculus of the medulla oblongata, central chromatolysis in the trigeminal nerve ganglion cells and axonal degeneration in the sciatic nerves. At the same dose, animals revealed aberrations in neurogenesis at late-stage differentiation as evidenced by decreases of both doublecortin(+) and dihydropyrimidinase-like 3(+) cells in the subgranular zone (SGZ) and increased reelin(+) or calbindin-2(+) γ-aminobutyric acid-ergic interneurons and neuron-specific nuclear protein(+) mature neurons in the dentate hilus. These effects were essentially similar to that observed in offspring after maternal exposure to glycidol. These results suggest that glycidol causes aberrations in adult neurogenesis in the SGZ at the late stage involving the process of neurite extension similar to the developmental exposure study in a standard 28-day toxicity study.

  19. Menstrual cyclicity of finger joint size and grip strength in patients with rheumatoid arthritis.

    PubMed Central

    Rudge, S R; Kowanko, I C; Drury, P L

    1983-01-01

    Daily measurements of finger joint size, grip strength, and body weight have been made throughout 2 complete menstrual cycles in 7 female patients with rheumatoid arthritis and 6 healthy female controls. Sine wave analysis showed significant individual cyclical rhythms (p less than 0.05) for finger joint size (5 patients, 4 controls), nude weight (5 patients, 3 controls), and grip strength (4 patients, 3 controls). In addition analysis of group data, on the assumption of a 28-day cycle, showed a significant cycle for grip strength in the rheumatoid patients, with a nadir at 28 days. In the normal subjects much of the cyclical variation in finger joint size could be explained by changes in weight (median 49.5%), but this was not so in patients with rheumatoid arthritis (median 2.8%). These findings suggest the existence of a cyclical variation in disease activity in rheumatoid arthritis. PMID:6882039

  20. Immunotoxicological profile of chloramine in female B6C3F1 mice when administered in the drinking water for 28 days.

    PubMed

    Guo, Tai L; Germolec, Dori R; Collins, Bradley J; Luebke, Robert W; Auttachoat, Wimolnut; Smith, Matthew J; White, Kimber L

    2011-01-01

    Monochloramine has been used to provide a disinfecting residual in water distribution systems where it is difficult to maintain an adequate free-chlorine residual or where disinfection by-product formation is of concern. The goal of this study was to characterize the immunotoxic effects of chloramine in female B(6)C(3)F(1) mice when administered via the drinking water. Mice were exposed to chloramine-containing deionized tap water at 2, 10, 20, 100, or 200 ppm for 28 days. No statistically significant differences in drinking water consumption, body weight, body weight gain, organ weights, or hematological parameters between the exposed and control animals were noted during the experimental period. There were no changes in the percentages and numbers of total B-lymphocytes, T-lymphocytes, CD4(+) and CD8(+) T-lymphocytes, natural killer (NK) cells, and macrophages in the spleen. Exposure to chloramine did not affect the IgM antibody-forming cell response to sheep red blood cells (SRBC) or anti-SRBC IgM antibody production. Minimal effects, judged to be biologically insignificant, were observed in the mixed-leukocyte response and NK activity. In conclusion, chloramine produced no toxicological and immunotoxic effects in female B(6)C(3)F(1) mice when administered for 28 days in the drinking water at concentrations ranging from 2-200 ppm.

  1. GLUTAMINE AND HYPERAMMONEMIC CRISES IN PATIENTS WITH UREA CYCLE DISORDERS

    PubMed Central

    Lee, B.; Diaz, G.A.; Rhead, W.; Lichter-Konecki, U.; Feigenbaum, A.; Berry, S.A.; Le Mons, C.; Bartley, J.; Longo, N.; Nagamani, S.C.; Berquist, W.; Gallagher, R.C.; Harding, C.O.; McCandless, S.E.; Smith, W.; Schulze, A.; Marino, M.; Rowell, R.; Coakley, D.F.; Mokhtarani, M.; Scharschmidt, B.F.

    2016-01-01

    Blood ammonia and glutamine levels are used as biomarkers of control in patients with urea cycle disorders (UCDs). This study was undertaken to evaluate glutamine variability and utility as a predictor of hyperammonemic crises (HACs) in UCD patients. Methods The relationships between glutamine and ammonia levels and the incidence and timing of HACs were evaluated in over 100 adult and pediatric UCD patients who participated in clinical trials of glycerol phenylbutyrate. Results The median (range) intra-subject 24-hour coefficient of variation for glutamine was 15% (8–29%) as compared with 56% (28%–154%) for ammonia, and the correlation coefficient between glutamine and concurrent ammonia levels varied from 0.17 to 0.29. Patients with baseline (fasting) glutamine values >900 µmol/L had higher baseline ammonia levels (mean [SD]: 39.6 [26.2] µmol/L) than patients with baseline glutamine ≤900 µmol/L (26.6 [18.0] µmol/L). Glutamine values >900 µmol/L during the study were associated with an approximately 2-fold higher HAC risk (odds ratio [OR]=1.98; p=0.173). However, glutamine lost predictive significance (OR=1.47; p=0.439) when concomitant ammonia was taken into account, whereas the predictive value of baseline ammonia ≥ 1.0 upper limit of normal (ULN) was highly statistically significant (OR=4.96; p=0.013). There was no significant effect of glutamine >900 µmol/L on time to first HAC crisis (hazard ratio [HR]=1.14; p=0.813), but there was a significant effect of baseline ammonia ≥ 1.0 ULN (HR=4.62; p=0.0011). Conclusions The findings in this UCD population suggest that glutamine is a weaker predictor of HACs than ammonia and that the utility of the predictive value of glutamine will need to take into account concurrent ammonia levels. PMID:26586473

  2. Muscle Oxygen Dynamics During Cycling Exercise in Angina Pectoris Patients.

    PubMed

    Takagi, Shun; Murase, Norio; Kime, Ryotaro; Niwayama, Masatsugu; Osada, Takuya; Katsumura, Toshihito

    2016-01-01

    Muscle O2 dynamics during ramp cycling exercise were compared between angina pectoris patients (AP; n = 7, age: 73 ± 6 years) after coronary artery bypass grafting and age-, height-, and body weight-matched elderly control subjects (CON; n = 7, age: 74 ± 8 years). Muscle O2 saturation (SmO2) and relative change in deoxygenated (∆deoxy-Hb) and total hemoglobin concentration (∆total-Hb) were measured continuously during exercise in the vastus lateralis (VL) by near infrared spatial resolved spectroscopy. Pulmonary O2 uptake (VO2) was also monitored throughout exercise to determine peak VO2. In AP, SmO2 was significantly higher, and ∆deoxy-Hb was significantly lower during exercise, compared to CON. In all subjects, ∆SmO2 (values at peak exercise minus values at resting) was negatively correlated to peak VO2 (r = -0.52, p < 0.05), and ∆deoxy-Hb at peak exercise tended to be negatively associated with peak VO2 (r = 0.48, p = 0.07). Blunted skeletal muscle deoxygenation response was observed in AP patients, which may be related to lower aerobic capacity in AP patients. PMID:27526156

  3. The application of cycling and cycling combined with feedback in the rehabilitation of stroke patients: a review.

    PubMed

    Barbosa, David; Santos, Cristina P; Martins, Maria

    2015-02-01

    Stroke is a leading cause of long-term disabilities, such as hemiparesis, inability to walk without assistance, and dependence of others in the activities of daily living. Motor function rehabilitation after stroke demands for methods oriented to the recovery of the walking capacity. Because of the similarities with walking, cycling leg exercise may present a solution to this problem. The aim of this article is to review the state of the art applications of cycling leg exercise as a (1) motor function rehabilitation method and an (2) aerobic training method for stroke patients as well as the commonly used (3) assessment tools. The cycling characteristics and applications, the applied test protocols as well as the tools used to assess the state and the recovery of patients and types of cycling devices are presented. In addition, the potential benefits of the use of other therapies, like feedback, together with cycling are explored. The application of cycling leg exercise alone and combined with feedback in stroke rehabilitation approaches has shown promising results. Positive effects on motor abilities were found in subacute and chronic patients. However, larger and normalized studies and assessments are needed because there is a high heterogeneity in the patients' characteristics, protocols and metrics. This wil allow the comparison between different studies related with cycling.

  4. Metrological characterization of a cycle-ergometer to optimize the cycling induced by functional electrical stimulation on patients with stroke.

    PubMed

    Comolli, Lorenzo; Ferrante, Simona; Pedrocchi, Alessandra; Bocciolone, Marco; Ferrigno, Giancarlo; Molteni, Franco

    2010-05-01

    Functional electrical stimulation (FES) is a well established method in the rehabilitation of stroke patients. Indeed, a bilateral movement such as cycling induced by FES would be crucial for these patients who had an unilateral motor impairment and had to recover an equivalent use of limbs. The aim of this study was to develop a low-cost meteorologically qualified cycle-ergometer, optimized for patients with stroke. A commercial ergometer was instrumented with resistive strain gauges and was able to provide the torque produced at the right and left crank, independently. The developed system was integrated with a stimulator, obtaining a novel FES cycling device able to control in real-time the movement unbalance. A dynamic calibration of the sensors was performed and a total torque uncertainty was computed. The system was tested on a healthy subject and on a stroke patient. Results demonstrated that the proposed sensors could be successfully used during FES cycling sessions where the maximum torque produced is about 9Nm, an order of magnitude less than the torque produced during voluntary cycling. This FES cycling system will assist in future investigations on stroke rehabilitation by means of FES and in new exercise regimes designed specifically for patients with unilateral impairments.

  5. Metrological characterization of a cycle-ergometer to optimize the cycling induced by functional electrical stimulation on patients with stroke.

    PubMed

    Comolli, Lorenzo; Ferrante, Simona; Pedrocchi, Alessandra; Bocciolone, Marco; Ferrigno, Giancarlo; Molteni, Franco

    2010-05-01

    Functional electrical stimulation (FES) is a well established method in the rehabilitation of stroke patients. Indeed, a bilateral movement such as cycling induced by FES would be crucial for these patients who had an unilateral motor impairment and had to recover an equivalent use of limbs. The aim of this study was to develop a low-cost meteorologically qualified cycle-ergometer, optimized for patients with stroke. A commercial ergometer was instrumented with resistive strain gauges and was able to provide the torque produced at the right and left crank, independently. The developed system was integrated with a stimulator, obtaining a novel FES cycling device able to control in real-time the movement unbalance. A dynamic calibration of the sensors was performed and a total torque uncertainty was computed. The system was tested on a healthy subject and on a stroke patient. Results demonstrated that the proposed sensors could be successfully used during FES cycling sessions where the maximum torque produced is about 9Nm, an order of magnitude less than the torque produced during voluntary cycling. This FES cycling system will assist in future investigations on stroke rehabilitation by means of FES and in new exercise regimes designed specifically for patients with unilateral impairments. PMID:20171923

  6. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    SciTech Connect

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

  7. A 28-day oral toxicity study of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, in F344 rats.

    PubMed

    Hagiwara, Akihiro; Imai, Norio; Sano, Masashi; Kawabe, Mayumi; Tamano, Seiko; Kitamura, Satoshi; Omoto, Toshio; Asai, Iwao; Yasuhara, Kazuo; Hayashi, Shim-Mo

    2010-06-01

    This study was designed to evaluate any adverse effect of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, when administered to both sexes of F344 rats at dietary levels of 0, 1.25, 2.5, and 5.0% for 28 days. The treatment had no adverse effects on clinical signs, mortality, body weights and food and water consumption, or on urinalysis, ophthalmology, hematology, blood biochemistry, and histopathology findings. At necropsy, slight increased absolute and relative cecum weights, evident in females ingesting 2.5% and 5.0% dietary levels, were considered to be a physiological adaptation to the poorly absorbed fermentation-derived cellulose. The non-observed-adverse-effect level (NOAEL) from the present study was concluded to be 5.0% in the diet (5,331 mg/kg body weights/day for males, and 5,230 mg/kg body weights/day for females).

  8. Ingesting a preworkout supplement containing caffeine, creatine, β-alanine, amino acids, and B vitamins for 28 days is both safe and efficacious in recreationally active men.

    PubMed

    Kendall, Kristina L; Moon, Jordan R; Fairman, Ciaran M; Spradley, Brandon D; Tai, Chih-Yin; Falcone, Paul H; Carson, Laura R; Mosman, Matt M; Joy, Jordan M; Kim, Michael P; Serrano, Eric R; Esposito, Enrico N

    2014-05-01

    The purpose of this study was to determine the safety and efficacy of consuming a preworkout supplement (SUP) containing caffeine, creatine, β-alanine, amino acids, and B vitamins for 28 days. We hypothesized that little to no changes in kidney and liver clinical blood markers or resting heart rate and blood pressure (BP) would be observed. In addition, we hypothesized that body composition and performance would improve in recreationally active males after 28 days of supplementation. In a double-blind, placebo-controlled study, participants were randomly assigned to ingest one scoop of either the SUP or placebo every day for 28 days, either 20 minutes before exercise or ad libitum on nonexercise days. Resting heart rate and BP, body composition, and fasting blood samples were collected before and after supplementation. Aerobic capacity as well as muscular strength and endurance were also measured. Significant (P < .05) main effects for time were observed for resting heart rate (presupplementation, 67.59 ± 7.90 beats per minute; postsupplementation, 66.18 ± 7.63 beats per minute), systolic BP (presupplementation, 122.41 ± 11.25 mm Hg; postsupplementation, 118.35 ± 11.58 mm Hg), blood urea nitrogen (presupplementation, 13.12 ± 2.55 mg/dL; postsupplementation, 15.24 ± 4.47 mg/dL), aspartate aminotransferase (presupplementation, 34.29 ± 16.48 IU/L; postsupplementation, 24.76 ± 4.71 IU/L), and alanine aminotransferase (presupplementation, 32.76 ± 19.72 IU/L; postsupplementation, 24.88 ± 9.68 IU/L). Significant main effects for time were observed for body fat percentage (presupplementation, 15.55% ± 5.79%; postsupplementation, 14.21% ± 5.38%; P = .004) and fat-free mass (presupplementation, 70.80 ± 9.21 kg; postsupplementation, 71.98 ± 9.27 kg; P = .006). A significant decrease in maximal oxygen consumption (presupplementation, 47.28 ± 2.69 mL/kg per minute; postsupplementation, 45.60 ± 2.81 mL/kg per minute) and a significant increase in percentage of

  9. Ingesting a preworkout supplement containing caffeine, creatine, β-alanine, amino acids, and B vitamins for 28 days is both safe and efficacious in recreationally active men.

    PubMed

    Kendall, Kristina L; Moon, Jordan R; Fairman, Ciaran M; Spradley, Brandon D; Tai, Chih-Yin; Falcone, Paul H; Carson, Laura R; Mosman, Matt M; Joy, Jordan M; Kim, Michael P; Serrano, Eric R; Esposito, Enrico N

    2014-05-01

    The purpose of this study was to determine the safety and efficacy of consuming a preworkout supplement (SUP) containing caffeine, creatine, β-alanine, amino acids, and B vitamins for 28 days. We hypothesized that little to no changes in kidney and liver clinical blood markers or resting heart rate and blood pressure (BP) would be observed. In addition, we hypothesized that body composition and performance would improve in recreationally active males after 28 days of supplementation. In a double-blind, placebo-controlled study, participants were randomly assigned to ingest one scoop of either the SUP or placebo every day for 28 days, either 20 minutes before exercise or ad libitum on nonexercise days. Resting heart rate and BP, body composition, and fasting blood samples were collected before and after supplementation. Aerobic capacity as well as muscular strength and endurance were also measured. Significant (P < .05) main effects for time were observed for resting heart rate (presupplementation, 67.59 ± 7.90 beats per minute; postsupplementation, 66.18 ± 7.63 beats per minute), systolic BP (presupplementation, 122.41 ± 11.25 mm Hg; postsupplementation, 118.35 ± 11.58 mm Hg), blood urea nitrogen (presupplementation, 13.12 ± 2.55 mg/dL; postsupplementation, 15.24 ± 4.47 mg/dL), aspartate aminotransferase (presupplementation, 34.29 ± 16.48 IU/L; postsupplementation, 24.76 ± 4.71 IU/L), and alanine aminotransferase (presupplementation, 32.76 ± 19.72 IU/L; postsupplementation, 24.88 ± 9.68 IU/L). Significant main effects for time were observed for body fat percentage (presupplementation, 15.55% ± 5.79%; postsupplementation, 14.21% ± 5.38%; P = .004) and fat-free mass (presupplementation, 70.80 ± 9.21 kg; postsupplementation, 71.98 ± 9.27 kg; P = .006). A significant decrease in maximal oxygen consumption (presupplementation, 47.28 ± 2.69 mL/kg per minute; postsupplementation, 45.60 ± 2.81 mL/kg per minute) and a significant increase in percentage of

  10. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study.

    PubMed

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600mg/kg body weight/day for 28days. In the subgranular zone (SGZ), 600mg/kg CPZ increased the number of cleaved caspase-3(+) apoptotic cells. At ≥120mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥120mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥120mg/kg decreased phosphorylated TRKB(+) interneurons, although the number of reelin(+) interneurons was unchanged. At 600mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells.

  11. Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats

    PubMed Central

    Han, Chung-Tack; Kim, Myoung-Jun; Moon, Seol-Hee; Jeon, Yu-Rim; Hwang, Jae-Sik; Nam, Chunja; Park, Chong-Woo; Lee, Sun-Ho; Na, Jae-Bum; Park, Chan-Sung; Park, Hee-Won; Lee, Jung-Min; Jang, Ho-Song; Park, Sun-Hee; Han, Kyoung-Goo; Choi, Young Whan

    2015-01-01

    Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes. PMID:26877842

  12. VS411 Reduced Immune Activation and HIV-1 RNA Levels in 28 Days: Randomized Proof-of-Concept Study for AntiViral-HyperActivation Limiting Therapeutics

    PubMed Central

    Lori, Franco; De Forni, Davide; Katabira, Elly; Baev, Denis; Maserati, Renato; Calarota, Sandra A.; Cahn, Pedro; Testori, Marco; Rakhmanova, Aza; Stevens, Michael R.

    2012-01-01

    Background A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4+ T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects. Methods Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests. Results VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4+ T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: −1.47 log10 copies/mL; CD4+ T cell count: +135 cells/mm3) and fewest adverse events. Conclusions VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system

  13. Acute and sub-chronic (28 days) oral toxicity evaluation of tincture Baccharis trimera (Less) Backer in male and female rodent animals.

    PubMed

    da Silva, Andreia R H; Reginato, Fernanda Z; Guex, Camille G; Figueredo, Kássia C; da C Araldi, Isabel C; de Freitas, Robson B; Boligon, Aline A; Athayde, Margareth L; Mazzanti, Cinthia Melazzo de Andrade; Hübscher, Gilberti H; de F Bauermann, Liliane

    2016-02-01

    The infusion of Baccharis trimera (Less) DC, popularly known as "carqueja" (broom), is popularly used in the treatment of hepatic and digestive problems. In this study, we evaluated the acute and sub-chronic oral toxicities of B. trimera tincture on male and female Wistar rats according to Organization for Economic Cooperation and Development (OECD, guidelines 423 e 407, respectively). The B. trimera tincture was administered by oral gavage in a single dose (2000 mg/kg) in doses of 100, 200 and 400 mg/kg daily for 28 days. Blood was collected to analyze hematological and biochemical parameters. Kidneys and liver were homogenized to determine lipid peroxidation and δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) enzyme activities. In acute treatment, tincture did not induce any signs of toxicity or mortality. Daily oral administration produced no significant changes in the hematological and biochemical parameters, except for the hepatic enzymes alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) that showed a reduction in both sexes. Moreover, the B. trimera tincture did not increase lipid peroxidation or affected ALA-D and CAT activities. In conclusion, the tincture of B. trimera may be considered relatively safe in this protocol.

  14. Perinatal activity of the hypothalamic-pituitary-gonadal axis in the lamb. IV. Testicular responsiveness to hCG from 1 through 28 days of life.

    PubMed

    Hamel, R; Forest, M G; Haour, F; Polychronakos, C; Charpenet, G; Gibb, W; Collu, R; Durcharme, J R

    1981-01-01

    Previous studies in this laboratory have shown the existence of an early postnatal activation of the hypothalamic-pituitary-gonadal axis (HPGA) in the male lamb which was present at 2 and 4 weeks of age. In order to define more precisely the time sequence of HPGA activity, we have studied the in vivo and in vitro testicular responsiveness to human chorionic gonadotropin (hCG) of the immature lamb at 1, 3, 7, 14, 21 and 28 days of life. Plasma testosterone (T) increments (delta) after hCG were lower in 1-day-old animals than in other age groups. Testicular concentrations of T, dehydroepiandrosterone and 17-hydroxyprogesterone increased from 1 to 14 days. Testicular 17, 20 lyase activity rose significantly with age but was not influenced by hCG. hCG and dibutyryl cyclic AMP increased significantly the T production by enriched interstitial cell preparation at 1, 3, and 7 days, the greatest response being found at 7 days. hCG also increased significantly the T production at 14 days. These data suggest that the lamb testis has the capacity to respond to hCG in vivo and to various stimuli vitro from the 1st day of life and that the response reaches a plateau from 2 to 4 weeks after birth.

  15. Safety assessment of SDA soybean oil: results of a 28-day gavage study and a 90-day/one generation reproduction feeding study in rats.

    PubMed

    Hammond, Bruce G; Lemen, Joan K; Ahmed, Gulam; Miller, Kathleen D; Kirkpatrick, Jeannie; Fleeman, Tammye

    2008-12-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is limited by their instability and potential to impart off-flavors. Stearidonic acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food matrices. SDA is present in fish oils (0.5-4%) and in nutraceuticals (echium, borage oil). Genes for Delta6, Delta15 desaturases were introduced into soybeans that convert linoleic and alpha-linolenic acid to SDA (15-30% fatty acids). Since addition of SDA soybean oil into human foods increases SDA intake, toxicology studies were undertaken to assess its safety. In a 28-day pilot study, rats were gavaged with SDA soybean oil at dosages up to 3g/kg body weight/day; no treatment-related adverse effects were observed. A 90-day/one generation rat reproduction study was subsequently conducted where SDA soybean oil was added to diets to provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment-related adverse effects on parental animals or on reproductive performance and progeny development. PMID:18804141

  16. Influence of coefficient of variation in determining significant difference of quantitative values obtained from 28-day repeated-dose toxicity studies in rats.

    PubMed

    Kobayashi, Katsumi; Sakuratani, Yuki; Abe, Takemaru; Yamazaki, Kazuko; Nishikawa, Satoshi; Yamada, Jun; Hirose, Akihiko; Kamata, Eiichi; Hayashi, Makoto

    2011-01-01

    In order to understand the influence of coefficient of variation (CV) in determining significant difference of quantitative values of 28-day repeated-dose toxicity studies, we examined 59 parameters of 153 studies conducted in accordance with Chemical Substance Control Law in 12 test facilities. Sex difference was observed in 12 parameters and 10 parameters showed large CV in females. The minimum CV was 0.74% for sodium. CV of electrolytes was comparatively small, whereas enzymes had large CV. Large differences in CV were observed for major parameters among 7-8 test facilities. The changes in CV were grossly classified into 11. Our study revealed that a statistical significant difference is usually detected if there is a difference of 7% in mean values between the groups and the groups have a CV of about 7%. A parameter with a CV as high as 30% may be significantly different, if the difference of the mean between the groups is 30%. It would be ideal to use median value to assess the treatment-related effect, rather than mean, when the CV is very high. We recommend using CV of the body weight as a standard to judge the adverse effect level.

  17. Absence of adverse effects of sodium metabisulphite in manufactured biscuits: results of subacute (28-days) and subchronic (85-days) feeding studies in rats.

    PubMed

    Ribera, D; Jonker, D; Narbonne, J F; O'Brien, J; Antignac, E

    2001-02-01

    Sulphites are extensively used in the food and drinks industry. Their toxicity has been previously evaluated by addition to the diet or drinking water of laboratory animals. Because interactions between sulphites and food constituents occur, the present work was conducted to determine the subacute and subchronic toxicity of sulphite-bound compounds in a finished product: manufactured biscuits. The studies were performed on Sprague Dawley, rats for 28 and 85 days of dietary exposure. Diets were prepared from sulphited or untreated (controls) biscuits with the addition of sugar, protein, vitamins and minerals according to the nutritional requirements of the animals. Groups of 10 male and 10 female rats were administered diets containing sulphited biscuits at levels of 0, 10, 35 and 75%, corresponding to 10-15, 35-45, 150-170 and 310-340 mg SO2/kg diet. In both studies, no death or clinical abnormalities were reported. Growth rate, food consumption and food conversion efficiency were not affected by treatment. No dose-related changes were observed for haematology, clinical chemistry, ocular examination, renal-function, urinalysis, organ weights or gross and microscopic examinations. The liver concentrations of vitamins A, B1, C and E were not significantly changed except for an increase in vitamin E in high-dose males after 28 days' exposure. Based on these data, the no-observed-adverse-effect level (NOAEL) of sulphites in baked biscuits was judged to be 310 mg SO2/kg diet or 25 mg/kg body weight/day.

  18. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    PubMed

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome.

  19. CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients

    PubMed Central

    Molloy, Alexander J; Clarke, France; Herridge, Margaret S; Koo, Karen K Y; Rudkowski, Jill; Seely, Andrew J E; Pellizzari, Joseph R; Tarride, Jean-Eric; Mourtzakis, Marina; Karachi, Timothy; Cook, Deborah J

    2016-01-01

    Introduction Early exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT. Methods and analysis 60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0–4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients' muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1–2 patients per month per centre, (2) protocol violation rate <20%, (3) outcome measure ascertainment >80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics. Ethics and dissemination Each participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors. Trial registration number NCT02377830; Pre

  20. New task force aims to revamp revenue cycle with a 'patient-centric' focus.

    PubMed

    2015-05-01

    The Revenue Cycle Management Task Force of the Heathcare Information and Management Systems Society is addressing the next generation of revenue cycle management processes and tools. Payers, providers, vendors, and consultants are involved. Front-end processes such as patient access, business analytics, and point-of-service collections are a key focus. Patient access will need new technology or updated legacy systems. Patients will be able to manage their care with a single portal.

  1. In vivo study with quartz-containing ceramic dusts: Inflammatory effects of two factory samples in lungs after intratracheal instillation in a 28-day study with rats

    NASA Astrophysics Data System (ADS)

    Creutzenberg, O.; Ziemann, C.; Hansen, T.; Ernst, H.; Jackson, P.; Cartlidge, D.; Brown, R.

    2009-02-01

    As various quartz polymorphs react differently in lungs, a differentiation of effects is needed while setting occupational exposure levels. The objective of this European Collective Research Project SILICERAM was to characterize differences in biological activity of four quartz species, i.) 2 quartz-containing materials collected at typical ceramic manufacturing sites (Tableware granulate, TG and Tableware cast, TC) versus ii.) a designed ceramic dust sample (Contrived Sample, CS) and iii.) ground quartz DQ12 (well-characterised standard quartz (Positive Control, PC) and TiO2 (negative control). TG and TC had been selected as the most promising two candidates based on a preceding in vitro screening of 5 factory samples. Total doses of 5 mg per rat of the TG and TC, 1.1 mg of the CS and 0.33 mg of the PC corresponding to 0.29, 0.16, 0.29 and 0.29 mg quartz per rat, respectively, were administered to rats by intratracheal instillation. After 3 days, bronchoalveolar lavagate (BAL) analysis resulted in polymorphonuclear neutrophil (PMN) levels of 15%, 25%, 0.6% and 25% in the TG, TC, CS and PC groups, respectively. At 28 days, the values were 29%, 20%, 7% and 45%. Histopathologically, the TG and TC groups showed very slight to slight effects, the PC group, however, stronger effects after the same period. In conclusion, the following ranking was found: PC > TG > TC > CS > TiO2 > Vehicle Control. Thus, a clear differentiation of effects for TG and TC, CS and PC was found. From a regulatory point of view, the substance-specific toxic potentials of TG and TC may need to be considered when devising occupational exposure limits.

  2. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Mandimika, Tafadzwa; Schrøder, Malene; Meyer, Otto; Slob, Wout; Peijnenburg, Ad; Poulsen, Morten

    2009-06-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of alpha-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.

  3. No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days.

    PubMed

    Witt, Kristine L; Malarkey, David E; Hobbs, Cheryl A; Davis, Jeffrey P; Kissling, Grace E; Caspary, William; Travlos, Gregory; Recio, Leslie

    2010-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282-1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats.

  4. Integration of Pig-a, micronucleus, chromosome aberration and comet assay endpoints in a 28-day rodent toxicity study with urethane

    PubMed Central

    Stankowski, Leon F.; Aardema, Marilyn J.; Lawlor, Timothy E.; Pant, Kamala; Roy, Shambhu; Xu, Yong; Elbekai, Reem

    2015-01-01

    As part of the international Pig-a validation trials, we examined the induction of Pig-a mutant reticulocytes and red blood cells (RETCD59− and RBCCD59−, respectively) in peripheral blood of male Sprague Dawley® rats treated with urethane (25, 100 and 250mg/kg/day) or saline by oral gavage for 29 days. Additional endpoints integrated into this study were: micronucleated reticulocytes (MN-RET) in peripheral blood; chromosome aberrations (CAb) and DNA damage (%tail intensity via the comet assay) in peripheral blood lymphocytes (PBL); micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow; and DNA damage (comet) in various organs at termination (the 29th dose was added for the comet endpoint at sacrifice). Ethyl methanesulfonate (EMS; 200mg/kg/day on Days 3, 4, 13, 14, 15, 27, 28 and 29) was evaluated as the concurrent positive control (PC). All animals survived to termination and none exhibited overt toxicity, but there were significant differences in body weight and body weight gain in the 250-mg/kg/day urethane group, as compared with the saline control animals. Statistically significant, dose-dependent increases were observed for urethane for: RETCD59− and RBCCD59− (on Days 15 and 29); MN-RET (on Days 4, 15 and 29); and MN-PCE (on Day 29). The comet assay yielded positive results in PBL (Day 15) and liver (Day 29), but negative results for PBL (Days 4 and 29) and brain, kidney and lung (Day 29). No significant increases in PBL CAb were observed at any sample time. Except for PBL CAb (likely due to excessive cytotoxicity), EMS-induced significant increases in all endpoints/tissues. These results compare favorably with earlier in vivo observations and demonstrate the utility and sensitivity of the Pig-a in vivo gene mutation assay, and its ability to be easily integrated, along with other standard genotoxicity endpoints, into 28-day rodent toxicity studies. PMID:25934985

  5. Overexpression of Cell Cycle Proteins of Peripheral Lymphocytes in Patients with Alzheimer's Disease

    PubMed Central

    Kim, Hyeran; Kwon, Young-Ah; Ahn, Inn Sook; Kim, Sangha; Kim, Seonwoo; Jo, Sangmee Ahn

    2016-01-01

    Objective Biological markers for Alzheimer's disease (AD) will help clinicians make objective diagnoses early during the course of dementia. Previous studies have suggested that cell cycle dysregulation begins earlier than the onset of clinical manifestations in AD. Methods We examined the lymphocyte expression of cell cycle proteins in AD patients, dementia controls (DC), and normal controls (NC). One-hundred seventeen subjects (36 AD, 31 DC, and 50 NC) were recruited. The cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were measured in peripheral lymphocytes. Cell cycle protein expression in the three groups was compared after adjusting for age and sex. Results The levels of cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were significantly higher in AD patients than in the NC subjects. The DC group manifested intermediate levels of cell cycle proteins compared with the AD patients and the NC subjects. The present study indicates that cell cycle proteins are upregulated in the peripheral lymphocytes of AD patients. Conclusion Cell cycle dysregulation in peripheral lymphocytes may present a promising starting point for identifying peripheral biomarkers of AD. PMID:26766955

  6. Nitrogen removal and mass balance in newly-formed Myriophyllum aquaticum mesocosm during a single 28-day incubation with swine wastewater treatment.

    PubMed

    Liu, Feng; Zhang, Shunan; Wang, Yi; Li, Yong; Xiao, Runlin; Li, Hongfang; He, Yang; Zhang, Miaomiao; Wang, Di; Li, Xi; Wu, Jinshui

    2016-01-15

    The aim of this research was to assess the applicability of Myriophyllum (M.) aquaticum for swine wastewater treatment. Nitrogen (N) removal processes were investigated in M. aquaticum mesocosms with swine wastewater (SW), 50% diluted swine wastewater (50% SW), and two strengths of synthetic wastewater, 200 mg [Formula: see text] L(-1) (200 [Formula: see text] ) and 400 mg [Formula: see text] L(-1) (400 [Formula: see text] ). During a 28-day incubation period, the average [Formula: see text] and TN removal rates were 99.8% and 94.2% for 50% SW and 99.8% and 93.8% for SW, which were greater than 86.5% and 83.7% for 200 [Formula: see text] , and 73.7% and 74.1% for 400 [Formula: see text] , respectively. A maximum areal total nitrogen (TN) removal rate of 157.8 mg N m(-2) d(-1) was found in M. aquaticum mesocosms with SW. During the incubation period, the observed dynamics of [Formula: see text] concentrations in water and gene copy numbers of ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), nirK and nirS in soil unraveled strong nitrification and denitrification processes occurring in M. aquaticum mesocosms with swine wastewater. The N mass balance analysis indicated that plant uptake and soil N accumulation accounted for 17.9-42.2% and 18.0-43.8% of the initial TN load, respectively. The coupled nitrification and denitrification process was calculated to account for, on average, 36.8% and 62.8% of TN removal for 50% SW and SW, respectively. These findings demonstrated that the N uptake by M. aquaticum contributed to a considerable proportion of N removal. In particular, the activities of ammonia-oxidizing and denitrification microbes responsible for nitrification and denitrification processes in M. aquaticum mesocosm accelerated [Formula: see text] and TN removal from swine wastewater.

  7. Altered autonomic regulation of cardiac function during head-up tilt after 28-day head-down bed-rest with counter-measures.

    PubMed

    Hughson, R L; Yamamoto, Y; Maillet, A; Fortrat, J O; Pavy-Le Traon, A; Butler, G C; Güell, A; Gharib, C

    1994-05-01

    The effects of 28 days continuous 6 degrees head-down tilt bed-rest on heart rate variability and the slope of the spontaneous arterial baroreflex were evaluated during supine rest and the first 10 min of 60 degrees head-up tilt. Twelve healthy men were assigned to either a no counter-measure (No-CM), or a counter-measure (CM) group so that there was no difference in maximal oxygen uptake. Counter-measures consisted of short-term, high resistance exercise for 6 days per week from days 7-28, and lower body negative pressure (-28 mmHg) for 15 min on days 16, 18, 20 and 22-28. In spite of balanced between-group fitness, mean RR-interval was different between the No-CM and the CM group prior to bed-rest, but neither this nor any other variables showed significant counter-measure by bed-rest interaction effects. Therefore, all data presented are from the main effects of bed-rest or tilt from the analysis of variance. RR-interval was reduced significantly by bed-rest and by tilt (P < 0.0001). Indicators from spectral analysis of heart-rate variability suggested reduced parasympathetic nervous system activity with bed-rest (P < 0.01) and head-up tilt (P < 0.05), and increased sympathetic nervous system activity after bed-rest (P < 0.01). An indicator of complexity of cardiovascular control mechanisms, taken from the slope (beta) of log spectral power vs. log frequency relationship, suggested reduced complexity with bed-rest (P < 0.05) and head-up tilt (P < 0.01). The spontaneous baroreflex slope was reduced significantly by bed-rest (P < 0.03) and by head-up tilt (P < 0.04). Taken together, these data support the concept of altered autonomic nervous system function in the aetiology of cardiovascular deconditioning with bed-rest or space travel; and it would appear that no benefit is derived from these specific counter-measures.

  8. Integration of Pig-a, micronucleus, chromosome aberration and comet assay endpoints in a 28-day rodent toxicity study with urethane.

    PubMed

    Stankowski, Leon F; Aardema, Marilyn J; Lawlor, Timothy E; Pant, Kamala; Roy, Shambhu; Xu, Yong; Elbekai, Reem

    2015-05-01

    As part of the international Pig-a validation trials, we examined the induction of Pig-a mutant reticulocytes and red blood cells (RET(CD59-) and RBC(CD59-), respectively) in peripheral blood of male Sprague Dawley(®) rats treated with urethane (25, 100 and 250mg/kg/day) or saline by oral gavage for 29 days. Additional endpoints integrated into this study were: micronucleated reticulocytes (MN-RET) in peripheral blood; chromosome aberrations (CAb) and DNA damage (%tail intensity via the comet assay) in peripheral blood lymphocytes (PBL); micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow; and DNA damage (comet) in various organs at termination (the 29th dose was added for the comet endpoint at sacrifice). Ethyl methanesulfonate (EMS; 200mg/kg/day on Days 3, 4, 13, 14, 15, 27, 28 and 29) was evaluated as the concurrent positive control (PC). All animals survived to termination and none exhibited overt toxicity, but there were significant differences in body weight and body weight gain in the 250-mg/kg/day urethane group, as compared with the saline control animals. Statistically significant, dose-dependent increases were observed for urethane for: RET(CD59-) and RBC(CD59-) (on Days 15 and 29); MN-RET (on Days 4, 15 and 29); and MN-PCE (on Day 29). The comet assay yielded positive results in PBL (Day 15) and liver (Day 29), but negative results for PBL (Days 4 and 29) and brain, kidney and lung (Day 29). No significant increases in PBL CAb were observed at any sample time. Except for PBL CAb (likely due to excessive cytotoxicity), EMS-induced significant increases in all endpoints/tissues. These results compare favorably with earlier in vivo observations and demonstrate the utility and sensitivity of the Pig-a in vivo gene mutation assay, and its ability to be easily integrated, along with other standard genotoxicity endpoints, into 28-day rodent toxicity studies.

  9. A repeated 28-day oral dose toxicity study of 17alpha-methyltestosterone in rats, based on the 'enhanced OECD Test Guideline 407' for screening the endocrine-disrupting chemicals.

    PubMed

    Okazaki, Kazushi; Imazawa, Takayoshi; Nakamura, Hideaki; Furukawa, Fumio; Nishikawa, Akiyoshi; Hirose, Masao

    2002-01-01

    As part of the international validation project to establish the Enhanced OECD Test Guideline 407, we performed a 28-day repeated-dose toxicity study of 17alpha-methyltestosterone, an exogenous androgen agonist. Special attention was paid to the sensitivity of additional parameters for detecting endocrine-related effects of endocrine-disrupting chemicals, based on the existing Test Guideline 407. Seven-week-old Crj:CD(SD)IGS rats were allocated to one of four groups, each consisting of ten males and ten females, and 17alpha-methyltestosterone was administered daily by gavage at doses of 0 (control), 5, 20 and 80 mg/kg body weight per day. Male rats were killed on the day after the 28th administration and females on the day of the diestrus stage during the 4 day period after the 28th administration. Male rats receiving 80 mg/kg 17alpha-methyltestosterone demonstrated decreases in testis and epididymis weights, atrophy of seminiferous tubules and Leydig cells, and degenerated pachytene spermatocytes in the testes and degenerated germ cells in the epididymides as major alterations. Female rats showed abnormal estrous cycles, decreases in ovary and adrenal weights, increase in immature follicles with decreased corpus lutea in the ovaries at doses of 5 mg/kg and higher, as well as atrophy of zona reticularis in the adrenals and increase in mammary gland secretion at 20 mg/kg and above. Dilatation of the lumina and apoptosis of endometrial cells in the uterus, mucinification in the vagina and increase in serum follicle-stimulating hormone were seen with 80 mg/kg. Among the parameters examined in the present experimental system, effects of 17alpha-methyltestosterone on endocrine-related organs were detected in organ weights and histopathological examination of both sexes, and in serum hormones and estrous cycle of females. Based on these results, the no-observed-adverse-effect level (NOAEL) in the present study was estimated to be below 5 mg/kg per day. In particular

  10. A limit cycle oscillator model for cycling mood variations of bipolar disorder patients derived from cellular biochemical reaction equations

    NASA Astrophysics Data System (ADS)

    Frank, T. D.

    2013-08-01

    We derive a nonlinear limit cycle model for oscillatory mood variations as observed in patients with cycling bipolar disorder. To this end, we consider two signaling pathways leading to the activation of two enzymes that play a key role for cellular and neural processes. We model pathway cross-talk in terms of an inhibitory impact of the first pathway on the second and an excitatory impact of the second on the first. The model also involves a negative feedback loop (inhibitory self-regulation) for the first pathway and a positive feedback loop (excitatory self-regulation) for the second pathway. We demonstrate that due to the cross-talk the biochemical dynamics is described by an oscillator equation. Under disease-free conditions the oscillatory system exhibits a stable fixed point. The breakdown of the self-inhibition of the first pathway at higher concentration levels is studied by means of a scalar control parameter ξ, where ξ equal to zero refers to intact self-inhibition at all concentration levels. Under certain conditions, stable limit cycle solutions emerge at critical parameter values of ξ larger than zero. These oscillations mimic pathological cycling mood variations that emerge due to a disease-induced bifurcation. Consequently, our modeling analysis supports the notion of bipolar disorder as a dynamical disease. In addition, our study establishes a connection between mechanistic biochemical modeling of bipolar disorder and phenomenological nonlinear oscillator approaches to bipolar disorder suggested in the literature.

  11. Effects of combined inspiratory muscle and cycle ergometer training on exercise performance in patients with COPD.

    PubMed

    Wanke, T; Formanek, D; Lahrmann, H; Brath, H; Wild, M; Wagner, C; Zwick, H

    1994-12-01

    Cycle ergometer training plays an important role in the rehabilitation of patients with chronic obstructive pulmonary disease (COPD), but the usefulness of specific inspiratory muscle training as part of pulmonary rehabilitation remains uncertain. To determine whether inspiratory muscle training could intensify the known beneficial effects of cycle ergometer training on exercise performance in these patients, we compared the effect of an 8 week inspiratory muscle training combined with cycle ergometer training with that of an 8 week cycle ergometer training alone on inspiratory muscle performance and general exercise capacity. Patients were randomly assigned to the two training groups; 21 patients received additional inspiratory muscle training (Group 1) and 21 did not (Group 2). Maximal sniff assessed oesophageal and transdiaphragmatic pressures served as parameters for global inspiratory muscle strength and diaphragmatic strength, respectively. The duration for which the patient could breathe against a constant inspiratory pressure load was used as an index of inspiratory muscle endurance. Exercise capacity was determined by an incremental symptom-limited cycle ergometer test. After the training period, inspiratory muscle performance improved significantly in the patients with inspiratory muscle training, but not in those without. Both training regimens increased maximal power output and oxygen uptake, but this improvement was significantly greater in the patients with inspiratory muscle training than in those without.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Empowering patients: total product life cycle for medical devices.

    PubMed

    Ciarkowski, Arthur A

    2003-01-01

    Patients today demand a stake in the care of their own health. The expectation is that patients who take responsibility for their own care will communicate more effectively with their health care team and be productive citizens in our society. Medical technology today and those products visible on the horizon, coupled in a telehealth network, provide promise to empower patients to participate fully in the management of their own health. Technology alone, however, will not integrate the elements required for an effective telehealth system. This chapter considers the non-technical matters of this issue such as trends in the medical device industry, trends in the point of care, public health care policies, and the role of government regulation, working together to achieve these public health goals.

  13. Altered lower leg muscle activation patterns in patients with cerebral palsy during cycling on an ergometer

    PubMed Central

    Alves-Pinto, Ana; Blumenstein, Tobias; Turova, Varvara; Lampe, Renée

    2016-01-01

    Objective Cycling on a recumbent ergometer constitutes one of the most popular rehabilitation exercises in cerebral palsy (CP). However, no control is performed on how muscles are being used during training. Given that patients with CP present altered muscular activity patterns during cycling or walking, it is possible that an incorrect pattern of muscle activation is being promoted during rehabilitation cycling. This study investigated patterns of muscular activation during cycling on a recumbent ergometer in patients with CP and whether those patterns are determined by the degree of spasticity and of mobility. Methods Electromyographic (EMG) recordings of lower leg muscle activation during cycling on a recumbent ergometer were performed in 14 adult patients diagnosed with CP and five adult healthy participants. EMG recordings were done with an eight-channel EMG system built in the laboratory. The activity of the following muscles was recorded: Musculus rectus femoris, Musculus biceps femoris, Musculus tibialis anterior, and Musculus gastrocnemius. The degree of muscle spasticity and mobility was assessed using the Modified Ashworth Scale and the Gross Motor Function Classification System, respectively. Muscle activation patterns were described in terms of onset and duration of activation as well as duration of cocontractions. Results Muscle activation in CP was characterized by earlier onsets, longer periods of activation, a higher occurrence of agonist–antagonist cocontractions, and a more variable cycling tempo in comparison to healthy participants. The degree of altered muscle activation pattern correlated significantly with the degree of spasticity. Conclusion This study confirmed the occurrence of altered lower leg muscle activation patterns in patients with CP during cycling on a recumbent ergometer. There is a need to develop feedback systems that can inform patients and therapists of an incorrect muscle activation during cycling and support the training

  14. Improved cycle outcomes after laparoscopic ovarian diathermy in hyper-responder patients with previous ART failure.

    PubMed

    Pabuccu, Recai; Pabuccu, Emre Goksan; Gursoy, Asli Yarci; Caglar, Gamze Sinem; Yilmaz, Muserref Banu; Ozdegirmenci, Ozlem

    2014-01-01

    Excessive response to ovarian stimulation is common among hyper-responder patients undergoing assisted reproductive technology (ART). Cycle cancellations and severe ovarian hyperstimulation syndrome (OHSS) are all detrimental consequences observed within this cohort and several approaches have been proposed to enhance outcomes. The current study is designed to evaluate whether laparoscopic ovarian diathermy (LOD) improves ART outcomes and pregnancy rates by reducing Anti-mullerian hormone (AMH) levels in a group of patients who had a history of recurrent ART failure and high response. A total of 40 hyper-responder patients with history of previous ART failure were included. Group I consisted of 22 patients that underwent LOD prior to ART. Group II consisted of 18 patients that underwent only ART. Cycle outcomes of groups were compared. Following LOD, significant reduction in AMH levels were detected in group I (4.75 ng/mL to 2.25 ng/mL). Clinical pregnancies were similar among groups (40% versus 27.8% p = 0.65). There was no cycle cancellation in Group I, whereas there were three cycle cancellations observed due to OHSS in Group II. Our results indicate that LOD might offer enhanced fertility outcomes and may reduce the likelihood of cycle cancellations in hyper-responders with previous ART failures.

  15. Report of 3 Patients With Urea Cycle Defects Treated With Related Living-Donor Liver Transplant.

    PubMed

    Özçay, Figen; Barış, Zeren; Moray, Gökhan; Haberal, Nihan; Torgay, Adnan; Haberal, Mehmet

    2015-11-01

    Urea cycle defects are a group of metabolic disorders caused by enzymatic disruption of the urea cycle pathway, transforming nitrogen to urea for excretion from the body. Severe cases present in early infancy with life-threatening metabolic decompensation, and these episodes of hyperammonemia can be fatal or result in permanent neurologic damage. Despite the progress in pharmacologic treatment, long-term survival is poor especially for severe cases. Liver transplant is an alternative treatment option, providing sufficient enzymatic activity and decreasing the risk of metabolic decompensation. Three patients with urea cycle defects received related living-donor liver transplants at our hospital. Patients presented with late-onset ornithine transcarbamylase deficiency, argininosuccinate lyase deficiency, and citrullinemia. Maximum pretransplant ammonia levels were between 232 and 400 μmol/L (normal range is 18-72 μmol/L), and maximum posttransplant values were 52 to 94 μmol/L. All patients stopped medical treatment and dietary protein restriction for urea cycle defects after transplant. The patient with late-onset ornithine transcarbamylase deficiency already had motor deficits related to recurrent hyperammonemia attacks pretransplant. A major improvement could not be achieved, and he is wheelchair dependent at the age of 6 years. The other 2 patients had normal motor and mental skills before transplant, which have continued 12 and 14 months after transplant. Hepatic artery thrombosis in the patient with the ornithine transcarbamylase deficiency, intraabdominal infection in the patient with argininosuccinate lyase deficiency, and posterior reversible encephalopathy syndrome in the patient with citrullinemia were early postoperative complications. Histopathologic changes in livers explanted from patients with ornithine transcarbamylase deficiency and citrullinemia were nonspecific. The argininosuccinate lyase-deficient patient had portoportal fibrosis and cirrhotic

  16. Cycling exercise with functional electrical stimulation improves postural control in stroke patients.

    PubMed

    Lo, Hsin-Chang; Hsu, Yung-Chun; Hsueh, Ya-Hsin; Yeh, Chun-Yu

    2012-03-01

    The aim of this study is to determine whether short term functional electrical stimulation (FES)-assisted cycling training can affect the postural control of stroke patients, and whether the application of FES can enhance the effect of cycling training. 20 stroke patients were randomly assigned to the FES-cycling group (FES-CG) or the cycling group (CG). Measurements were completed before and immediately after each 20 min training sessions. The measurements included a balance test (to quantify the postural control ability), a Hoffmann's reflex/motor response ratio (H/M ratio) test and a pendulum test (to quantify the muscle tone). In the balance test, some parameters in all directions exhibited significant intervention effects between the FES-CG group and the CG group. The H/M ratios (p=.014; .005, FES-CG and CG respectively) and relaxation index (p=.005; .047, FES-CG and CG respectively) revealed significant difference between FES-CG and CG group. The change ratios of directional control in the forward direction and H/M ratio revealed significant difference (p=.022; .015) between FES-CG and CG among subjects with higher muscle tone. The stroke subjects' postural control was improved while their muscle tone was reduced after the 20 min cycling training program both with and without FES. We conclude that cycling training, with or without FES may reduce spasticity in stroke patients. The application of FES in cycling exercise was shown to be more effective in stroke patients with higher muscle tone.

  17. Cycling exercise with functional electrical stimulation improves postural control in stroke patients.

    PubMed

    Lo, Hsin-Chang; Hsu, Yung-Chun; Hsueh, Ya-Hsin; Yeh, Chun-Yu

    2012-03-01

    The aim of this study is to determine whether short term functional electrical stimulation (FES)-assisted cycling training can affect the postural control of stroke patients, and whether the application of FES can enhance the effect of cycling training. 20 stroke patients were randomly assigned to the FES-cycling group (FES-CG) or the cycling group (CG). Measurements were completed before and immediately after each 20 min training sessions. The measurements included a balance test (to quantify the postural control ability), a Hoffmann's reflex/motor response ratio (H/M ratio) test and a pendulum test (to quantify the muscle tone). In the balance test, some parameters in all directions exhibited significant intervention effects between the FES-CG group and the CG group. The H/M ratios (p=.014; .005, FES-CG and CG respectively) and relaxation index (p=.005; .047, FES-CG and CG respectively) revealed significant difference between FES-CG and CG group. The change ratios of directional control in the forward direction and H/M ratio revealed significant difference (p=.022; .015) between FES-CG and CG among subjects with higher muscle tone. The stroke subjects' postural control was improved while their muscle tone was reduced after the 20 min cycling training program both with and without FES. We conclude that cycling training, with or without FES may reduce spasticity in stroke patients. The application of FES in cycling exercise was shown to be more effective in stroke patients with higher muscle tone. PMID:22153770

  18. G1/S Cell Cycle Checkpoint Defect in Lymphocytes from Patients with Alzheimer's Disease

    PubMed Central

    Song, Misun; Kwon, Young-Ah; Lee, Yujin; Kim, Hyeran; Yun, Ji Hea; Kim, Seonwoo

    2012-01-01

    Objective We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle. Methods Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin. Results The patients with AD were older than the normal controls (AD 74.03±7.90 yr vs. control 68.28±6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29±6.32% vs. 76.03±9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45±6.09% vs. 6.03±5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects. Conclusion The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death. PMID:23251208

  19. Cycling induced by electrical stimulation improves muscle activation and symmetry during pedaling in hemiparetic patients.

    PubMed

    Ambrosini, Emilia; Ferrante, Simona; Ferrigno, Giancarlo; Molteni, Franco; Pedrocchi, Alessandra

    2012-05-01

    A randomized controlled trial, involving 35 post-acute hemiparetic patients, demonstrated that a four-week treatment of cycling induced by functional electrical stimulation (FES-cycling) promotes motor recovery. Analyzing additional data acquired during that study, the present work investigated whether these improvements were associated to changes in muscle strength and motor coordination. Participants were randomized to receive FES-cycling or placebo FES-cycling. Clinical outcome measures were: the Motricity Index (MI), the gait speed, the electromyography activation of the rectus femoris and biceps femoris, and the mechanical work produced by each leg during voluntary pedaling. To provide a comparison with normal values, healthy adults also carried out the pedaling test. Patients were evaluated before, after training, and at follow-up visits. A significant treatment effect in favor of FES-treated patients was found in terms of MI scores and unbalance in mechanical works, while differences in gait speed were not significant (ANCOVA). Significant improvements in the activation of the paretic muscles were highlighted in the FES group, while no significant change was found in the placebo group (Friedman test). Our findings suggested that improvements in motor functions induced by FES-cycling training were associated with a more symmetrical involvement of the two legs and an improved motor coordination. PMID:22514205

  20. Pregnancy outcome of assisted reproductive technology cycle in patients with hypogonadotropic hypogonadism

    PubMed Central

    Pandurangi, Monna; Tamizharasi, M.; Reddy, N. Sanjeeva

    2015-01-01

    CONTEXT: Ovulation induction in patients with hypogonadotropic hypogonadism (HH) is a challenge to the treating physician. The threshold for ovarian response in HH may differ substantially from that of normal patients. To reach that threshold levels of follicle stimulating hormone, in a step-up protocol longer duration of stimulation is required in some cases so as to prevent multiple pregnancy and to eliminate the risk of ovarian hyperstimulation syndrome. AIM: To evaluate the duration of stimulation, quality of oocytes, and embryo, and the pregnancy outcome in the assisted reproductive technology (ART) cycles in patients with HH. MATERIALS AND METHODS: Over the period of 4 years, we had 14 patients with HH in whom 21 cycles of ovulation induction were done. Of these 7 patients underwent oocyte retrieval and intracytoplasmic sperm injection (ICSI). We present a retrospective study of these 7 patients who underwent ART to evaluate the duration of stimulation, quality of oocytes and embryo, and the pregnancy outcome. RESULTS: In the study group on ovulation induction with gonadotropins, only one patient had the duration of stimulation of the standard 12 days, the remaining 6 patients took ≥12 days to respond to stimulation (maxium being 54 days). Mean ET in these patients was 8.9 mm. Six patients had >70% good quality MII oocytes. One patient responded poorly and had only 2 good quality MII oocytes (50%). After ICSI procedure, resultant embryos were of grade 1 and 2 in all the patients irrespective of the duration of stimulation. Fertilization rate in these patients was 85% (except in one 50% fertilization rate), and the cumulative pregnancy rate was 68.6%. CONCLUSION: In the patients with HH the quality of oocytes and embryos, and the pregnancy rate is not affected even if the duration of stimulation is prolonged. PMID:26538857

  1. Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.

    PubMed

    Scaglia, Fernando; Carter, Susan; O'Brien, William E; Lee, Brendan

    2004-04-01

    Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea. These disorders often result in life-threatening hyperammonemia and hyperglutaminemia. A combination of sodium phenylbutyrate and sodium phenylacetate/benzoate is used in the clinical management of children with urea cycle defects as a glutamine trap, diverting nitrogen from urea synthesis to alternatives routes of excretion. We have observed that patients treated with these compounds have selective branched chain amino acid (BCAA) deficiency despite adequate dietary protein intake. However, the direct effect of alternative therapy on the steady state levels of plasma branched chain amino acids has not been well characterized. We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. Steady-state leucine levels were noted to be significantly lower in treated urea cycle disorder patients when compared to either untreated ornithine transcarbamylase deficiency females or control subjects (P<0.0001). This effect was reproduced in control subjects who had depressed leucine levels when treated with sodium phenylacetate/benzoate (P<0.0001). Our studies suggest that this therapeutic modality has a substantial impact on the metabolism of branched chain amino acids in urea cycle disorder patients. These findings suggest that better titration of protein restriction could be achieved with branched chain amino acid supplementation in patients with UCDs who are on alternative route therapy.

  2. Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients.

    PubMed

    Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel; Vinberg, Maj

    2014-09-01

    Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3 were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder patients during a 6-12 months period and compared with repeated measurements in healthy control subjects. Careful attention was given to standardization of all procedures and adjustment for potential confounders of BDNF and NT-3. In linear mixed models, adjusting for demographical and lifestyle factors, levels of BDNF were significantly elevated in bipolar disorder patients in euthymic- (p<0.05), depressed- (p<0.005) and manic/hypomanic (p<0.005) states compared with healthy control subjects. Within bipolar disorder patients, adjusting for medication, there was no significant difference in BDNF levels between affective states, with equally elevated levels present in euthymic-, depressive- and manic/hypomanic patients. Levels of BDNF were higher in patients with longer duration of illness compared with patients with shorter duration of illness. We found no difference in NT-3 levels between bipolar disorder patients in any affective state compared with healthy control subjects and no difference in NT-3 levels between affective states in bipolar disorder patients. The results suggest that

  3. Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

    PubMed

    Burrage, Lindsay C; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H; Nagamani, Sandesh C S

    2014-01-01

    Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. PMID:25042691

  4. An automatic identification procedure to promote the use of FES-cycling training for hemiparetic patients.

    PubMed

    Ambrosini, Emilia; Ferrante, Simona; Schauer, Thomas; Ferrigno, Giancarlo; Molteni, Franco; Pedrocchi, Alessandra

    2014-01-01

    Cycling induced by Functional Electrical Stimulation (FES) training currently requires a manual setting of different parameters, which is a time-consuming and scarcely repeatable procedure. We proposed an automatic procedure for setting session-specific parameters optimized for hemiparetic patients. This procedure consisted of the identification of the stimulation strategy as the angular ranges during which FES drove the motion, the comparison between the identified strategy and the physiological muscular activation strategy, and the setting of the pulse amplitude and duration of each stimulated muscle. Preliminary trials on 10 healthy volunteers helped define the procedure. Feasibility tests on 8 hemiparetic patients (5 stroke, 3 traumatic brain injury) were performed. The procedure maximized the motor output within the tolerance constraint, identified a biomimetic strategy in 6 patients, and always lasted less than 5 minutes. Its reasonable duration and automatic nature make the procedure usable at the beginning of every training session, potentially enhancing the performance of FES-cycling training. PMID:25193368

  5. Telemetric Blood Pressure Assessment in Angiotensin II-Infused ApoE-/- Mice: 28 Day Natural History and Comparison to Tail-Cuff Measurements.

    PubMed

    Haggerty, Christopher M; Mattingly, Andrea C; Gong, Ming C; Su, Wen; Daugherty, Alan; Fornwalt, Brandon K

    2015-01-01

    Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of arterial pulse pressure in anesthetized mice would have sufficient accuracy to enable calculations of aortic distensibility with minimal error. Telemetry devices and osmotic mini-pumps filled with saline or angiotensin-II were surgically implanted in male apolipoprotein-E deficient (ApoE(-/-)) mice. Blood pressure in the aortic arch was measured continuously via telemetry. In addition, simultaneous blood pressure measurements with a volume/pressure tail-cuff system were performed under anesthesia at specific intervals to assess agreement between techniques. Compared to controls, mice infused with angiotensin-II had an overall statistically significant increase in systolic pressure, with no overall difference in pulse pressure; however, pulse pressure did increase significantly with time. Systolic measurements agreed well between telemetry and tail-cuff (coefficient of variation = 10%), but agreement of pulse pressure was weak (20%). In fact, group-averaged pulse pressure from telemetry was a better predictor of a subject's pulse pressure on a given day than a simultaneous tail-cuff measurement. Furthermore, these approximations introduced acceptable errors (15.1 ± 12.8%) into the calculation of aortic distensibility. Contrary to our hypothesis

  6. D-aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men.

    PubMed

    Willoughby, Darryn S; Leutholtz, Brian

    2013-10-01

    It was hypothesized that D-aspartic acid (D-ASP) supplementation would not increase endogenous testosterone levels or improve muscular performance associated with resistance training. Therefore, body composition, muscle strength, and serum hormone levels associated with the hypothalamo-pituitary-gonadal axis were studied after 28 days of resistance training and D-ASP supplementation. Resistance-trained men resistance trained 4 times/wk for 28 days while orally ingesting either 3 g of placebo or 3 g of D-ASP. Data were analyzed with 2 × 2 analysis of variance (P < .05). Before and after resistance training and supplementation, body composition and muscle strength, serum gonadal hormones, and serum D-ASP and d-aspartate oxidase (DDO) were determined. Body composition and muscle strength were significantly increased in both groups in response to resistance training (P < .05) but not different from one another (P > .05). Total and free testosterone, luteinizing hormone, gonadotropin-releasing hormone, and estradiol were unchanged with resistance training and D-ASP supplementation (P > .05). For serum D-ASP and DDO, D-ASP resulted in a slight increase compared with baseline levels (P > .05). For the D-ASP group, the levels of serum DDO were significantly increased compared with placebo (P < .05). The gonadal hormones were unaffected by 28 days of D-ASP supplementation and not associated with the observed increases in muscle strength and mass. Therefore, at the dose provided, D-ASP supplementation is ineffective in up-regulating the activity of the hypothalamo-pituitary-gonadal axis and has no anabolic or ergogenic effects in skeletal muscle.

  7. A Randomized Clinical Trial on Comparing The Cycle Characteristics of Two Different Initiation Days of Letrozole Treatment in Clomiphene Citrate Resistant PCOS Patients in IUI Cycles

    PubMed Central

    Ghomian, Nayereh; Khosravi, Ashraf; Mousavifar, Nezhat

    2015-01-01

    Background There are still many questions about the ideal protocol for letrozole (LTZ) as the commonest aromatase inhibitor (AI) used in ovulation induction. The aim of this study is to compare the ultrasonographic and hormonal characteristics of two different initiation times of LTZ in clomiphene citrate (CC) failure patients and to study androgen dynamics during the cycle. Materials and Methods This randomized clinical trial was done from March to November 2010 at the Mashhad IVF Center, a university based IVF center. Seventy infertile polycystic ovarian syndrome (PCOS) patients who were refractory to at least 3 CC treatment cycles were randomly divided into two groups. Group A (n=35) receiving 5 mg LTZ on cycle days 3-7 (CD3), and group B (n=35) receiving the same amount on cycle days 5-9 (CD5). Hormonal profile and ultrasonographic scanning were done on cycle day 3 and three days after completion of LTZ treatment (cycle day 10 or 12). Afterward, 5,000-10,000 IU human chorionic gonadotropin (hCG) was injected if at least one follicle ≥18 mm was seen in ultrasonographic scanning. Intrauterine insemination (IUI) has been done 36-40 hours later. The cycle characteristics, the ovulation and pregnancy rate were compared between two groups. The statistical analysis was done using Fisher’s exact test, t test, logistic regression, and Mann-Whitney U test. Results There were no significant differences between two groups considering patient characteristics. The ovulation rate (48.6 vs. 32.4% in group A and B, respectively), the endometrial thickness, the number of mature follicles, and length of follicular phase were not significantly different between the two groups. Conclusion LTZ is an effective treatment in CC failure PCOS patients. There are no significant differences regarding ovulation and pregnancy rates between two different protocols of LTZ starting on days 3 and 5 of menstrual cycle (Registration Number: IRCT201307096467N3). PMID:25918588

  8. Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy

    PubMed Central

    Zehnacker, Laura; Abe, Emuri; Mathez, Dominique; Alvarez, Jean-Claude; Leibowitch, Jacques; Azoulay, Stéphane

    2014-01-01

    Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC) were still measurable for all drugs after 85 h or 110 h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required. PMID:25431661

  9. A Phase I Trial of Tipifarnib With Radiation Therapy, With and Without Temozolomide, for Patients With Newly Diagnosed Glioblastoma

    SciTech Connect

    Nghiemphu, Phioanh Leia; Wen, Patrick Y.; Drappatz, Jan; Fink, Karen; Malkin, Mark G.; Lieberman, Frank S.; DeAngelis, Lisa M.; Torres-Trejo, Alejandro; Chang, Susan M.; Abrey, Lauren; Fine, Howard A.; Demopoulos, Alexis; Lassman, Andrew B.; Kesari, Santosh; Prados, Michael D.; Cloughesy, Timothy F.

    2011-12-01

    Purpose: To determine the maximum tolerated dose (MTD) of tipifarnib in combination with conventional radiotherapy for patients with newly diagnosed glioblastoma. The MTD was evaluated in three patient cohorts, stratified based on concurrent use of enzyme-inducing antiepileptic drugs (EIAED) or concurrent treatment with temozolomide (TMZ): Group A: patients not receiving EIAED and not receiving TMZ; Group A-TMZ: patients not receiving EIAED and receiving treatment with TMZ; Group B: any patients receiving EIAED but not TMZ. Patients and Methods: After diagnostic surgery or biopsy, treatment with tipifarnib started 5 to 9 days before initiating radiotherapy, twice daily, in 4-week cycles using discontinuous dosing (21 out of 28 days), until toxicity or progression. For Group A-TMZ, patients also received TMZ daily during radiotherapy and then standard 5/28 days dosing after radiotherapy. Dose-limiting toxicity (DLT) was determined over the first 10 weeks of therapy for all cohorts. Results: Fifty-one patients were enrolled for MTD determination: 10 patients in Group A, 21 patients in Group A-TMZ, and 20 patients in Group B. In the Group A and Group A-TMZ cohorts, patients achieved the intended MTD of 300 mg twice daily (bid) with DLTs including rash and fatigue. For Group B, the MTD was determined as 300 mg bid, half the expected dose. The DLTs included rash and one intracranial hemorrhage. Thirteen of the 20 patients evaluated in Group A-TMZ were alive at 1 year. Conclusion: Tipifarnib is well tolerated at 300 mg bid given discontinuously (21/28 days) in 4-week cycles, concurrently with standard chemo/radiotherapy. A Phase II study should evaluate the efficacy of tipifarnib with radiation and TMZ in patients with newly diagnosed glioblastoma and not receiving EIAED.

  10. Evaluation of motor performances of hemiplegic patients using a virtual cycling wheelchair: an exploratory trial.

    PubMed

    Sugita, Norihiro; Yoshizawa, Makoto; Kojima, Yoshihisa; Abe, Makoto; Homma, Noriyasu; Seki, Kazunori; Handa, Nobuyasu

    2013-01-01

    Cycling is known to be an effective rehabilitation exercise for hemiplegic patients who face difficulty during walking because of stroke or other brain disorders. A cycling wheelchair (CWC) is a useful tool to provide exercise for these patients and improve their quality of life. In previous studies, our group developed a system that allows patients to safely practice driving a CWC in a virtual environment. However, it has been difficult to check their motor performances and determine the effects of the exercise on a daily basis. This study is an exploratory trial for developing a method to evaluate the motor performances of users based on their CWC pedaling patterns. An experiment with some hemiplegic patients and healthy subjects was conducted and their pedaling patterns were analyzed. Results showed a significant difference between the hemiplegic patients and healthy subjects in an index that reflects pedaling balance between the feet. This result indicates a possible method of evaluating the motor performances of users based on their pedaling patterns.

  11. Phase I Study of Vorinostat in Combination with Temozolomide in Patients with High-Grade Gliomas: North American Brain Tumor Consortium Study 04-03

    PubMed Central

    Lee, Eudocia Q.; Puduvalli, Vinay K.; Reid, Joel M.; Kuhn, John G.; Lamborn, Kathleen R.; Cloughesy, Timothy F.; Chang, Susan M.; Drappatz, Jan; Yung, W. K. Alfred; Gilbert, Mark R.; Robins, H. Ian; Lieberman, Frank S.; Lassman, Andrew B.; McGovern, Renee M.; Xu, Jihong; Desideri, Serena; Ye, Xiabu; Ames, Matthew M.; Espinoza-Delgado, Igor; Prados, Michael D.; Wen, Patrick Y.

    2013-01-01

    Purpose A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG). Experimental Design This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m2/day × 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m2/day × 5 days of the first cycle and 200 mg/m2/day × 5 days of the subsequent 28-day cycles. Results In Part 1, the MTD of vorinostat administered on days 1-7 and 15-21 of every 28 day cycle in combination with TMZ was 500 mg daily. Dose-limiting toxicities (DLTs) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In Part 2, the MTD of vorinostat on days 1-7 and 15-21 of every 28 day cycle combined with TMZ was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells. Conclusion Vorinostat in combination with temozolomide is well-tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway. PMID:22923449

  12. A phase I trial of tipifarnib with radiation therapy, with and without temozolomide, for patients with newly diagnosed glioblastoma

    PubMed Central

    Nghiemphu, Phioanh Leia; Wen, Patrick Y.; Lamborn, Kathleen R.; Drappatz, Jan; Robins, H. Ian; Fink, Karen; Malkin, Mark G.; Lieberman, Frank S.; DeAngelis, Lisa M.; Torres-Trejo, Alejandro; Chang, Susan M.; Abrey, Lauren; Fine, Howard A.; Demopoulos, Alexis; Lassman, Andrew B.; Kesari, Santosh; Mehta, Minesh P.; Prados, Michael D.; Cloughesy, Timothy F.

    2010-01-01

    Purpose To determine the maximum tolerated dose (MTD) of tipifarnib in combination with conventional radiotherapy (RT) for patients with newly diagnosed glioblastoma (GBM). MTD was evaluated in three patient cohorts, stratified based on concurrent use of enzyme inducing antiepileptic drugs (EIAED) or concurrent treatment with temozolomide (TMZ): Group A - patients not receiving EIAED and not receiving TMZ; Group A-TMZ - patients not on EIAED, and on treatment with TMZ; Group B – any patients receiving EIAED, but no TMZ. Methods and Materials After diagnostic surgery or biopsy, treatment with tipifarnib started 5–9 days before initiating RT, twice daily, in four-week cycles using discontinuous dosing (21 out of 28 days), until toxicity or progression. For Group A-TMZ, patients also received TMZ daily during radiotherapy and then standard 5/28 days dosing after radiotherapy. Dose limiting toxicity (DLT) was determined over the first 10 weeks of therapy for all cohorts. Results Fifty-one patients were enrolled for MTD determination: 10 patients in Group A, 21 patients in Group A-TMZ, 20 patients in Group B. In Group A and Group A-TMZ cohorts, patients achieved the intended MTD of 300 mg bid with DLTs including rash and fatigue. For Group B, the MTD was determined as 300 mg bid, half the expected dose. DLTs included rash and 1 intracranial hemorrhage. Thirteen of the 20 patients evaluated in Group A-TMZ were alive at one year. Conclusion Tipifarnib is well tolerated at 300 mg bid given discontinuously (21/28 days) in 4-week cycles, concurrently with standard chemo/radiotherapy. A phase II study should evaluate the efficacy of tipifarnib with radiation and TMZ in patients with newly diagnosed GBM and not on EIAED. PMID:20934264

  13. Do Xpert MTB/RIF Cycle Threshold Values Provide Information about Patient Delays for Tuberculosis Diagnosis?

    PubMed Central

    Ssengooba, Willy; Respeito, Durval; Mambuque, Edson; Blanco, Silvia; Bulo, Helder; Mandomando, Inacio; de Jong, Bouke C.; Cobelens, Frank G.; García-Basteiro, Alberto L.

    2016-01-01

    Introduction Early diagnosis and initiation to appropriate treatment is vital for tuberculosis (TB) control. The XpertMTB/RIF (Xpert) assay offers rapid TB diagnosis and quantitative estimation of bacterial burden through Cycle threshold (Ct) values. We assessed whether the Xpert Ct value is associated with delayed TB diagnosis as a potential monitoring tool for TB control programme performance. Materials and Methods This analysis was nested in a prospective study under the routine TB surveillance procedures of the National TB Control Program in Manhiça district, Maputo province, Mozambique. Presumptive TB patients were tested using smear microscopy and Xpert. We explored the association between Xpert Ct values and self-reported delay of Xpert-positive TB patients as recorded at the time of diagnosis enrolment. Patients with >60 days of TB symptoms were considered to have long delays. Results Of 1,483 presumptive TB cases, 580 were diagnosed as TB of whom 505 (87.0%) were due to pulmonary TB and 302 (94.1%) were Xpert positive. Ct values (range, 9.7–46.4) showed a multimodal distribution. The median (IQR) delay was 30 (30–45) days. Ct values showed no correlation with delay (R2 = 0.001, p = 0.621), nor any association with long delays: adjusted odds ratios (AOR) (95% confidence interval [CI]) comparing to >28 cycles 0.99 (0.50–1.96; p = 0.987) for 23–28 cycles, 0.93 (0.50–1.74; p = 0.828) for 16–22 cycles; and 1.05 (0.47–2.36; p = 0.897) for <16 cycles. Being HIV-negative (AOR [95% CI]), 2.05 (1.19–3.51, p = 0.009) and rural residence 1.74 (1.08–2.81, p = 0.023), were independent predictors of long delays. Conclusion Xpert Ct values were not associated with patient delay for TB diagnosis and cannot be used as an indicator of TB control program performance. PMID:27611466

  14. Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in Sprague-Dawley rats in a 28-day OECD 412 inhalation study and assessment of systems toxicology.

    PubMed

    Phillips, Blaine; Esposito, Marco; Verbeeck, Jan; Boué, Stéphanie; Iskandar, Anita; Vuillaume, Gregory; Leroy, Patrice; Krishnan, Subash; Kogel, Ulrike; Utan, Aneli; Schlage, Walter K; Bera, Monali; Veljkovic, Emilija; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2015-01-01

    Toxicity of nebulized nicotine (Nic) and nicotine/pyruvic acid mixtures (Nic/Pyr) was characterized in a 28-day Organization for Economic Co-operation and Development 412 inhalation study with additional transcriptomic and lipidomic analyses. Sprague-Dawley rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, saline, nicotine (50 µg/l), sodium pyruvate (NaPyr, 33.9 µg/l) or equimolar Nic/Pyr mixtures (18, 25 and 50 µg nicotine/l). Saline and NaPyr caused no health effects, but rats exposed to nicotine-containing aerosols had decreased body weight gains and concentration-dependent increases in liver weight. Blood neutrophil counts were increased and lymphocyte counts decreased in rats exposed to nicotine; activities of alkaline phosphatase and alanine aminotransferase were increased, and levels of cholesterol and glucose decreased. The only histopathologic finding in non-respiratory tract organs was increased liver vacuolation and glycogen content. Respiratory tract findings upon nicotine exposure (but also some phosphate-buffered saline aerosol effects) were observed only in the larynx and were limited to adaptive changes. Gene expression changes in the lung and liver were very weak. Nic and Nic/Pyr caused few significant changes (including Cyp1a1 gene upregulation). Changes were predominantly related to energy metabolism and fatty acid metabolism but did not indicate an obvious toxicity-related response. Nicotine exposure lowered plasma lipids, including cholesteryl ester (CE) and free cholesterol and, in the liver, phospholipids and sphingolipids. Nic, NaPyr and Nic/Pyr decreased hepatic triacylglycerol and CE. In the lung, Nic and Nic/Pyr increased CE levels. These data suggest that only minor biologic effects related to inhalation of Nic or Nic/Pyr aerosols were observed in this 28-day study.

  15. Real-Time Patient Survey Data During Routine Clinical Activities for Rapid-Cycle Quality Improvement

    PubMed Central

    Jones, Robert E

    2015-01-01

    Background Surveying patients is increasingly important for evaluating and improving health care delivery, but practical survey strategies during routine care activities have not been available. Objective We examined the feasibility of conducting routine patient surveys in a primary care clinic using commercially available technology (Web-based survey creation, deployment on tablet computers, cloud-based management of survey data) to expedite and enhance several steps in data collection and management for rapid quality improvement cycles. Methods We used a Web-based data management tool (survey creation, deployment on tablet computers, real-time data accumulation and display of survey results) to conduct four patient surveys during routine clinic sessions over a one-month period. Each survey consisted of three questions and focused on a specific patient care domain (dental care, waiting room experience, care access/continuity, Internet connectivity). Results Of the 727 available patients during clinic survey days, 316 patients (43.4%) attempted the survey, and 293 (40.3%) completed the survey. For the four 3-question surveys, the average time per survey was overall 40.4 seconds, with a range of 5.4 to 20.3 seconds for individual questions. Yes/No questions took less time than multiple choice questions (average 9.6 seconds versus 14.0). Average response time showed no clear pattern by order of questions or by proctor strategy, but monotonically increased with number of words in the question (<20 words, 21-30 words, >30 words)—8.0, 11.8, 16.8, seconds, respectively. Conclusions This technology-enabled data management system helped capture patient opinions, accelerate turnaround of survey data, with minimal impact on a busy primary care clinic. This new model of patient survey data management is feasible and sustainable in a busy office setting, supports and engages clinicians in the quality improvement process, and harmonizes with the vision of a learning health

  16. Novel protocol for scheduling oocyte retrieval in IVM cycles in PCOS patients: a case series.

    PubMed

    Farhi, Jacob; Sapir, Onit; Maman, Maor; Fisch, Benjamin; Ben-Haroush, Avi

    2011-12-01

    In-vitro maturation (IVM) is associated with a longer egg-collection procedure in the operating room and a longer oocyte-handling time in the IVF laboratory than standard IVF. Hence, if the designated day of oocyte retrieval could be planned in advance, the workload pressure on that specific day can be planned in advance. This study presents a simple method for advance scheduling of IVM in patients with polycystic ovary syndrome (PCOS). A fixed protocol of oral contraceptive pill administered prior to gonadotrophin priming and based on the days of the week enable the exact dating of the oocyte retrieval day, thereby increasing patient convenience and improving control of the IVF-unit workload. This protocol was compared with immediate-start IVM and resulted in a similar pregnancy rate (43.8% and 40.0% per cycle, respectively).

  17. BLOOD AMMONIA AND GLUTAMINE AS PREDICTORS OF HYPERAMMONEMIC CRISES IN UREA CYCLE DISORDER PATIENTS

    PubMed Central

    Lee, Brendan; Diaz, George A.; Rhead, William; Lichter-Konecki, U.; Feigenbaum, Annette; Berry, Susan A.; Le Mons, C.; Bartley, James A; Longo, Nicola; Nagamani, Sandesh C.; Berquist, William; Gallagher, Renata; Bartholomew, Dennis; Harding, Cary O.; Korson, Mark S.; McCandless, Shawn E.; Smith, Wendy; Cederbaum, Stephen; Wong, Derek; Merritt, J. Lawrence; Schulze, A.; Vockley, Gerard.; Kronn, David; Zori, Roberto; Summar, Marshall; Milikien, D.A.; Marino, M.; Coakley, D.F.; Mokhtarani, M.; Scharschmidt, B.F.

    2014-01-01

    Purpose To examine predictors of ammonia exposure and hyperammonemic crises (HAC) in patients with urea cycle disorders (UCDs). Methods The relationships between fasting ammonia, daily ammonia exposure, and HACs were analyzed in >100 UCD patients. Results Fasting ammonia correlated strongly with daily ammonia exposure (r=0.764, p<0.001). For patients with fasting ammonia levels <0.5 ULN, 0.5 to <1.0 ULN, and ≥1.0 ULN, the probability of a normal average daily ammonia value was 87%, 60%, and 39%, respectively, and 10.3%, 14.1%, and 37.0% of these patients experienced ≥1 HAC over 12 months. Time to first HAC was shorter (p=0.008) and relative risk (4.5×; p=0.011) and rate (~5×, p=0.006) of HACs higher in patients with fasting ammonia ≥1.0 ULN vs. <0.5ULN; relative risk was even greater (20×; p=0.009) in patients ≥6 years. A 10 or 25 μmol/L increase in ammonia exposure increased the relative risk of a HAC by 50% and >200% (p<0.0001), respectively. The relationship between ammonia and HAC risk appeared independent of treatment, age, UCD subtype, dietary protein intake, or blood urea nitrogen. Fasting glutamine correlated weakly with AUC0-24 and was not a significant predictor of HACs. Conclusions Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of HACs, suggesting that UCD patients may benefit from tight ammonia control. PMID:25503497

  18. Novel Metabolic Abnormalities in the Tricarboxylic Acid Cycle in Peripheral Cells From Huntington's Disease Patients.

    PubMed

    Naseri, Nima N; Bonica, Joseph; Xu, Hui; Park, Larry C; Arjomand, Jamshid; Chen, Zhengming; Gibson, Gary E

    2016-01-01

    Metabolic dysfunction is well-documented in Huntington's disease (HD). However, the link between the mutant huntingtin (mHTT) gene and the pathology is unknown. The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the production of NADH for conversion to ATP via the electron transport chain (ETC). The objective of this study was to test for differences in enzyme activities, mRNAs and protein levels related to the TCA cycle between lymphoblasts from healthy subjects and from patients with HD. The experiments utilize the advantages of lymphoblasts to reveal new insights about HD. The large quantity of homogeneous cell populations permits multiple dynamic measures to be made on exactly comparable tissues. The activities of nine enzymes related to the TCA cycle and the expression of twenty-nine mRNAs encoding for these enzymes and enzyme complexes were measured. Cells were studied under baseline conditions and during metabolic stress. The results support our recent findings that the activities of the pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase (SDH) are elevated in HD. The data also show a large unexpected depression in MDH activities. Furthermore, message levels for isocitrate dehydrogenase 1 (IDH1) were markedly increased in in HD lymphoblasts and were responsive to treatments. The use of lymphoblasts allowed us to clarify that the reported decrease in aconitase activity in HD autopsy brains is likely due to secondary hypoxic effects. These results demonstrate the mRNA and enzymes of the TCA cycle are critical therapeutic targets that have been understudied in HD. PMID:27611087

  19. Krebs cycle, pentose phosphate pathway, and glycolysis in the uninvolved gastric mucosa of peptic ulcer and gastric cancer patients.

    PubMed

    Orwell, R L; Piper, D W

    1977-12-01

    Uninvolved gastric mucosa from duodenal ulcer, gastric ulcer, and gastric cancer patients was incubated with [1-14C]glucose and [6-14C]glucose in order to assess the relative contributions of the pentose phosphate pathway and Krebs cycle to glucose metabolism. [14C]Glucose counts retained by the tissue, glycolysis, and pyruvate formation were also measured. Tumor tissue from the cancer patients was included in the study. Less than 1.2% of the glucose entering the tissues was metabolized via the pentose phosphate pathway; suggesting that this pathway plays a minor role in energy production from glucose. The major determinant of energy production was the Krebs cycle. Its contribution to glucose metabolism was greatest in the body mucosa of duodenal ulcer patients, less in the uninvolved body mucosa of gastric ulcer patients, and lower still in the corresponding body mucosa of gastric cancer patients. The low levels of Krebs cycle activity seen in the latter tissue resembled those of uninvolved antral mucosa. The smallest Krebs cycle contribution was seen in tumor tissue. [14C]Glucose counts retained by the tissue and glycolysis both tended to vary inversely with Krebs cycle activity among the tissues studied. Thus, both were small in the body mucosa of noncancer patients and somewhat larger in the body mucosa of cancer patients, in uninvolved antral mucosa and in tumor tissue.

  20. Behavior of rhesus monkeys during artificial menstrual cycles.

    PubMed

    Michael, R P; Zumpe, D; Bonsall, R W

    1982-12-01

    Daily subcutaneous injections of estradiol, progesterone, and testosterone were given to ovariectomized rhesus monkeys in amounts that imitated accurately the changing plasma levels of hormones in intact females with natural menstrual cycles. Because these cycles in ovariectomized, treated females were terminated by normal vaginal bleeding every 28 days and showed a mid-cycle gonadotropin surge, we termed them "artificial menstrual cycles." In dyadic mating tests, changes in the females' access times (lever pressing) for males, and in the males' ejaculatory performance, were closely similar during natural and artificial cycles, and there were well-marked behavioral rhythms. These rhythms were lost during 28-day control periods when ovariectomized females received injections of vehicle alone. Differences in ejaculatory performance during natural and artificial cycles could be accounted for by an order effect. It is concluded that the artificial cycle provides a valid and useful paradigm for a more detailed study of the neuroendocrine regulation of primate reproductive behavior. PMID:7153385

  1. Modified natural cycle frozen-thawed embryo transfer in patients with repeated implantation failure: An observational study

    PubMed Central

    Arefi, Soheila; Hoseini, Ahmad; Farifteh, Fattaneh; Zeraati, Hojjat

    2016-01-01

    Background: Natural endometrium in Frozen-thawed Embryo Transfer (FET) may have some benefits upon implantation in patients with Repeated Implantation Failure (RIF). It might be due to possible differences between natural and stimulated endometrial growth factors and cytokins secretions. Objective: The objective of this study was to compare the pregnancy rate of FET on modified natural cycle versus hormone replacement therapy (HRT) cycle endometrium in patients with RIF. Materials and Methods: In this observational study the pregnancy rate of patients with RIF undergoing day 3 FET in natural cycle endometrium (group 1, n=56), were compared with another group of patients with RIF in whom frozen-thawed day 3 embryos were transferred on HRT cycle (group 2, n=52). Results: The pregnancy rate in group 1 was 41.07%, compared with the pregnancy rate of group 2; 36.5% (p=0.63). The abortion rate was not significantly different among the groups. Conclusion: It can be concluded that FET in a modified natural cycle is comparable with HRT cycle in patients with RIF. PMID:27525331

  2. Intradialytic aerobic cycling exercise alleviates inflammation and improves endothelial progenitor cell count and bone density in hemodialysis patients.

    PubMed

    Liao, Min-Tser; Liu, Wen-Chih; Lin, Fu-Huang; Huang, Ching-Feng; Chen, Shao-Yuan; Liu, Chuan-Chieh; Lin, Shih-Hua; Lu, Kuo-Cheng; Wu, Chia-Chao

    2016-07-01

    Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients. PMID:27399127

  3. Benzo[a]pyrene (BP) DNA adduct formation in DNA repair–deficient p53 haploinsufficient [Xpa(−/−)p53(+/−)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days

    PubMed Central

    Poirier, Miriam C.

    2012-01-01

    We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a]pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(−/−)p53(+/−) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N 2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)–DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(−/−)p53(+/−) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(−/−)p53(+/−) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(−/−)p53(+/−) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP–DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(−/−)p53(+/−) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH–DNA adduct levels consistently in human organs. PMID:22828138

  4. Changes in cross-bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy.

    PubMed

    Ottenheijm, Coen A C; Lawlor, Michael W; Stienen, Ger J M; Granzier, Henk; Beggs, Alan H

    2011-05-15

    Nemaline myopathy, the most common non-dystrophic congenital myopathy, is caused by mutations in six genes, all of which encode thin-filament proteins, including NEB (nebulin) and TPM3 (α tropomyosin). In contrast to the mechanisms underlying weakness in NEB-based myopathy, which are related to loss of thin-filament functions normally exerted by nebulin, the pathogenesis of muscle weakness in patients with TPM3 mutations remains largely unknown. Here, we tested the hypothesis that the contractile phenotype of TPM3-based myopathy is different from that of NEB-based myopathy and that this phenotype is a direct consequence of the loss of the specific functions normally exerted by tropomyosin. To test this hypothesis, we used a multidisciplinary approach, including muscle fiber mechanics and confocal and electron microscopy to characterize the structural and functional phenotype of muscle fibers from five patients with TPM3-based myopathy and compared this with that of unaffected control subjects. Our findings demonstrate that patients with TPM3-based myopathy display a contractile phenotype that is very distinct from that of patients with NEB-based myopathy. Whereas both show severe myofilament-based muscle weakness, the contractile dysfunction in TPM3-based myopathy is largely explained by changes in cross-bridge cycling kinetics, but not by the dysregulation of sarcomeric thin-filament length that plays a prominent role in NEB-based myopathy. Interestingly, the loss of force-generating capacity in TPM3-based myopathy appears to be compensated by enhanced thin-filament activation. These findings provide a scientific basis for differential therapeutics aimed at restoring contractile performance in patients with TPM3-based versus NEB-based myopathy. PMID:21357678

  5. Shuttle walking versus maximal cycle testing: clinical correlates in patients with kyphoscoliosis.

    PubMed

    López-Campos, José Luis; Cejudo, Pilar; Ortega, Francisco; López-Márquez, Isabel; Márquez-Martín, Eduardo; Capote, Francisco; Echevarría, Miriam; Montemayor, Teodoro; Barrot, Emilia

    2008-02-29

    A cross-sectional prospective design was used to compare the effectiveness of the shuttle walking test (SWT) and the maximal cycle ergometry test (CET) to assess the functional capacity of patients with chronic hypercapnic respiratory failure due to severe kyphoscoliosis. Twenty-four patients completed both the SWT and CET. Heart rate, blood pressure, leg fatigue, chest pain and dyspnea (Borg's scale) were measured immediately after each test. Correlation coefficients and Bland-Altman analysis were used to compare the two methods. Borg's dyspnea, leg and chest pain after exercise were not significantly different between tests. Only heart rate (SWT 130[20.7] versus CET 116[28.75]; p = 0.048) and diastolic blood pressure (SWT: 85.5[13.75] versus CET 95[17.5]; p = 0.021) were slightly but significantly different between the two protocols. There was a good positive correlation between the distance walked in SWT and maximal oxygen consumption (r = 0.675; p < 0.001). SWT and CET testing elicited similar clinical and hemodynamic responses. SWT is a feasible measure of functional capacity in this patient group.

  6. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes.

    PubMed

    Garcia-Manero, G; Gore, S D; Kambhampati, S; Scott, B; Tefferi, A; Cogle, C R; Edenfield, W J; Hetzer, J; Kumar, K; Laille, E; Shi, T; MacBeth, K J; Skikne, B

    2016-04-01

    CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31-87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2-24) for the 14-day dosing schedule and 6 (1-24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS. PMID:26442612

  7. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes.

    PubMed

    Garcia-Manero, G; Gore, S D; Kambhampati, S; Scott, B; Tefferi, A; Cogle, C R; Edenfield, W J; Hetzer, J; Kumar, K; Laille, E; Shi, T; MacBeth, K J; Skikne, B

    2016-04-01

    CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31-87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2-24) for the 14-day dosing schedule and 6 (1-24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS.

  8. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes

    PubMed Central

    Garcia-Manero, G; Gore, S D; Kambhampati, S; Scott, B; Tefferi, A; Cogle, C R; Edenfield, W J; Hetzer, J; Kumar, K; Laille, E; Shi, T; MacBeth, K J; Skikne, B

    2016-01-01

    CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31–87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2–24) for the 14-day dosing schedule and 6 (1–24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS. PMID:26442612

  9. Platelet response during the second cycle of decitabine treatment predicts response and survival for myelodysplastic syndrome patients.

    PubMed

    Jung, Hyun Ae; Maeng, Chi Hoon; Kim, Moonjin; Kim, Sungmin; Jung, Chul Won; Jang, Jun Ho

    2015-06-30

    Despite the efficacy of decitabine to myelodysplastic syndrome (MDS), there is a wide range of responses, and no definite predictive marker has been identified. This study aimed to describe the efficacy of decitabine and to identify potential predictors of response and survival in patients with MDS. We retrospectively analyzed clinical data of MDS patients at Samsung Medical Center between August 2008 and August 2011. The response assessment was conducted using the International Working Group (IWG) response criteria for MDS. We analyzed 101 MDS patients (total 613 cycles) who received decitabine for a median of four cycles. The overall response was 52.5% (n = 53/101). The median time to any response was two cycles with the median overall survival of 16.7 months. Patients who showed hematologic improvement had significantly longer survival than those who did not (9.8 vs. 22.9 months, p = 0.004). The difference in OS was evident in the Intermediate-2/High risk group (p = 0.002) but not in the Intermediate-1 risk group (p = 0.145). Multivariate analysis confirmed that platelet response (no platelet transfusions for at least 3 days) during the second cycle of treatment was an independent predictor for response, OS and Leukemia free survival. Based on the results of this study, for patients with hematological improvement, recovery of platelet count by the second cycle of therapy can be used as an early predictive marker of improved survival and an increased response rate.

  10. Immunoreactive insulin in diabetes mellitus patient sera detected by ultrasensitive ELISA with thio-NAD cycling.

    PubMed

    Ito, Etsuro; Kaneda, Mugiho; Kodama, Hiromi; Morikawa, Mika; Tai, Momoko; Aoki, Kana; Watabe, Satoshi; Nakaishi, Kazunari; Hashida, Seiichi; Tada, Satoshi; Kuroda, Noriyuki; Imachi, Hitomi; Murao, Koji; Yamashita, Masakane; Yoshimura, Teruki; Miura, Toshiaki

    2015-12-01

    To minimize patient suffering, the smallest possible volume of blood should be collected for diagnosis and disease monitoring. When estimating insulin secretion capacity and resistance to insulin in diabetes mellitus (DM), increasing insulin assay immunosensitivity would reduce the blood sample volume required for testing. Here we present an ultrasensitive ELISA coupled with thio-NAD cycling to measure immunoreactive insulin in blood serum. Only 5 μL of serum was required for testing, with a limit of detection (LOD) for the assay of 10(-16) moles/assay. Additional recovery tests confirmed this method can detect insulin in sera. Comparisons between a commercially available immunoreactive insulin kit and our ultrasensitive ELISA using the same commercially available reference demonstrated good data correlation, providing further evidence of assay accuracy. Together, these results demonstrate our ultrasensitive ELISA could be a powerful tool in the diagnosis and treatment of not only DM but also many other diseases in the future.

  11. An aqueous extract of Salacia oblonga root, a herb-derived peroxisome proliferator-activated receptor-alpha activator, by oral gavage over 28 days induces gender-dependent hepatic hypertrophy in rats.

    PubMed

    Rong, Xianglu; Kim, Moon Sun; Su, Ning; Wen, Suping; Matsuo, Yukimi; Yamahara, Johji; Murray, Michael; Li, Yuhao

    2008-06-01

    Activation of peroxisome proliferator-activated receptor (PPAR)-alpha by natural and synthetic chemicals induces hepatic hypertrophy. An aqueous extract of Salacia oblonga root (SOW) is an Ayurvedic medicine with anti-diabetic and anti-obesity properties. In the present study, it was found that SOW (100, 300 and 900mg/kg, once daily by oral gavage over a 28 day period) elicited dose-related increases in liver weight (LW) by 1.6%, 13.4% and 42.5%, respectively, and in the ratio of LW to body weight by 8.8%, 16.7% and 40.2%, respectively, in male rats. These effects were less pronounced in females. SOW selectively increased liver mass in male rats but Sudan red staining was not different, which indicates that hepatic lipid accumulation was similar in both genders. However, SOW even at the highest dosage did not influence serum ALT and AST activities in male or female rats. Moreover, SOW was found to activate PPAR-alpha in human hepatoma-derived HepG2 cells, as evidenced by the upregulation of PPAR-alpha and acyl-CoA oxidase mRNA expression. Thus, SOW-dependent PPAR-alpha activation may precede the development of the gender difference in hepatic hypertrophy; this process may be influenced by sex hormone status. PMID:18397819

  12. Circulating Tumor Cells Following First Chemotherapy Cycle: An Early and Strong Predictor of Outcome in Patients With Metastatic Breast Cancer

    PubMed Central

    Custodio, Sara; de las Casas, Maria-Luisa Maestro; García-Sáenz, José-Ángel; de la Torre, Julio-César; Bellón-Cano, Jose-María; López-Tarruella, Sara; Vidaurreta-Lazaro, Marta; de la Orden, Virginia; Jerez, Yolanda; Márquez-Rodas, Iván; Casado, Antonio; Sastre, Javier; Díaz-Rubio, Eduardo

    2013-01-01

    We investigated the prognostic significance of circulating tumor cells (CTCs) determined immediately before the second cycle of chemotherapy in patients with metastatic breast cancer (MBC). The CTC counts were taken at baseline, before the first cycle of chemotherapy (CTC-0), and on day 21 before commencing the second cycle of chemotherapy (CTC-21) in consecutive MBC patients. The study's primary objectives were to analyze relationships between CTC-21 count and overall survival (OS). Based on the current literature, the CTC measurements were dichotomized as 0–4 versus ≥5 CTCs. Of 117 patients recruited, 99 were evaluable. Patients with 0–4 CTCs on day 21 had a significantly better OS than those with ≥5 CTCs (median OS: 38.5 months vs. 8.7 months). They also had a significantly better progression-free survival (PFS; median: 9.4 months vs. 3.0 months) and clinical benefit rate (77% vs. 44%). The OS of patients whose baseline CTCs were ≥5 but dropped to <5 on day 21 was apparently similar to those who had <5 CTCs at baseline. In a Cox regression analysis, CTC-21 was the only independent variable significantly predicting OS and PFS. Our data indicate that CTCs determined immediately before the second cycle of chemotherapy is an early and strong predictor of treatment outcome in MBC patients. PMID:23873719

  13. Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle.

    PubMed

    Li, Xiaoyan; Luthra, Rakesh; Morrow, Phuong K; Fisher, Maxine D; Reiner, Maureen; Barron, Richard L; Langeberg, Wendy J

    2016-10-01

    Patients receiving myelosuppressive chemotherapy with certain comorbidities are at increased risk of febrile neutropenia. A comprehensive evaluation of febrile neutropenia-related comorbidities across cancers is needed. This study compared comorbidity prevalence among patients with cancer who did and did not develop febrile neutropenia during the first chemotherapy cycle. This case-control study used administrative claims from adult patients with non-Hodgkin lymphoma or breast, lung, colorectal, ovarian, or gastric cancer who received chemotherapy between 2007 and 2012. Each patient who developed febrile neutropenia (case) was matched with up to four patients without febrile neutropenia (controls) by cancer type, metastasis, chemotherapy regimen, age group, and sex. For each comorbidity (identified in the year before chemotherapy began), the adjusted odds ratio (aOR) for febrile neutropenia by cancer type was evaluated using conditional logistic regression models adjusted for potential confounding factors. Of 31,331 eligible patients, 672 developed febrile neutropenia in the first chemotherapy cycle. A total of 3312 febrile neutropenia cases and matched controls were analyzed. Across tumor types, comorbidity prevalence was higher in patients who developed febrile neutropenia than in those without febrile neutropenia. Among patients with breast cancer, osteoarthritis was more prevalent in patients with febrile neutropenia (aOR, 1.85; 95% CI, 1.07 to 3.18). Among patients with non-Hodgkin lymphoma, renal disease was more prevalent in patients with febrile neutropenia (aOR, 2.25; 95% CI, 1.23 to 4.11). Patients who developed febrile neutropenia in the first chemotherapy cycle presented with comorbidities more often than otherwise similar patients who did not develop febrile neutropenia. These findings warrant further investigation and support the inclusion of comorbidities into febrile neutropenia risk models.

  14. Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders.

    PubMed

    MacLeod, Erin L; Hall, Kevin D; McGuire, Peter J

    2016-01-01

    Nutritional management of acute metabolic decompensation in amino acid inborn errors of metabolism (AA IEM) aims to restore nitrogen balance. While nutritional recommendations have been published, they have never been rigorously evaluated. Furthermore, despite these recommendations, there is a wide variation in the nutritional strategies employed amongst providers, particularly regarding the inclusion of parenteral lipids for protein-free caloric support. Since randomized clinical trials during acute metabolic decompensation are difficult and potentially dangerous, mathematical modeling of metabolism can serve as a surrogate for the preclinical evaluation of nutritional interventions aimed at restoring nitrogen balance during acute decompensation in AA IEM. A validated computational model of human macronutrient metabolism was adapted to predict nitrogen balance in response to various nutritional interventions in a simulated patient with a urea cycle disorder (UCD) during acute metabolic decompensation due to dietary non-adherence or infection. The nutritional interventions were constructed from published recommendations as well as clinical anecdotes. Overall, dextrose alone (DEX) was predicted to be better at restoring nitrogen balance and limiting nitrogen excretion during dietary non-adherence and infection scenarios, suggesting that the published recommended nutritional strategy involving dextrose and parenteral lipids (ISO) may be suboptimal. The implications for patients with AA IEM are that the medical course during acute metabolic decompensation may be influenced by the choice of protein-free caloric support. These results are also applicable to intensive care patients undergoing catabolism (postoperative phase or sepsis), where parenteral nutritional support aimed at restoring nitrogen balance may be more tailored regarding metabolic fuel selection.

  15. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation

    PubMed Central

    Lipton, Jeff H.; Rea, Delphine; Digumarti, Raghunadharao; Chuah, Charles; Nanda, Nisha; Benichou, Annie-Claude; Craig, Adam R.; Michallet, Mauricette; Nicolini, Franck E.; Kantarjian, Hagop

    2012-01-01

    Chronic myeloid leukemia (CML) patients with the BCR-ABL T315I mutation do not benefit from therapy with currently approved tyrosine kinase inhibitors. Omacetaxine mepesuccinate is a protein synthesis inhibitor that has demonstrated activity in cells harboring the T315I mutation. This phase 2 trial assessed the efficacy of omacetaxine in CML patients with T315I and tyrosine kinase inhibitor failure. Patients received subcutaneous omacetaxine 1.25 mg/m2 twice daily, days 1-14, every 28 days until hematologic response or a maximum of 6 cycles, and then days 1-7 every 28 days as maintenance. Results for patients treated in chronic phase are reported here. Patients (n = 62) received a median of 7 (range, 1-41) cycles. Complete hematologic response was achieved in 48 patients (77%; 95% lower confidence limit, 65%); median response duration was 9.1 months. Fourteen patients (23%; 95% lower confidence limit, 13%) achieved major cytogenetic response, including complete cytogenetic response in 10 (16%). Median progression free-survival was 7.7 months. Grade 3/4 hematologic toxicity included thrombocytopenia (76%), neutropenia (44%), and anemia (39%) and was typically manageable by dose reduction. Nonhematologic adverse events were mostly grade 1/2 and included infection (42%), diarrhea (40%), and nausea (34%). Omacetaxine may provide a safe and effective treatment for CML patients with T315I mutation. This study is registered at www.clinicaltrials.gov as NCT00375219. PMID:22896000

  16. A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

    PubMed

    Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

    2015-12-01

    3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively. PMID:26434797

  17. Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer.

    PubMed

    Altmäe, Signe; Tamm-Rosenstein, Karin; Esteban, Francisco J; Simm, Jaak; Kolberg, Liis; Peterson, Hedi; Metsis, Madis; Haldre, Kai; Horcajadas, José A; Salumets, Andres; Stavreus-Evers, Anneli

    2016-06-01

    Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women. IPA and DAVID were used for functional analyses of differentially expressed genes. The TRANSFAC database was used to identify oestrogen and progesterone response elements upstream of differentially expressed genes. Cluster analysis demonstrated that natural cycles are associated with a better endometrial receptivity transcriptome than artificial cycles. Artificial cycles seemed to have a stronger negative effect on expression of genes and pathways crucial for endometrial receptivity, including ESR2, FSHR, LEP, and several interleukins and matrix metalloproteinases. Significant overrepresentation of oestrogen response elements among the genes with deteriorated expression in artificial cycles (P < 0.001) was found; progesterone response elements predominated in genes with amended expression with artificial cycles (P = 0.0052).

  18. Using a Cyclical Diagram to Visualize the Events of the Ovulatory Menstrual Cycle

    ERIC Educational Resources Information Center

    Ho, Ivan Shun; Parmar, Navneet K.

    2014-01-01

    Over the past 10 years, college textbooks in human anatomy and physiology have typically presented the events of the ovulatory menstrual cycle in a linear format, with time in days shown on the x-axis, and hormone levels, follicular development, and uterine lining on the y-axis. In addition, the various events are often shown over a 28-day cycle,…

  19. Reproducibility of incremental maximal cycle ergometer testing in patients with restrictive lung disease.

    PubMed Central

    Marciniuk, D. D.; Watts, R. E.; Gallagher, C. G.

    1993-01-01

    BACKGROUND--Exercise testing has become an important tool in the diagnosis and treatment of restrictive lung disease. The reproducibility of variables measured during exercise testing was examined in subjects with stable restrictive lung disease. METHODS--Six subjects, who had never previously undergone exercise testing, each underwent three maximal incremental exercise studies on a bicycle ergometer conducted during a 28 day period. RESULTS--Data collected at rest, before exercise, were not significantly different during the three study days. Comparison of results at the end of the exercise tests from the three studies also revealed no evidence of a significant learning effect. Reproducibility of exercise performance by subjects was assessed by the coefficient of variation. The mean within subject coefficient of variation at the end of the exercise tests was 5.6% for work rate, 7.9% for exercise duration, and 9.5% for dyspnoea. The mean within subject coefficient of variation obtained at the end of the exercise tests was 5.3% for oxygen uptake (VO2), 2.5% for oxygen saturation (SaO2), 4.0% for heart rate (HR), 5.5% for minute ventilation (VE), 5.8% for respiratory frequency (f), and 4.6% for tidal volume (VT). The mean within subject coefficient of variation at 40% and 70% of maximal work rates for VO2 was 5.7% and 5.6% respectively, for SaO2 1.3% and 1.5%, for HR 4.8% and 4.0%, for VE 6.3% and 6.6%, for f 10.1% and 7.8%, and for VT 6.0% and 4.5%. CONCLUSIONS--Variables measured during clinical exercise testing in subjects with restrictive lung disease are highly reproducible. No significant learning effect was found on repeated testing in subjects who had never previously undergone exercise testing. PMID:8236071

  20. Characterization of the use of a cycle ergometer to assist in the physical therapy treatment of critically ill patients

    PubMed Central

    Pires-Neto, Ruy Camargo; Pereira, Aná Luiza; Parente, Camila; de Sant'Anna, Guadalupe Nery; Esposito, Daniela Daguer; Kimura, Aline; Fu, Carolina; Tanaka, Clarice

    2013-01-01

    Objective The objective of this study was to use a cycle ergometer to assess cardiorespiratory changes during active exercise and to verify patients' satisfaction with this type of activity. Methods A single intervention involving active lower limb exercise was performed with a cycle ergometer (without load) for 5 minutes. The following variables were measured before, during and immediately after exercise: heart rate, blood pressure, respiratory rate, peripheral oxygen saturation and the Borg dyspnea scale score. Following the exercise, the patients answered a questionnaire to evaluate their satisfaction with this type of activity. Results A total of 38 patients (65% male) with a mean age of 48 ± 16 years old participated in the study. Enrolled patients presented a sequential organ failure assessment (SOFA) score of 2 (0 - 5 scale). During the exercise, 16% of the patients used ventilation support and 55% of them were breathing at room air. A comparison of the initial and final values of the variables indicated increases in the heart rate (92±17 beats/min vs. 95±18 beats/min; p<0.05), the respiratory rate (19 ± 8 breaths/min vs. 23±8 breaths/min; p<0.05) and the Borg dyspnea scale score (1.3±1.8 vs. 2.8±2.2; p<0.05). In addition, 85% of the patients reported enjoying the activity. Only 25% of the patients reported some discomfort, and 100% of the patients wanted to repeat this type of activity in future treatments. Conclusion During the cycle ergometer exercises, minor cardiorespiratory changes were observed in the patients. The evaluated patients reported high satisfaction with this type of activity. PMID:23887758

  1. Design of a symmetry controller for cycling induced by electrical stimulation: preliminary results on post-acute stroke patients.

    PubMed

    Ambrosini, Emilia; Ferrante, Simona; Schauer, Thomas; Ferrigno, Giancarlo; Molteni, Franco; Pedrocchi, Alessandra

    2010-08-01

    This study deals with the design of a controller for cycling induced by functional electrical stimulation. The controller will be exploitable in the rehabilitation of hemiparetic patients who need to recover motor symmetry. It uses the pulse width as the control variable in the stimulation of the two legs in order to nullify the unbalance between the torques produced at the two crank arms. It was validated by means of isokinetic trials performed both by healthy subjects and stroke patients. The results showed that the controller was able to reach, and then maintain, a symmetrical pedaling. In the future, the controller will be validated on a larger number of stroke patients.

  2. Design of a symmetry controller for cycling induced by electrical stimulation: preliminary results on post-acute stroke patients.

    PubMed

    Ambrosini, Emilia; Ferrante, Simona; Schauer, Thomas; Ferrigno, Giancarlo; Molteni, Franco; Pedrocchi, Alessandra

    2010-08-01

    This study deals with the design of a controller for cycling induced by functional electrical stimulation. The controller will be exploitable in the rehabilitation of hemiparetic patients who need to recover motor symmetry. It uses the pulse width as the control variable in the stimulation of the two legs in order to nullify the unbalance between the torques produced at the two crank arms. It was validated by means of isokinetic trials performed both by healthy subjects and stroke patients. The results showed that the controller was able to reach, and then maintain, a symmetrical pedaling. In the future, the controller will be validated on a larger number of stroke patients. PMID:20528850

  3. [Early Stages of Parkinson's Disease: Comparative Characteristics of Sleep-Wakefulness Cycle in Patients and Model Animals].

    PubMed

    Kovalzon, V M; Ugrumov, M V; Pronina, T S; Dorokhov, V B; Manolov, A I; Dolgikh, V V; Ukraintseva, Y V; Moiseenko, L S; Poluektov, M G; Kalinkin, A L

    2015-01-01

    The results of study of sleep-wakefulness cycle in experimental models of pre-clinical and early clinical stages of Parkinson's disease present and compared to some clinical examples. The conclusion is, the increase in activity level and decrease in total amount of slow wave and paradoxical sleep in model animals are taking place at the same circadian period of the secretion of pineal melatonin as sleep disorders in patients.

  4. [Early Stages of Parkinson's Disease: Comparative Characteristics of Sleep-Wakefulness Cycle in Patients and Model Animals].

    PubMed

    Kovalzon, V M; Ugrumov, M V; Pronina, T S; Dorokhov, V B; Manolov, A I; Dolgikh, V V; Ukraintseva, Y V; Moiseenko, L S; Poluektov, M G; Kalinkin, A L

    2015-01-01

    The results of study of sleep-wakefulness cycle in experimental models of pre-clinical and early clinical stages of Parkinson's disease present and compared to some clinical examples. The conclusion is, the increase in activity level and decrease in total amount of slow wave and paradoxical sleep in model animals are taking place at the same circadian period of the secretion of pineal melatonin as sleep disorders in patients. PMID:26859995

  5. Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia

    PubMed Central

    Rider, Nicholas L.; Strauss, Kevin A.; Morton, D. Holmes; Adair, Margaret; Bonilla, Francisco A.; Ochs, Hans D.; Gelfand, Erwin W.; Pessach, Itai M.; Walter, Jolan E.; King, Alejandra; Giliani, Silvia; Pai, Sung-Yun; Notarangelo, Luigi D.

    2015-01-01

    Background Cartilage-hair hypoplasia (CHH) is characterized by metaphyseal dysplasia, bone marrow failure, increased risk of malignancies, and a variable degree of immunodeficiency. CHH is caused by mutations in the RNA component of the mitochondrial RNA processing (RMRP) endoribonuclease gene, which is involved in ribosomal assembly, telomere function, and cell cycle control. Objectives We aimed to define thymic output and characterize immune function in a cohort of patients with molecularly defined CHH with and without associated clinical immunodeficiency. Methods We studied the distribution of B and T lymphocytes (including recent thymic emigrants), in vitro lymphocyte proliferation, cell cycle, and apoptosis in 18 patients with CHH compared with controls. Results Patients with CHH have a markedly reduced number of recent thymic emigrants, and their peripheral T cells show defects in cell cycle control and display increased apoptosis, resulting in poor proliferation on activation. Conclusion These data confirm that RMRP mutations result in significant defects of cell-mediated immunity and provide a link between the cellular phenotype and the immunodeficiency in CHH. PMID:21570718

  6. Laser assisted zona hatching does not improve live birth rate in patients undergoing their first ICSI cycles

    PubMed Central

    Razi, Mohammad Hossein; Halvaei, Iman; Razi, Yasamin

    2013-01-01

    Background: Routine use of assisted hatching (AH) following ICSI is a controversial issue in the literature. There are rare studies regarding the effect of laser assisted hatching (LAH) on live birth rate. Objective: Our main goal was to evaluate the effect of LAH on delivery rate as well as congenital anomaly in patients undergoing their first ICSI cycle. Materials and Methods: A total of 182 patients subjected to ICSI were randomly aliquot into two groups of experiment and control. In experiment group, the embryos were subjected to LAH to open a hole in ZP (about 10-12 µm) while in control group, the transferred embryos were intact with no AH. The patients were followed for clinical pregnancy and delivery rate as well as congenital anomaly. All the patients were infertile due to male factor infertility and LAH and embryo transfer were done on day 2. Results: Laboratory and clinical characteristics of two groups of experiment and control were the same. There were insignificant differences between two groups of experiment and control for clinical pregnancy rate (20% vs. 23.9%, respectively, p=0.3) and live birth rate (11.11% vs. 8.6%, respectively, p=0.6). Also no significant differences were observed between two groups of experiment and control for multiple pregnancy as well as congenital anomaly. Conclusion: Routine use of LAH in first ICSI cycle for male factor patients may have no beneficial effects on clinical pregnancy and live birth rate. PMID:24639729

  7. Impact of Lean on patient cycle and waiting times at a rural district hospital in KwaZulu-Natal

    PubMed Central

    Naidoo, Logandran

    2016-01-01

    Background Prolonged waiting time is a source of patient dissatisfaction with health care and is negatively associated with patient satisfaction. Prolonged waiting times in many district hospitals result in many dissatisfied patients, overworked and frustrated staff, and poor quality of care because of the perceived increased workload. Aim The aim of the study was to determine the impact of Lean principles techniques, and tools on the operational efficiency in the outpatient department (OPD) of a rural district hospital. Setting The study was conducted at the Catherine Booth Hospital (CBH) – a rural district hospital in KwaZulu-Natal, South Africa. Methods This was an action research study with pre-, intermediate-, and post-implementation assessments. Cycle and waiting times were measured by direct observation on two occasions before, approximately two-weekly during, and on two occasions after Lean implementation. A standardised data collection tool was completed by the researcher at each of the six key service nodes in the OPD to capture the waiting times and cycle times. Results All six service nodes showed a reduction in cycle times and waiting times between the baseline assessment and post-Lean implementation measurement. Significant reduction was achieved in cycle times (27%; p < 0.05) and waiting times (from 11.93 to 10 min; p = 0.03) at the Investigations node. Although the target reduction was not achieved for the Consulting Room node, there was a significant reduction in waiting times from 80.95 to 74.43 min, (p < 0.001). The average efficiency increased from 16.35% (baseline) to 20.13% (post-intervention). Conclusion The application of Lean principles, tools and techniques provides hospital managers with an evidence-based management approach to resolving problems and improving quality indicators. PMID:27543283

  8. FES cycling.

    PubMed

    Newham, D J; Donaldson, N de N

    2007-01-01

    Spinal cord injury (SCI) leads to a partial or complete disruption of motor, sensory, and autonomic nerve pathways below the level of the lesion. In paraplegic patients, functional electrical stimulation (FES) was originally widely considered as a means to restore walking function but this was proved technically very difficult because of the numerous degrees of freedom involved in walking. FES cycling was developed for people with SCI and has the advantages that cycling can be maintained for reasonably long periods in trained muscles and the risk of falls is low. In the article, we review research findings relevant to the successful application of FES cycling including the effects on muscle size, strength and function, and the cardiovascular and bone changes. We also describe important practical considerations in FES cycling regarding the application of surface electrodes, training and setting up the stimulator limitations, implanted stimulators and FES cycling including FES cycling in groups and other FES exercises such as FES rowing.

  9. Hallucinations and sleep-wake cycle in Alzheimer's disease: a questionnaire-based study in 218 patients.

    PubMed

    Sinforiani, E; Terzaghi, M; Pasotti, C; Zucchella, C; Zambrelli, E; Manni, R

    2007-04-01

    The aim was to evaluate the relationship between hallucinations and the sleep-wake cycle in a sample of Alzheimer's disease (AD) patients in the early-moderate stage. Two hundred and eighteen AD patients (66 males, 152 females, mean age 74.3+/-6.85) were administered a sleep questionnaire in the presence of a care-giver. Twenty-six out of 218 (12%) reported the occurrence of hallucinations, mainly visual. In 18/28 (69%) hallucinations occurred when the patient was awake and in 8 (31%) hallucinations were reported to occur close to a specific phase of the sleep-wake cycle. Vivid dreams were reported in 25/218 (11%) and violent sleep-related and dream-related behaviours (probable REM behaviour episodes) in 22/218 (10%). Both REM phenomena were more frequent in AD hallucinators than in AD non-hallucinators (26.9% vs. 9.3%, and 26.9% vs. 7.8%, p<0.007). Our data indicate a lower incidence of hallucinations and presumable REM behaviour disorder (RBD) in AD, at least in the early-moderate phase, than that observed in synucleinopathies. However, the higher occurrence of vivid dreams and RBD in AD patients with hallucinations compared to those without hallucinations indicates a potential role of disordered REM sleep in influencing the occurrence of hallucinations in AD, similar to what has been observed in synucleinopathies.

  10. Folate and nutrients involved in the 1-carbon cycle in the pretreatment of patients for colorectal cancer.

    PubMed

    Ferrari, Ariana; de Carvalho, Aline Martins; Steluti, Josiane; Teixeira, Juliana; Marchioni, Dirce Maria Lobo; Aguiar, Samuel

    2015-06-02

    To assess the ingestion of folate and nutrients involved in the 1-carbon cycle in non-treated patients with colorectal adenocarcinoma in a reference center for oncology in southeastern Brazil. In total, 195 new cases with colorectal adenocarcinoma completed a clinical evaluation questionnaire and a Food Frequency Questionnaire (FFQ). Blood samples from 161 patients were drawn for the assessment of serum folate. A moderate correlation was found between serum concentrations of folate, folate intake and the dietary folate equivalent (DFE) of synthetic supplements. Mulatto or black male patients with a primary educational level had a higher intake of dietary folate. Of patients obtaining folate from the diet alone or from dietary supplements, 11.00% and 0.10%, respectively, had intake below the recommended level. Of the patients using dietary supplements, 35% to 50% showed high levels of folic acid intake. There was a prevalence of inadequacy for vitamins B2, B6 and B12, ranging from 12.10% to 20.18%, while 13.76% to 22.55% of patients were likely to have adequate choline intake. The considerable percentage of patients with folate intake above the recommended levels deserves attention because of the harmful effects that this nutrient may have in the presence of established neoplastic lesions.

  11. Effects of the menstrual cycle on bispectral index and anesthetic requirement in patients with preoperative intravenous dexmedetomidine following propofol induction

    PubMed Central

    Zhou, Xiaomin; Wang, Tingting; Huang, Shaoqiang

    2014-01-01

    Several studies have suggested that the menstrual cycle has the impact on sedation. No previous study has evaluated the effects of the menstrual cycle on sedation level and propofol requirement with preoperative intravenous dexmedetomidine. Sixty-four adult fertile women receiving general anesthesia for elective gynecologic surgery were included in the study. Patients were classified into four groups on the basis of the phase of menstrual cycle and whether infused dexmedetomidine preoperatively: Group FS: the follicular phase (days 8-12) and preoperative intravenous normal saline; Group FD: the follicular phase (days 8-12) and preoperative intravenous dexmedetomidine; Group LS: the luteal phase (days 20-24) and normal saline; Group LD: the luteal phase (days 20-24) and dexmedetomidine. The patients were infused respectively dexmedetomidine at 0, 1.0, 0 and 1.0 μg/kg over 10 min, and then propofol TCI, which was administered with target plasma concentration at 4.0 μg/ml. BIS, heart rate, MAP were recorded until BIS to 50. In the LD group, the descent range of the BIS values was significantly sharpest among the four groups at loss of eyelash reflex. From propofol administered to loss of eyelash reflex and BIS values reach to 50, propofol requirements were significantly least and duration were shortest in the LD group among the four groups. Menstrual cycle phases affect the sedation of propofol induction with preoperative intravenous dexmedetomidine, which is deeper in the luteal phase. We should cautious of excessive sedation by propofol anesthesia with preoperative dexmedetomidine in the luteal phase. PMID:25664087

  12. Self-Reported Treatment-Associated Symptoms among Patients with Urea Cycle Disorders Participating in Glycerol Phenylbutyrate Clinical Trials

    PubMed Central

    Nagamani, Sandesh C. S.; Diaz, George A.; Rhead, William; Berry, Susan A.; Le Mons, Cynthia; Lichter-Konecki, Uta; Bartley, James; Feigenbaum, Annette; Schulze, Andreas; Longo, Nicola; Berquist, William; Gallagher, Renata; Bartholomew, Dennis; Harding, Cary O.; Korson, Mark S.; McCandless, Shawn E.; Smith, Wendy; Vockley, Jerry; Kronn, David; Zori, Robert; Cederbaum, Stephen; Merritt, J. Lawrence; Wong, Derek; Coakley, Dion F.; Scharschmidt, Bruce F.; Dickinson, Klara; Marino, Miguel; Lee, Brendan H.; Mokhtarani, Masoud

    2016-01-01

    Background Health care outcomes have been increasingly assessed through health-related quality of life (HRQoL) measures. While the introduction of nitrogen-scavenging medications has improved survival in patients with urea cycle disorders (UCDs), they are often associated with side effects that may affect patient compliance and outcomes. Methods Symptoms commonly associated with nitrogen-scavenging medications were evaluated in 100 adult and pediatric participants using a non-validated UCD-specific questionnaire. Patients or their caregivers responded to a pre-defined list of symptoms known to be associated with the use of these medications. Responses were collected at baseline (while patients were receiving sodium phenylbutyrate [NaPBA]) and during treatment with glycerol phenylbutyrate (GPB). Results After 3 months of GPB dosing, there were significant reductions in the proportion of patients with treatment-associated symptoms (69% vs. 46%; p<0.0001), the number of symptoms per patient (2.5 vs. 1.1; p<0.0001), and the frequency of the more commonly reported individual symptoms such as body odor, abdominal pain, nausea, burning sensation in mouth, vomiting, and heartburn (p<0.05). The reduction in symptoms was observed in both pediatric and adult patients. The presence or absence of symptoms or change in severity did not correlate with plasma ammonia levels or NaPBA dose. Conclusions The reduction in symptoms following 3 months of open-label GPB dosing was similar in pediatric and adult patients and may be related to chemical structure and intrinsic characteristics of the product rather than its effect on ammonia control. PMID:26296711

  13. Characteristics and determinants of endurance cycle ergometry and six-minute walk distance in patients with COPD

    PubMed Central

    2014-01-01

    Background Exercise tolerance can be assessed by the cycle endurance test (CET) and six-minute walk test (6MWT) in patients with Chronic Obstructive Pulmonary Disease (COPD). We sought to investigate the characteristics of functional exercise performance and determinants of the CET and 6MWT in a large clinical cohort of COPD patients. Methods A dataset of 2053 COPD patients (43% female, age: 66.9 ± 9.5 years, FEV1% predicted: 48.2 ± 23.2) was analyzed retrospectively. Patients underwent, amongst others, respiratory function evaluation; medical tests and questionnaires, one maximal incremental cycle test where peak work rate was determined and two functional exercise tests: a CET at 75% of peak work rate and 6MWT. A stepwise multiple linear regression was used to assess determinants. Results On average, patients had impaired exercise tolerance (peak work rate: 56 ± 27% predicted, 6MWT: 69 ± 17% predicted). A total of 2002 patients had CET time of duration (CET-Tend) less than 20 min while only 51 (2.5%) of the patients achieved 20 min of CET-Tend . In former patients, the percent of predicted peak work rate achieved differed significantly between men (48 ± 21% predicted) and women (67 ± 31% predicted). In contrast, CET-Tend was longer in men (286 ± 174 s vs 250 ± 153 s, p < 0.001). Also, six minute walking distance (6MWD) was higher in men compared to women, both in absolute terms as in percent of predicted (443 m, 67%predicted vs 431 m, 72%predicted, p < 0.05). Gender was associated with the CET-Tend but BMI, FEV1 and FRC were related to the 6MWD highlighting the different determinants of exercise performance between CET and 6MWT. Conclusions CET-Tend is a valuable outcome of CET as it is related to multiple clinical aspects of disease severity in COPD. Gender difference should temper the interpretation of CET. PMID:24885117

  14. DNA cell cycle distribution and glutathione (GSH) content according to circadian stage in bone marrow of cancer patients.

    PubMed Central

    Smaaland, R.; Abrahamsen, J. F.; Svardal, A. M.; Lote, K.; Ueland, P. M.

    1992-01-01

    DNA cell cycle distribution and glutathione (GSH) content in bone marrow were measured both at daytime and midnight over single 24 h periods in 15 cancer patients. Between patients the S-phase demonstrated a difference from lowest to highest value of 700%, whereas the corresponding difference for the G2/M-phase was nearly 900%. The mean GSH content measured in the bone marrow at the two timepoints was 2.24 +/- 0.21 nmol mg-1 protein, range 0.91-4.19 nmol mg-1 protein. A statistically significant higher fraction of cells in S-phase and G2/M-phase was found at daytime as compared to midnight when excluding the four patients with an abnormal circadian variation in cortisol. No significant temporal variation in total bone marrow GSH content was found, although a weak correlation between S-phase and GSH content was demonstrated (r = 0.42; P less than 0.05). This correlation was strengthened when not including the six patients with an abnormal cortisol pattern (4) and bone marrow infiltration (2) (r = 0.66; P = 0.005). Cells in S-phase demonstrated a positive correlation with cells in G2/M-phase (r = 0.64; P less than 0.0001). A negative correlation was found between GSH content and age (r = 0.53; P less than 0.005). Finally, a statistically significant positive correlation was demonstrated between cortisol and both S-phase and G2/M-phase (r = 0.57; P less than 0.001 and r = 0.38; P less than 0.05, respectively). The present study suggests a possibility of optimising cancer therapy and use of hematopoietic growth factors by determining individual average values and circadian stage dependent variation in bone marrow DNA cell cycle distribution. Furthermore, GSH content in bone marrow may predict this tissue's sensitivity to cytotoxic agents. PMID:1637674

  15. Novel Metabolic Abnormalities in the Tricarboxylic Acid Cycle in Peripheral Cells From Huntington’s Disease Patients

    PubMed Central

    Naseri, Nima N.; Bonica, Joseph; Xu, Hui; Park, Larry C.; Arjomand, Jamshid; Chen, Zhengming; Gibson, Gary E.

    2016-01-01

    Metabolic dysfunction is well-documented in Huntington’s disease (HD). However, the link between the mutant huntingtin (mHTT) gene and the pathology is unknown. The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the production of NADH for conversion to ATP via the electron transport chain (ETC). The objective of this study was to test for differences in enzyme activities, mRNAs and protein levels related to the TCA cycle between lymphoblasts from healthy subjects and from patients with HD. The experiments utilize the advantages of lymphoblasts to reveal new insights about HD. The large quantity of homogeneous cell populations permits multiple dynamic measures to be made on exactly comparable tissues. The activities of nine enzymes related to the TCA cycle and the expression of twenty-nine mRNAs encoding for these enzymes and enzyme complexes were measured. Cells were studied under baseline conditions and during metabolic stress. The results support our recent findings that the activities of the pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase (SDH) are elevated in HD. The data also show a large unexpected depression in MDH activities. Furthermore, message levels for isocitrate dehydrogenase 1 (IDH1) were markedly increased in in HD lymphoblasts and were responsive to treatments. The use of lymphoblasts allowed us to clarify that the reported decrease in aconitase activity in HD autopsy brains is likely due to secondary hypoxic effects. These results demonstrate the mRNA and enzymes of the TCA cycle are critical therapeutic targets that have been understudied in HD. PMID:27611087

  16. Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: Long-term follow up on IBCSG Trial IX

    PubMed Central

    Aebi, S.; Sun, Z.; Braun, D.; Castiglione-Gertsch, M.; Rabaglio, M.; Gelber, R. D.; Crivellari, D.; Lindtner, J.; Snyder, R.; Karlsson, P.; Simoncini, E.; Gusterson, B. A.; Viale, G.; Regan, M. M.; Coates, A. S.; Goldhirsch, A.

    2011-01-01

    Background: The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed. Patients and methods: After stratification by ER status, 1669 postmenopausal patients with operable lymph node-negative breast cancer were randomly assigned to three 28-day courses of ‘classical’ CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF→tamoxifen) or to tamoxifen alone for 5 years. Results: ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF→tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes. Conclusion: CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy. PMID:21282282

  17. Abnormal Facial Emotion Recognition in Depression: Serial Testing in an Ultra-Rapid-Cycling Patient.

    ERIC Educational Resources Information Center

    George, Mark S.; Huggins, Teresa; McDermut, Wilson; Parekh, Priti I.; Rubinow, David; Post, Robert M.

    1998-01-01

    Mood disorder subjects have a selective deficit in recognizing human facial emotion. Whether the facial emotion recognition errors persist during normal mood states (i.e., are state vs. trait dependent) was studied in one male bipolar II patient. Results of five sessions are presented and discussed. (Author/EMK)

  18. Effect of dialysis dose and membrane flux on hemoglobin cycling in hemodialysis patients.

    PubMed

    He, Liyu; Fu, Min; Chen, Xian; Liu, Hong; Chen, Xing; Peng, Xiaofei; Liu, Fuyou; Peng, Youming

    2015-04-01

    Many studies found that hemoglobin (Hb) fluctuation was closely related to the prognosis of the maintenance hemodialysis patients. We investigated the association of factors relating dialysis dose and dialyzer membrane with Hb levels. We undertook a randomized clinical trial in 140 patients undergoing thrice-weekly dialysis and assigned patients randomly to a standard or high dose of dialysis; Hb level was measured every month for 12 months. In the standard-dose group, the mean (±SD) urea reduction ratio was 65.1% ± 7.3%, the single-pool Kt/V was 1.26 ± 0.11, and the equilibrated Kt/V was 1.05 ± 0.09; in the high-dose group, the values were 73.5% ± 8.7%, 1.68 ± 0.15, and 1.47 ± 0.11, respectively. The standard deviation (SD) and residual SD (liner regression of Hb) values of Hb were significantly higher in the standard-dose group and low-flux group. The percentage achievement of target Hb in the high-dose dialysis group and high-flux dialyzer group was significantly higher than the standard-dose group and low-flux group, respectively. Patients undergoing hemodialysis thrice weekly appear to have benefit from a higher dialysis dose than that recommended by current KDQQI (Kidney Disease Qutcome Quality Initiative) guidelines or from the use of a high-flux membrane, which is in favor of maintaining stable Hb levels.

  19. Effective hospital revenue cycle management: is there a trade-off between the amount of patient revenue and the speed of revenue collection?

    PubMed

    Rauscher, Simone; Wheeler, John R C

    2008-01-01

    Effective hospital revenue cycle management practices have gained in importance in today's hospital business environment, in which many hospitals are confronted with stricter regulations and billing requirements, more thorough preauthorization and precertification, underpayments, and greater delays in payments. In this article, we provide a brief description of current hospital revenue cycle management practices. Next, we suggest measures of the financial benefits of revenue cycle management in terms of increases in the amount and speed of patient revenue collection. We consider whether there is a trade-off between the amount of patient revenue a hospital earns and the speed with which revenue is collected. Using financial statement data from California hospitals for 2004 to 2006, we test empirically the relationships among key financial measures of effective hospital revenue cycle management. We find that hospitals with higher speeds of revenue collection tend to record higher amounts of net patient revenue per adjusted discharge, lower contractual allowances, and lower bad debts. Charity care provision, on the other hand, tends to be higher among hospitals with higher speeds of revenue collection. We conclude that there is no evidence of a trade-off between the amount of patient revenue and the speed of revenue collection but that these financial benefits of effective hospital revenue cycle management often go hand in hand. We thus provide early indication that these outcomes are complementary, suggesting that effective hospital revenue cycle management achieves multiple positive results.

  20. Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies

    PubMed Central

    Garcia-Manero, Guillermo; Cogle, Christopher R.; Gore, Steven D.; Hetzer, Joel; Kumar, Keshava; Skikne, Barry; MacBeth, Kyle J.

    2015-01-01

    CC-486 (oral azacitidine) is an epigenetic modifier in development for patients with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two-part study, a 7-day CC-486 dosing schedule showed clinical activity, was generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486 beyond 7 days would increase duration of azacitidine exposure. We hypothesized that extended dosing would therefore provide more sustained epigenetic activity. Reported here are the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of CC-486 extended dosing schedules in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML) from part 2 of this study. PK and/or PD data were available for 59 patients who were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once-daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once-daily schedules and the 200mg twice-daily 21-day schedule significantly (all P < .05) reduced global DNA methylation in whole blood at all measured time points (days 15, 22, and 28 of the treatment cycle), with sustained hypomethylation at cycle end compared with baseline. CC-486 exposures and reduced DNA methylation were significantly correlated. Patients who had a hematologic response had significantly greater methylation reductions than non-responding patients. These data demonstrate that extended dosing of CC-486 sustains epigenetic effects through the treatment cycle. Trial Registration ClinicalTrials.gov NCT00528983 PMID:26296092

  1. Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas.

    PubMed

    Holkova, Beata; Kmieciak, Maciej; Bose, Prithviraj; Yazbeck, Victor Y; Barr, Paul M; Tombes, Mary Beth; Shrader, Ellen; Weir-Wiggins, Caryn; Rollins, April D; Cebula, Erin M; Pierce, Emily; Herr, Megan; Sankala, Heidi; Hogan, Kevin T; Wan, Wen; Feng, Changyong; Peterson, Derick R; Fisher, Richard I; Grant, Steven; Friedberg, Jonathan W

    2016-01-01

    A phase 1 study with carfilzomib and vorinostat was conducted in 20 B-cell lymphoma patients. Vorinostat was given orally twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 followed by carfilzomib (given as a 30-min infusion) on days 1, 2, 8, 9, 15, and 16. A treatment cycle was 28 days. Dose escalation initially followed a standard 3 + 3 design, but adapted a more conservative accrual rule following dose de-escalation. The maximum tolerated dose was 20 mg/m2 carfilzomib and 100 mg vorinostat (twice daily). The dose-limiting toxicities were grade 3 pneumonitis, hyponatremia, and febrile neutropenia. One patient had a partial response and two patients had stable disease. Correlative studies showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response.

  2. Phase 1 Trial of Carfilzomib (PR-171) in Combination with Vorinostat (SAHA) in Patients with Relapsed or Refractory B-Cell Lymphomas

    PubMed Central

    Holkova, Beata; Kmieciak, Maciej; Bose, Prithviraj; Yazbeck, Victor Y; Barr, Paul M.; Tombes, Mary Beth; Shrader, Ellen; Weir-Wiggins, Caryn; Rollins, April D.; Cebula, Erin M.; Pierce, Emily; Herr, Megan; Sankala, Heidi; Hogan, Kevin T.; Wan, Wen; Feng, Changyong; Peterson, Derick R.; Fisher, Richard I.; Grant, Steven; Friedberg, Jonathan W.

    2016-01-01

    A phase 1 study with carfilzomib and vorinostat was conducted in 20 B-cell lymphoma patients. Vorinostat was given orally twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 followed by carfilzomib (given as a 30 min infusion) on days 1, 2, 8, 9, 15, and 16. A treatment cycle was 28 days. Dose escalation initially followed a standard 3+3 design, but adapted a more conservative accrual rule following dose de-escalation. The maximum tolerated dose was 20 mg/m2 carfilzomib and 100 mg vorinostat (twice daily). The dose-limiting toxicities were grade 3 pneumonitis, hyponatremia, and febrile neutropenia. One patient had a partial response and 2 patients had stable disease. Correlative studies showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response. PMID:26284612

  3. Carboplatin pharmacokinetics in a patient receiving hemodialysis.

    PubMed

    Fong, Mei Ka; Fetterly, Gerald J; McDougald, Lori J; Iyer, Renuka V

    2014-02-01

    With refinements and advances in hemodialysis techniques, survival for patients with end-stage renal disease has improved significantly. To our knowledge, however, no prospective trials have been performed in patients receiving hemodialysis who are also diagnosed with cancer and are candidates for chemotherapy. We describe a 73-year-old man who was diagnosed with high-grade neuroendocrine carcinoma, metastatic to the bone and lymph nodes, and was undergoing hemodialysis. Although cisplatin is more commonly used in the treatment of metastatic neuroendocrine cancers, it may not be the best option in patients who suffer from renal insufficiency. Carboplatin is a second-generation, nonnephrotoxic platinum analog that can be hemodialyzed, although no formal guidelines are available regarding the dosing for patients receiving hemodialysis. This case describes a patient who was treated with five cycles of combination carboplatin 115 mg/m(2) on day 1 and etoposide 50 mg/m(2) on day 1 and day 3 of a 28-day cycle. Dialysis was performed for 3.5 hours starting 90 minutes after completion of carboplatin on day 1. Pharmacokinetic assessments were performed at 1, 2, 4, and 12 hours after chemotherapy infusion on day 1 of cycle 1. Total carboplatin concentrations in plasma and platinum ultrafiltrate were measured. The plasma concentration of free platinum at the end of the infusion was 31,000 ng/ml, and the area under the plasma concentration-time curve was 2.9 minute·mg/ml. No significant carboplatin-related toxicities were reported. This case report indicates that carboplatin can be safely administered in patients receiving hemodialysis.

  4. Thermochemical cycles

    NASA Technical Reports Server (NTRS)

    Funk, J. E.; Soliman, M. A.; Carty, R. H.; Conger, W. L.; Cox, K. E.; Lawson, D.

    1975-01-01

    The thermochemical production of hydrogen is described along with the HYDRGN computer program which attempts to rate the various thermochemical cycles. Specific thermochemical cycles discussed include: iron sulfur cycle; iron chloride cycle; and hybrid sulfuric acid cycle.

  5. Assessment of the menstrual cycle upon total hemoglobin, water concentration, and oxygen saturation in the female breast

    NASA Astrophysics Data System (ADS)

    Jiang, Shudong; Pogue, Brian W.; Srinivasan, Subhadra; Soho, Sandra; Poplack, Steven P.; Tosteson, Tor D.; Paulsen, Keith D.

    2003-07-01

    Near-infrared imaging can be used in humans to characterize changes in breast tumor tissue by imaging total hemoglobin and water concentrations as well as oxygen saturation. In order to improve our understanding of these changes, we need to carefully quantify the range of variation possible in normal tissues for these parameters. In this study, the effect of the subject"s menstrual cycle was examined by imaging their breast at the follicular (7-14 days of the cycle) and secretory phases (21-28 days of the cycle), using our NIR tomographic system. In this system, a three layer patient interface is used to measure 3 planes along the breast from chest wall towards the nipple at 1cm increments. Seven volunteers in their 40s were observed for 2 menstrual cycles and all of these volunteers recently had normal mammograms (ACR 1) with heterogeneously dense breast composition. The results show that average total hemoglobin in the breast increased in many subjects between 0 to 15% from the follicular phase to secretory phase. Oxygen saturation and water concentration changes between these 2 parts of the cycle were between -6.5% to 12% for saturation and between -33% to 28% for water concentration. While the data averaged between subjects showed no significant change existed between phases, it was clear that individual subjects did exhibit changes in composition which were consistent from cycle to cycle. Understanding what leads to this heterogeneity between subjects will be an important factor in utilizing these measurements in clinical practice.

  6. Clinical outcomes of three- or five-day treatment with clomiphene citrate combined with gonadotropins and a timed intercourse cycle in polycystic ovary syndrome patients

    PubMed Central

    Bae, Sung-Ah; Joo, Jong-Kil; Choi, Jong-Ryeol; Kim, Sun-Suk

    2015-01-01

    Objective This study aimed to investigate the effect of a new clomiphene citrate (CC) regimen on preventing thin endometrial lining in polycystic ovary syndrome (PCOS) patients receiving CC plus gonadotropin treatment with a timed intercourse cycle. Methods A total of 114 women with PCOS were included in this trial. Patients were divided into two groups and treated in accordance with the controlled ovarian stimulation (COS) protocol. In group A, 104 COS cycles in 67 patients were included, and in each cycle 150 mg CC was given for three days, starting from day 3. In group B, 69 COS cycles in 47 patients were included, in which 100 mg CC was given for five days, starting from day 3. The thickness of the endometrium was measured on the day of human chorionic gonadotropin (hCG) injection. Timed intercourse was recommended at 24 and 48 hours after the hCG injection. Results Additional doses of human menopausal gonadotropin and the number of days of hCG administration were not significantly different between the two groups. Endometrial thickness on the day of hCG administration was significantly larger in group A than group B (9.4±2.1 mm vs. 8.5±1.7 mm, p=0.004). The pregnancy rate was significantly higher in group A than in group B (38.4% vs. 21.7%, p=0.030). Conclusion Three-day CC treatment resulted in a significantly higher pregnancy rate than the standard five-day CC treatment in a timed intercourse cycle in PCOS patients. Facilitating adequate endometrial growth via the early discontinuation of CC might be a crucial factor in achieving a higher pregnancy rate. PMID:26473110

  7. Does intrauterine saline infusion by intrauterine insemination (IUI) catheter as endometrial injury during IVF cycles improve pregnancy outcomes among patients with recurrent implantation failure?: An RCT

    PubMed Central

    Salehpour, Saghar; Zamaniyan, Marzieh; Saharkhiz, Nasrin; Zadeh modares, Shahrzad; Hosieni, Sedighe; Seif, Samira; Malih, Narges; Rezapoor, Parinaz; Sohrabi, Mohammad-Reza

    2016-01-01

    Background: Recurrent implantation failure is one of the most issues in IVF cycles. Some researchers found that beneficial effects of endometrial Scratching in women with recurrent implantation failure, while some authors demonstrated contrary results Objective: The present study aimed to investigate the effect of intrauterine. Saline infusion as a form of endometrial injury, during fresh in vitro fertilization-embryo transfer cycle, among patients with recurrent implantation failure. Materials and Methods: In this clinical trial study 63 women undergoing assisted reproductive technology were divided into two groups either local endometrial injury by intrauterine saline infusion during day 3-5 of the ongoing controlled ovarian stimulation cycle, or IVF protocol performed without any other intervention in Taleghani Hospital, Tehran, Iran. The main outcome measure was clinical pregnancy rates. Results: Patients who received intra uterine saline infusion (n=20), had significantly lower clinical pregnancy numbers (1 vs. 9, p<0.05) and implantation rates (4.7% vs. 41.6%, p<0.05), compared to controls (n=39). However, there was no significant difference in miscarriage rates (9.4% vs. 8.7%, p>0.05) and multiple pregnancy numbers (1 vs. 3, p>0.05) between groups. Conclusion: When intrauterine saline infusion as a form of endometrial injury is performed during the ongoing IVF cycles it has negative effect on reproductive outcomes among patients with recurrent implantation failure. PMID:27738660

  8. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    PubMed

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

  9. Vagifem is superior to vaginal Premarin in induction of endometrial thickness in the frozen-thawed cycle patients with refractory endometria: A randomized clinical trial

    PubMed Central

    Zolghadri, Jaleh; Haghbin, Hossein; Dadras, Nasrin; Behdin, Shabnam

    2014-01-01

    Background: Embryo transfer to a developed endometrium is an important prognostic factor in frozen-thawed embryo transfer cycle outcome. Vaginal estrogen, such as Vagifem vaginal tablets and Premarin vaginal cream, is a regimen used for the patients with refractive endometria. Objective: Our objective was to compare the effects of Vagifem and Premarin on the endometrial thickness of the patients with refractive endometria. Materials and Methods: In this randomized clinical trial, 30 patients with refractive endometria in frozen-thawed embryo transfer cycles received Vagifem vaginal tablets and 30 women received Premarin vaginal cream. Endometrial thickness was measured on the 14th day of drug administration. Results: Comparing the endometrial thicknesses of the two groups showed that the endometria of the Vagifem group was significantly thicker than that of the Premarin group (5.93±0.38 vs. 6.74±0.32; p<0.001). Conclusion: Vagifem is superior to Premarin in induction of endometrial thickness in frozen-thawed embryo transfer cycles in the patients with refractive endometria. PMID:25071850

  10. Hospital revenue cycle management and payer mix: do Medicare and Medicaid undermine hospitals' ability to generate and collect patient care revenue?

    PubMed

    Rauscher, Simone; Wheeler, John R C

    2010-01-01

    The continuing efforts of government payers to contain hospital costs have raised concerns among hospital managers that serving publicly insured patients may undermine their ability to manage the revenue cycle successfully. This study uses financial information from two sources-Medicare cost reports for all US hospitals for 2002 to 2007 and audited financial statements for all bond-issuing, not-for-profit hospitals for 2000 to 2006 to examine the relationship between hospitals' shares of Medicare and Medicaid patients and the amount of patient care revenue they generate as well as the speed with which they collect their revenue. Hospital-level fixed effects regression analysis finds that hospitals with higher Medicare and Medicaid payer mix collect somewhat higher average patient care revenues than hospitals with more privately insured and self-pay patients. Hospitals with more Medicare patients also collect on this revenue faster; serving more Medicaid patients is not associated with the speed of patient revenue collection. For hospital managers, these findings may represent good news. They suggest that, despite increases in the number of publicly insured patients served, managers have frequently been able to generate adequate amounts of patient revenue and collect it in a timely fashion.

  11. Hospital revenue cycle management and payer mix: do Medicare and Medicaid undermine hospitals' ability to generate and collect patient care revenue?

    PubMed

    Rauscher, Simone; Wheeler, John R C

    2010-01-01

    The continuing efforts of government payers to contain hospital costs have raised concerns among hospital managers that serving publicly insured patients may undermine their ability to manage the revenue cycle successfully. This study uses financial information from two sources-Medicare cost reports for all US hospitals for 2002 to 2007 and audited financial statements for all bond-issuing, not-for-profit hospitals for 2000 to 2006 to examine the relationship between hospitals' shares of Medicare and Medicaid patients and the amount of patient care revenue they generate as well as the speed with which they collect their revenue. Hospital-level fixed effects regression analysis finds that hospitals with higher Medicare and Medicaid payer mix collect somewhat higher average patient care revenues than hospitals with more privately insured and self-pay patients. Hospitals with more Medicare patients also collect on this revenue faster; serving more Medicaid patients is not associated with the speed of patient revenue collection. For hospital managers, these findings may represent good news. They suggest that, despite increases in the number of publicly insured patients served, managers have frequently been able to generate adequate amounts of patient revenue and collect it in a timely fashion. PMID:21294440

  12. Severe and prolonged lymphopenia observed in patients treated with bendamustine and erlotinib for metastatic triple negative breast cancer

    PubMed Central

    Ruppert, Amy S.; Lynn, Melinda; Mrozek, Ewa; Ramaswamy, Bhuvaneswari; Lustberg, Maryam B.; Wesolowski, Robert; Ottman, Susan; Carothers, Sarah; Bingman, Anissa; Reinbolt, Raquel; Kraut, Eric H.; Shapiro, Charles L.

    2013-01-01

    Purpose Triple negative breast cancers (TNBC) frequently have high epidermal growth factor receptor (EGFR) expression and are sensitive to DNA-damaging agents. Improved therapies are needed for this aggressive malignancy. Patients and methods We performed a phase I trial of bendamustine and erlotinib, an EGFR tyrosine kinase inhibitor, in patients with metastatic TNBC, ECOG performance status ≤2, and ≤1 prior chemotherapy for metastatic disease. Each 28-day cycle included intravenous bendamustine on days 1, 2 and oral erlotinib on days 5–21 with dose escalation according to a 3 + 3 phase I study design. Dose-limiting toxicity (DLT) was determined by toxicities related to study therapy observed during cycle 1. Results Eleven patients were treated, 5 on dose level 1 and 6 on dose level 2. One patient had DLT on dose level 2. However, cumulative toxicities were observed, including grade 3/4 lymphopenia in 91 % (95 % CI 0.59–0.998) with progressively decreased CD4 counts and grade ≥3 infections in 36 % (95 % CI 0.11–0.69) of patients. Conclusions Combination therapy with bendamustine and erlotinib causes excessive toxicity with severe, prolonged lymphopenia, depressed CD4 counts, and opportunistic infections and should not be pursued further. Future trials of bendamustine combinations in TNBC patients should account for potential cumulative lymphocyte toxicity necessitating patient monitoring during and after treatment. PMID:23430121

  13. Prognostic Value of Lactate and Central Venous Oxygen Saturation after Early Resuscitation in Sepsis Patients

    PubMed Central

    Jo, Ik Joon; Suh, Gee Young; Jeon, Kyeongman

    2016-01-01

    The objective of this study was to evaluate the prognostic value of static and dynamic variables of central venous oxygen saturation (ScvO2) and lactate in patients with severe sepsis or septic shock who underwent early quantitative resuscitation. We also investigated whether ScvO2 measured after initial resuscitation could provide additive prognostic value to that of lactate. We analyzed the sepsis registry for patients presenting to the emergency department and included patients with simultaneous measurements of lactate and ScvO2 at the time of presentation (H0) and 6 hours (H6) after resuscitation. The primary outcome was 28-day mortality and multivariable logistic analysis was used to adjust for confounders. A total of 363 patients were included, and the overall 28-day mortality was 18%. The area under the receiver operator characteristic curve for predicting 28-day mortality was as follows: lactate (H6), 0.81; lactate (H0), 0.73; relative lactate change, 0.67; ScvO2 (H6), 0.65; relative ScvO2 change 0.59; ScvO2 (H0), 0.58. Patients with lactate normalization showed significantly lower 28-day mortality compared to patients without lactate normalization (3% vs. 28%, P<0.01). However, in those who achieved ScvO2 (H6) ≥70%, there was a significant difference in 28-mortality only in patients without lactate normalization (21% vs. 39%, P<0.01) but no difference in those with lactate normalization (4% vs. 3%, P = 0.71). In multivariable analysis, lactate normalization was significantly associated with 28-day mortality (adjusted odds ratio [OR] for 28-day mortality, 0.20; 95% confidence interval [CI], 0.07–0.54; P <0.01), but ScvO2 (H6) ≥70% showed only a marginal association (the adjusted OR for 28-day mortality, 0.51; 95% CI, 0.26–1.01; P = 0.05). ScvO2 (H6) ≥70% was associated with 28-day mortality only in cases without lactate normalization in subgroup analysis (adjusted OR 0.37, 95% CI, 0.18–0.79; P = 0.01). Six-hour lactate was the strongest

  14. Short versus Long Gonadotropin-Releasing Hormone Analogue Suppression Protocols in IVF/ICSI Cycles in Patients of Various Age Ranges

    PubMed Central

    Li, Yubin; Xu, Yanwen; Zhou, Canquan

    2015-01-01

    Objective To compare the two GnRH-a protocols (long GnRH-a protocol and short GnRH-a protocol) for ovarian stimulation in IVF/ICSI cycles in patients of various age ranges. Methods A total of 5662 IVF-ET/ICSI cycles from 2010 to 2013 were retrospectively identified. The cycles were divided into two groups: a long protocol group and short protocol group. In each group, the patients were divided into four age ranges: <31 years, 31 to 35 years, 36 to 40 years, and >40 years. The duration of stimulation, total dose of Gn, implantation rate and pregnancy rate were compared. Results The total dose of Gn was significantly higher, and the duration of stimulation was significantly longer, in the long protocol group than in the short protocol group for all age ranges (P<0.05). If the patients were of the same age range, the number of oocytes retrieved, MII oocytes, and high-quality embryos in the long protocol group were all significantly greater than those in the short protocol group (P<0.05). In the long protocol group, the clinical pregnancy rates of the four age ranges were 52.76%, 44.33%, 36.15% and 13.33%, respectively, which were significantly higher than those in the short protocol group (33.33%, 24.58%, 22.49% and 8.72%, respectively; P<0.05). The same trend was also found in the implantation rates of the four age ranges. As the age increased, the clinical pregnancy and implantation rates, as well as the number of oocytes retrieved, MII oocytes, and high-quality embryos, of the long protocol group significantly decreased (P<0.05). Conclusions Our study demonstrated that regardless of patient age, the long protocol was superior to the short protocol in terms of the number of retrieved oocytes, as well as the implantation and pregnancy rates. PMID:26208150

  15. Premature Progesterone Elevation Does Not Affect Pregnancy Outcome in High-Responder Patients Undergoing Short-Interval Coasting in IVF Cycles

    PubMed Central

    Acet, Mustafa; Aktün, Lebriz Hale; Başaranoğlu, Serdar; Yorgunlar, Betül; Acet, Tuba; Deregözü, Ayşegül

    2015-01-01

    Background We aimed to present the relationship between premature progesterone elevation (PPE) and clinical outcomes in high-responder patients who had a coasting period of <4 days in length due to their high risk of developing ovarian hyperstimulation syndrome (OHSS) and who were treated with a long-acting gonadotropin-releasing hormone agonist (GnRH-agonist) protocol in in vitro fertilization-embryo transfer (IVF-ET) cycles. Material/Methods This retrospective study was conducted at the University Hospital Assisted Reproductive Technology Center. The outcomes of 101 patients undergoing IVF- intracytoplasmic sperm injection (ICSI) cycles who showed a high response to COH (estradiol >4000 pg/ml and/or >20 follicles each ≥10 mm in diameter and at least 20% ≥15 mm) and who were coasted for <4 days were evaluated. Number of oocytes, 2 pronuclei (PN) embryos, implantation rate, and live birth rate were measured. Results The incidence of PPE was 32.6%. Compared with those without PPE, patients with PPE had a higher number of oocytes retrieved. Total mature and fertilized oocytes and the mean number of embryos transferred were not significantly different between groups. Live birth rates (41.9% vs. 38.7%) and implantation rates (26.5% vs. 23%) were also not significantly divergent in the PPE and non-PPE groups, respectively. Conclusions P concentrations ≥1.3 ng/ml on the day of human chorionic gonadotropin (hCG) administration, designated in this study as PPE, does not appear to be related to adverse effects in terms of clinical outcomes in high-responder patients undergoing coasting <4 days due to their high risk of developing OHSS treated with a long-acting GnRH-a protocol in IVF-embryo transfer cycles. PMID:26634938

  16. Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial.

    PubMed

    Lepretre, Stephane; Aurran, Therese; Mahé, Beatrice; Cazin, Bruno; Tournilhac, Olivier; Maisonneuve, Herve; Casasnovas, Olivier; Delmer, Alain; Leblond, Veronique; Royer, Bruno; Corront, Bernadette; Chevret, Sylvie; Delépine, Roselyne; Vaudaux, Sandrine; Van Den Neste, Eric; Béné, Marie Christine; Letestu, Remi; Cymbalista, Florence; Feugier, Pierre

    2012-05-31

    A French and Belgian multicenter phase 3 trial was conducted in medically fit patients with untreated chronic lymphocytic leukemia. Of 178 patients enrolled in the study, 165 were randomly assigned to receive 6 courses of oral fludarabine and cyclophosphamide (FC) in combination with rituximab (FCR; 375 mg/m(2) in cycle one, 500 mg/m(2) in all subsequent cycles) or alemtuzumab (FCCam; 30 mg subcutaneously injected on cycle days 1-3); each cycle was 28 days. Recruitment was halted prematurely because of excess toxicity; 8 patients died in the FCCam group, 3 from lymphoma and 5 from in-fection. Overall response rates were 91% with FCR and 90% with FCCam (P = .79). Complete remission rates were 33.75% with FCR and 19.2% with FCCam (P = .04). Three-year progression-free survival was 82.6% with FCR and 72.5% with FCCam (P = .21). Three-year overall survival was similar between the 2 arms at 90.1% in the FCR arm and 86.4% in the FCCam arm (P = .27). These results indicate that the FCCam regimen for the treatment of advanced chronic lymphocytic leukemia was not more effective than the FCR regimen and was associated with an unfavorable safety profile, representing a significant limitation of its use. This study is registered with www.clinicaltrials.gov as number NCT00564512. PMID:22337714

  17. A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax®) in patients with peritoneal malignancies

    PubMed Central

    Johnson, Gary A.; Maulhardt, Holly A.; Moore, Kathleen M.; McMeekin, D. S.; Schulz, Thomas K.; Reed, Gregory A.; Roby, Katherine F.; Mackay, Christine B.; Smith, Holly J.; Weir, Scott J.; Wick, Jo A.; Markman, Maurie; diZerega, Gere S.; Baltezor, Michael J.; Espinosa, Jahna; Decedue, Charles J.

    2015-01-01

    Purpose This multicenter, open-label, dose-escalating, phase I study evaluated the safety, tolerability, pharmacokinetics and preliminary tumor response of a nanoparticulate formulation of paclitaxel (Nanotax®) administered intraperitoneally for multiple treatment cycles in patients with solid tumors predominantly confined to the peritoneal cavity for whom no other curative systemic therapy treatment options were available. Methods Twenty-one patients with peritoneal malignancies received Nanotax® in a modified dose-escalation approach utilizing an accelerated titration method. All patients enrolled had previously received chemotherapeutics and undergone surgical procedures, including 33 % with optimal debulking. Six doses (50–275 mg/m2) of Cremophor-free Nanotax® were administered intraperitoneally for one to six cycles (every 28 days). Results Intraperitoneal (IP) administration of Nanotax® did not lead to increases in toxicity over that typically associated with intravenous (IV) paclitaxel. No patient reported ≥Grade 2 neutropenia and/or ≥Grade 3 neurologic toxicities. Grade 3 thrombocytopenia unlikely related to study medication occurred in one patient. The peritoneal concentration–time profile of paclitaxel rose during the 2 days after dosing to peritoneal fluid concentrations 450–2900 times greater than peak plasma drug concentrations and remained elevated through the entire dose cycle. Best response assessments were made in 16/21 patients: Four patients were assessed as stable or had no response and twelve patients had increasing disease. Five of 21 patients with advanced cancers survived longer than 400 days after initiation of Nanotax® IP treatment. Conclusions Compared to IV paclitaxel administration, Cremophor-free IP administration of Nanotax® provides higher and prolonged peritoneal paclitaxel levels with minimal systemic exposure and reduced toxicity. PMID:25898813

  18. Intrafollicular levels of matrix metalloproteinases-2 and -9 in patients with polycystic ovaries are not associated with pregnancy rate during IVF cycle.

    PubMed

    Baka, Stavroula; Zourla, Konstantina; Malamitsi-Puchner, Ariadne; Makrakis, Evangelos; Kaparos, George; Demeridou, Stella; Moustakarias, Theodore; Tzanakaki, Despoina; Hassiakos, Dimitris; Kouskouni, Evangelia

    2009-01-01

    This study aimed to detect the levels of matrix metalloproteinases (MMP)-2 and -9, using enzyme-linked immunosorbent assays, in the follicular fluid of 35 patients with polycystic ovaries, compare them with the levels found in 35 normally ovulating women enrolled in their first in vitro fertilization (IVF) cycle and then correlate them with pregnancy rates in these two groups. Levels of MMP-9 were found significantly increased in women with polycystic ovaries when compared with the controls, while MMP-2 levels were higher in women with polycystic ovaries without reaching statistical significance. The two groups did not differ in age, in the number of embryos transferred or in pregnancy rates. In conclusion, the results indicated an increased gelatinolytic activity in patients with polycystic ovaries after ovarian stimulation for IVF treatment without detecting any association between levels of MMP-2 and 9 and IVF pregnancy rates. PMID:19368130

  19. Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients.

    PubMed

    Chen, Jinyun; Pande, Mala; Huang, Yu-Jing; Wei, Chongjuan; Amos, Christopher I; Talseth-Palmer, Bente A; Meldrum, Cliff J; Chen, Wei V; Gorlov, Ivan P; Lynch, Patrick M; Scott, Rodney J; Frazier, Marsha L

    2013-02-01

    Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle-related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle-related genes and 31 DNA repair-related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan-Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P < 5 × 10(-4)). Furthermore, risk modeling using CART analysis defined combinations of genotypes for these SNPs with which subjects could be classified into low-risk, moderate-risk and high-risk groups that had median ages of colorectal cancer onset of 63, 50 and 42 years, respectively. The age-associated risk of colorectal cancer in the high-risk group was more than four times the risk in the low-risk group (hazard ratio = 4.67, 95% CI = 3.16-6.92). The additional genetic markers identified may help in refining risk groups for more tailored screening and follow-up of non-Hispanic white patients with Lynch syndrome. PMID:23125224

  20. Combined progesterone (IM + V) versus vaginal progesterone for luteal support in cleavage-stage embryo transfer cycles of good prognosis patients.

    PubMed

    Pabuccu, E G; Pabuccu, R; Evliyaoglu Ozdegirmenci, O; Bostancı Durmus, A; Keskin, M

    2016-01-01

    Many reports led to the consensus on the use of progesterone (P) for luteal-phase support. Vaginal P application is the method of choice due to its simplicity and high patient convenience but is hampered by application difficulties and personal or cultural aversions. Inappropriate vaginal P use may alter successful implantation, leading physicians to consider alternate P application routes. A worldwide survey revealed that intramuscular plus vaginal P (combined P) is the method used in nearly one-third of in vitro fertilization (IVF) cycles, particularly in Asia and North America; unfortunately, the outcomes of this approach have not been clearly elucidated. In the current analysis, we evaluated any additional benefit of short course parenteral P in addition to vaginal P capsules during a specific period in terms of implantation, pregnancy rates, miscarriages and ectopic pregnancies in cleavage stage embryo transfer (ET) cycles of good-prognosis patients. Despite significantly higher implantation rates in the combined arm, clinical and ongoing pregnancies were comparable in both groups, whereas a trend toward increased pregnancy rates was observed with combined support. The available data are too limited to draw conclusions.

  1. Menstrual cycle and protein requirements of women.

    PubMed

    Calloway, D H; Kurzer, M S

    1982-02-01

    A nitrogen balance study was done to determine the protein requirement of healthy young women and to evaluate the impact of the menstrual cycle on nitrogen utilization. Six healthy young women were fed a defined formula diet with progressively decreasing levels of egg white protein: 4 mg nitrogen/basal kcal for 42 days, 3 mg nitrogen/basal kcal for 28 days and 2.5 mg nitrogen/basal kcal for 22 days. Dietary energy was fixed at about 38 kcal/kg body weight and exercise was standardized. Excreta, menstrual fluids, and integumentary losses were collected. A statistically significant (P less than .001) biphasic cycle in urinary nitrogen excretion was found in every subject. Linear regression analysis predicted nitrogen requirement to be 73 +/- 20 mg nitrogen/kg body weight. When expressed per kilogram of body weight, there appears to be no significant difference in protein requirement between women and men. The urinary nitrogen cycle, however, was found to be unique to women, implying a hormonal regulation of nitrogen utilization. The failure to account for this cycle in women could lead to erroneous estimates of nitrogen requirement or large coefficients of variation.

  2. Menstrual Cycle

    MedlinePlus

    ... Pregnancy This information in Spanish ( en español ) The menstrual cycle Day 1 starts with the first day of ... drop around Day 25 . This signals the next menstrual cycle to begin. The egg will break apart and ...

  3. Biogeochemical Cycling

    NASA Technical Reports Server (NTRS)

    Bebout, Brad; Fonda, Mark (Technical Monitor)

    2002-01-01

    This lecture will introduce the concept of biogeochemical cycling. The roles of microbes in the cycling of nutrients, production and consumption of trace gases, and mineralization will be briefly introduced.

  4. An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer

    PubMed Central

    Kozloff, M.; Chuang, E.; Starr, A.; Gowland, P. A.; Cataruozolo, P. E.; Collier, M.; Verkh, L.; Huang, X.; Kern, K. A.; Miller, K.

    2010-01-01

    Background: Sunitinib has shown single-agent activity in patients with previously treated metastatic breast cancer (MBC). We investigated the safety of the combination of sunitinib and paclitaxel in an exploratory study of patients with locally advanced or MBC. Methods: Patients received oral sunitinib 25 mg/day (with escalation to 37.5 mg/day as tolerated) on a continuous daily dosing schedule and paclitaxel 90 mg/m2 on days 1, 8, and 15 of each 28-day cycle. Study endpoints included safety (primary endpoint), pharmacokinetics, and antitumor activity. Results: Twenty-two patients were enrolled. The most frequent adverse events (AEs) were fatigue/asthenia (77%), dysgeusia (68%), and diarrhea (64%). Grade 3 AEs included neutropenia (43%), fatigue/asthenia (27%), neuropathy (18%), and diarrhea (14%). No drug–drug interaction was observed on the basis of pharmacokinetic analysis. Of 18 patients with measurable disease at baseline, 7 (38.9%) achieved objective responses (including 2 complete and 5 partial responses). Clinical responses were observed in three of nine patients with triple-negative receptor status (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor-2 negative). Conclusions: These data indicate that sunitinib and paclitaxel in combination are well tolerated in patients with locally advanced or MBC. No drug–drug interaction was detected and there was preliminary evidence of antitumor activity. PMID:20032126

  5. Revenue cycle management: part I.

    PubMed

    Crew, Matt

    2006-01-01

    The revenue cycle starts long before a patient is seen and continues until a claim is completely resolved. Each step in the revenue cycle must be clearly defined and easy to follow. Use of various tools such as templates, forms, reports, spreadsheets, and components of your practice management system will help to provide the consistency you need for profitable revenue cycle management.

  6. Tolerability to romidepsin in patients with relapsed/refractory T-cell lymphoma

    PubMed Central

    2014-01-01

    Background Histone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations. Methods Patients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses. Results Overall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1–2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles. Conclusions This study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic

  7. Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients

    PubMed Central

    Ochoa-Gonzalez, Fatima; Cervantes-Villagrana, Alberto R.; Fernandez-Ruiz, Julio C.; Nava-Ramirez, Hilda S.; Hernandez-Correa, Adriana C.; Enciso-Moreno, Jose A.; Castañeda-Delgado, Julio E.

    2016-01-01

    Background Several epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation. Material and Methods HaCaT Cells were exposed to various concentrations of metformin and cell viability was evaluated by a Resazurin assay; Proliferation was also evaluated with a colony formation assay and with CFSE dilution assay by flow cytometry. Cell cycle was also evaluated by flow cytometry by PI staining. An animal model of wound healing was used to evaluate the effect of metformin in wound closure. Also, an analysis of patients receiving metformin treatment was performed to determine the effect of metformin treatment on the outcome and wound area. Statistical analysis was performed on SPSS v. 18 and GraphPad software v.5. Results Metformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin. Conclusions Metformin treatment reduces cell proliferation and reduces wound healing in an animal model

  8. Population pharmacokinetic modeling and dosing simulations of nitrogen-scavenging compounds: disposition of glycerol phenylbutyrate and sodium phenylbutyrate in adult and pediatric patients with urea cycle disorders.

    PubMed

    Monteleone, Jon P R; Mokhtarani, M; Diaz, G A; Rhead, W; Lichter-Konecki, U; Berry, S A; Lemons, C; Dickinson, K; Coakley, D; Lee, B; Scharschmidt, B F

    2013-07-01

    Sodium phenylbutyrate and glycerol phenylbutyrate mediate waste nitrogen excretion in the form of urinary phenylacetylglutamine (PAGN) in patients with urea cycle disorders (UCDs); rare genetic disorders characterized by impaired urea synthesis and hyperammonemia. Sodium phenylbutyrate is approved for UCD treatment; the development of glycerol phenylbutyrate afforded the opportunity to characterize the pharmacokinetics (PK) of both compounds. A population PK model was developed using data from four Phase II/III trials that collectively enrolled patients ages 2 months to 72 years. Dose simulations were performed with particular attention to phenylacetic acid (PAA), which has been associated with adverse events in non-UCD populations. The final model described metabolite levels in plasma and urine for both drugs and was characterized by (a) partial presystemic metabolism of phenylbutyric acid (PBA) to PAA and/or PAGN, (b) slower PBA absorption and greater presystemic conversion with glycerol phenylbutyrate, (c) similar systemic disposition with saturable conversion of PAA to PAGN for both drugs, and (d) body surface area (BSA) as a significant covariate accounting for age-related PK differences. Dose simulations demonstrated similar PAA exposure following mole-equivalent PBA dosing of both drugs and greater PAA exposure in younger patients based on BSA.

  9. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors.

    PubMed

    Shimizu, Toshio; Seto, Takashi; Hirai, Fumihiko; Takenoyama, Mitsuhiro; Nosaki, Kaname; Tsurutani, Junji; Kaneda, Hiroyasu; Iwasa, Tsutomu; Kawakami, Hisato; Noguchi, Kazuo; Shimamoto, Takashi; Nakagawa, Kazuhiko

    2016-06-01

    Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n = 2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n = 1), grade 3 AST elevation (n = 1), grade 1 pneumonitis (n = 1), and grade 1 thyroid-stimulating hormone elevation (n = 1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC.

  10. Phase II Study of Short-Course Radiotherapy Plus Concomitant and Adjuvant Temozolomide in Elderly Patients With Glioblastoma

    SciTech Connect

    Minniti, Giuseppe; Lanzetta, Gaetano; Scaringi, Claudia; Caporello, Paola; Salvati, Maurizio; Arcella, Antonella; De Sanctis, Vitaliana; Giangaspero, Felice; Enrici, Riccardo Maurizi

    2012-05-01

    Purpose: Radiotherapy (RT) and chemotherapy may prolong survival in older patients (age {>=}70 years) with glioblastoma multiforme (GBM), although the survival benefits remain poor. This Phase II multicenter study was designed to evaluate the efficacy and safety of an abbreviated course of RT plus concomitant and adjuvant temozolomide (TMZ) in older patients with GBM. Patients and Methods: Seventy-one eligible patients 70 years of age or older with newly diagnosed GBM and a Karnofsky performance status {>=}60 were treated with a short course of RT (40 Gy in 15 fractions over 3 weeks) plus TMZ at the dosage of 75 mg/m{sup 2} per day followed by 12 cycles of adjuvant TMZ (150-200 mg/m{sup 2} for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival and toxicity. Results: The Median OS was 12.4 months, and the 1-year and 2-year OS rates were 58% and 20%, respectively. The median and 1-year rates of progression-free survival were 6 months and 20%, respectively. All patients completed the planned programme of RT. Grade 3 or 4 adverse events occurred in 16 patients (22%). Grade 3 and 4 neutropenia and/or thrombocytopenia occurred in 10 patients (15%), leading to the interruption of treatment in 6 patients (8%). Nonhematologic Grade 3 toxicity was rare, and included fatigue in 4 patients and cognitive disability in 1 patient. Conclusions: A combination of an abbreviated course of RT plus concomitant and adjuvant TMZ is well tolerated and may prolong survival in elderly patients with GBM. Future randomized studies need to evaluate the efficacy and toxicity of different schedules of RT in association with chemotherapy.

  11. Evaluation of short cycles of ultrasound application in nanoemulsions to obtain nanocapsules.

    PubMed

    Carneiro, Simone Pinto; Cruz, Ricardo Machado; dos Santos, Orlando David Henrique

    2015-11-01

    Ultrasound is widely used in several chemical reactions and other process, including production of nanocapsules by in situ polymerization. In this work, the main objective was to evaluate the impacts and viability of successive ultrasound application in nanoemulsions to obtain nanocapsules. Initiator potassium persulfate (KPS) concentration, number of ultrasound cycles and reaction time influences on polymerization efficiency and droplet size were evaluated. This work revealed the successful in situ production of nanocapsules using successive shorts cycles of ultrasound. Number of cycles was the only parameter that not exerted significant influence in polymerization yield. Particle size decay was observed in all nanoemulsions after the first ultrasound application, the same was not observed in further cycles. Gravimetric assessment showed remarkable increase of monomer conversion, indicating that once started polymerization continued at least until 28 days after ultrasound application. Concluding, ultrasound short cycles can be used with no harm to formulation, if carefully performed and, furthermore is a potential cost-effective route for polymerization reactions.

  12. Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma

    PubMed Central

    Eguchi, Takashi; Kadota, Kyuichi; Chaft, Jamie; Evans, Brent; Kidd, John; Tan, Kay See; Dycoco, Joe; Kolquist, Kathryn; Davis, Thaylon; Hamilton, Stephanie A.; Yager, Kraig; Jones, Joshua T.; Travis, William D.; Jones, David R.; Hartman, Anne-Renee; Adusumilli, Prasad S.

    2016-01-01

    Purpose The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes. Methods Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer–specific mortality as the primary outcome. Results In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer–specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14–2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer–specific mortality (HR=1.77; 95% CI, 1.18–2.66; P=0.006). Five-year lung cancer–specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer–specific survival (P<0.001 and 0.015, respectively), compared with low mPS. Conclusion This study validates CCP score and mPS as independent prognostic markers for lung cancer–specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone. PMID:27153551

  13. Independent predictors for lifetime and recent substance use disorders in patients with rapid-cycling bipolar disorder: focus on anxiety disorders.

    PubMed

    Gao, Keming; Chan, Philip K; Verduin, Marcia L; Kemp, David E; Tolliver, Bryan K; Ganocy, Stephen J; Bilali, Sarah; Brady, Kathleen T; Findling, Robert L; Calabrese, Joseph R

    2010-01-01

    We set out to study independent predictor(s) for lifetime and recent substance use disorders (SUDs) in patients with rapid-cycling bipolar disorder (RCBD). Extensive Clinical Interview and Mini-International Neuropsychiatric Interview were used to ascertain DSM-IV Axis I diagnoses of RCBD, anxiety disorders, and SUDs. Data from patients enrolling into four similar clinical trials were used. Where appropriate, univariate analyses with t-test or chi-square were applied. Stepwise logistic regression was used to examine the relationship among predictor variables and lifetime and recent SUDs. Univariate analysis showed that patients with co-occurring anxiety disorders (n = 261) had significantly increased rates of lifetime (odds ratio [OR]= 2.1) and recent (OR = 1.9) alcohol dependence as well as lifetime (OR = 3.4) and recent (OR = 2.5) marijuana dependence compared to those without co-occurring anxiety disorder (n = 303). In logistic regression analyses, generalized anxiety disorder (GAD) was associated with increased risk for lifetime SUDs (OR = 2.34), alcohol dependence (OR = 1.73), and marijuana dependence (OR = 3.36) and recent marijuana dependence (OR = 3.28). A history of physical abuse was associated with increased risk for lifetime SUDs (OR = 1.71) and recent marijuana dependence (OR = 3.47). Earlier onset of first mania/hypomania was associated with increased risk for lifetime SUDs (5% per year), and recent marijuana dependence (12% per year) and later treatment with a mood stabilizer were also associated with increased risk for recent SUDs (8% per year). Positive associations between GAD, later treatment with a mood stabilizer, and early childhood trauma and history of SUDs suggest that adequate treatment of comorbid anxiety, early treatment with a mood stabilizer, and prevention of childhood trauma may reduce the risk for the development of SUDs in patients with bipolar disorder.

  14. First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas

    PubMed Central

    Patnaik, A.; Appleman, L. J.; Tolcher, A. W.; Papadopoulos, K. P.; Beeram, M.; Rasco, D. W.; Weiss, G. J.; Sachdev, J. C.; Chadha, M.; Fulk, M.; Ejadi, S.; Mountz, J. M.; Lotze, M. T.; Toledo, F. G. S.; Chu, E.; Jeffers, M.; Peña, C.; Xia, C.; Reif, S.; Genvresse, I.; Ramanathan, R. K.

    2016-01-01

    Background To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). Patients and methods Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1–1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [18F]-fluorodeoxyglucose positron emission tomography (18FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. Results Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced 18FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. Conclusion Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib

  15. First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas

    PubMed Central

    Patnaik, A.; Appleman, L. J.; Tolcher, A. W.; Papadopoulos, K. P.; Beeram, M.; Rasco, D. W.; Weiss, G. J.; Sachdev, J. C.; Chadha, M.; Fulk, M.; Ejadi, S.; Mountz, J. M.; Lotze, M. T.; Toledo, F. G. S.; Chu, E.; Jeffers, M.; Peña, C.; Xia, C.; Reif, S.; Genvresse, I.; Ramanathan, R. K.

    2016-01-01

    Background To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). Patients and methods Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1–1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [18F]-fluorodeoxyglucose positron emission tomography (18FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. Results Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced 18FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. Conclusion Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib

  16. A phase I trial to determine the safety of imatinib in combination with vatalanib in patients with advanced malignancies.

    PubMed

    Spigel, David; Jones, Suzanne; Hainsworth, John; Infante, Jeff; Greco, F Anthony; Thompson, Dana; Doss, Habib; Burris, Howard

    2011-05-01

    The role of tyrosine kinase inhibitors (TKIs) in the treatment of advanced malignancies is well established. Imatinib and vatalanib are oral TKIs with different mechanisms of action. This trial sought to establish the safety, tolerability, and maximum tolerated dose (MTD) of the two agents in combination. Secondary objectives included determination of potential pharmacologic interactions among vatalanib and imatinib and observation of antitumor activity. Patients with biopsy-proven advanced refractory solid tumors were enrolled in this single-center dose-escalation trial. Patients initially received imatinib and vatalanib once daily following a 14-day run-in period of daily oral vatalanib only, and were observed for a full 28-day treatment cycle prior to dose escalation. An amendment divided the vatalanib dose into two daily doses and gradually escalated the dose over a 2-3 week period. Patients continued combination therapy until disease progression or intolerable toxicity. Forty-five patients were enrolled between September 2004 and November 2007. As of September 2009, a total of 247 cycles of treatment had been administered (range: 1 -44+, median = 2 ). The MTD was determined to be vatalanib 1250 mg daily and imatinib 400 mg daily. Thirty-five patients (78%) were evaluable for response; 2 patients achieved PR, while 14 patients had SD ( 10 had stable disease ≥ 6 cycles). The combination of vatalanib and imatinib was well tolerated. Twice-daily vatalanib dosing improved tolerability and ease of full-dose administration. These results suggest that vatalanib-containing combinations may be active and tolerable, warranting further study. PMID:21469980

  17. Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study)

    PubMed Central

    Hilbe, Wolfgang; Pall, Georg; Kocher, Florian; Pircher, Andreas; Zabernigg, August; Schmid, Thomas; Schumacher, Michael; Jamnig, Herbert; Fiegl, Michael; Gächter, Anne; Freund, Martin; Kendler, Dorota; Manzl, Claudia; Zelger, Bettina; Popper, Helmut; Wöll, Ewald

    2015-01-01

    Background Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles. Methods Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2) and docetaxel (75 mg/m2 d1) q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly). The primary endpoint was radiological response according to RECIST. Results 40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95%) underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months. Conclusions Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected. Trial Registration EU Clinical Trials Register; Eudract-Nr: 2006-004639-31 PMID:26020783

  18. Prevalence of menstrual cycles and outcome of 50 pregnancies after high-dose chemotherapy and auto-SCT in non-Hodgkin and Hodgkin lymphoma patients younger than 40 years.

    PubMed

    Akhtar, S; Youssef, I; Soudy, H; Elhassan, T A M; Rauf, S M; Maghfoor, I

    2015-12-01

    Data are limited regarding the prevalence of menstrual cycles and pregnancies after high-dose chemotherapy (HDC) and auto-stem cell transplantation (SCT). Female patients who underwent HDC auto-SCT for non-Hodgkin and Hodgkin lymphoma (1997-2012) were reviewed. The selection criteria were as follows: (1) alive without disease 12 and 24 months after auto-SCT for menstrual cycles and pregnancy, respectively, (2) age <40 years at auto-SCT, and (3) no primary infertility. One-hundred and seventy-six females underwent single auto-SCT. Eighty-nine were eligible for menstrual cycles and pregnancy analysis. Median age at auto-SCT was 25 years (14-40 years), at pregnancy 27 years (20-37 years), median follow-up 65 months (range 24-190). Regular menstrual-cycles resumed in 56/89 patients (63%). Increasing age (P=0.02) and number of prior chemotherapy cycles (P=0.02) are associated with higher risk of amenorrhea. Forty patients tried to get pregnant, 26 (65%) became pregnant 50 times: 43 (86%) live birth, 7 (14%) miscarriage and 2/50 had birth defects. Twenty-four patients practiced breastfeeding (median duration 4 months (1-24 months)). Enough breast milk production was reported 62.5% vs 100% in those patients who did or did not receive above the diaphragm radiation therapy, respectively, (P=0.066). Our data highlights significantly higher than perceived incidence of menstrual cycle resumption, successful pregnancies and breastfeeding after HDC auto-SCT. PMID:26237168

  19. Cycle Analysis

    SciTech Connect

    Wright, Steven A.

    2012-03-20

    1. The Cycle Analysis code is an Microsoft Excel code that performs many different types of thermodynamic cycle analysis for power producing systems. The code will calculate the temperature and pressure and all other thermodynamic properties at the inlet and outlet of each component. The code also calculates the power that is produced, the efficiency, and the heat transported in the heater, gas chiller and recuperators. The code provides a schematic of the loop and provides the temperature and pressure at each location in the loop. The code also provides a T-S (temperature-entropy) diagram of the loop and often it provides an pressure enthalpy plot as well. 2. This version of the code concentrates on supercritical CO2 power cycles, but by simply changing the name of the working fluid many other types of fluids can be analyzed. The Cycle Analysis code provided here contains 18 different types of power cycles. Each cycle is contained in one worksheet or tab that the user can select. The user can change the yellow highlighted regions to perform different thermodynamic cycle analysis.

  20. Cycle Analysis

    2012-03-20

    1. The Cycle Analysis code is an Microsoft Excel code that performs many different types of thermodynamic cycle analysis for power producing systems. The code will calculate the temperature and pressure and all other thermodynamic properties at the inlet and outlet of each component. The code also calculates the power that is produced, the efficiency, and the heat transported in the heater, gas chiller and recuperators. The code provides a schematic of the loop andmore » provides the temperature and pressure at each location in the loop. The code also provides a T-S (temperature-entropy) diagram of the loop and often it provides an pressure enthalpy plot as well. 2. This version of the code concentrates on supercritical CO2 power cycles, but by simply changing the name of the working fluid many other types of fluids can be analyzed. The Cycle Analysis code provided here contains 18 different types of power cycles. Each cycle is contained in one worksheet or tab that the user can select. The user can change the yellow highlighted regions to perform different thermodynamic cycle analysis.« less

  1. Endocrine assessment of ovarian cycle activity in wild female mountain gorillas (Gorilla beringei beringei).

    PubMed

    Habumuremyi, Sosthene; Stephens, Colleen; Fawcett, Katie A; Deschner, Tobias; Robbins, Martha M

    2016-04-01

    Variability of fertility (i.e. number of births per female per year) has been reported in females of many primate species but only a few studies have explored the associated physiological and behavioral patterns. To investigate the proximate mechanisms of variability in fertility of wild female mountain gorillas (Gorilla beringei beringei), we quantified the occurrence of ovulation, matings, and successful pregnancies among females. We examined the profiles of immunoreactive pregnanediol-3-glucuronide (iPdG) for sixteen females (seven nulliparous and nine parous females, including one geriatric female; average sampling period for fecal sample collection and behavioral observations per female=175 days; SD=94 days, range=66-358 days) monitored by the staff of the Dian Fossey Gorilla Fund's Karisoke Research Center in Parc National des Volcans, Rwanda. We quantified ovarian cycles from iPdG profiles using an algorithm that we developed by adjusting the method of Kassam et al. (1996) to the characteristics of ovarian cycle profiles based on fecal hormone measurements. The mean length of ovarian cycles was 29±4 days (median: 28 days, N=13 cycles), similar to ovarian cycle lengths of other great apes and humans. As expected, we found that female mountain gorillas exhibit longer follicular phases (mean±SD: 21±3 days, N=13 cycles) than luteal phases (mean±SD: 8±3 days, N=13 cycles). We also found that the frequency of ovarian cycles was greater in parous females (i.e. 20 ovarian cycles across 44 periods of 28 days; 45.5%) than in nulliparous females (i.e. two ovarian cycles across 34 periods of 28 days; 6%). However, the frequency of days on which matings were observed did not differ significantly between parous and nulliparous females, nor between pregnant and non-pregnant females. Five pregnancies were detected with iPdG levels, but only three resulted in live births, indicating miscarriages of the other two. In sum, this study provides information on the underlying

  2. Endocrine assessment of ovarian cycle activity in wild female mountain gorillas (Gorilla beringei beringei).

    PubMed

    Habumuremyi, Sosthene; Stephens, Colleen; Fawcett, Katie A; Deschner, Tobias; Robbins, Martha M

    2016-04-01

    Variability of fertility (i.e. number of births per female per year) has been reported in females of many primate species but only a few studies have explored the associated physiological and behavioral patterns. To investigate the proximate mechanisms of variability in fertility of wild female mountain gorillas (Gorilla beringei beringei), we quantified the occurrence of ovulation, matings, and successful pregnancies among females. We examined the profiles of immunoreactive pregnanediol-3-glucuronide (iPdG) for sixteen females (seven nulliparous and nine parous females, including one geriatric female; average sampling period for fecal sample collection and behavioral observations per female=175 days; SD=94 days, range=66-358 days) monitored by the staff of the Dian Fossey Gorilla Fund's Karisoke Research Center in Parc National des Volcans, Rwanda. We quantified ovarian cycles from iPdG profiles using an algorithm that we developed by adjusting the method of Kassam et al. (1996) to the characteristics of ovarian cycle profiles based on fecal hormone measurements. The mean length of ovarian cycles was 29±4 days (median: 28 days, N=13 cycles), similar to ovarian cycle lengths of other great apes and humans. As expected, we found that female mountain gorillas exhibit longer follicular phases (mean±SD: 21±3 days, N=13 cycles) than luteal phases (mean±SD: 8±3 days, N=13 cycles). We also found that the frequency of ovarian cycles was greater in parous females (i.e. 20 ovarian cycles across 44 periods of 28 days; 45.5%) than in nulliparous females (i.e. two ovarian cycles across 34 periods of 28 days; 6%). However, the frequency of days on which matings were observed did not differ significantly between parous and nulliparous females, nor between pregnant and non-pregnant females. Five pregnancies were detected with iPdG levels, but only three resulted in live births, indicating miscarriages of the other two. In sum, this study provides information on the underlying

  3. The urea cycle disorders.

    PubMed

    Helman, Guy; Pacheco-Colón, Ileana; Gropman, Andrea L

    2014-07-01

    The urea cycle is the primary nitrogen-disposal pathway in humans. It requires the coordinated function of six enzymes and two mitochondrial transporters to catalyze the conversion of a molecule of ammonia, the α-nitrogen of aspartate, and bicarbonate into urea. Whereas ammonia is toxic, urea is relatively inert, soluble in water, and readily excreted by the kidney in the urine. Accumulation of ammonia and other toxic intermediates of the cycle lead to predominantly neurologic sequelae. The disorders may present at any age from the neonatal period to adulthood, with the more severely affected patients presenting earlier in life. Patients are at risk for metabolic decompensation throughout life, often triggered by illness, fasting, surgery and postoperative states, peripartum, stress, and increased exogenous protein load. Here the authors address neurologic presentations of ornithine transcarbamylase deficiency in detail, the most common of the urea cycle disorders, neuropathology, neurophysiology, and our studies in neuroimaging. Special attention to late-onset presentations is given.

  4. Does the use of gonadotropin-releasing hormone antagonists in natural IVF cycles for poor responder patients cause more harm than benefit?

    PubMed

    Aksoy, Senai; Yakin, Kayhan; Seyhan, Ayse; Oktem, Ozgur; Alatas, Cengiz; Ata, Baris; Urman, Bulent

    2016-06-01

    Poor ovarian response to controlled ovarian stimulation (COS) is one of the most critical factors that substantially limits the success of assisted reproduction techniques (ARTs). Natural and modified natural cycle IVF are two options that could be considered as a last resort. Blocking gonadotropin-releasing hormone (GnRH) actions in the endometrium via GnRH receptor antagonism may have a negative impact on endometrial receptivity. We analysed IVF outcomes in 142 natural (n = 30) or modified natural (n = 112) IVF cycles performed in 82 women retrospectively. A significantly lower proportion of natural cycles reached follicular aspiration compared to modified natural cycles (56.7% vs. 85.7%, p < 0.001). However, the difference between the numbers of IVF cycles ending in embryo transfer (26.7% vs. 44.6%) was not statistically significant between natural cycle and modified natural IVF cycles. Clinical pregnancy (6.7% vs. 7.1%) and live birth rates per initiated cycle (6.7% vs. 5.4%) were similar between the two groups. Notably, the implantation rate was slightly lower in modified natural cycles (16% vs. 25%, p > 0.05). There was a trend towards higher clinical pregnancy (25% vs. 16%) and live birth (25% vs. 12%) rates per embryo transfer in natural cycles compared to modified natural cycles, but the differences did not reach statistical significance.

  5. Comparison of oxygen uptake during cycle ergometry with and without functional electrical stimulation in patients with COPD: protocol for a randomised, single-blind, placebo-controlled, cross-over trial

    PubMed Central

    Medrinal, Clément; Prieur, Guillaume; Debeaumont, David; Robledo Quesada, Aurora; Combret, Yann; Quieffin, Jean; Contal, Olivier; Lamia, Bouchra

    2016-01-01

    Introduction Chronic obstructive pulmonary disease (COPD) has systemic repercussions that can lead to peripheral muscle dysfunction. Muscle atrophy reduces aerobic capacity, greatly limiting activities of daily living and quality of life. Pulmonary rehabilitation is the gold standard treatment for these patients, however, patients may not be able to reach sufficient training intensities for benefits to occur. Technologies such as functional electrical stimulation (FES) are currently being adapted and tested to enhance exercise training. We hypothesise that FES coupled with cycling (FES-cycling) will improve maximal uptake of oxygen (VO2) and aerobic capacity more than endurance training with placebo stimulation. Methods A randomised, single-blind, placebo-controlled crossover trial will be carried out to evaluate the effects of FES-cycling on VO2 during endurance exercise on a cycle ergometer in patients with COPD. 25 patients with COPD will carry out two 30 min sessions at a constant load; one session with active and one with placebo FES. The primary outcome is oxygen uptake recorded with a metabolic measurement system. Secondary outcomes include ventilation equivalent for oxygen, ventilation equivalent for carbon dioxide, cardiac output, lactate values, perceived dyspnoea and perceived muscle fatigue. Results and conclusions Approval has been granted by our Institutional Review Board (Comité de Protection des Personnes Nord-Ouest 3). The results of the trial will be presented at national and international meetings and published in peer-reviewed journals. Trial registration number NCT02594722. PMID:27110364

  6. Stage I of Phase II study assessing efficacy, safety and tolerability of barasertib (AZD1152) versus LDAC in elderly AML patients

    PubMed Central

    Kantarjian, Hagop M; Martinelli, Giovanni; Jabbour, Elias J; Quintás-Cardama, Alfonso; Ando, Kiyoshi; Bay, Jacques-Olivier; Wei, Andrew; Gröpper, Stefanie; Papayannidis, Cristina; Owen, Kate; Pike, Laura; Schmitt, Nicola; Stockman, Paul K; Giagounidis, Aristoteles

    2013-01-01

    Background This Phase II study evaluated the efficacy, safety and tolerability of the Aurora B kinase inhibitor barasertib, compared with low-dose cytosine arabinoside (LDAC), in patients aged ≥60 years with acute myeloid leukemia (AML). Methods Patients were randomized 2:1 to open-label barasertib 1200 mg (7-day iv infusion) or LDAC 20 mg (sc twice-daily for 10 days) in 28-day cycles. The primary endpoint was objective complete response rate (OCRR: CR + CRi [Cheson criteria, additionally requiring CRi reconfirmation ≥21 days after first appearance and associated with partial recovery of platelets and neutrophils]). Secondary endpoints included overall survival (OS) and safety. Results 74 patients (barasertib, n=48; LDAC, n=26) completed ≥1 cycle. A significant improvement in OCRR was observed with barasertib (35.4% vs 11.5%; difference, 23.9% [95% CI, 2.7–39.9]; P<0.05). Although not formally sized to compare OS data, the median OS with barasertib was 8.2 months versus 4.5 months with LDAC. (HR=0.88, 95% CI, 0.49-1.58; P=0.663;). Stomatitis and febrile neutropenia were the most common adverse events with barasertib versus LDAC (71% vs 15%; 67% vs 19%, respectively). Conclusions Barasertib showed a significant improvement in OCRR versus LDAC, with a more toxic but manageable safety profile that was consistent with previous studies. Clinicaltrials.gov, NCT00952588. PMID:23605952

  7. Relationship Between Upper Respiratory Tract Influenza Test Result and Clinical Outcomes Among Critically Ill Influenza Patients.

    PubMed

    Reddy, Krishna P; Bajwa, Ednan K; Parker, Robert A; Onderdonk, Andrew B; Walensky, Rochelle P

    2016-01-01

    Among critically ill patients with lower respiratory tract (LRT)-confirmed influenza, we retrospectively observed worse 28-day clinical outcomes in upper respiratory tract (URT)-negative versus URT-positive subjects. This finding may reflect disease progression and highlights the need for influenza testing of both URT and LRT specimens to improve diagnostic yield and possibly inform prognosis. PMID:26966696

  8. Weekly paclitaxel therapy for gastric cancer in patients with renal dysfunction: A case report.

    PubMed

    Kanematsu, Kyohei; Tsujimoto, Hironori; Nomura, Shinsuke; Horiguchi, Hiroyuki; Ito, Nozomi; Yamazaki, Kenji; Hiraki, Shuichi; Aosasa, Suefumi; Yamamoto, Junji; Hase, Kazuo

    2016-11-01

    A 57-year-old woman was admitted to National Defense Medical College hospital for treatment of gastric cancer with pyloric stenosis. She had been diagnosed with chronic kidney disease (CKD) 10 years prior, but received no hemodialysis. Because of peritoneal dissemination, a palliative distal gastrectomy was performed. In consideration of renal dysfunction, we decided for chemotherapy with paclitaxel, but not S-1 plus cisplatin regimen which is renal toxic agents. On the 29th postoperative day, chemotherapy using paclitaxel was initiated at a dose of 80 mg/m(2). Paclitaxel was administered weekly on days 1, 8, and 15 on a 28-day cycle. The patient tolerated 13 courses of this treatment without any severe adverse effect, such as exacerbation of renal function. Despite the gradual increase in the level of tumor markers, metastases were not detected via radiography during the clinical course. Moreover, renal function was maintained for the duration of the clinical course. To date, standard chemotherapeutic treatment for patients with CKD has not been established. We conclude that weekly paclitaxel is a suitable treatment regimen for patients with renal failure requiring chemotherapy for advanced gastric cancer. PMID:27656282

  9. Lactate clearance is associated with mortality in septic patients with acute kidney injury requiring continuous renal replacement therapy

    PubMed Central

    Passos, Rogério da Hora; Ramos, Joao Gabriel Rosa; Gobatto, André; Mendonça, Evandro José Bulhões; Miranda, Eva Alves; Dutra, Fábio Ricardo Dantas; Coelho, Maria Fernanda R; Pedroza, Andrea C; Batista, Paulo Benigno Pena; Dutra, Margarida Maria Dantas

    2016-01-01

    Abstract The aim of the study was to assess the clinical utility of lactate measured at different time points to predict mortality at 48 hours and 28 days in septic patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Consecutive critically ill patients with septic AKI requiring CRRT were prospectively studied. Variables were collected at initiation of CRRT and 24 hours later. In total, 186 patients were analyzed. Overall mortality at 48 hours was 28% and at 28 days was 69%. Initial lactate, lactate at 24 hours and the proportion of patients with a lactate clearance superior to 10% were different between survivors at 28 days [2.0 mmol/L, 1.95 mmol/L and 18/45 (40%)] and nonsurvivors [3.46 mmol, 4.66 mmol, and 18/94 (19%)]. Multivariate analysis demonstrated that lactate at 24 hours and lactate clearance, but not initial lactate, were independently associated to mortality. Area under the ROC curves for 28-day mortality was 0.635 for initial lactate; 0.828 for lactate at 24 hours and 0.701 for lactate clearance. Lactate clearance and lactate after 24 hours of CRRT, but not initial lactate, were independently associated with mortality in septic AKI patients undergoing CRRT. Serial lactate measurements may be useful prognostic markers than initial lactate in these patients. PMID:27749594

  10. A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma

    PubMed Central

    Larkin, J M G; Hughes, S A; Beirne, D A; Patel, P M; Gibbens, I M; Bate, S C; Thomas, K; Eisen, T G; Gore, M E

    2006-01-01

    Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m−2 days 1–5 every 28 days and lomustine 60 mg m–2 on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. PMID:17146474

  11. A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma.

    PubMed

    Larkin, J M G; Hughes, S A; Beirne, D A; Patel, P M; Gibbens, I M; Bate, S C; Thomas, K; Eisen, T G; Gore, M E

    2007-01-15

    Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. PMID:17146474

  12. Vapor Compression Cycle Design Program (CYCLE_D)

    National Institute of Standards and Technology Data Gateway

    SRD 49 NIST Vapor Compression Cycle Design Program (CYCLE_D) (PC database for purchase)   The CYCLE_D database package simulates the vapor compression refrigeration cycles. It is fully compatible with REFPROP 9.0 and covers the 62 single-compound refrigerants . Fluids can be used in mixtures comprising up to five components.

  13. Phase II Study of Mocetinostat (MGCD0103) In Patients with Relapsed and Refractory Classical Hodgkin Lymphoma

    PubMed Central

    Younes, Anas; Oki, Yasuhiro; Bociek, R. Gregory; Kuruvilla, John; Fanale, Michelle; Neelapu, Sattva; Copeland, Amanda; Buglio, Daniela; Galal, Ahmed; Besterman, Jeffrey; Li, Zuomei; Drouin, Michel; Patterson, Tracy; Ward, M. Renee; Paulus, Jessica K.; Ji, Yuan; Medeiros, L. Jeffrey; Martell, Robert E.

    2015-01-01

    BACKGROUND The prognosis of patients with relapsed Hodgkin lymphoma, especially those who relapsed after stem cell transplant, remains poor, and the development of new agents for this relatively young patient population represents an unmet medical need. In this study, we examined the safety and efficacy of mocetinostat, an oral isotype-selective histone deacetylase inhibitor, in patients with relapsed classical Hodgkin lymphoma METHODS Patients with relapsed or refractory classical Hodgkin lymphoma aged 18 years or older were treated with mocetinostat administered as an oral dose three-times weekly, in 28-day cycles. Two dose cohorts were evaluated (85 mg and 110 mg). Patients were treated until disease progression or prohibitive toxicity. The primary objective was to estimate the disease control rate induced by mocetinostat, defined as CR, PR or SD (for at least 6 cycles) analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00358982 FINDINGS A total of 51 patients were enrolled. Initially, 23 patients were enrolled in the 110 mg cohort. Subsequently, 28 additional patients were treated with a reduced dose of 85 mg to improve treatment tolerance. Based on intent to treat analysis, the overall disease control rate was 34.8% and 25% for the 110 mg and 85 mg groups, respectively. Thirty-four out of 42 (81%) patients who completed at least 2 cycles of therapy had a decrease in their tumor measurements. Forty-seven percent (24/51) discontinued therapy due to disease progression, 57% (16/28) in the 85 mg cohort and 34% in the 110 mg cohort. Twenty-four percent (12/51) discontinued due to adverse events, 32% (9/28) in the 85 mg cohort and 13% (3/23) in the 110 mg cohort. The most frequent treatment-related grade 3 and 4 adverse events included neutropenia, which was observed in 4 (17.4%) patients in the 110 mg group and in 3 (10.7%) patients in the 85 mg group; fatigue (in 5 (21.7%) of the 110 mg group vs 3 (10

  14. Seclusion and the lunar cycles.

    PubMed

    Mason, T

    1997-06-01

    1. The lunar cycle's influence over psychological disturbances in the human being is known as the Transylvanian effect. 2. Seclusion is used predominantly for the control and management of violence and aggression in patients. 3. If the Transylvanian effect is supported, a relationship between lunar cycles and the use of seclusion should exist; no such correlation, however, was found in this study. PMID:9189846

  15. Revenue cycle management.

    PubMed

    Manley, Ray; Satiani, Bhagwan

    2009-11-01

    With the widening gap between overhead expenses and reimbursement, management of the revenue cycle is a critical part of a successful vascular surgery practice. It is important to review the data on all the components of the revenue cycle: payer contracting, appointment scheduling, preregistration, registration process, coding and capturing charges, proper billing of patients and insurers, follow-up of accounts receivable, and finally using appropriate benchmarking. The industry benchmarks used should be those of peers in identical groups. Warning signs of poor performance are discussed enabling the practice to formulate a performance improvement plan.

  16. TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenström's macroglobulinemia.

    PubMed

    Ghobrial, Irene M; Siegel, David S; Vij, Ravi; Berdeja, Jesus G; Richardson, Paul G; Neuwirth, Rachel; Patel, Chirag G; Zohren, Fabian; Wolf, Jeffrey L

    2016-06-01

    The PI3K/AKT/mTOR signaling pathways are frequently dysregulated in multiple human cancers, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and Waldenström's macroglobulinemia (WM). This was the first clinical study to evaluate the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and preliminary clinical activity of TAK-228, an oral TORC1/2 inhibitor, in patients with MM, NHL, or WM. Thirty-nine patients received TAK-228 once daily (QD) at 2, 4, 6, or 7 mg, or QD for 3 days on and 4 days off each week (QDx3d QW) at 9 or 12 mg, in 28-day cycles. The overall median age was 61.0 years (range 46-85); 31 patients had MM, four NHL, and four WM. Cycle 1 DLTs occurred in five QD patients (stomatitis, urticaria, blood creatinine elevation, fatigue, and nausea and vomiting) and four QDx3d QW patients (erythematous rash, fatigue, asthenia, mucosal inflammation, and thrombocytopenia). The MTDs were determined to be 4 mg QD and 9 mg QDx3d QW. Thirty-six patients (92%) reported at least one drug-related toxicity; the most common grade ≥3 drug-related toxicities were thrombocytopenia (15%), fatigue (10%), and neutropenia (5%). TAK-228 exhibited a dose-dependent increase in plasma exposure and no appreciable accumulation with repeat dosing; mean plasma elimination half-life was 6-8 hr. Of the 33 response-evaluable patients, one MM patient had a minimal response, one WM patient achieved partial response, one WM patient had a minor response, and 18 patients (14 MM, two NHL, and two WM) had stable disease. These findings encourage further studies including combination strategies. PMID:26800393

  17. TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenström's macroglobulinemia.

    PubMed

    Ghobrial, Irene M; Siegel, David S; Vij, Ravi; Berdeja, Jesus G; Richardson, Paul G; Neuwirth, Rachel; Patel, Chirag G; Zohren, Fabian; Wolf, Jeffrey L

    2016-06-01

    The PI3K/AKT/mTOR signaling pathways are frequently dysregulated in multiple human cancers, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and Waldenström's macroglobulinemia (WM). This was the first clinical study to evaluate the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and preliminary clinical activity of TAK-228, an oral TORC1/2 inhibitor, in patients with MM, NHL, or WM. Thirty-nine patients received TAK-228 once daily (QD) at 2, 4, 6, or 7 mg, or QD for 3 days on and 4 days off each week (QDx3d QW) at 9 or 12 mg, in 28-day cycles. The overall median age was 61.0 years (range 46-85); 31 patients had MM, four NHL, and four WM. Cycle 1 DLTs occurred in five QD patients (stomatitis, urticaria, blood creatinine elevation, fatigue, and nausea and vomiting) and four QDx3d QW patients (erythematous rash, fatigue, asthenia, mucosal inflammation, and thrombocytopenia). The MTDs were determined to be 4 mg QD and 9 mg QDx3d QW. Thirty-six patients (92%) reported at least one drug-related toxicity; the most common grade ≥3 drug-related toxicities were thrombocytopenia (15%), fatigue (10%), and neutropenia (5%). TAK-228 exhibited a dose-dependent increase in plasma exposure and no appreciable accumulation with repeat dosing; mean plasma elimination half-life was 6-8 hr. Of the 33 response-evaluable patients, one MM patient had a minimal response, one WM patient achieved partial response, one WM patient had a minor response, and 18 patients (14 MM, two NHL, and two WM) had stable disease. These findings encourage further studies including combination strategies.

  18. Menu Cycles.

    ERIC Educational Resources Information Center

    Clayton, Alfred; Almony, John

    The curriculum guide for commercial foods instruction is designed to aid the teacher in communicating the importance of menu cycles in commercial food production. It also provides information about the necessary steps in getting food from the raw form to the finished product, and then to the consumer. In addition to providing information on how to…

  19. NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells.

    PubMed

    Chang, Xiaojing; Xu, Xiaoyang; Ma, Jinguo; Xue, Xiaoying; Li, Zhenhua; Deng, Peng; Zhang, Shuanglong; Zhi, Yu; Chen, Jing; Dai, Dongqiu

    2014-09-01

    N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.

  20. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.

    PubMed

    Foà, Robin; Del Giudice, Ilaria; Cuneo, Antonio; Del Poeta, Giovanni; Ciolli, Stefania; Di Raimondo, Francesco; Lauria, Francesco; Cencini, Emanuele; Rigolin, Gian Matteo; Cortelezzi, Agostino; Nobile, Francesco; Callea, Vincenzo; Brugiatelli, Maura; Massaia, Massimo; Molica, Stefano; Trentin, Livio; Rizzi, Rita; Specchia, Giorgina; Di Serio, Francesca; Orsucci, Lorella; Ambrosetti, Achille; Montillo, Marco; Zinzani, Pier Luigi; Ferrara, Felicetto; Morabito, Fortunato; Mura, Maria Angela; Soriani, Silvia; Peragine, Nadia; Tavolaro, Simona; Bonina, Silvia; Marinelli, Marilisa; De Propris, Maria Stefania; Starza, Irene Della; Piciocchi, Alfonso; Alietti, Alessandra; Runggaldier, Eva Josephine; Gamba, Enrica; Mauro, Francesca Romana; Chiaretti, Sabina; Guarini, Anna

    2014-05-01

    In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.

  1. Increased plasma serotonin metabolite 5-hydroxyindole acetic acid concentrations are associated with impaired systolic and late diastolic forward flows during cardiac cycle and elevated resistive index at popliteal artery and renal insufficiency in type 2 diabetic patients with microalbuminuria.

    PubMed

    Saito, Jun; Suzuki, Eiji; Tajima, Yoshitaka; Takami, Kazuhisa; Horikawa, Yukio; Takeda, Jun

    2016-01-01

    Although lower extremity arterial disease is frequently accompanied by diabetes mellitus, the association of circulating biomarkers with flow components during the cardiac cycle in lower-leg arteries has yet to be fully elucidated. We enrolled 165 type 2 diabetic patients with normal ankle-brachial index (ABI 1.0-1.4), comprising 106 normoalbuminuric and 59 microalbuminuric patients, and 40 age-matched nondiabetic subjects consecutively admitted to our hospital. Serum high sensitivity C-reactive protein (hsCRP) level and plasma von Willebrand factor ristocetin cofactor activity (VWF) and vasoconstrictor serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) concentrations were measured. An automatic device was used to measure ABI and brachial-ankle pulse wave velocity (baPWV). Flow components during the cardiac cycle, total flow volume, and resistive index at popliteal artery were evaluated using gated magnetic resonance imaging. Although estimated glomerular filtration rate (eGFR), early diastolic flow reversal, heart rate, and ABI were similar between the groups, diabetic patients had higher log hsCRP (p<0.001), VWF (p<0.001), 5-HIAA (p=0.002), resistive index (p<0.001) and baPWV (p<0.001) and lower systolic (p=0.026) and late diastolic (p<0.001) forward flows and total flow volume (p<0.001) than nondiabetic subjects. Multivariate analyses demonstrated that 5-HIAA in microalbuminuric patients showed higher associations with systolic and late diastolic forward flows during the cardiac cycle, total flow volume and resistive index at popliteal artery, and eGFR compared to normoalbuminuric patients. In microalbuminuric patients, 5-HIAA was a significant independent determinant among these factors. Thus, increased plasma 5-HIAA levels are involved in the pathogenesis of impaired blood flow in lower extremities and renal insufficiency in diabetic patients with microalbuminuria.

  2. Estimation of survival and gonotrophic cycle length of Culicoides variipennis (Diptera: Ceratopogonidae) in California.

    PubMed

    Work, T M; Mullens, B A; Jessup, D A

    1991-06-01

    The use of a time series analysis to estimate the survival rate and gonotrophic cycle length of Culicoides variipennis at 2 California sites is described. Collections were made daily for 28 days in Yolo County (northern California) and for 25 days in Riverside County (southern California) in July and August of 1989, respectively, using CO2-baited suction traps. The time series analysis of these collections yielded a gonotrophic cycle length estimate of 3 days. Stage-specific and daily survivorship estimates 0.242 and 0.623, respectively, were determined for the northern California site. The time series method was found unsuitable for estimating the gonotrophic cycle length or daily survivorship at the southern California site. PMID:1895081

  3. Phase II study of first-line sagopilone plus prednisone in patients with castration-resistant prostate cancer: a phase II study of the Department of Defense Prostate Cancer Clinical Trials Consortium

    PubMed Central

    Beer, T M; Smith, D C; Hussain, A; Alonso, M; Wang, J; Giurescu, M; Roth, K; Wang, Y

    2012-01-01

    Background: Preclinical studies in prostate cancer (PC) models demonstrated the anti-tumour activity of the first fully synthetic epothilone, sagopilone. This is the first study to investigate the activity and safety of sagopilone in patients with metastatic castration-resistant PC (CRPC). Methods: Chemotherapy-naïve patients with metastatic CRPC received sagopilone (one cycle: 16 mg m−2 intravenously over 3 h q3w) plus prednisone (5 mg twice daily). The primary efficacy evaluation was prostate-specific antigen (PSA) response rate (⩾50% PSA reduction confirmed ⩾28 days apart). According to the Simon two-stage design, ⩾3 PSA responders were necessary within the first 13 evaluable patients for recruitment to continue until 46 evaluable patients were available. Results: In all, 53 patients received ⩾2 study medication cycles, with high compliance. Mean individual dose was 15.1±1.4 mg m−2 during initial six cycles, mean dose intensity 94±9%. The confirmed PSA response rate was 37%. Median overall progression-free survival was 6.4 months. The most commonly reported adverse events (>10% of patients) were peripheral neuropathy (94.3%), fatigue (54.7%) and pain in the extremities (47.2%). Sagopilone was associated with very little haematological toxicity. Conclusion: This study shows that first-line sagopilone has noteworthy anti-tumour activity and a clinically significant level of neuropathy for patients with metastatic chemotherapy-naïve CRPC. PMID:22850553

  4. Pharmacokinetics and excretion of (14)C-omacetaxine in patients with advanced solid tumors.

    PubMed

    Nijenhuis, Cynthia M; Hellriegel, Edward; Beijnen, Jos H; Hershock, Diane; Huitema, Alwin D R; Lucas, Luc; Mergui-Roelvink, Marja; Munteanu, Mihaela; Rabinovich-Guilatt, Laura; Robertson, Philmore; Rosing, Hilde; Spiegelstein, Ofer; Schellens, Jan H M

    2016-10-01

    Background Omacetaxine mepesuccinate is indicated in adults with chronic myeloid leukemia resistant and/or intolerant to ≥ 2 tyrosine kinase inhibitor treatments. This phase I study assessed the disposition, elimination, and safety of (14)C-omacetaxine in patients with solid tumors. Methods The study comprised a 7-days pharmacokinetic assessment followed by a treatment period of ≤ six 28-days cycles. A single subcutaneous dose of 1.25 mg/m(2) (14)C-omacetaxine was administered to six patients. Blood, urine, and feces were collected through 168 h or until radioactivity excreted within 24 h was <1 % of the dose. Total radioactivity (TRA) was measured in all matrices and concentrations of omacetaxine, 4'-desmethylhomoharringtonine (4'-DMHHT), and cephalotaxine were measured in plasma and urine. For each treatment cycle, patients received 1.25 mg/m(2) omacetaxine twice daily for 7 days. Results Mean TRA recovered was approximately 81 % of the dose, with approximately half of the radioactivity recovered in feces and half in urine. Approximately 20 % of the dose was excreted unchanged in urine; cephalotaxine (0.4 % of dose) and 4' DMHHT (9 %) were also present. Plasma concentrations of TRA were higher than the sum of omacetaxine and known metabolites, suggesting the presence of other (14)C-omacetaxine-derived compounds. Fatigue and anemia were common, consistent with the known toxicity profile of omacetaxine. Conclusion Renal and hepatic processes contribute to the elimination of (14)C-omacetaxine-derived radioactivity in cancer patients. In addition to omacetaxine and its known metabolites, other (14)C-omacetaxine-derived materials appear to be present in plasma and urine. Omacetaxine was adequately tolerated, with no new safety signals. PMID:27221729

  5. Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder.

    PubMed

    Camacho, José A; Rioseco-Camacho, Natalia; Andrade, Dario; Porter, John; Kong, Jin

    2003-08-01

    We recently characterized the mitochondrial ornithine transporter (ORNT1), the gene defective in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, a urea cycle disorder. Despite the apparent functional ablation of ORNT1 in 10 French-Canadian probands with the ORNT1-F188 Delta allele, these patients are mildly affected when compared to patients with other urea cycle disorders such as deficiency of ornithine transcarbamylase. Given that the inner mitochondrial membrane is impermeable to solutes, we hypothesize that other unidentified carriers have some degree of functional redundancy with ORNT1. Using conserved sequences of mammalian and fungal mitochondrial ornithine transporters, we screened the Expressed Sequence Tag database for additional transporters belonging to the ORNT subfamily. Here we identify a new intronless gene, ORNT2, located on chromosome 5. The gene product of ORNT2 is 88% identical to ORNT1, targets to the mitochondria and is expressed in human liver, pancreas, kidney, and cultured fibroblasts from control and HHH patients. When ORNT2 is overexpressed transiently in cultured fibroblasts from HHH patients, it rescues the deficient ornithine metabolism in these cells. Our results suggest that ORNT2 may in part be responsible for the milder phenotype in HHH patients secondary to a gene redundancy effect. We believe ORNT2 arose from a retrotransposition event. To our knowledge, this is the first report of a functional retroposon (ORNT2) that can rescue the disease phenotype of the gene it arose from, ORNT1. As such, ORNT2 may eventually become a candidate for pharmacological-based approaches to correct a urea cycle disorder. PMID:12948741

  6. Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7.

    PubMed

    Namer, Barbara; Ørstavik, Kristin; Schmidt, Roland; Kleggetveit, Inge-Petter; Weidner, Christian; Mørk, Cato; Kvernebo, Mari Skylstad; Kvernebo, Knut; Salter, Hugh; Carr, Thomas Hedley; Segerdahl, Märta; Quiding, Hans; Waxman, Stephen George; Handwerker, Hermann Otto; Torebjörk, Hans Erik; Jørum, Ellen; Schmelz, Martin

    2015-09-01

    Seven patients diagnosed with erythromelalgia (EM) were investigated by microneurography to record from unmyelinated nerve fibers in the peroneal nerve. Two patients had characterized variants of sodium channel Nav1.7 (I848T, I228M), whereas no mutations of coding regions of Navs were found in 5 patients with EM. Irrespective of Nav1.7 mutations, more than 50% of the silent nociceptors in the patients with EM showed spontaneous activity. In the patient with mutation I848T, all nociceptors, but not sympathetic efferents, displayed enhanced early subnormal conduction in the velocity recovery cycles and the expected late subnormality was reversed to supranormal conduction. The larger hyperpolarizing shift of activation might explain the difference to the I228M mutation. Sympathetic fibers that lack Nav1.8 did not show supranormal conduction in the patient carrying the I848T mutation, confirming in human subjects that the presence of Nav1.8 crucially modulates conduction in cells expressing EM mutant channels. The characteristic pattern of changes in conduction velocity observed in the patient with the I848T gain-of function mutation in Nav1.7 could be explained by axonal depolarization and concomitant inactivation of Nav1.7. If this were true, activity-dependent hyperpolarization would reverse inactivation of Nav1.7 and account for the supranormal CV. This mechanism might explain normal pain thresholds under resting conditions. PMID:25993546

  7. Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7.

    PubMed

    Namer, Barbara; Ørstavik, Kristin; Schmidt, Roland; Kleggetveit, Inge-Petter; Weidner, Christian; Mørk, Cato; Kvernebo, Mari Skylstad; Kvernebo, Knut; Salter, Hugh; Carr, Thomas Hedley; Segerdahl, Märta; Quiding, Hans; Waxman, Stephen George; Handwerker, Hermann Otto; Torebjörk, Hans Erik; Jørum, Ellen; Schmelz, Martin

    2015-09-01

    Seven patients diagnosed with erythromelalgia (EM) were investigated by microneurography to record from unmyelinated nerve fibers in the peroneal nerve. Two patients had characterized variants of sodium channel Nav1.7 (I848T, I228M), whereas no mutations of coding regions of Navs were found in 5 patients with EM. Irrespective of Nav1.7 mutations, more than 50% of the silent nociceptors in the patients with EM showed spontaneous activity. In the patient with mutation I848T, all nociceptors, but not sympathetic efferents, displayed enhanced early subnormal conduction in the velocity recovery cycles and the expected late subnormality was reversed to supranormal conduction. The larger hyperpolarizing shift of activation might explain the difference to the I228M mutation. Sympathetic fibers that lack Nav1.8 did not show supranormal conduction in the patient carrying the I848T mutation, confirming in human subjects that the presence of Nav1.8 crucially modulates conduction in cells expressing EM mutant channels. The characteristic pattern of changes in conduction velocity observed in the patient with the I848T gain-of function mutation in Nav1.7 could be explained by axonal depolarization and concomitant inactivation of Nav1.7. If this were true, activity-dependent hyperpolarization would reverse inactivation of Nav1.7 and account for the supranormal CV. This mechanism might explain normal pain thresholds under resting conditions.

  8. Efficacy and safety of lenalinomide combined with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma.

    PubMed

    Ivanov, Vadim; Coso, Diane; Chetaille, Bruno; Esterni, Benjamin; Olive, Daniel; Aurran-Schleinitz, Therese; Schiano, Jean Marc; Stoppa, Anne-Marie; Broussais-Guillaumot, Florence; Blaise, Didier; Bouabdallah, Reda

    2014-11-01

    Initial clinical trials demonstrated that lenalidomide monotherapy has a significant activity against some subtypes of lymphoma, but in diffuse large B-cell lymphoma (DLBCL) its activity is limited. The combination of lenalidomide with rituximab may be a promising therapeutic strategy. We retrospectively analyzed clinical outcomes in 17 patients with relapsed/refractory (R/R) DLBCL treated with lenalidomide, 25 mg/day for 21/28 days and rituximab, 375 mg/m(2) on day 7 of every lenalidomide cycle, for a maximum of 12 months. The overall response rate (ORR) was 41.2% with 35.3% complete response (CR), while median response duration was 26.5 months at a median follow-up of 24.9 months. Two patients with CR relapsed after 4 and 27 months of CR, and another four are actually in CR at + 13, + 23, + 24 and + 29 months. The estimated 24-month overall survival (OS) was 45% and progression-free survival (PFS) was 38%. Adverse events were manageable and mostly included thrombocytopenia and neutropenia. Lenalidomide-rituximab is active in R/R DLBCL with an important percentage of continuous CR.

  9. [The development of the activity-rest cycle in the rabbit fetus].

    PubMed

    Belich, A I; Nazarova, L A

    1988-01-01

    On 25-30-day rabbit foetuses, in chronic experiments using constant synchronous recording of the motor activity and heart rate, studies have been made of temporal organization of the activity-rest cycle. Already in 25-day foetus, three functional conditions may be distinguished: active, intermediate and resting ones, the duration of the latter increasing to the end of gestation up to 8-10 min, whereas the duration of the intermediate phase decreases, reaching its minimum to the 30th day if not being completely reduced. Cyclic pattern of active and resting phases is observed in 28-day foetuses; to the 29th-30th day, these phases from a unique activity-rest cycle, its duration reaching 20-30 min to the end of intrauterine period. It is suggested that the resting phase in foetal rabbits serves as a basis for the development of polyphasic sleep in adult animals. PMID:3414220

  10. Predicting pneumonia mortality using CURB-65, PSI, and patient characteristics in patients presenting to the emergency department of a comprehensive cancer center.

    PubMed

    Gonzalez, Carmen; Johnson, Tami; Rolston, Kenneth; Merriman, Kelly; Warneke, Carla; Evans, Scott

    2014-08-01

    The prognostic accuracy of the CURB-65 criteria and pneumonia severity index (PSI) in immunocompromised cancer patients with pneumonia is unknown. We sought to determine whether CURB-65 and PSI predict 28-day mortality in cancer patients with pneumonia, and identify other factors that predispose cancer patients with pneumonia to a high mortality risk. We assessed sensitivities, specificities, predictive values, and areas under the receiver operating curve area under the curve (AUC) of the CURB-65 and PSI in predicting the 28-day mortality of cancer patients presenting to our institution's emergency department with pneumonia. We used the DeLong and Clarke-Pearson approach to determine whether the addition of other risk factors improved the scales' performances. The overall and pneumonia-related 28-day mortality rates were 20.2% (n = 44) and 17.4% (n = 38), respectively. In predicting 28-day mortality, the CURB-65 score had sensitivity of 45% and specificity of 81%, and the PSI score had sensitivity of 82% and specificity of 34%. The CURB-65 and PSI discriminated poorly between fatal and nonfatal pneumonia cases (AUCs, 0.664 and 0.658, respectively; 95% confidence interval [CI], 0.57-0.75 for each). The addition of radiation therapy (RT) within 4 weeks and stem cell transplant (SCT) significantly improved the AUCs of the CURB-65 (0.75; 95% CI, 0.67-0.83) and PSI (0.73; 95% CI, 0.65-0.82). Inadequate performances of CURB-65 and PSI demonstrate that a tool for predicting pneumonia-related mortality in cancer patients and other immunocompromised populations is needed. Pneumonia patients who have undergone recent RT or (SCT) are at a high risk of dying from pneumonia and require special consideration when assessing pneumonia-related mortality risk.

  11. Upregulation of MALAT-1 and its association with survival rate and the effect on cell cycle and migration in patients with esophageal squamous cell carcinoma.

    PubMed

    Yao, Wenjian; Bai, Yu; Li, Yan; Guo, Ling; Zeng, Ping; Wang, Yonglian; Qi, Bo; Liu, Shangguo; Qin, Xiuguang; Li, Yongzhen; Zhao, Baosheng

    2016-04-01

    The aim of this study is to investigate whether metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) can be used as a potential therapy target for human esophageal squamous cell carcinoma. MALAT-1 expression levels were detected in 137 paired EC samples and adjacent nonneoplastic tissues. Human esophageal carcinoma cell lines EC9706 and KYSE150 were transfected with MALAT-1 small interference RNA. Cell proliferation, migration/invasion ability, cell cycle, and apoptosis were assessed. MALAT-1 expressed higher levels in esophageal cancer tissues when compared with paired adjacent normal tissues. This high expression was associated with a decreased survival rate. MALAT-1 knockdown induced a decrease in proliferation-enhanced apoptosis, inhibited migration/invasion, and reduced colony formation and led to cell cycle arrest at the G2/M phase. These data indicates that MALAT-1 could be exploited for therapeutic benefit.

  12. Disrupted cell cycle arrest and reduced proliferation in corneal fibroblasts from GCD2 patients: A potential role for altered autophagy flux

    SciTech Connect

    Choi, Seung-il; Dadakhujaev, Shorafidinkhuja; Maeng, Yong-Sun; Ahn, So-yeon; Kim, Tae-im; Kim, Eung Kweon

    2015-01-02

    Highlights: • Reduced cell proliferation in granular corneal dystrophy type 2. • Abnormal cell cycle arrest by defective autophagy. • Decreased Cyclin A1, B1, and D1 in Atg7 gene knockout cells. • Increase in p16 and p27 expressions were observed in Atg7 gene knockout cells. - Abstract: This study investigates the role of impaired proliferation, altered cell cycle arrest, and defective autophagy flux of corneal fibroblasts in granular corneal dystrophy type 2 (GCD2) pathogenesis. The proliferation rates of homozygous (HO) GCD2 corneal fibroblasts at 72 h, 96 h, and 120 h were significantly lower (1.102 ± 0.027, 1.397 ± 0.039, and 1.527 ± 0.056, respectively) than those observed for the wild-type (WT) controls (1.441 ± 0.029, 1.758 ± 0.043, and 2.003 ± 0.046, respectively). Flow cytometry indicated a decreased G{sub 1} cell cycle progression and the accumulation of cells in the S and G{sub 2}/M phases in GCD2 cells. These accumulations were associated with decreased levels of Cyclin A1, B1, and E1, and increased expression of p16 and p27. p21 and p53 expression was also significantly lower in GCD2 cells compared to the WT. Interestingly, treatment with the autophagy flux inhibitor, bafilomycin A{sub 1}, resulted in similarly decreased Cyclin A1, B1, D1, and p53 expression in WT fibroblasts. Furthermore, similar findings, including a decrease in Cyclin A1, B1, and D1 and an increase in p16 and p27 expression were observed in autophagy-related 7 (Atg7; known to be essential for autophagy) gene knockout cells. These data provide new insight concerning the role of autophagy in cell cycle arrest and cellular proliferation, uncovering a number of novel therapeutic possibilities for GCD2 treatment.

  13. Treatment for patients with multidrug resistant Acinetobacter baumannii pulmonary infection

    PubMed Central

    PAN, TAO; LIU, XIAOYUN; XIANG, SHOUGUI; JI, WENLI

    2016-01-01

    Bacterial infections are common but have become increasingly resistant to drugs. The aim of the present study was to examine the combined treatment of traditional Chinese and Western medicine in 30 cases of pulmonary infection with multidrug resistant Acinetobacter baumannii. Patients were divided into groups A and B according to drug treatments. Cefoperazone or sulbactam and tanreqing were administered in group A, and cefoperazone or sulbactam in group B. The curative effect and prognosis of the two groups were recorded and the remaining treatments were performed routinely in the clinic. For the combined therapy group, which was administered sulperazone and tanreqing, 8 patients were recovered, 6 patients had significant effects, 3 patients exhibited some improvement and 1 patient had no response. One of the patients did not survive after 28 days. By contrast, there were 4 patients that were successfully treated, 3 patients with significant effects, 2 patients with some improvement and 2 patients had no response in the sulperazone group, and 4 patients did not survive after 28 days. In conclusion, the combined therapy of cefoperazone or sulbactam supplemented with tanreqing was identified to be more effective than cefoperazone or sulbactam as monotherapy, for treating multidrug resistant Acinetobacter baumannii. PMID:27073447

  14. Hydrological cycle.

    PubMed

    Gonçalves, H C; Mercante, M A; Santos, E T

    2011-04-01

    The Pantanal hydrological cycle holds an important meaning in the Alto Paraguay Basin, comprising two areas with considerably diverse conditions regarding natural and water resources: the Plateau and the Plains. From the perspective of the ecosystem function, the hydrological flow in the relationship between plateau and plains is important for the creation of reproductive and feeding niches for the regional biodiversity. In general, river declivity in the plateau is 0.6 m/km while declivity on the plains varies from 0.1 to 0.3 m/km. The environment in the plains is characteristically seasonal and is home to an exuberant and abundant diversity of species, including some animals threatened with extinction. When the flat surface meets the plains there is a diminished water flow on the riverbeds and, during the rainy season the rivers overflow their banks, flooding the lowlands. Average annual precipitation in the Basin is 1,396 mm, ranging from 800 mm to 1,600 mm, and the heaviest rainfall occurs in the plateau region. The low drainage capacity of the rivers and lakes that shape the Pantanal, coupled with the climate in the region, produce very high evaporation: approximately 60% of all the waters coming from the plateau are lost through evaporation. The Alto Paraguay Basin, including the Pantanal, while boasting an abundant availability of water resources, also has some spots with water scarcity in some sub-basins, at different times of the year. Climate conditions alone are not enough to explain the differences observed in the Paraguay River regime and some of its tributaries. The complexity of the hydrologic regime of the Paraguay River is due to the low declivity of the lands that comprise the Mato Grosso plains and plateau (50 to 30 cm/km from east to west and 3 to 1.5 cm/km from north to south) as well as the area's dimension, which remains periodically flooded with a large volume of water. PMID:21537597

  15. A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia

    PubMed Central

    Schliemann, Christoph; Gerss, Joachim; Wiebe, Stefanie; Mikesch, Jan-Henrik; Knoblauch, Nicola; Sauer, Tim; Angenendt, Linus; Kewitz, Tobias; Urban, Marc; Butterfass-Bahloul, Trude; Edemir, Sabine; Vehring, Kerstin; Müller-Tidow, Carsten

    2016-01-01

    Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles. Dose-limiting toxicity (DLT) was defined as non-hematological severe adverse reaction CTC grade ≥ 4 with possible or definite relationship to nintedanib. Between April 2012 and October 2013, 13 patients (median age 73 [range: 62–86] years) were enrolled. One patient did not receive study medication and was replaced. Nine (69%) patients had relapsed or refractory disease and 6 (46%) patients had unfavorable cytogenetics. The most frequently reported treatment-related adverse events (AE) were gastrointestinal events. Twelve SAEs irrespective of relatedness were reported. Two SUSARs were observed, one fatal hypercalcemia and one fatal gastrointestinal infection. Two patients (17%) with relapsed AML achieved a complete remission (one CR, one CRi) and bone marrow blast reductions without fulfilling PR criteria were observed in 3 patients (25%). One-year overall survival was 33%. Nintedanib combined with LDAC shows an adequate safety profile and survival data are promising in a difficult-to-treat patient population. Continuation of this trial with a phase II recommended dose of 2 x 200 mg nintedanib in a randomized, placebo-controlled phase II study is planned. The trial is registered to EudraCT as 2011-001086-41. Trial Registration: ClinicalTrials.gov NCT01488344 PMID:27716819

  16. Weekly regimen of paclitaxel and carboplatin as first-line chemotherapy in elderly patients with stage IIIB-IV non small cell lung cancer (NSCLC): results of a phase II study.

    PubMed

    Rozzi, A; Nardoni, C; Corona, M; Restuccia, M R; Falbo, T; Lanzetta, G

    2010-12-01

    Single-agent chemotherapy is the preferred treatment option in chemonaive elderly patients with advanced nonsmall-cell lung cancer (NSCLC). The role of combination chemotherapy in this setting is uncertain although several studies report satisfactory efficacy and safety using weekly paclitaxel and carboplatin (AUC=6) as first-line chemotherapy in elderly patients. It is still unclear which schedule of this regimen which could offer the best therapeutic index. The aim of this study was to evaluate the activity and tolerability of concomitant weekly administration of paclitaxel and carboplatin in untreated elderly patients with advanced NSCLC. From february 2005 to April 2008 36 consecutive elderly patients with advanced NSCLC were enrolled. Median age was 74 years (range, 70-83 years) and median ECOG PS was 1 (range, 0-1). patients received carboplatin (AUC=2) and paclitaxel 80 mg/m² on days 1,8 and 15 every 28 days. All patients were evaluable for efficacy and toxicity; a median of 4 cycles was administered. Twelve patients had partial response (33%; 95% C.I. 15,8-52,3%), 10 patients (28%) showed stable disease. The median time to progression (TTP) was 5.7 months (95% C.I. 3.1-8.6 months) with a median overall survival (MOS) of 9 months (95% C.I. 4.4-13.9 months). Toxicity was mild with no cases of febrile neutropenia; 5 patients (14%) developed grade 2 neuropathy. Our study confirms the substantial activity of weekly regimen of paclitaxel and carboplatin. Due to its favorable profile of toxicity this schedule could represent an interesting therapeutic option in selected chemonaive elderly patients with advanced NSCLC.

  17. Mortality Risk Factors for Patients with Septic Shock after Implementation of the Surviving Sepsis Campaign Bundles

    PubMed Central

    Kim, Moo Hyun; Jeong, Woo Yong; Jung, In Young; Oh, Dong Hyun; Kim, Yong Chan; Kim, Eun Jin; Jeong, Su Jin; Ku, Nam Su; Kim, June Myung

    2016-01-01

    Background Septic shock remains a leading cause of death, despite advances in critical care management. The Surviving Sepsis Campaign (SSC) has reduced morbidity and mortality. This study evaluated risk factors for mortality in patients with septic shock who received treatment following the SSC bundles. Materials and Methods This retrospective cohort study included patients with septic shock who received treatments following SSC bundles in an urban emergency department between November 2007 and November 2011. Primary and secondary endpoints were all-cause 7- and 28-day mortality. Results Among 436 patients, 7- and 28-day mortality rates were 7.11% (31/436) and 14% (61/436), respectively. In multivariate analysis, high lactate level (odds ratio [OR], 1.286; 95% confidence interval [CI], 1.016–1.627; P=0.036) and low estimated glomerular filtration rate (OR, 0.953; 95% CI, 0.913–0.996; P=0.032) were independent risk factors for 7-day mortality. Risk factors for 28-day mortality were high lactate level (OR, 1.346; 95% CI, 1.083–1.673; P=0.008) and high Acute Physiology and Chronic Health Evaluation II score (OR, 1.153; 95% CI, 1.029–1.293; P=0.014). Conclusion The risk of mortality of septic shock patients remains high in patients with high lactate levels and acute kidney injury. PMID:27659434

  18. Vatalanib population pharmacokinetics in patients with myelodysplastic syndrome: CALGB 10105 (Alliance)

    PubMed Central

    Wang, Xiaofeng; Owzar, Kouros; Gupta, Pankaj; Larson, Richard A; Mulkey, Flora; Miller, Antonius A; Lewis, Lionel D; Hurd, David; Vij, Ravi; Ratain, Mark J; Murry, Daryl J

    2014-01-01

    Aims Vatalanib is an oral anti-angiogenesis agent that inhibits vascular endothelial growth factor receptor tyrosine kinases, which in patients showed auto induction of metabolism and variability in pharmacokinetic (PK) disposition. The objective was to characterize the population PK and time-dependent change in vatalanib clearance and assess exposure–toxicity relationship in patients with myelodysplastic syndrome (MDS). Methods This was an open-label phase II study of vatalanib in MDS patients receiving 750–1250 mg once daily in 28-day cycles. Serial blood samples were obtained and plasma vatalanib concentrations measured by HPLC. Population PK analysis was performed using nonmem 7.2 with FO estimation since FOCE failed. The final model was evaluated using goodness-of-fit plots, bootstrap analysis, and visual predictive check. Results Pharmacokinetic data were complete for 137 patients (86 M, 51 F), of median age 70 years (range 20–91). A one-compartment model with lagged first-order absorption and time-dependent change in oral clearance was fitted to the vatalanib plasma concentration versus time data. The population means for pre-induction and post-induction oral clearance were 24.1 l h–1 (range: 9.6–45.5) and 54.9 l h–1 (range: 39.8–75.6), respectively. The apparent oral clearance increased 2.3-fold, (range: 1.7–4.1-fold) from first dose to steady state. Our data did not identify a significant relationship of the predefined covariates with vatalanib pharmacokinetics, although power to detect such a relationship was limited. Conclusions Vatalanib pharmacokinetics were highly variable and the extent of auto induction was not determined to correlate with any of the pre-defined covariates. PMID:24838014

  19. The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra-Abdominal Infection Patients: A Retrospective Cohort Study

    PubMed Central

    Wu, Qin; Ren, Jianan; Wang, Gefei; Li, Guanwei; Gu, Guosheng; Wu, Xiuwen; Li, Yuan; Chen, Jun; Zhao, Yunzhao; Li, Jieshou

    2016-01-01

    Background Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies. Methods We retrospectively studied 267 consecutively enrolled patients with intra-abdominal infections. Occurrence of thrombocytopenia was scanned for all patients. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with occurrence of hospital-acquired thrombocytopenia were included in a multivariable logistic regression analysis to determine thrombocytopenia predictors. Results Median APACHE II score and SOFA score of the whole cohort was 12 and 3 respectively. The overall ICU mortality was 7.87% and the 28-day mortality was 8.98%. The incidence of thrombocytopenia among intra-abdominal infection patients was 21.73%. Regardless of preexisting or hospital-acquired one, thrombocytopenia is associated with an increased ICU mortality and 28-day mortality as well as length of ICU or hospital stay. A higher SOFA and ISTH score at admission were significant hospital-acquired thrombocytopenia risk factors. Conclusions This is the first study to identify a high incidence of thrombocytopenia in patients with intra-abdominal infections. Our findings suggest that the inflammatory milieu of intra-abdominal infections may uniquely predispose those patients to thrombocytopenia. More effective thrombocytopenia prevention strategies are necessary in intra-abdominal infection patients. PMID:26808492

  20. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in section 3 of TSCA and in 40 CFR Part 792—Good Laboratory Practice Standards apply to this section. The... strains of young healthy adult animals should be employed. The females should be nulliparous and...

  1. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in section 3 of TSCA and in 40 CFR Part 792—Good Laboratory Practice Standards apply to this section. The... strains of young healthy adult animals should be employed. The females should be nulliparous and...

  2. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in section 3 of TSCA and in 40 CFR Part 792—Good Laboratory Practice Standards apply to this section. The... strains of young healthy adult animals should be employed. The females should be nulliparous and...

  3. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in section 3 of TSCA and in 40 CFR Part 792—Good Laboratory Practice Standards apply to this section. The... strains of young healthy adult animals should be employed. The females should be nulliparous and...

  4. Jet Fuel Kerosene is not Immunosuppressive in Mice or Rats Following Inhalation for 28 Days

    PubMed Central

    White, Kimber L.; DeLorme, Michael P.; Beatty, Patrick W.; Smith, Matthew J.; Peachee, Vanessa L.

    2013-01-01

    Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels. The present studies were conducted, in compliance with Good Laboratory Practice (GLP) regulations, to evaluate the effects of jet fuel kerosene on the immune system, in conjunction with an accurate, quantitative characterization of the aerosol and vapor exposure concentrations. Two female rodent species (B6C3F1 mice and Crl:CD rats) were exposed by nose-only inhalation to jet fuel kerosene at targeted concentrations of 0, 500, 1000, or 2000 mg/m3 for 6 h daily for 28 d. Humoral, cell-mediated, and innate immune functions were subsequently evaluated. No marked effects were observed in either species on body weights, spleen or thymus weights, the T-dependent antibody-forming cell response (plaque assay), or the delayed-type hypersensitivity (DTH) response. With a few exceptions, spleen cell numbers and phenotypes were also unaffected. Natural killer (NK) cell activity in mice was unaffected, while the NK assessment in rats was not usable due to an unusually low response in all groups. These studies demonstrate that inhalation of jet fuel kerosene for 28 d at levels up to 2000 mg/m3 did not adversely affect the functional immune responses of female mice and rats. PMID:24028664

  5. Tenderness of pasture versus grain fed beef aged 14 and 28 days

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumer interest in pasture versus grain fed beef has been on the rise in recent years. This interest could be sparked by the public’s concerns of beef management techniques and processing impacts on the nutrition and safety of their food, as well as the environmental impact of each management type...

  6. Toxicologic evaluation of tungsten: 28-day inhalation study of tungsten blue oxide in rats.

    PubMed

    Rajendran, Narayanan; Hu, Shu-Chieh; Sullivan, Dennis; Muzzio, Miguel; Detrisac, Carol J; Venezia, Carmen

    2012-12-01

    The toxicity and toxicokinetics of tungsten blue oxide (TBO) were examined. TBO is an intermediate in the production of tungsten powder, and has shown the potential to cause cellular damage in in vitro studies. However, in vivo evidence seems to indicate a lack of adverse effects. The present study was undertaken to address the dearth of longer-term inhalation toxicity studies of tungsten oxides by investigating the biological responses induced by TBO when administered via nose-only inhalation to rats at levels of 0.08, 0.325, and 0.65 mg TBO/L of air for 6 h/day for 28 consecutive days, followed by a 14-day recovery period. Inhaled TBO was absorbed systemically and blood levels of tungsten increased as inhaled concentration increased. Among the tissues analyzed for tungsten levels, lung, femur and kidney showed increased levels, with lung at least an order of magnitude greater than kidney or femur. By exposure day 14, tungsten concentration in tissues had reached steady-state. Increased lung weight was noted for both terminal and recovery animals and was attributed to deposition of TBO in the lungs, inducing a macrophage influx. Microscopic evaluation of tissues revealed a dose-related increase in alveolar pigmented macrophages, alveolar foreign material and individual alveolar foamy macrophages in lung. After a recovery period there was a slight reduction in the incidence and severity of histopathological findings. Based on the absence of other adverse effects, the increased lung weights and the microscopic findings were interpreted as nonadverse response to exposure and were not considered a specific reaction to TBO.

  7. Relative toxicity of bifenthrin to Hyalella azteca in 10 day versus 28 day exposures.

    PubMed

    Anderson, Brian S; Phillips, Bryn M; Voorhees, Jennifer P; Petersen, Megan A; Jennings, Lydia L; Fojut, Tessa L; Vasquez, Martice E; Siegler, Catherine; Tjeerdema, Ronald S

    2015-04-01

    Many watersheds in the Central Valley region of California are listed as impaired due to pyrethroid-associated sediment toxicity. The Central Valley Regional Water Quality Control Board is developing numeric sediment quality criteria for pyrethroids, beginning with bifenthrin. Criteria are being developed using existing data, along with data from 10 d and 28 d toxicity tests with Hyalella azteca conducted as part of the current study. A single range-finder and 2 definitive tests were conducted for each test duration. Median lethal concentrations (LC50s), as well as LC20s and inhibition concentrations (IC20s) were calculated based on measured whole sediment bifenthrin concentrations and interstitial water concentrations. Sediment LC50s were also corrected for organic C content. Average LC50s were not significantly different in 10 d versus 28 d tests with H. azteca: 9.1 and 9.6 ng/g bifenthrin for 10 d and 28 d tests, respectively. Average LC20 values were also similar with concentrations at 7.1 and 7.0 for 10 d and 28 d tests, respectively. Bifenthrin inhibition concentrations (IC20s) based on amphipod growth were variable, particularly in the 28 d tests, where a clear dose-response relationship was observed in only 1 of the definitive experiments. Average amphipod growth IC20s were 3.9 and 9.0 ng/g for 10 d and 28 d tests, respectively. Amphipod growth calculated as biomass resulted in IC20s of 4.1 and 6.3 ng/g for the 10 d and 28 d tests, respectively. Lack of a clear growth effect in the longer term test may be related to the lack of food adjustment to account for amphipod mortality in whole sediment exposures. The average C-corrected LC50s were 1.03 and 1.09 μg/g OC for the 10 d and 28 d tests, respectively. Interstitial water LC50s were determined as the measured dissolved concentration of bifenthrin relative to interstitial water dissolved organic carbon. The average LC50s for dissolved interstitial water bifenthrin were 4.23 and 4.28 ng/L for the 10 d and 28 d tests, respectively. In addition, a set of 10 d and 28 d tests were conducted at 15 °C to assess the relative toxicity of bifenthrin at a lower temperature than the standard 23 °C test temperature. These results showed that bifenthrin was more toxic at the lower temperature, with LC50s of 5.1 and 3.4 ng/g bifenthrin in 10 d and 28 d tests, respectively. Amphipod growth at 15 °C after a 28 d exposure resulted in the lowest effect concentration of all experiments conducted (IC20 = 0.61 ng/g). This article discusses how bifenthrin dose-response data from 10 d and 28 d exposures inform development of sediment quality criteria for this pesticide for California Central Valley watersheds.

  8. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    NASA Astrophysics Data System (ADS)

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-06-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

  9. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... dose level. If interim sacrifices are planned, the number should be increased by the number of animals.... Measurements of food consumption should be made at least weekly. If the test substance is administered via the... requirements of the Toxic Substances Control Act (TSCA) (15 U.S.C.......

  10. Oestrous cycle of the common wombat, Vombatus ursinus, in Victoria, Australia.

    PubMed

    West, M; Galloway, D; Shaw, J; Trouson, A; Paris, M C J

    2004-01-01

    Wild-caught female common wombats from Victoria, Australia, were studied in captivity to investigate the oestrous cycle by assessing vaginal cytology and peripheral plasma progesterone concentrations. Eight wombats, five adults (21-29 kg) and three subadults (19-23 kg), which were held for between 2 weeks and 11 months did not cycle in captivity. Their progesterone concentrations were consistently low (< or = 6.9 nmol L(-1)) and vaginal smears contained predominantly superficial epithelial cells. Three wombats (21-27 kg), held in captivity for >1 year, regularly cycled (when bodyweights exceeded 23.5 kg). Information gathered from four consecutive cycles in each of these three wombats revealed a follicular phase with low progesterone concentrations (< or = 6.9 nmol L(-1)) and vaginal smears with a high percentage of superficial epithelial cells alternating with periods of high progesterone concentrations (range 41.6-123.8 nmol L(-1)) and smears in which parabasal-intermediate epithelial cells predominated. The average length of the monitored oestrous cycles was 47.2 days (35-60 days). The follicular phase lasted ~19 days and the luteal phase lasted ~28 days. In conclusion, wombats can cycle regularly in captivity even under conditions of intensive monitoring. PMID:15304207

  11. Oestrous cycle of the common wombat, Vombatus ursinus, in Victoria, Australia.

    PubMed

    West, M; Galloway, D; Shaw, J; Trouson, A; Paris, M C J

    2004-01-01

    Wild-caught female common wombats from Victoria, Australia, were studied in captivity to investigate the oestrous cycle by assessing vaginal cytology and peripheral plasma progesterone concentrations. Eight wombats, five adults (21-29 kg) and three subadults (19-23 kg), which were held for between 2 weeks and 11 months did not cycle in captivity. Their progesterone concentrations were consistently low (< or = 6.9 nmol L(-1)) and vaginal smears contained predominantly superficial epithelial cells. Three wombats (21-27 kg), held in captivity for >1 year, regularly cycled (when bodyweights exceeded 23.5 kg). Information gathered from four consecutive cycles in each of these three wombats revealed a follicular phase with low progesterone concentrations (< or = 6.9 nmol L(-1)) and vaginal smears with a high percentage of superficial epithelial cells alternating with periods of high progesterone concentrations (range 41.6-123.8 nmol L(-1)) and smears in which parabasal-intermediate epithelial cells predominated. The average length of the monitored oestrous cycles was 47.2 days (35-60 days). The follicular phase lasted ~19 days and the luteal phase lasted ~28 days. In conclusion, wombats can cycle regularly in captivity even under conditions of intensive monitoring.

  12. Early Anti-Pseudomonal Acquisition in Young Patients with Cystic Fibrosis: Rationale and Design of the EPIC Clinical Trial and Observational Study

    PubMed Central

    Treggiari, Miriam M; Rosenfeld, Margaret; Mayer-Hamblett, Nicole; Retsch-Bogart, George; Gibson, Ronald L.; Williams, Judy; Emerson, Julia; Kronmal, Richard A; Ramsey, Bonnie W

    2009-01-01

    Background The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood. Purpose The present studies are designed to evaluate risk factors and outcomes associated with early Pa acquisition, and the benefits and harms of four anti-pseudomonal treatment regimens in young CF patients initiated after the first Pa positive respiratory culture. Methods The Early Pseudomonas Infection Control (EPIC) program consists of two studies, a randomized multicenter trial in CF patients ages 1–12 years at first isolation of Pa from a respiratory culture, and a longitudinal cohort study enrolling Pa-negative patients. Using a factorial design, trial participants are assigned for 18 months to either anti-pseudomonal treatment on a scheduled quarterly basis (cycled therapy) or based on recovery of Pa from quarterly respiratory cultures (culture-based therapy). The study drugs include inhaled tobramycin (300 mg BID) for 28 days, combined with either oral ciprofloxacin (15–20 mg/kg BID) or oral placebo for 14 days. The primary endpoints of the trial are the time to pulmonary exacerbation requiring IV antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. The broad goals of the observational study are to describe the risk factors and outcomes associated with early acquisition of Pa. 306 patients were randomized in the clinical trial and 1,787 were enrolled in the cohort study. Conclusions These companion studies will provide valuable epidemiological and microbiological information on early CF lung disease and Pa acquisition, and safety and clinical efficacy data on anti-pseudomonal treatment strategies for early Pa infections in the

  13. The menstrual cycle and susceptibility to coriolis-induced sickness.

    PubMed

    Cheung, B; Heskin, R; Hofer, K; Gagnon, M

    2001-01-01

    Survey studies on motion sickness susceptibility suggest that females tend to report greater severity in illness and higher incidence of vomiting than males. Menstruation is said to be a contributing factor. A recent study suggested that females were least susceptible to seasickness during ovulation in a "round the world" yacht race. Sixteen subjects (18-36 years old) were exposed to Coriolis cross-coupling stimulation in the laboratory. They were tested once during permenstruation (Day 1-5), ovulation (Day 12-15) and premenstruation (Day 24-28), based on a normalized 28-day cycle, in a randomised design. Physiological measurements of motion sickness included forearm and calf cutaneous blood flow. Subjective evaluation of sickness symptoms was based on Graybiel's diagnostic criteria and Golding's rating method. Our results indicated that under controlled laboratory conditions, different phases of the menstrual cycle appear to have no influence on subjective symptoms of motion sickness or on cutaneous blood flow increase in the forearm and calf. The lack of commonality between the types and levels of hormones that are released during motion sickness and those that are involved in different menstrual phases appears to support our findings.

  14. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors

    PubMed Central

    Kris, M. G.; Camidge, D. R.; Giaccone, G.; Hida, T.; Li, B. T.; O'Connell, J.; Taylor, I.; Zhang, H.; Arcila, M. E.; Goldberg, Z.; Jänne, P. A.

    2015-01-01

    Background HER2 mutations and amplifications have been identified as oncogenic drivers in lung cancers. Dacomitinib, an irreversible inhibitor of HER2, EGFR (HER1), and HER4 tyrosine kinases, has demonstrated activity in cell-line models with HER2 exon 20 insertions or amplifications. Here, we studied dacomitinib in patients with HER2-mutant or amplified lung cancers. Patients and methods As a prespecified cohort of a phase II study, we included patients with stage IIIB/IV lung cancers with HER2 mutations or amplification. We gave oral dacomitinib at 30–45 mg daily in 28-day cycles. End points included partial response rate, overall survival, and toxicity. Results We enrolled 30 patients with HER2-mutant (n = 26, all in exon 20 including 25 insertions and 1 missense mutation) or HER2-amplified lung cancers (n = 4). Three of 26 patients with tumors harboring HER2 exon 20 mutations [12%; 95% confidence interval (CI) 2% to 30%] had partial responses lasting 3+, 11, and 14 months. No partial responses occurred in four patients with tumors with HER2 amplifications. The median overall survival was 9 months from the start of dacomitinib (95% CI 7–21 months) for patients with HER2 mutations and ranged from 5 to 22 months with amplifications. Treatment-related toxicities included diarrhea (90%; grade 3/4: 20%/3%), dermatitis (73%; grade 3/4: 3%/0%), and fatigue (57%; grade 3/4: 3%/0%). One patient died on study likely due to an interaction of dacomitinib with mirtazapine. Conclusions Dacomitinib produced objective responses in patients with lung cancers with specific HER2 exon 20 insertions. This observation validates HER2 exon 20 insertions as actionable targets and justifies further study of HER2-targeted agents in specific HER2-driven lung cancers. ClinicalTrials.gov NCT00818441. PMID:25899785

  15. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    SciTech Connect

    Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.; and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

  16. Wilms Tumor Gene (WT1) Peptide–based Cancer Vaccine Combined With Gemcitabine for Patients With Advanced Pancreatic Cancer

    PubMed Central

    Nishida, Sumiyuki; Koido, Shigeo; Takeda, Yutaka; Homma, Sadamu; Komita, Hideo; Takahara, Akitaka; Morita, Satoshi; Ito, Toshinori; Morimoto, Soyoko; Hara, Kazuma; Tsuboi, Akihiro; Oka, Yoshihiro; Yanagisawa, Satoru; Toyama, Yoichi; Ikegami, Masahiro; Kitagawa, Toru; Eguchi, Hidetoshi; Wada, Hiroshi; Nagano, Hiroaki; Nakata, Jun; Nakae, Yoshiki; Hosen, Naoki; Oji, Yusuke; Tanaka, Toshio; Kawase, Ichiro; Kumanogoh, Atsushi; Sakamoto, Junichi; Doki, Yuichiro; Mori, Masaki; Ohkusa, Toshifumi; Tajiri, Hisao

    2014-01-01

    Wilms tumor gene (WT1) protein is an attractive target for cancer immunotherapy. We aimed to investigate the feasibility of a combination therapy consisting of gemcitabine and WT1 peptide–based vaccine for patients with advanced pancreatic cancer and to make initial assessments of its clinical efficacy and immunologic response. Thirty-two HLA-A*24:02+ patients with advanced pancreatic cancer were enrolled. Patients received HLA-A*24:02-restricted, modified 9-mer WT1 peptide (3 mg/body) emulsified with Montanide ISA51 adjuvant (WT1 vaccine) intradermally biweekly and gemcitabine (1000 mg/m2) on days 1, 8, and 15 of a 28-day cycle. This combination therapy was well tolerated. The frequencies of grade 3–4 adverse events for this combination therapy were similar to those for gemcitabine alone. Objective response rate was 20.0% (6/30 evaluable patients). Median survival time and 1-year survival rate were 8.1 months and 29%, respectively. The association between longer survival and positive delayed-type hypersensitivity to WT1 peptide was statistically significant, and longer survivors featured a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes both before and after treatment. WT1 vaccine in combination with gemcitabine was well tolerated for patients with advanced pancreatic cancer. Delayed-type hypersensitivity-positivity to WT1 peptide and a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes could be useful prognostic markers for survival in the combination therapy with gemcitabine and WT1 vaccine. Further clinical investigation is warranted to determine the effectiveness of this combination therapy. PMID:24509173

  17. Anti-Müllerian hormone levels as a predictor of clinical pregnancy in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer cycles in patients over 40 years of age

    PubMed Central

    Park, Hyun Jong; Lyu, Sang Woo; Seok, Hyun Ha; Yoon, Tae Ki

    2015-01-01

    Objective The aim of the current study was to determine the predictive value of anti-Müllerian hormone (AMH) levels for pregnancy outcomes in patients over 40 years of age who underwent in vitro fertilization or intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. Methods We retrospectively analyzed the medical records of 188 women aged 40 to 44 years who underwent IVF/ICSI-fresh ET cycles due to unexplained infertility in the fertility center of CHA Gangnam Medical Center. Patients were divided into group A, with AMH levels <1.0 ng/mL (n=97), and group B, with AMH levels ≥1.0 ng/mL (n=91). We compared the clinical pregnancy rate (CPR) in the two groups and performed logistic regression analysis to identify factors that had a significant effect on the CPR. Results The CPR was significantly lower in group A than group B (7.2% vs. 24.2%, p<0.001). In multivariate logistic regression analysis, AMH levels were the only factor that had a significant impact on the CPR (odds ratio, 1.510; 95% confidence interval, 1.172-1.947). The area under the receiver operating characteristic curve for AMH levels as a predictor of the CPR was 0.721. When the cut-off level of AMH was set at 1.90 ng/mL, the CPR was 6.731-fold higher in the group with AMH levels ≥1.90 ng/mL than in the group with AMH levels <1.90 ng/mL (p<0.001). Conclusion Our study showed that AMH levels were predictive of clinical pregnancy in infertility patients over 40 years of age. Further prospective studies should be conducted to validate the predictive capability of AMH levels for the outcome of clinical pregnancy. PMID:26816873

  18. Blocking DNA Repair in Advanced BRCA-Mutated Cancer

    Cancer.gov

    In this trial, patients with relapsed or refractory advanced cancer and confirmed BRCA mutations who have not previously been treated with a PARP inhibitor will be given BMN 673 by mouth once a day in 28-day cycles.

  19. Supplemental dose of antithrombin use in disseminated intravascular coagulation patients after abdominal sepsis.

    PubMed

    Tagami, Takashi; Matsui, Hiroki; Fushimi, Kiyohide; Yasunaga, Hideo

    2015-08-31

    The effectiveness of supplemental dose antithrombin administration (1,500 to 3,000 IU/ day) for patients with sepsis-associated disseminated intravascular coagulation (DIC), especially sepsis due to abdominal origin, remains uncertain. This was a retrospective cohort study of patients with mechanically ventilated septic shock and DIC after emergency surgery for perforation of the lower intestinal tract using a nationwide administrative database, Japanese Diagnosis Procedure Combination inpatient database. A total of 2,164 patients treated at 612 hospitals during the 33-month study period between 2010 and 2013 were divided into an antithrombin group (n=1,021) and a control group (n=1,143), from which 518 propensity score-matched pairs were generated. Although there was no significant 28-day mortality difference between the two groups in the unmatched groups (control vs antithrombin: 25.7 vs 22.9 %; difference, 2.8 %; 95 % confidence interval [CI], -0.8-6.4), a significant difference existed between the two groups in propensity-score weighted groups (26.3 vs 21.7 %; difference, 4.6 %; 95 % CI, 2.0-7.1) and propensity-score matched groups (27.6 vs 19.9 %; difference, 7.7 %; 95 % CI, 2.5-12.9). Logistic regression analyses showed a significant association between antithrombin use and lower 28-day mortality in propensity-matched groups (odds ratio, 0.65; 95 % CI, 0.49-0.87). Analysis using the hospital antithrombin-prescribing rate as an instrumental variable showed that receipt of antithrombin was associated with a 6.5 % (95 % CI, 0.05-13.0) reduction in 28-day mortality. Supplemental dose of antithrombin administration may be associated with reduced 28-day mortality in sepsis-associated DIC patients after emergency laparotomy for intestinal perforation.

  20. Phase II Trial of Hypofractionated IMRT With Temozolomide for Patients With Newly Diagnosed Glioblastoma Multiforme

    SciTech Connect

    Reddy, Krishna; Damek, Denise; Gaspar, Laurie E.; Ney, Douglas; Waziri, Allen; Lillehei, Kevin; Stuhr, Kelly; Kavanagh, Brian D.; Chen Changhu

    2012-11-01

    Purpose: To report toxicity and overall survival (OS) in patients with newly diagnosed glioblastoma multiforme (GBM) treated with hypofractionated intensity-modulated radiotherapy (hypo-IMRT) with concurrent and adjuvant temozolomide (TMZ). Methods and Materials: Patients with newly diagnosed GBM after biopsy or resection and with adequate performance status and organ or bone marrow function were eligible for this study. Patients received postoperative hypo-IMRT to the surgical cavity and residual tumor seen on T1-weighted brain MRI with a 5-mm margin to a total dose of 60 Gy in 10 fractions (6 Gy/fraction) and to the T2 abnormality on T2-weighted MRI with 5-mm margin to 30 Gy in 10 fractions (3 Gy/fraction). Concurrent TMZ was given at 75 mg/m{sup 2}/day for 28 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m{sup 2}/day for 5 days every 28 days. Toxicities were defined using Common Terminology Criteria for Adverse Events version 3.0. Results: Twenty-four patients were treated, consisting of 14 men, 10 women; a median age of 60.5 years old (range, 27-77 years); and a median Karnofsky performance score of 80 (range, 60-90). All patients received hypo-IMRT and concurrent TMZ according to protocol, except for 2 patients who received only 14 days of concurrent TMZ. The median number of adjuvant TMZ cycles was 6.5 (range, 0-14).With a median follow-up of 14.8 months (range, 2.7-34.2 months) for all patients and a minimum follow-up of 20.6 months for living patients, no instances of grade 3 or higher nonhematologic toxicity were observed. The median OS was 16.6 months (range, 4.1-35.9 months). Six patients underwent repeated surgery for suspected tumor recurrence; necrosis was found in 50% to 100% of the resected specimens. Conclusion: In selected GBM patients, 60 Gy hypo-IMRT delivered in 6-Gy fractions over 2 weeks with concurrent and adjuvant TMZ is safe. OS in this small cohort of patients was comparable to that treated with current standard of care

  1. Integrating hospital and physician revenue cycle operations.

    PubMed

    Lockett, Kevin M

    2014-03-01

    Standardized revenue cycle processes should be a key component of the coordinated care delivery strategy organizations will require to complete the transition to population health management. Integrating hospital and physician revenue cycle operations can help organizations better navigate new payment models, reduce costs, and improve value. The most comprehensive approach involves integrating patient access and registration, coding operations, and receivables management across different settings.

  2. Phase II trial of hypofractionated intensity-modulated radiation therapy combined with temozolomide and bevacizumab for patients with newly diagnosed glioblastoma.

    PubMed

    Ney, Douglas E; Carlson, Julie A; Damek, Denise M; Gaspar, Laurie E; Kavanagh, Brian D; Kleinschmidt-DeMasters, B K; Waziri, Allen E; Lillehei, Kevin O; Reddy, Krishna; Chen, Changhu

    2015-03-01

    Bevacizumab blocks the effects of VEGF and may allow for more aggressive radiotherapy schedules. We evaluated the efficacy and toxicity of hypofractionated intensity-modulated radiation therapy with concurrent and adjuvant temozolomide and bevacizumab in patients with newly diagnosed glioblastoma. Patients with newly diagnosed glioblastoma were treated with hypofractionated intensity modulated radiation therapy to the surgical cavity and residual tumor with a 1 cm margin (PTV1) to 60 Gy and to the T2 abnormality with a 1 cm margin (PTV2) to 30 Gy in 10 daily fractions over 2 weeks. Concurrent temozolomide (75 mg/m(2) daily) and bevacizumab (10 mg/kg) was administered followed by adjuvant temozolomide (200 mg/m(2)) on a standard 5/28 day cycle and bevacizumab (10 mg/kg) every 2 weeks for 6 months. Thirty newly diagnosed patients were treated on study. Median PTV1 volume was 131.1 cm(3) and the median PTV2 volume was 342.6 cm(3). Six-month progression-free survival (PFS) was 90 %, with median follow-up of 15.9 months. The median PFS was 14.3 months, with a median overall survival (OS) of 16.3 months. Grade 4 hematologic toxicity included neutropenia (10 %) and thrombocytopenia (17 %). Grades 3/4 non-hematologic toxicity included fatigue (13 %), wound dehiscence (7 %) and stroke, pulmonary embolism and nausea each in 1 patient. Presumed radiation necrosis with clinical decline was seen in 50 % of patients, two with autopsy documentation. The study was closed early to accrual due to this finding. This study demonstrated 90 % 6-month PFS and OS comparable to historic data in patients receiving standard treatment. Bevacizumab did not prevent radiation necrosis associated with this hypofractionated radiation regimen and large PTV volumes may have contributed to high rates of presumed radiation necrosis. PMID:25524817

  3. [Menstrual cycle disorders in adolescence].

    PubMed

    Escobar, María E; Pipman, Viviana; Arcari, Andrea; Boulgourdjian, Elisabeth; Keselman, Ana; Pasqualini, Titania; Alonso, Guillermo; Blanco, Miguel

    2010-08-01

    The high prevalence of menstrual disorders during the first years after menarche is well recognized. This is usually a cause of concern for parents and patients, and a common reason for visiting the pediatrician. The immaturity of the hypothalamic-pituitary-ovarian axis is the major cause of these disorders, but there are also some general organic or emotional conditions that may alter the menstrual cycle, which is a sensitive indicator of health. Physiology of the menstrual cycle, its alterations, etiology, assessment, diagnosis and treatment are reviewed in this article.

  4. Plasma progesterone levels during oestrous cycle and their relationship with the ovulation rate in Red Sokoto (Maradi) goats.

    PubMed

    Pathiraja, N; Oyedipe, E O; Gyang, E O; Obasi, A

    1991-01-01

    Twenty-five 2-3-year-old cycling does weighing 17-25 kg were obtained from semi-nomadic farmers and managed under controlled conditions while simulating the traditional management system. Oestrus was synchronized using progestogen impregnated vaginal pessaries. Blood samples were collected daily for progesterone assay from the day of pessary withdrawal up to one complete oestrous cycle. Oestrus was checked twice daily using vasectomized bucks. Ovulation rate was determined by direct observation of the ovaries following laparotomy on day 5-7 of the oestrous cycle. Following oestrus synchronization, mean ovulation rate was 1.68 +/- 0.13. Mean oestrous cycle length and duration of oestrus were 21.30 +/- 0.28 days and 21.37 +/- 0.24 hours respectively. Plasma progesterone concentrations ranged from non-detectable levels on the day of oestrus to 5.2 +/- 0.28 ng ml at mid-cycle. The duration of elevated progesterone level (greater than 2 ng/ml) was about 12 days. The peak progesterone values did not differ between animals with different ovulation rates. However, the plasma progesterone concentration during the early cycle (days 0-6) was significantly lower in the single ovulators compared with others. There were no major differences in plasma progesterone levels during the oestrous cycle of Red Sokoto does with different ovulation rates. PMID:2018918

  5. A Phase II Study of 2-Methoxyestradiol (2ME2) NanoCrystal® Dispersion (NCD) in Patients with Taxane-Refractory, Metastatic Castrate-Resistant Prostate Cancer (CRPC)

    PubMed Central

    Harrison, Michael R.; Hahn, Noah M.; Pili, Roberto; Oh, William K.; Hammers, Hans; Sweeney, Christopher; Kim, KyungMann; Perlman, Scott; Arnott, Jamie; Sidor, Carolyn; Wilding, George; Liu, Glenn

    2010-01-01

    Purpose 2ME2 (Panzem®) is a non-estrogenic derivative of estradiol with antiproliferative and antiangiogenic activity. Preclinical data support antitumor activity in prostate cancer. This trial evaluated the efficacy of 2ME2 NCD in patients with taxane-refractory, metastatic CRPC. Experimental Design Patients with metastatic CRPC who had progressed on only one prior taxane-based regimen were eligible. All patients received 2ME2 NCD at 1500 mg orally four times daily, repeated in 28 day cycles. The primary endpoint was progression free survival at month 6, with a secondary endpoint of PSA response. An exploratory endpoint was metabolic response on FDG-PET imaging. Results A total of 50 pts was planned. The study was terminated after 21 pts when a futility analysis showed the primary endpoint was unlikely to be reached. The median number of cycles on study was 2 (range <1 to 12). Adverse events (AE) of grade ≥3 related to the study drug occurred in 7 unique patients (33%): elevations in liver function tests, fatigue or weakness, gastrointestinal hemorrhage, and hyponatremia. Paired FDG-PET scans were obtained for 11 pts. No metabolic responses were observed. Conclusions 2ME2 NCD did not appear to have clinically significant activity in this study. 2ME2 NCD was well-tolerated and showed some evidence of biologic activity. Given the aggressive biology in this taxane-refractory population, the potential benefit from a cytostatic agent like 2ME2 might better be realized in the pre-chemotherapy (or rising PSA only) stage of CRPC. PMID:20499131

  6. Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study

    PubMed Central

    2014-01-01

    Introduction Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome. Methods In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality. Results Median time to AT was 2.1 (IQR 0.8 – 6.0) hours and 3 hours (-0.1 – 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001). Conclusions A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality. PMID:24589043

  7. Efficacy and patient-reported outcomes with dose-intense temozolomide in patients with newly diagnosed pure and mixed anaplastic oligodendroglioma: a phase II multicenter study.

    PubMed

    Ahluwalia, Manmeet S; Xie, Hao; Dahiya, Saurabh; Hashemi-Sadraei, Nooshin; Schiff, David; Fisher, Paul G; Chamberlain, Marc C; Pannullo, Susan; Newton, Herbert B; Brewer, Cathy; Wood, Laura; Prayson, Richard; Elson, Paul; Peereboom, David M

    2015-03-01

    Standard initial therapy for patients with pure and mixed anaplastic oligodendrogliomas (AO/MAO) includes chemotherapy and radiation therapy. Anaplastic oligodendrogliomas with 1p/19q co-deletion are more responsive to chemotherapy. There is concern for potential long-term CNS toxicity of radiation. Hence an approach using chemotherapy initially and reserving radiation for progressive disease is attractive. This multicenter phase II trial included patients with newly diagnosed AO/MAO with central pathology review and 1p/19q assay. Temozolomide was given 150 mg/m(2) days 1-7 and 15-21, every 28 days for 8 cycles. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rate, overall survival (OS), treatment toxicity and health-related quality of life (HRQL). Data from 62 patients enrolled between December 2001 and April 2007 at seven centers were analyzed. Among patients with measurable disease, 8 % achieved complete remission, 56 % had stable disease and 36 % had progression. The median PFS and OS were 27.2 months (95 % CI 11.9-36.3) and 105.8 months (95 % CI 51.5-N/A), respectively. Both 1p loss and 1p/19q co-deletion were positive prognostic factors for PFS (p < 0.001) and OS (p < 0.001); and there was some suggestion that 1p/19q co-deletion also predicted better response to chemotherapy (p = 0.007). Grade 3/4 toxicities were mainly hematological. Significantly improved HRQL in the future uncertainty domain of the brain cancer module was seen after cycle 4 (p < 0.001). This trial achieved outcomes similar to those reported previously. Toxicities from dose-intense temozolomide were manageable. Improvement in at least one HRQL domain increased over time. This trial supports the further study of first-line temozolomide monotherapy as an alternative to radiation therapy for patients with newly diagnosed AO/MAO with 1p 19q co-deleted tumors.

  8. Cell Cycle Regulation and Melanoma.

    PubMed

    Xu, Wen; McArthur, Grant

    2016-06-01

    Dysregulation of cell cycle control is a hallmark of melanomagenesis. Agents targeting the G1-S and G2-M checkpoints, as well as direct anti-mitotic agents, have all shown promising preclinical activity in melanoma. However, in vivo, standalone single agents targeting cell cycle regulation have only demonstrated modest efficacy in unselected patients. The advent of specific CDK 4/6 inhibitors targeting the G1-S transition, with an improved therapeutic index, is a significant step forward. Potential synergy exists with the combination of CDK4/6 inhibitors with existing therapies targeting the MAPK pathway, particularly in subsets of metastatic melanomas such as NRAS and BRAF mutants. This reviews summaries of the latest developments in both preclinical and clinical data with cell cycle-targeted therapies in melanoma. PMID:27106898

  9. RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

    SciTech Connect

    Chinnaiyan, Prakash; Won, Minhee; Wen, Patrick Y.; Wendland, Merideth; Dipetrillo, Thomas A.; Corn, Benjamin W.; Mehta, Minesh P.

    2013-08-01

    Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established daily dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.

  10. Solar Cycle 25: Another Moderate Cycle?

    NASA Astrophysics Data System (ADS)

    Cameron, R. H.; Jiang, J.; Schüssler, M.

    2016-06-01

    Surface flux transport simulations for the descending phase of Cycle 24 using random sources (emerging bipolar magnetic regions) with empirically determined scatter of their properties provide a prediction of the axial dipole moment during the upcoming activity minimum together with a realistic uncertainty range. The expectation value for the dipole moment around 2020 (2.5 ± 1.1 G) is comparable to that observed at the end of Cycle 23 (about 2 G). The empirical correlation between the dipole moment during solar minimum and the strength of the subsequent cycle thus suggests that Cycle 25 will be of moderate amplitude, not much higher than that of the current cycle. However, the intrinsic uncertainty of such predictions resulting from the random scatter of the source properties is considerable and fundamentally limits the reliability with which such predictions can be made before activity minimum is reached.

  11. Risk factors for mortality in patients with Stenotrophomonas maltophilia bacteremia

    PubMed Central

    Jeon, Yong Duk; Jeong, Woo Yong; Kim, Moo Hyun; Jung, In Young; Ahn, Mi Young; Ann, Hea Won; Ahn, Jin Young; Han, Sang Hoon; Choi, Jun Yong; Song, Young Goo; Kim, June Myung; Ku, Nam Su

    2016-01-01

    Abstract Stenotrophomonas maltophilia is a nosocomial pathogen associated with high morbidity and mortality, particularly in immunocompromised or critically ill patients. In this study, we investigated the risk factors for mortality in patients with S. maltophilia bacteremia. Retrospectively, medical records from all patients with S. maltophilia bacteremia between December 2005 and 2014 at Severance Hospital, a 2000-bed tertiary care hospital in Seoul, Korea, were reviewed. Analysis was performed to identify factors associated with 28-day mortality. In total, 142 bacteremia patients were enrolled in this study. The overall 28-day mortality rate was 36.6%. Based on the univariate analysis, hematologic malignancy (P = 0.015), Sepsis-related Organ Failure Assessment (SOFA) score (P < 0.001) and the removal of a central venous catheter (CVC) (P = 0.040) were significantly related to mortality. In the intensive care unit patients, the Acute Physiology and Chronic Health Evaluation II score (P = 0.001) also had significance. Based on the multivariate analysis, the SOFA score (odds ratio [OR] = 1.323; 95% confidence interval [CI]: 1.159, 1.509; P < 0.001) and removal of the CVC (OR = 0.330; 95% CI: 0.109, 0.996; P = 0.049) were independent factors associated with mortality. Our results suggest that removing a CVC may considerably reduce mortality in patients with S. maltophilia bacteremia. PMID:27495046

  12. High-Level Expression of Toll-Like Receptors on Dendritic Cells in Adult Patients with Burns on ≥90% of Total Body Surface Area (TBSA)

    PubMed Central

    Zhang, Xu; Li, Na; Meng, Yan; Zhang, Renjing; Bian, Jinjun; Yao, Ying; Li, Jinbao; Deng, Xiaoming

    2016-01-01

    Background As a serious clinical problem, severe burn injury disturbs the immune system, resulting in progressive suppression of immune response. TLRs are associated with immune system activation, but the effect of TLRs levels on circulating cDCs of severe burn injury patients has not been fully assessed. Material/Methods Ten patients with total body surface area (TBSA) burned >90% admitted to our institution were enrolled in this study. We analyzed TLR2, TLR4, and TLR9 expression on the circulating cDCs by using multicolor flow cytometric analysis in patients at 14 days to 28 days after burn injury according to mortality, and We also assessed Demographics, clinical outcomes, organ function, and inflammatory and acute-phase responses. Results No difference in TBSA, sex, age, or number of operations before the first 14 days after injury were observed between surviving and non-surviving burn patients. The levels of TLR2, TLR4, and TLR9 in circulating cDCs were significantly and consistently elevated in all patients compared to age-matched healthy volunteers, and survivors exhibited higher TLR2 and TLR4 values than non-survivors. Of the survivors, TLR2 and TLR4 levels were higher at 28 days than at 14 days after injury, while the difference in TLR9 levels was not significant. TLR2 levels of non-survivors at 28 days after injury decreased, and the TLR4 and TLR9 levels showed no significant difference. Conclusions TLRs levels in circulating cDCs are highly activated in severe burn injury patients up to 28 days after injury. The low expression of TLR2 in cDCs may be useful as a potential marker predicting the poor prognosis of severe burn patients. PMID:27686145

  13. Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach.

    PubMed

    Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

    2016-01-01

    Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID:26847922

  14. Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach

    PubMed Central

    Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

    2016-01-01

    Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID:26847922

  15. Risk Factors for Mortality in Patients with Serratia marcescens Bacteremia

    PubMed Central

    Kim, Sun Bean; Jeon, Yong Duk; Kim, Jung Ho; Kim, Jae Kyoung; Ann, Hea Won; Choi, Heun; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Jeong, Su Jin; Han, Sang Hoon; Choi, Jun Yong; Song, Young Goo; Kim, June Myung

    2015-01-01

    Purpose Over the last 30 years, Serratia marcescens (S. marcescens) has emerged as an important pathogen, and a common cause of nosocomial infections. The aim of this study was to identify risk factors associated with mortality in patients with S. marcescens bacteremia. Materials and Methods We performed a retrospective cohort study of 98 patients who had one or more blood cultures positive for S. marcescens between January 2006 and December 2012 in a tertiary care hospital in Seoul, South Korea. Multiple risk factors were compared with association with 28-day all-cause mortality. Results The 28-day mortality was 22.4% (22/98 episodes). In a univariate analysis, the onset of bacteremia during the intensive care unit stay (p=0.020), serum albumin level (p=0.011), serum C-reactive protein level (p=0.041), presence of indwelling urinary catheter (p=0.023), and Sequential Oran Failure Assessment (SOFA) score at the onset of bacteremia (p<0.001) were significantly different between patients in the fatal and non-fatal groups. In a multivariate analysis, lower serum albumin level and an elevated SOFA score were independently associated with 28-day mortality [adjusted odds ratio (OR) 0.206, 95% confidential interval (CI) 0.044-0.960, p=0.040, and adjusted OR 1.474, 95% CI 1.200-1.810, p<0.001, respectively]. Conclusion Lower serum albumin level and an elevated SOFA score were significantly associated with adverse outcomes in patients with S. marcescens bacteremia. PMID:25683980

  16. Phase I Trial of Hypofractionated Intensity-Modulated Radiotherapy With Temozolomide Chemotherapy for Patients With Newly Diagnosed Glioblastoma Multiforme

    SciTech Connect

    Chen Changhu; Damek, Denise; Gaspar, Laurie E.; Waziri, Allen; Lillehei, Kevin; Kleinschmidt-DeMasters, B.K.; Robischon, Monica; Stuhr, Kelly; Rusthoven, Kyle E.; Kavanagh, Brian D.

    2011-11-15

    Purpose: To determine the maximal tolerated biologic dose intensification of radiotherapy using fractional dose escalation with temozolomide (TMZ) chemotherapy in patients with newly diagnosed glioblastoma multiforme. Methods and Materials: Patients with newly diagnosed glioblastoma multiforme after biopsy or resection and with adequate performance status, bone marrow, and organ function were eligible. The patients underwent postoperative intensity-modulated radiotherapy (IMRT) with concurrent and adjuvant TMZ. All patients received a total dose of 60 Gy to the surgical cavity and residual tumor, with a 5-mm margin. IMRT biologic dose intensification was achieved by escalating from 3 Gy/fraction (Level 1) to 6 Gy/fraction (Level 4) in 1-Gy increments. Concurrent TMZ was given at 75 mg/m{sup 2}/d for 28 consecutive days. Adjuvant TMZ was given at 150-200 mg/m{sup 2}/d for 5 days every 28 days. Dose-limiting toxicity was defined as any Common Terminology Criteria for Adverse Events, version 3, Grade 3-4 nonhematologic toxicity, excluding Grade 3 fatigue, nausea, and vomiting. A standard 3+3 Phase I design was used. Results: A total of 16 patients were accrued (12 men and 4 women, median age, 69 years; range, 34-84. The median Karnofsky performance status was 80 (range, 60-90). Of the 16 patients, 3 each were treated at Levels 1 and 2, 4 at Level 3, and 6 at Level 4. All patients received IMRT and concurrent TMZ according to the protocol, except for 1 patient, who received 14 days of concurrent TMZ. The median number of adjuvant TMZ cycles was 7.5 (range, 0-12). The median survival was 16.2 months (range, 3-33). One patient experienced vision loss in the left eye 7 months after IMRT. Four patients underwent repeat surgery for suspected tumor recurrence 6-12 months after IMRT; 3 had radionecrosis. Conclusions: The maximal tolerated IMRT fraction size was not reached in our study. Our results have shown that 60 Gy IMRT delivered in 6-Gy fractions within 2 weeks with

  17. Biologic Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Antibody Formation in Patients Treated with GM-CSF (Sargramostim) as Adjuvant Therapy of Melanoma

    PubMed Central

    Spitler, Lynn E.; Cao, Huynh; Piironen, Timo; Whiteside, Theresa L.; Weber, Robert W.; Cruickshank, Scott

    2014-01-01

    OBJECTIVES We investigated the development of binding and neutralizing antibodies to GM-CSF in patients receiving prolonged therapy with GM-CSF as adjuvant therapy of melanoma and the impact of these antibodies on biologic effects. METHODS Fifty-three patients with high-risk melanoma which had been surgically excised were treated with GM-CSF, 125 µg/m2 daily for 14 days every 28 days for 1 year following surgical resection of disease. Serum samples for antibodies to GM-CSF were measured before treatment and on Study Days 155 and 351. Blood draws for testing biologic effects were keyed to GM-CSF administration: Days 0 (before), 15 (after 14 days on GM-CSF), 29 (after 14 days off GM-CSF), 155, and 351 (after 14 days on GM-CSF in the 6th and 13th cycle of treatment). RESULTS Of 53 patients enrolled, 43 were evaluable for the development of anti-GM-CSF antibodies. Of these, 93% developed binding antibodies and 42% developed both binding and neutralizing antibodies. The increase in the white blood cell (WBC) count, percent eosinophils, or neopterin levels engendered by GM-CSF administration, was abrogated or markedly decreased in patients with neutralizing antibodies but not in patients who developed only binding antibodies. CONCLUSIONS Ninety-three percent of patients with melanoma treated with GM-CSF as adjuvant therapy develop antibodies to GM-CSF. In those with neutralizing antibodies, a diminution of the biologic effects of GM-CSF was observed. The development of neutralizing antibodies might also abrogate the potential clinical benefit of this treatment and should be considered in the design of future clinical trials. PMID:25286079

  18. Spinal loads during cycling on an ergometer.

    PubMed

    Rohlmann, Antonius; Zander, Thomas; Graichen, Friedmar; Schmidt, Hendrik; Bergmann, Georg

    2014-01-01

    Cycling on an ergometer is an effective exercise for improving fitness. However, people with back problems or previous spinal surgery are often not aware of whether cycling could be harmful for them. To date, little information exists about spinal loads during cycling. A telemeterized vertebral body replacement allows in vivo measurement of implant loads during the activities of daily living. Five patients with a severe compression fracture of a lumbar vertebral body received these implants. During one measurement session, four of the participants exercised on a bicycle ergometer at various power levels. As the power level increased, the maximum resultant force and the difference between the maximum and minimum force (force range) during each pedal revolution increased. The average maximum-force increases between the two power levels 25 and 85 W were 73, 84, 225 and 75 N for the four patients. The corresponding increases in the force range during a pedal revolution were 84, 98, 166 and 101 N. There were large variations in the measured forces between the patients and also within the same patient, especially for high power levels. In two patients, the maximum forces during high-power cycling were higher than the forces during walking measured on the same day. Therefore, the authors conclude that patients with back problems should not cycle at high power levels shortly after surgery as a precaution.

  19. Cycling To Awareness.

    ERIC Educational Resources Information Center

    Kozak, Stan

    1999-01-01

    Encourages environmental and outdoor educators to promote bicycling. In the community and the curriculum, cycling connects environmental issues, health and fitness, law and citizenship, appropriate technology, and the joy of being outdoors. Describes the Ontario Cycling Association's cycling strategy and its four components: school cycling…

  20. HIV Life Cycle

    MedlinePlus

    HIV Overview The HIV Life Cycle (Last updated 9/8/2016; last reviewed 9/8/2016) Key Points HIV gradually destroys the immune ... life cycle. What is the connection between the HIV life cycle and HIV medicines? Antiretroviral therapy (ART) ...

  1. A phase I study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors.

    PubMed

    Ngamphaiboon, Nuttapong; Dy, Grace K; Ma, Wen Wee; Zhao, Yujie; Reungwetwattana, Thanyanan; DePaolo, Dawn; Ding, Yi; Brady, William; Fetterly, Gerald; Adjei, Alex A

    2015-02-01

    Based on preclinical data demonstrating cytotoxic synergy between sorafenib and entinostat, a phase I study of this combination was conducted in patients with advanced solid tumors. Enrollment followed the traditional "3 + 3" dose escalation scheme. Entinostat was given orally once every 2 weeks, starting at a dose of 4 mg and escalating to 6 and 10 mg every 2 weeks. Sorafenib was administered as a continuous oral dose, escalating from 200 to 400 mg twice daily. A treatment cycle was 28 days. A total of 31 patients with advanced solid tumors were enrolled on the study. The three dose-limiting toxicities (DLTs) observed were grade 3 hand-foot syndrome, nausea/vomiting, and fatigue. MTD was not reached. The recommended phase II dose was defined as the full dose of the respective drugs administered individually. The most common grade 3-4 toxicities were muscle weakness (13 %), skin rash (10 %), fatigue (6 %), diarrhea (6 %), and hand-foot syndrome (3 %). One NSCLC patient achieved a partial response. Two patients (adenocarcinoma of GE junction and Hurthle cell carcinoma of the thyroid) were on the study for more than 9 months with stable disease. The combination of entinostat and sorafenib was well tolerated. Entinostat 10 mg orally once every 2 weeks in combination with sorafenib 400 mg orally twice daily, representing full single agent doses of each drug was identified as the recommended phase 2 dose (RP2D). These data support future clinical development of the combination of entinostat and sorafenib. PMID:25371323

  2. Introduction to combined cycles

    NASA Astrophysics Data System (ADS)

    Moore, M. J.

    Ideas and concepts underlying the technology of combined cycles including the scientific principles involved and the reasons these cycles are in fashion at the present time, are presented. A cycle is a steady flow process for conversion of heat energy into work, in which a working medium passes through a range of states, returning to its original state. Cycles for power production are the steam cycle, which is a closed cycle, and the gas turbine, which represents an open cycle. Combined cycle thermodynamic parameters, are discussed. The general arrangement of the plant is outlined and important features of their component parts described. The scope for future development is discussed. It is concluded that for the next few years the natural gas fired combined cycle will be the main type of plant installed for electricity generation and cogeneration. Whilst gas turbines may not increase substantially in unit size, there remains scope for further increase in firing temperature with consequent increase in cycle performance. However the larger global reserves of coal are providing an incentive to the development of plant for clean coal combustion using the inherent advantage of the combined cycle to attain high efficiencies.

  3. Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours

    PubMed Central

    Mahalingam, D; Wilding, G; Denmeade, S; Sarantopoulas, J; Cosgrove, D; Cetnar, J; Azad, N; Bruce, J; Kurman, M; Allgood, V E; Carducci, M

    2016-01-01

    Background: Mipsagargin (G-202; (8-O-(12-aminododecanoyl)-8-O-debutanoyl thapsigargin)-Asp-γ-Glu-γ-Glu-γ-GluGluOH)) is a novel thapsigargin-based targeted prodrug that is activated by PSMA-mediated cleavage of an inert masking peptide. The active moiety is an inhibitor of the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump protein that is necessary for cellular viability. We evaluated the safety of mipsagargin in patients with advanced solid tumours and established a recommended phase II dosing (RP2D) regimen. Methods: Patients with advanced solid tumours received mipsagargin by intravenous infusion on days 1, 2 and 3 of 28-day cycles and were allowed to continue participation in the absence of disease progression or unacceptable toxicity. The dosing began at 1.2 mg m−2 and was escalated using a modified Fibonacci schema to determine maximally tolerated dose (MTD) with an expansion cohort at the RP2D. Plasma was analysed for mipsagargin pharmacokinetics and response was assessed using RECIST criteria. Results: A total of 44 patients were treated at doses ranging from 1.2 to 88 mg m−2, including 28 patients in the dose escalation phase and 16 patients in an expansion cohort. One dose-limiting toxicity (DLT; Grade 3 rash) was observed in the dose escalation portion of the study. At 88 mg m−2, observations of Grade 2 infusion-related reaction (IRR, 2 patients) and Grade 2 creatinine elevation (1 patient) led to declaration of 66.8 mg m−2 as the recommended phase II dose (RP2D). Across the study, the most common treatment-related adverse events (AEs) were fatigue, rash, nausea, pyrexia and IRR. Two patients developed treatment-related Grade 3 acute renal failure that was reversible during the treatment-free portion of the cycle. To help ameliorate the IRR and creatinine elevations, a RP2D of 40 mg m−2 on day 1 and 66.8 mg m−2 on days 2 and 3 with prophylactic premedications and hydration on each

  4. Comparing the brain CT scan interpretation of emergency medicine team with radiologists' report and its impact on patients' outcome.

    PubMed

    Talebian, Mohammad-Taghi; Kavandi, Elahe; Farahmand, Shervin; Shahlafar, Neda; Arbab, Mona; Seyedhosseini-Davarani, Seyedhossein; Nejati, Amir; Bagheri-Hariri, Shahram

    2015-06-01

    Requesting non-enhanced brain CT scans for trauma and non-trauma patients in ER is very common. In this study, the impact of incorrect brain CT scan interpretations by emergency medicine team on patients' primary and secondary outcome was evaluated in the setting where neuroradiologist reports are not always available. During a 3-month period, 450 patients were enrolled and followed for 28 days. All CT scans were interpreted by the emergency medicine team, and the patients were managed accordingly. Neuroradiologists' reports were considered as gold standard, and the patients were then grouped into the agreement or disagreement group. A panel of experts further evaluated the disagreement group and placed them in clinically significant and insignificant. The agreement rate between emergency medicine team and neuroradiologists was 86.4 %. The inter-rater reliability between emergency team and neuroradiologists was substantial (kappa = 0.68) and statistically significant (p < 0.0001). Only five patients did not receive the necessary management, and among them, only one patient died, and 12 patients received unnecessary management including repeated CT scan, brain MRI, and lumbar puncture. Forty-one patients were managed clinically appropriate in spite of misinterpretation. A 28-day follow-up showed a mortality rate of 0.2 %; however, expert panel believed the death of this patient was not related to the CT scan misinterpretation. We conclude that although the disagreement rate in this study was 13.6 %, primary and secondary outcomes were not clinically jeopardized according to the expert panel idea and 28-day follow-up results.

  5. Rapidity and Modality of Imaging for Acute Low Back Pain in Elderly Patients

    PubMed Central

    Pham, Hoangmai H.; Landon, Bruce E.; Reschovsky, James D.; Wu, Beny; Schrag, Deborah

    2010-01-01

    Background Most quality metrics focus on underuse of services, leaving unclear the factors associated with potential overuse. Objective To assess associations between physician and patient characteristics, and the rapidity and modality of imaging for uncomplicated low back pain (LBP) Setting Fee-for-service Medicare Population 35,039 beneficiaries with acute LBP and treated by one of 4,567 primary care physicians (PCPs) responding to the 2000-2001 or 2004-2005 Community Tracking Study Physician Surveys. Methods We analyzed Medicare claims from 2000-2002 and 2004-2006. We modified a measure of inappropriate imaging developed by the National Committee on Quality Assurance. Without assessing appropriateness of imaging for specific cases, we characterized the rapidity (within 28 days, within 29-180 days, none within 180 days) and modality of imaging (CT/MRI, only radiograph, no imaging). We used ordered logit models to assess relationships between imaging and patient demographics, and physician/practice characteristics including exposure to financial incentives based on patient satisfaction, clinical quality, cost profiling, or productivity. Results 28.8% of 35,039 beneficiaries with LBP were imaged within 28 days, and an additional 4.6% between 28-180 days. Among imaged patients, 88.2% had a radiograph, while 11.8% had CT/MRI as their initial study. White patients received higher levels of imaging than black patients or those of other races [29.7%, 24.8%, 18.9% (p<0.001) for imaging within 28 days and 10.8%, 9.1%, 7.2% (p<0.05) for CT/MRI, respectively]. Medicaid patients received less rapid or advanced imaging than other patients. Patients had more rapid imaging and advanced imaging if their PCP worked in large practices. Compared to no incentives, clinical quality-based incentives were associated with less advanced imaging (10.5% vs. 1.4% for within 28 days, respectively, p<0.001), while incentive combinations including satisfaction measures were associated with

  6. Low cycle fatigue

    NASA Technical Reports Server (NTRS)

    Solomon, H. D. (Editor); Kaisand, L. R. (Editor); Halford, G. R. (Editor); Leis, B. N. (Editor)

    1988-01-01

    The papers contained in this volume focus on various aspects of low cycle fatigue, including cyclic deformation, crack propagation, high-temperature low cycle fatigue, microstructural defects, multiaxial and variable amplitude loading, and life prediction. Papers are presented on the low cycle fatigue of some aluminum alloys, prediction of crack growth under creep-fatigue loading conditions, high-temperature low cycle fatigue behavior and lifetime prediction of a nickel-base ODS alloy, and an integrated approach to creep-fatigue life prediction. Other topics discussed include thermal fatigue testing of coated monocrystalline superalloys, low cycle fatigue of Al-Mg-Si alloys, and the effect of superimposed stresses at high frequency on low cycle fatigue.

  7. Solar activity secular cycles

    NASA Astrophysics Data System (ADS)

    Kramynin, A. P.; Mordvinov, A. V.

    2013-12-01

    Long-term variations in solar activity secular cycles have been studied using a method for the expansion of reconstructed sunspot number series Sn( t) for 11400 years in terms of natural orthogonal functions. It has been established that three expansion components describe more than 98% of all Sn( t) variations. In this case, the contribution of the first expansion component is about 92%. The averaged form of the 88year secular cycle has been determined based on the form of the first expansion coordinate function. The quasi-periodicities modulating the secular cycle have been revealed based on the time function conjugate to the first function. The quasi-periodicities modulating the secular cycle coincide with those observed in the Sn( t) series spectrum. A change in the secular cycle form and the time variations in this form are described by the second and third expansion components, the contributions of which are about 4 and 2%, respectively. The variations in the steepness of the secular cycle branches are more pronounced in the 200-year cycle, and the secular cycle amplitude varies more evidently in the 2300-year cycle.

  8. THE RAPID CYCLING MEDICAL SYNCHROTRON RCMS.

    SciTech Connect

    PEGGS,S.; BARTON,D.; BEEBE-WANG,J.; CARDONA,J.; BRENNAN,M.; FISCHER,W.; GARDNER,C.; GASSNER,D.; ET AL

    2002-06-02

    Thirteen hadron beam therapy facilities began operation between 1990 and 2001 - 5 in Europe, 4 in North America, 3 in Japan, and 1 in South Africa [l]. Ten of them irradiate tumors with protons, 2 with Carbon- 12 ions, and 1 with both protons and Carbon-12. The facility with the highest patient throughput - a total of 6 174 patients in 11 years and as many as 150 patient treatments per day -is the Loma Linda University Medical Center, which uses a weak focusing slow cycling synchrotron to accelerate beam for delivery to passive scattering nozzles at the end of rotatable gantries [2, 3,4]. The Rapid Cycling Medical Synchrotron (RCMS) is a second generation synchrotron that, by contrast with the Loma Linda synchrotron, is strong focusing and rapid cycling, with a repetition rate of 30 Hz. Primary parameters for the RCMS are listed in Table 1.

  9. Influence of menstrual cycle phase on pulmonary function in asthmatic athletes.

    PubMed

    Stanford, Kristin I; Mickleborough, Timothy D; Ray, Shahla; Lindley, Martin R; Koceja, David M; Stager, Joel M

    2006-04-01

    The main aim of this study was to investigate whether there is a relationship between menstrual cycle phase and exercise-induced bronchoconstriction (EIB) in female athletes with mild atopic asthma. Seven eumenorrheic subjects with regular 28-day menstrual cycles were exercised to volitional exhaustion on day 5 [mid-follicular (FOL)] and day 21 [mid-luteal (LUT)] of their menstrual cycle. Pulmonary function tests were conducted pre- and post-exercise. The maximal percentage decline in post-exercise forced expiratory volume in 1 s (FEV(1)) and forced expiratory flow from 25 to 75% of forced vital capacity (FEF(25-75%)) was significantly greater (P<0.05) on day 21 (mid-LUT phase) (-17.35+/-2.32 and -26.28+/-6.04%, respectively), when salivary progesterone concentration was highest, compared to day 5 (mid-FOL phase) (-12.81+/-3.35 and -17.23+/-8.20%, respectively), when salivary progesterone concentration was lowest. The deterioration in the severity of EIB during the mid-LUT phase was accompanied by worsening asthma symptoms and increased bronchodilator use. There was a negative correlation between the percent change in pre- to post-exercise FEV(1) and salivary progesterone concentration. However, no such correlation was found between salivary estradiol and the percentage change in pre- to post-exercise FEV(1). This study has shown for the first time that menstrual cycle phase is an important determinant of the severity of EIB in female athletes with mild atopic asthma. Female asthmatic athletes may need to adjust their training and competition schedules to their menstrual cycle and to consider the potential negative effects of the LUT phase of the menstrual cycle on exercise performance.

  10. Levosimendan Versus Dobutamine in Myocardial Injury Patients with Septic Shock: A Randomized Controlled Trial

    PubMed Central

    Meng, Jian-biao; Hu, Ma-hong; Lai, Zhi-zhen; Ji, Chun-lian; Xu, Xiu-juan; Zhang, Geng; Tian, Shuyuan

    2016-01-01

    Background We aimed to investigate the effect of levosimendan on biomarkers of myocardial injury and systemic hemodynamics in patients with septic shock. Material/Methods After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 38 septic shock patients with low cardiac output (left ventricular ejective fraction), LEVF ≤45%) were randomly divided into two groups: levosimendan dobutamine. Patients in the levosimendan and dobutamine groups were maintained with intravenous infusion of levosimendan (0.2 μg/kg/minute) and dobutamine (5 μg/kg/minute) for 24 hours respectively. During treatment we monitored hemodynamics and LVEF, and measured levels of heart-type fatty acid binding protein (HFABP), troponin I (TNI), and brain natriuretic peptide(BNP). In addition, the length of mechanical ventilation, intensive care unit (ICU) stay, hospital stay, and 28-day mortality were compared between the two groups. Results The levosimendan group and the dobutamine group were well matched with respect to age (years, 55.4±1 7.5 versus 50.2±13.6) and gender (males, 68.4% versus 57.9%). Levosimendan-treated patients had higher stroke volume index (SVI), cardiac index (CI), LVEF, and left ventricular stroke work index (LVSWI), and lower extravascular lung water index (EVLWI) compared to dobutamine-treated patients (p<0.05). HFABP, TNI, and BNP in the levosimendan group were less than in the dobutamine group (p<0.05). There was no difference in the mechanical ventilation time, length of stay in ICU and hospital, and 28-day mortality between the two groups. Conclusions Compared with dobutamine, levosimendan reduces biomarkers of myocardial injury and improves systemic hemodynamics in patients with septic shock. However, it does not reduce the days on mechanical ventilation, length of stay in ICU and hospital, or 28-day mortality. PMID:27138236

  11. Incidence and management of adverse events in patients with relapsed and/or refractory multiple myeloma receiving single-agent carfilzomib.

    PubMed

    Harvey, R Donald

    2014-01-01

    Carfilzomib, a selective proteasome inhibitor approved in the USA in 2012, is a single agent for relapsed and refractory multiple myeloma. Carfilzomib is administered as a 2-10-minute infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle at a starting dose of 20 mg/m(2) for cycle 1 and a target dose of 27 mg/m(2) thereafter. In the pivotal Phase II study (PX-171-003-A1), carfilzomib 20/27 mg/m(2) provided durable responses in a heavily pretreated population with relapsed and refractory multiple myeloma (n=266), with an overall response rate of 22.9% and a median duration of response of 7.8 months. In an integrated safety analysis of four Phase II studies, common adverse events (32.7%-55.5%) included fatigue, anemia, nausea, thrombocytopenia, dyspnea, and diarrhea. Grade 3/4 adverse events were generally hematologic and included thrombocytopenia (23.4%), anemia (22.4%), and lymphopenia (18.1%). Serious adverse events included pneumonia (9.9%), acute renal failure (4.2%), pyrexia (3.4%), and congestive heart failure (3.4%). New or worsening peripheral neuropathy was infrequent (13.9% overall, 1.3% grade 3, no grade 4). This review discusses findings of the integrated safety analysis and provides practical experience from a single institution in managing treatment-related and disease-related adverse events. Individualized treatment with proactive management of side effects and complications allows patients with advanced multiple myeloma to remain on carfilzomib for extended periods.

  12. A phase I trial of the anti-KIR antibody IPH2101 and lenalidomide in patients with relapsed/refractory multiple myeloma

    PubMed Central

    Benson, Don M.; Cohen, Adam D.; Jagannath, Sundar; Munshi, Nikhil C.; Spitzer, Gary; Hofmeister, Craig C.; Efebera, Yvonne A.; Andre, Pascale; Zerbib, Robert; Caligiuri, Michael A.

    2015-01-01

    PURPOSE Natural killer (NK) cells may play an important role in the immune response to multiple myeloma (MM); however, MM cells express killer immunoglobulin-like receptor (KIR) ligands to prevent NK cell cytotoxicity. Lenalidomide can expand and activate NK cells in parallel with its direct effects against MM; however, dexamethasone may impair these favorable immunomodulatory properties. IPH2101, a first-in-class anti-inhibitory KIR antibody, has acceptable safety and tolerability in MM as a single agent. The present work sought to characterize lenalidomide and IPH2101 as a novel, steroid-sparing, dual immune therapy for MM. EXPERIMENTAL DESIGN A phase I trial enrolled 15 patients in three cohorts. Lenalidomide was administered per os at 10mg on cohort 1 and 25mg on cohorts 2 and 3 days 1–21 on a 28-day cycle with IPH2101 given intravenously on day 1 of each cycle at 0.2 mg/kg on cohort 1, 1mg/kg on cohort 2, and 2mg/kg on cohort 3. No corticosteroids were utilized. The primary endpoint was safety, secondary endpoints included clinical activity, pharmacokinetics (PK) and pharmacodynamics (PD). RESULTS The biologic endpoint of full KIR occupancy was achieved across the IPH2101 dosing interval. PD and PK of IPH2101 with lenalidomide were similar to data from a prior single agent IPH2101 trial. Five serious adverse events (SAEs) were reported. Five objective responses occurred. No autoimmunity was seen. CONCLUSIONS These findings suggest that lenalidomide in combination with anti-inhibitory KIR therapy warrants further investigation in MM as a steroid-sparing, dual immune therapy. This trial was registered at www.clinicaltrials.gov (reference: NCT01217203). PMID:25999435

  13. Measuring Cycling Effort.

    ERIC Educational Resources Information Center

    Jahnke, Thomas; Hamson, Mike

    1999-01-01

    Investigates the basic mechanics of cycling with a simple reckoning of how much effort is needed from the cyclist. The work done by the cyclist is quantified when the ride is on the flat and also when pedaling uphill. Proves that by making use of the available gears on a mountain bike, cycling uphill can be accomplished without pain. (Author/ASK)

  14. The carbon cycle revisited

    NASA Technical Reports Server (NTRS)

    Bolin, Bert; Fung, Inez

    1992-01-01

    Discussions during the Global Change Institute indicated a need to present, in some detail and as accurately as possible, our present knowledge about the carbon cycle, the uncertainties in this knowledge, and the reasons for these uncertainties. We discuss basic issues of internal consistency within the carbon cycle, and end by summarizing the key unknowns.

  15. Rock Cycle Roulette.

    ERIC Educational Resources Information Center

    Schmidt, Stan M.; Palmer, Courtney

    2000-01-01

    Introduces an activity on the rock cycle. Sets 11 stages representing the transitions of an earth material in the rock cycle. Builds six-sided die for each station, and students move to the stations depending on the rolling side of the die. Evaluates students by discussing several questions in the classroom. Provides instructional information for…

  16. Teaching the Krebs Cycle.

    ERIC Educational Resources Information Center

    Akeroyd, F. Michael

    1983-01-01

    Outlines a simple but rigorous treatment of the Krebs Cycle suitable for A-level Biology students. The importance of the addition of water molecules in various stages of the cycle is stressed as well as the removal of hydrogen atoms by the oxidizing enzymes. (JN)

  17. The Oxygen Cycle.

    ERIC Educational Resources Information Center

    Swant, Gary D.

    Produced for primary grades, this booklet provides study of the oxygen-carbon dioxide cycle in nature. Line drawings, a minimum amount of narrative, and a glossary of terms make up its content. The booklet is designed to be used as reading material, a coloring book, or for dramatic arts with students acting out parts of the cycle. This work was…

  18. Power Plant Cycling Costs

    SciTech Connect

    Kumar, N.; Besuner, P.; Lefton, S.; Agan, D.; Hilleman, D.

    2012-07-01

    This report provides a detailed review of the most up to date data available on power plant cycling costs. The primary objective of this report is to increase awareness of power plant cycling cost, the use of these costs in renewable integration studies and to stimulate debate between policymakers, system dispatchers, plant personnel and power utilities.

  19. Seeing the Carbon Cycle

    ERIC Educational Resources Information Center

    Drouin, Pamela; Welty, David J.; Repeta, Daniel; Engle-Belknap, Cheryl A.; Cramer, Catherine; Frashure, Kim; Chen, Robert

    2006-01-01

    In this article, the authors present a classroom experiment that was developed to introduce middle school learners to the carbon cycle. The experiment deals with transfer of CO[subscript 2] between liquid reservoirs and the effect CO[subscript 2] has on algae growth. It allows students to observe the influence of the carbon cycle on algae growth,…

  20. Reusable thermal cycling clamp

    NASA Technical Reports Server (NTRS)

    Debnam, W. J., Jr.; Fripp, A. L.; Crouch, R. K. (Inventor)

    1985-01-01

    A reusable metal clamp for retaining a fused quartz ampoule during temperature cycling in the range of 20 deg C to 1000 deg C is described. A compressible graphite foil having a high radial coefficient of thermal expansion is interposed between the fused quartz ampoule and metal clamp to maintain a snug fit between these components at all temperature levels in the cycle.

  1. Predicting the Sunspot Cycle

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.

    2009-01-01

    The 11-year sunspot cycle was discovered by an amateur astronomer in 1844. Visual and photographic observations of sunspots have been made by both amateurs and professionals over the last 400 years. These observations provide key statistical information about the sunspot cycle that do allow for predictions of future activity. However, sunspots and the sunspot cycle are magnetic in nature. For the last 100 years these magnetic measurements have been acquired and used exclusively by professional astronomers to gain new information about the nature of the solar activity cycle. Recently, magnetic dynamo models have evolved to the stage where they can assimilate past data and provide predictions. With the advent of the Internet and open data policies, amateurs now have equal access to the same data used by professionals and equal opportunities to contribute (but, alas, without pay). This talk will describe some of the more useful prediction techniques and reveal what they say about the intensity of the upcoming sunspot cycle.

  2. The impact of the DoH Commissioning for Quality and Innovation incentive on the success of venous thromboembolism risk assessment in hospitalised patients. A single institution experience in a quality outcome improvement over a 4-year cycle

    PubMed Central

    Sandhu, Polly; Ali, Vernisha; Jones, Garth; Baker, Christopher

    2016-01-01

    Objectives To i) demonstrate compliance with the Commissioning for Quality and Innovation for venous thromboembolism risk assessment ii) to undertake root cause analysis of Hospital Acquired Thrombosis and to investigate its impact on quality of care. Design Prospective monitoring of all admissions. Setting Imperial College Healthcare Hospitals, London. Participants All Hospital Provider Spells as defined on the NHS Data Model and Dictionary. Main outcome measures i) Percentage of patients undergoing Venous Thromboembolism Risk Assessment (VTE-RA) at and 24-hours after admission ii) root cause analysis of Hospital Acquired Thrombosis up to 90 days following discharge. Results Over a 48-month cycle 83% were overall VTE-RA assessed with 36% in the first 12 months but with significant improvement to ≥95% between April 2013 and April 2015, achieving compliance target since April 2012 involving a massive 633, 850 Spells over the 4 year period. We undertook root cause analysis of all VTE episodes from April 2013 to March 2014, to ascertain Hospital Acquired Thrombosis (HAT), we analysed 433, 174 inpatient days and found a HAT rate of 1 per 1000 with 23% and 24% for DVTs and PEs potentially avoidable respectively. We further analysed VTE risk stratification (n = 1000) and found 37.0% at high risk, 44.4% at medium risk and 18.6 % at low risk, indicating the need of thromboprophylaxis in 81.4% (high and medium) of whom 33.6% were excluded. Conclusions We achieved 95% RA compliance which has favourably impacted on our daily practice and improved the quality of the clinical care. PMID:27293773

  3. The Chlamydomonas cell cycle.

    PubMed

    Cross, Frederick R; Umen, James G

    2015-05-01

    The position of Chlamydomonas within the eukaryotic phylogeny makes it a unique model in at least two important ways: as a representative of the critically important, early-diverging lineage leading to plants; and as a microbe retaining important features of the last eukaryotic common ancestor (LECA) that has been lost in the highly studied yeast lineages. Its cell biology has been studied for many decades and it has well-developed experimental genetic tools, both classical (Mendelian) and molecular. Unlike land plants, it is a haploid with very few gene duplicates, making it ideal for loss-of-function genetic studies. The Chlamydomonas cell cycle has a striking temporal and functional separation between cell growth and rapid cell division, probably connected to the interplay between diurnal cycles that drive photosynthetic cell growth and the cell division cycle; it also exhibits a highly choreographed interaction between the cell cycle and its centriole-basal body-flagellar cycle. Here, we review the current status of studies of the Chlamydomonas cell cycle. We begin with an overview of cell-cycle control in the well-studied yeast and animal systems, which has yielded a canonical, well-supported model. We discuss briefly what is known about similarities and differences in plant cell-cycle control, compared with this model. We next review the cytology and cell biology of the multiple-fission cell cycle of Chlamydomonas. Lastly, we review recent genetic approaches and insights into Chlamydomonas cell-cycle regulation that have been enabled by a new generation of genomics-based tools.

  4. Cycles, Cycles Everywhere - Corals, Coccoliths, and Climate

    NASA Astrophysics Data System (ADS)

    Ridgwell, A.

    2004-05-01

    Critical to our understanding of both past and future climate change is the biogeochemcial cycle of carbon on Earth. This is popularly recognized in the context of the creation and destruction of solid organic matter such as vegetation and fossil fuels, which has a clear and intuitive relationship to the amount of carbon dioxide in the atmosphere. Less widely recognized is the cycling which involves solid inorganic carbon as carbonate minerals - the most abundant form of carbon present at or near the surface of the Earth, and one with a distinctly counter-intuitive relationship with atmospheric CO2. For instance, changes in the rate of production of coral skeletons may have played a role in Holocene climate change, but with increased carbonate carbon removal driving atmospheric CO2 higher and not lower. The carbonate skeletons produced by some species of plankton in the open ocean are also critical to the climate system. The sinking of these skeletal parts is currently suspected to be important in helping to transport organic matter to depth and thus temporarily isolating this carbon from the atmosphere. The deposition of plankton-derived carbonate to the sediments of the deep-sea also helps regulate atmospheric CO2 but on thousand year time-scales, and will play a key role in the eventual removal of fossil fuel carbon from the atmosphere. However, there is a growing awareness that carbonate production by plankton may be severely diminished in the future. Maybe the cycle of carbonate on Earth could be re-set to how it operated over two hundred million years ago. Here I review some of the current areas of interest in global carbonate cycling, particularly its relationship to climate change and to fundamental moments in the evolution of life.

  5. Mining the Learning Cycle.

    ERIC Educational Resources Information Center

    Hemler, Debra; King, Hobart

    1996-01-01

    Describes an approach that uses the learning cycle to meaningfully teach students about mineral properties while alleviating the tedious nature of identifying mineral specimens. Discusses mineral properties, cooperative learning, and mineral identification. (JRH)

  6. The Rock Cycle

    ERIC Educational Resources Information Center

    Singh, Raman J.; Bushee, Jonathan

    1977-01-01

    Presents a rock cycle diagram suitable for use at the secondary or introductory college levels which separates rocks formed on and below the surface, includes organic materials, and separates products from processes. (SL)

  7. Cycle isolation monitoring

    SciTech Connect

    Svensen, L.M. III; Zeigler, J.R.; Todd, F.D.; Alder, G.C.

    2009-07-15

    There are many factors to monitor in power plants, but one that is frequently overlooked is cycle isolation. Often this is an area where plant personnel can find 'low hanging fruit' with great return on investment, especially high energy valve leakage. This type of leakage leads to increased heat rate, potential valve damage and lost generation. The fundamental question to ask is 'What is 100 Btu/kW-hr of heat rate worth to your plant? On a 600 MW coal-fired power plant, a 1% leakage can lead to an 81 Btu/kW-hr impact on the main steam cycle and a 64 Btu/kW-hr impact on the hot reheat cycle. The article gives advice on methods to assist in detecting leaking valves and to monitor cycle isolation. A software product, TP. Plus-CIM was designed to estimate flow rates of potentially leaking valves.

  8. [Cycle ergometers in rehabilitation medicine: technical characteristics and selection criteria].

    PubMed

    Capodaglio, P; Sartorio, F; Colombo, R; Franchignoni, F

    2007-01-01

    The cycle ergometer is a commonly used means of testing and training patients with energetic disabilities (particularly in the area of cardiopulmonary diseases). Recent evidence suggests that cycle ergometers can also be useful in patients with subacute and chronic stroke, brain injury, chronic degenerative neurological conditions, and in spinal cord injury. Commercially available cycle ergometers show wide differences in terms of structure and function that have a direct impact on the specific rehabilitation protocols. The aims of this review paper are: a) to briefly review the physiology and biomechanics of exercise on a cycle ergometer; b) to review and discuss the technical specifications of the cycle ergometers suited to rehabilitation settings; c) to provide guidelines for selecting appropriate cycle ergometers for the different categories of rehabilitation patients. First, the physiology of exercise on the cycle ergometer and its biomechanical features are discussed, including the patterns of muscular activity during down- and up-stroke. Upright and recumbent ergometers and their specific clinical indications are compared. Finally, the technical characteristics of the cycle ergometers (load, motor, resistance, flywheel, belt, resilience, pedals, frame, display) are described and the specific requisites for the different patient categories undergoing rehabilitation are discussed in detail. Finally, guidelines are offered for identifying the main technical requisites for appropriate cycle ergometer selection in the different disabilities. PMID:18409268

  9. Synthetic battery cycling techniques

    NASA Technical Reports Server (NTRS)

    Leibecki, H.; Thaller, L. H.

    1982-01-01

    The group of techniques that as a class are referred to as synthetic battery cycling are described with reference to spacecraft battery systems. Synthetic battery cycling makes use of the capability of computer graphics to illustrate some of the basic characteristics of operation of individual electrodes within an operating electrochemical cell. It can also simulate the operation of an entire string of cells that are used as the energy storage subsystem of a power system.

  10. IFR fuel cycle

    SciTech Connect

    Battles, J.E.; Miller, W.E.; Lineberry, M.J.; Phipps, R.D.

    1992-04-01

    The next major milestone of the IFR program is engineering-scale demonstration of the pyroprocess fuel cycle. The EBR-II Fuel Cycle Facility has just entered a startup phase, which includes completion of facility modifications and installation and cold checkout of process equipment. This paper reviews the development of the electrorefining pyroprocess, the design and construction of the facility for the hot demonstration, the design and fabrication of the equipment, and the schedule and initial plan for its operation.

  11. IFR fuel cycle

    SciTech Connect

    Battles, J.E.; Miller, W.E. ); Lineberry, M.J.; Phipps, R.D. )

    1992-01-01

    The next major milestone of the IFR program is engineering-scale demonstration of the pyroprocess fuel cycle. The EBR-II Fuel Cycle Facility has just entered a startup phase, which includes completion of facility modifications and installation and cold checkout of process equipment. This paper reviews the development of the electrorefining pyroprocess, the design and construction of the facility for the hot demonstration, the design and fabrication of the equipment, and the schedule and initial plan for its operation.

  12. Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma

    PubMed Central

    Butowski, Nicholas; Chang, Susan M.; Lamborn, Kathleen R.; Polley, Mei–Yin; Pieper, Russell; Costello, Joseph F.; Vandenberg, Scott; Parvataneni, Rupa; Nicole, Angelina; Sneed, Patricia K.; Clarke, Jennifer; Hsieh, Emily; Costa, Bruno M.; Reis, Rui M.; Hristova-Kazmierski, Maria; Nicol, Steven J.; Thornton, Donald E.; Prados, Michael D.

    2011-01-01

    This open-label, single-arm, phase II study combined enzastaurin with temozolomide plus radiation therapy (RT) to treat glioblastoma multiforme (GBM) and gliosarcoma. Adults with newly diagnosed disease and Karnofsky performance status (KPS) ≥ 60 were enrolled. Treatment was started within 5 weeks after surgical diagnosis. RT consisted of 60 Gy over 6 weeks. Temozolomide was given at 75 mg/m2 daily during RT and then adjuvantly at 200 mg/m2 daily for 5 days, followed by a 23-day break. Enzastaurin was given once daily during RT and in the adjuvant period at 250 mg/day. Cycles were 28 days. The primary end point was overall survival (OS). Progression-free survival (PFS), toxicity, and correlations between efficacy and molecular markers analyzed from tumor tissue samples were also evaluated. A prospectively planned analysis compared OS and PFS of the current trial with outcomes from 3 historical phase II trials that combined novel agents with temozolomide plus RT in patients with GBM or gliosarcoma. Sixty-six patients were enrolled. The treatment regimen was well tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the current trial were comparable to those from a prior phase II study using erlotininb and were significantly better than those from 2 other previous studies that used thalidomide or cis-retinoic acid, all in combination with temozolomide plus RT. A positive correlation between O-6-methylguanine-DNA methyltransferase promoter methylation and OS was observed. Adjusting for age and KPS, no other biomarker was associated with survival outcome. Correlation of relevant biomarkers with OS may be useful in future trials. PMID:21896554

  13. Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma.

    PubMed

    Butowski, Nicholas; Chang, Susan M; Lamborn, Kathleen R; Polley, Mei-Yin; Pieper, Russell; Costello, Joseph F; Vandenberg, Scott; Parvataneni, Rupa; Nicole, Angelina; Sneed, Patricia K; Clarke, Jennifer; Hsieh, Emily; Costa, Bruno M; Reis, Rui M; Hristova-Kazmierski, Maria; Nicol, Steven J; Thornton, Donald E; Prados, Michael D

    2011-12-01

    This open-label, single-arm, phase II study combined enzastaurin with temozolomide plus radiation therapy (RT) to treat glioblastoma multiforme (GBM) and gliosarcoma. Adults with newly diagnosed disease and Karnofsky performance status (KPS) ≥ 60 were enrolled. Treatment was started within 5 weeks after surgical diagnosis. RT consisted of 60 Gy over 6 weeks. Temozolomide was given at 75 mg/m(2) daily during RT and then adjuvantly at 200 mg/m(2) daily for 5 days, followed by a 23-day break. Enzastaurin was given once daily during RT and in the adjuvant period at 250 mg/day. Cycles were 28 days. The primary end point was overall survival (OS). Progression-free survival (PFS), toxicity, and correlations between efficacy and molecular markers analyzed from tumor tissue samples were also evaluated. A prospectively planned analysis compared OS and PFS of the current trial with outcomes from 3 historical phase II trials that combined novel agents with temozolomide plus RT in patients with GBM or gliosarcoma. Sixty-six patients were enrolled. The treatment regimen was well tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the current trial were comparable to those from a prior phase II study using erlotinib and were significantly better than those from 2 other previous studies that used thalidomide or cis-retinoic acid, all in combination with temozolomide plus RT. A positive correlation between O-6-methylguanine-DNA methyltransferase promoter methylation and OS was observed. Adjusting for age and KPS, no other biomarker was associated with survival outcome. Correlation of relevant biomarkers with OS may be useful in future trials.

  14. Quantifying the Adaptive Cycle.

    PubMed

    Angeler, David G; Allen, Craig R; Garmestani, Ahjond S; Gunderson, Lance H; Hjerne, Olle; Winder, Monika

    2015-01-01

    The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994-2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems. PMID:26716453

  15. Solar Cycle Predictions

    NASA Technical Reports Server (NTRS)

    Pesnell, William Dean

    2012-01-01

    Solar cycle predictions are needed to plan long-term space missions; just like weather predictions are needed to plan the launch. Fleets of satellites circle the Earth collecting many types of science data, protecting astronauts, and relaying information. All of these satellites are sensitive at some level to solar cycle effects. Predictions of drag on LEO spacecraft are one of the most important. Launching a satellite with less propellant can mean a higher orbit, but unanticipated solar activity and increased drag can make that a Pyrrhic victory as you consume the reduced propellant load more rapidly. Energetic events at the Sun can produce crippling radiation storms that endanger all assets in space. Solar cycle predictions also anticipate the shortwave emissions that cause degradation of solar panels. Testing solar dynamo theories by quantitative predictions of what will happen in 5-20 years is the next arena for solar cycle predictions. A summary and analysis of 75 predictions of the amplitude of the upcoming Solar Cycle 24 is presented. The current state of solar cycle predictions and some anticipations how those predictions could be made more accurate in the future will be discussed.

  16. Quantifying the adaptive cycle

    USGS Publications Warehouse

    Angeler, David G.; Allen, Craig R.; Garmestani, Ahjond S.; Gunderson, Lance H.; Hjerne, Olle; Winder, Monika

    2015-01-01

    The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994–2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems.

  17. Quantifying the Adaptive Cycle

    PubMed Central

    Angeler, David G.; Allen, Craig R.; Garmestani, Ahjond S.; Gunderson, Lance H.; Hjerne, Olle; Winder, Monika

    2015-01-01

    The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994–2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems. PMID:26716453

  18. Inter-individual variance and cardiac cycle dependency of aortic root dimensions and shape as assessed by ECG-gated multi-slice computed tomography in patients with severe aortic stenosis prior to transcatheter aortic valve implantation: is it crucial for correct sizing?

    PubMed

    Lehmkuhl, Lukas; Foldyna, Borek; Von Aspern, Konstantin; Lücke, Christian; Grothoff, Matthias; Nitzsche, Stefan; Kempfert, Jörg; Haensig, Martin; Rastan, Ardawan; Walther, Thomas; Mohr, Friedrich-Wilhelm; Gutberlet, Matthias

    2013-03-01

    To evaluate the inter-individual variance and the variability of the aortic root dimensions during the cardiac cycle by computed tomography (CT) in patients with severe aortic stenosis prior to transcatheter aortic valve implantation (TAVI). Fifty-six patients (m/w = 16/40, 81 ± 6.8 years), scheduled for a transapical aortic valve implantation with available preprocedural ECG-gated CT were retrospectively included. The evaluation included sizing of the aortic annulus and the aortic sinus, measurements of the coronary topography, aortic valve planimetry and scoring of calcification. The new defined aortic annulus sphericity ratio revealed a mostly elliptical shape with increasing diastolic deformation. The calculated effective diameter (ED), determined from the annulus' lumen area, turned out to be the parameter least affected from cardiac cycle changes while systolic and diastolic annulus dimensions and shape (diameter and area) differed significantly (p < 0.001). In about 70 % of the patients with relevant paravalvular leaks the finally implanted prosthesis was too small according to the CT based calculated ED. The ostial height of the coronaries showed a high variability with a critical minimum range <5 mm. The degree of the aortic calcification did not have an influence on the aortic annulus deformation during the cardiac cycle, but on the occurrence of paravalvular leaks. The aortic root anatomy demonstrated a high inter-individual variability and cardiac cycle dependency. These results must be strongly considered during the patient evaluation prior to TAVI to avoid complications. The systolic effective diameter, as measured by ECG-gated CT, represents an appropriate parameter for sizing the aortic annulus.

  19. The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models.

    PubMed

    Garcia, P L; Miller, A L; Kreitzburg, K M; Council, L N; Gamblin, T L; Christein, J D; Heslin, M J; Arnoletti, J P; Richardson, J H; Chen, D; Hanna, C A; Cramer, S L; Yang, E S; Qi, J; Bradner, J E; Yoon, K J

    2016-02-18

    The primary aim of this study was to evaluate the antitumor efficacy of the bromodomain inhibitor JQ1 in pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (tumorgraft) models. A secondary aim of the study was to evaluate whether JQ1 decreases expression of the oncogene c-Myc in PDAC tumors, as has been reported for other tumor types. We used five PDAC tumorgraft models that retain specific characteristics of tumors of origin to evaluate the antitumor efficacy of JQ1. Tumor-bearing mice were treated with JQ1 (50 mg/kg daily for 21 or 28 days). Expression analyses were performed with tumors harvested from host mice after treatment with JQ1 or vehicle control. An nCounter PanCancer Pathways Panel (NanoString Technologies) of 230 cancer-related genes was used to identify gene products affected by JQ1. Quantitative RT-PCR, immunohistochemistry and immunoblots were carried out to confirm that changes in RNA expression reflected changes in protein expression. JQ1 inhibited the growth of all five tumorgraft models (P<0.05), each of which harbors a KRAS mutation; but induced no consistent change in expression of c-Myc protein. Expression profiling identified CDC25B, a regulator of cell cycle progression, as one of the three RNA species (TIMP3, LMO2 and CDC25B) downregulated by JQ1 (P<0.05). Inhibition of tumor progression was more closely related to decreased expression of nuclear CDC25B than to changes in c-Myc expression. JQ1 and other agents that inhibit the function of proteins with bromodomains merit further investigation for treating PDAC tumors. Work is ongoing in our laboratory to identify effective drug combinations that include JQ1.

  20. Variation of fluorescence spectroscopy during the menstrual cycle

    NASA Astrophysics Data System (ADS)

    Macaulay, Calum; Richards-Kortum, Rebecca; Utzinger, Urs; Fedyk, Amanda; Neely Atkinson, E.; Cox, Dennis; Follen, Michele

    2002-06-01

    Cervical autofluorescence has been demonstrated to have potential for real-time diagnosis. Inter-patient and intra-patient variations in fluorescence intensity have been measured. Inter-patient measurements may vary by a factor of ten, while intra-patient measurements may vary by a factor of two. Age and menopausal status have been demonstrated to account for some of the variations, while race and smoking have not. In order to explore in detail the role of the menstrual cycle in intra-patient variation, a study was designed to measure fluorescence excitation emission matrices (EEMs) in patients daily throughout one cycle. Ten patients with a history of normal menstrual cycles and normal Papanicolaou smears underwent daily measurements of fluorescence EEMs from three colposcopically normal sites throughout one menstrual cycle. Changes in signals from porphyrin, NADH, and FAD fluorescence and blood absorption were noted when the data was viewed in a graphical format. Visually interpreted features of the EEMs in this graphical format did not appear to correlate with the day of the menstrual cycle with the exception that blood absorption features were more prominent during the menstrual phase (during which bleeding occurs), suggesting that measurements during the menstrual phase should be avoided. Variations in cycle date likely do not account for inter- or intra-patient variations.

  1. Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD

    PubMed Central

    Corti, Caspar; Fally, Markus; Fabricius-Bjerre, Andreas; Mortensen, Katrine; Jensen, Birgitte Nybo; Andreassen, Helle F; Porsbjerg, Celeste; Knudsen, Jenny Dahl; Jensen, Jens-Ulrik

    2016-01-01

    Background This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD (AECOPD). Methods One-hundred and twenty adult patients admitted with AECOPD were enrolled in this open-label randomized trial. Patients were allocated to either the POC PCT-guided intervention arm (n=62) or the control arm, in which antibiotic therapy followed local guidelines (n=58). Results The median duration of antibiotic exposure was 3.5 (interquartile range [IQR] 0–10) days in the PCT-arm vs 8.5 (IQR 1–11) days in the control arm (P=0.0169, Wilcoxon) for the intention-to-treat population. The proportion of patients using antibiotics for ≥5 days within the 28-day follow-up was 41.9% (PCT-arm) vs 67.2% (P=0.006, Fisher’s exact) in the intention-to-treat population. For the per-protocol population, the proportions were 21.1% (PCT-arm) vs 73.9% (P<0.00001, Fisher’s exact). Within 28-day follow-up, one patient died in the PCT-arm and two died in the control arm. A composite harm end point consisting of death, rehospitalization, or intensive care unit admission, all within 28 days, showed no apparent difference. Conclusion Our study shows that the implementation of a POC PCT-guided algorithm can be used to substantially reduce antibiotic exposure in patients hospitalized with AECOPD, with no apparent harm. PMID:27382274

  2. Kalina cycle application to gas turbine combined cycles

    SciTech Connect

    Bjorge, R.W.; Corman, J.C.; Smith, R.W.

    1995-12-31

    Gas turbine-based combined cycles have gained broad market acceptance due to their favorable economics, high efficiency and excellent environmental performance. Combined-cycle performance improvements have tracked the rapid advance of gas turbine technology. The introduction of the steam-cooled STAG 107H and 109H combined-cycle systems with their 60% net plant efficiency capability is the latest step in this trend. High-efficiency steam bottoming cycles have also advanced, with the current state-of-the-art being the three-pressure reheat cycle. The Kalina Cycle utilizing a mixture of ammonia and water as the working fluid promises to further continue these combined cycle-performance improvements with dramatic changes in the bottoming cycle. These improvements are due to non-isothermal heat acquisition and heat rejection, as well as internal heat recuperation, which reduce losses of thermodynamic availability, or exergy, in the cycle. This paper discusses the application of the Kalina Cycle to gas turbine-based combined cycles, including system design and performance characteristics. It compares Kalina Cycle performance and economics with that of a state-of-the-art steam bottoming cycle, showing the potential economic advantages of this innovative cycle in combined-cycle applications. Several variants of the Kalina Cycle system and the Distillation Condensation Subsystem (DCSS), which replaces the condenser as the heat rejection and recuperation system of the Kalina Cycle, have been studied. Results show that the Kalina Cycle can enhance the gas turbine bottoming cycle power output by over 15% when compared with a three-pressure reheat Rankine bottoming cycle. This yields an efficiency improvement of 2-3 percentage points, a significant advance in the state-of-the-art. Based on these substantial performance gains, GE is pursuing the commercialization of the Kalina Cycle for combined-cycle applications under a worldwide exclusive license from Exergy, Inc.

  3. Modifying the luteal phase support in natural cycle frozen-thawed embryo transfer improves cycle outcome.

    PubMed

    Haas, Jigal; Lantsberg, Daniel; Feldman, Noa; Manela, Daphna; Machtinger, Ronit; Dar, Shir; Rabinovici, Jaron; Orvieto, Raoul

    2015-01-01

    With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250 mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer and 4 d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive β-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation. PMID:26288149

  4. The adductor pollicis muscle: a poor predictor of clinical outcome in ICU patients.

    PubMed

    Leong Shu-Fen, Claudia; Ong, Venetia; Kowitlawakul, Yanika; Ling, Teh Ai; Mukhopadhyay, Amartya; Henry, Jeya

    2015-01-01

    No nutrition assessment tools specifically tailored for intensive care unit (ICU) patients have been developed and validated in Singapore. Studies conducted in Brazilian populations suggest that the thickness of the adductor pollicis muscle (TAPM) may be used to assess nutritional status and predict mortality of critically ill patients. The aim of this study was to determine if TAPM can be used as a predictive indicator of mortality in Singapore ICU patients. TAPM values were obtained using skinfold calipers in 229 patients admitted to the medical ICU. TAPM measured in both hands showed no significant correlation with either the primary outcome (28-day mortality) or secondary outcomes (hospital outcome and hospital length of stay). This study demonstrated that TAPM does not predict 28-day mortality and hospital outcome, and is not correlated to length of stay in Singapore ICU patients. More studies are necessary to validate the use of TAPM as an anthropometric indicator of ICU outcome in other regions of the world. PMID:26693744

  5. Helium process cycle

    SciTech Connect

    Ganni, Venkatarao

    2007-10-09

    A unique process cycle and apparatus design separates the consumer (cryogenic) load return flow from most of the recycle return flow of a refrigerator and/or liquefier process cycle. The refrigerator and/or liquefier process recycle return flow is recompressed by a multi-stage compressor set and the consumer load return flow is recompressed by an independent consumer load compressor set that maintains a desirable constant suction pressure using a consumer load bypass control valve and the consumer load return pressure control valve that controls the consumer load compressor's suction pressure. The discharge pressure of this consumer load compressor is thereby allowed to float at the intermediate pressure in between the first and second stage recycle compressor sets. Utilizing the unique gas management valve regulation, the unique process cycle and apparatus design in which the consumer load return flow is separate from the recycle return flow, the pressure ratios of each recycle compressor stage and all main pressures associated with the recycle return flow are allowed to vary naturally, thus providing a naturally regulated and balanced floating pressure process cycle that maintains optimal efficiency at design and off-design process cycle capacity and conditions automatically.

  6. Helium process cycle

    SciTech Connect

    Ganni, Venkatarao

    2008-08-12

    A unique process cycle and apparatus design separates the consumer (cryogenic) load return flow from most of the recycle return flow of a refrigerator and/or liquefier process cycle. The refrigerator and/or liquefier process recycle return flow is recompressed by a multi-stage compressor set and the consumer load return flow is recompressed by an independent consumer load compressor set that maintains a desirable constant suction pressure using a consumer load bypass control valve and the consumer load return pressure control valve that controls the consumer load compressor's suction pressure. The discharge pressure of this consumer load compressor is thereby allowed to float at the intermediate pressure in between the first and second stage recycle compressor sets. Utilizing the unique gas management valve regulation, the unique process cycle and apparatus design in which the consumer load return flow is separate from the recycle return flow, the pressure ratios of each recycle compressor stage and all main pressures associated with the recycle return flow are allowed to vary naturally, thus providing a naturally regulated and balanced floating pressure process cycle that maintains optimal efficiency at design and off-design process cycle capacity and conditions automatically.

  7. Aromatase inhibitors in stimulated IVF cycles

    PubMed Central

    2011-01-01

    Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels PMID:21693033

  8. The global sulfur cycle

    NASA Technical Reports Server (NTRS)

    Sagan, D. (Editor)

    1985-01-01

    The results of the planetary biology microbial ecology's 1984 Summer Research Program, which examined various aspects of the global sulfur cycle are summarized. Ways in which sulfur flows through the many living and chemical species that inhabit the surface of the Earth were investigated. Major topics studied include: (1) sulfur cycling and metabolism of phototropic and filamentous sulfur bacteria; (2) sulfur reduction in sediments of marine and evaporite environments; (3) recent cyanobacterial mats; (4) microanalysis of community metabolism in proximity to the photic zone in potential stromatolites; and (5) formation and activity of microbial biofilms on metal sulfides and other mineral surfaces. Relationships between the global sulfur cycle and the understanding of the early evolution of the Earth and biosphere and current processes that affect global habitability are stressed.

  9. Superfluid thermodynamic cycle refrigerator

    DOEpatents

    Swift, Gregory W.; Kotsubo, Vincent Y.

    1992-01-01

    A cryogenic refrigerator cools a heat source by cyclically concentrating and diluting the amount of .sup.3 He in a single phase .sup.3 He-.sup.4 He solution. The .sup.3 He in superfluid .sup.4 He acts in a manner of an ideal gas in a vacuum. Thus, refrigeration is obtained using any conventional thermal cycle, but preferably a Stirling or Carnot cycle. A single phase solution of liquid .sup.3 He at an initial concentration in superfluid .sup.4 He is contained in a first variable volume connected to a second variable volume through a superleak device that enables free passage of .sup.4 He while restricting passage of .sup.3 He. The .sup.3 He is compressed (concentrated) and expanded (diluted) in a phased manner to carry out the selected thermal cycle to remove heat from the heat load for cooling below 1 K.

  10. Superfluid thermodynamic cycle refrigerator

    DOEpatents

    Swift, G.W.; Kotsubo, V.Y.

    1992-12-22

    A cryogenic refrigerator cools a heat source by cyclically concentrating and diluting the amount of [sup 3]He in a single phase [sup 3]He-[sup 4]He solution. The [sup 3]He in superfluid [sup 4]He acts in a manner of an ideal gas in a vacuum. Thus, refrigeration is obtained using any conventional thermal cycle, but preferably a Stirling or Carnot cycle. A single phase solution of liquid [sup 3]He at an initial concentration in superfluid [sup 4]He is contained in a first variable volume connected to a second variable volume through a superleak device that enables free passage of [sup 4]He while restricting passage of [sup 3]He. The [sup 3]He is compressed (concentrated) and expanded (diluted) in a phased manner to carry out the selected thermal cycle to remove heat from the heat load for cooling below 1 K. 12 figs.

  11. Nonhepatic hyperammonemic encephalopathy due to undiagnosed urea cycle disorder

    PubMed Central

    Nugent, Kenneth

    2015-01-01

    Ornithine transcarbamoylase deficiency is the most common inherited urea cycle disorder. In adults, its phenotypes are diverse. In asymptomatic patients with late presentations, symptom onset is often associated with a precipitating factor. We present a case of a woman with urea cycle disorder diagnosed after an acute peptic ulcer bleed and fasting. PMID:26130895

  12. Cognitive-Behavioral Therapy for Rapid Cycling Bipolar Disorder

    ERIC Educational Resources Information Center

    Reilly-Harrington, Noreen A.; Knauz, Robert O.

    2005-01-01

    This article describes the application of cognitive-behavioral therapy (CBT) to the treatment of rapid cycling bipolar disorder. Between 10% and 24% of bipolar patients experience a rapid cycling course, with 4 or more mood episodes occurring per year. Characterized by nonresponse to standard mood-stabilizing medications, rapid cyclers are…

  13. Breaking a vicious cycle.

    PubMed

    Hayes, Daniel F; Allen, Jeff; Compton, Carolyn; Gustavsen, Gary; Leonard, Debra G B; McCormack, Robert; Newcomer, Lee; Pothier, Kristin; Ransohoff, David; Schilsky, Richard L; Sigal, Ellen; Taube, Sheila E; Tunis, Sean R

    2013-07-31

    Despite prodigious advances in tumor biology research, few tumor-biomarker tests have been adopted as standard clinical practice. This lack of reliable tests stems from a vicious cycle of undervaluation, resulting from inconsistent regulatory standards and reimbursement, as well as insufficient investment in research and development, scrutiny of biomarker publications by journals, and evidence of analytical validity and clinical utility. We offer recommendations designed to serve as a roadmap to break this vicious cycle and call for a national dialogue, as changes in regulation, reimbursement, investment, peer review, and guidelines development require the participation of all stakeholders. PMID:23903752

  14. Cycles in fossil diversity

    SciTech Connect

    Rohde, Robert A.; Muller, Richard A.

    2004-10-20

    It is well-known that the diversity of life appears to fluctuate during the course the Phanerozoic, the eon during which hard shells and skeletons left abundant fossils (0-542 Ma). Using Sepkoski's compendium of the first and last stratigraphic appearances of 36380 marine genera, we report a strong 62 {+-} 3 Myr cycle, which is particularly strong in the shorter-lived genera. The five great extinctions enumerated by Raup and Sepkoski may be an aspect of this cycle. Because of the high statistical significance, we also consider contributing environmental factors and possible causes.

  15. Global water cycle

    NASA Technical Reports Server (NTRS)

    Robertson, Franklin R.; Christy, John R.; Goodman, Steven J.; Miller, Tim L.; Fitzjarrald, Dan; Lapenta, Bill; Wang, Shouping

    1991-01-01

    The primary objective is to determine the scope and interactions of the global water cycle with all components of the Earth system and to understand how it stimulates and regulates changes on both global and regional scales. The following subject areas are covered: (1) water vapor variability; (2) multi-phase water analysis; (3) diabatic heating; (4) MSU (Microwave Sounding Unit) temperature analysis; (5) Optimal precipitation and streamflow analysis; (6) CCM (Community Climate Model) hydrological cycle; (7) CCM1 climate sensitivity to lower boundary forcing; and (8) mesoscale modeling of atmosphere/surface interaction.

  16. Global water cycle

    NASA Technical Reports Server (NTRS)

    Robertson, Franklin; Goodman, Steven J.; Christy, John R.; Fitzjarrald, Daniel E.; Chou, Shi-Hung; Crosson, William; Wang, Shouping; Ramirez, Jorge

    1993-01-01

    This research is the MSFC component of a joint MSFC/Pennsylvania State University Eos Interdisciplinary Investigation on the global water cycle extension across the earth sciences. The primary long-term objective of this investigation is to determine the scope and interactions of the global water cycle with all components of the Earth system and to understand how it stimulates and regulates change on both global and regional scales. Significant accomplishments in the past year are presented and include the following: (1) water vapor variability; (2) multi-phase water analysis; (3) global modeling; and (4) optimal precipitation and stream flow analysis and hydrologic processes.

  17. Synthetic battery cycling techniques

    NASA Technical Reports Server (NTRS)

    Leibecki, H. F.; Thaller, L. H.

    1982-01-01

    Synthetic battery cycling makes use of the fast growing capability of computer graphics to illustrate some of the basic characteristics of operation of individual electrodes within an operating electrochemical cell. It can also simulate the operation of an entire string of cells that are used as the energy storage subsystem of a power system. The group of techniques that as a class have been referred to as Synthetic Battery Cycling is developed in part to try to bridge the gap of understanding that exists between single cell characteristics and battery system behavior.

  18. Understanding the petrochemical cycle

    SciTech Connect

    Sedriks, W.

    1996-10-01

    The presentation will examine the nature of the supply, demand and profitability cycles that appear to be endemic in the petrochemical industry. The focus will be on the underlying factors that cause cyclicality. Data for ethylene and first line derivatives will be used both to provide quantitative illustrations of the magnitude of the cyclical effects and to give an improved perspective on the forces that drive cylicality. We will also examine to what extent cycle timing may be predictable, and present some scenario based projections.

  19. Cycling/dispatching power plants

    SciTech Connect

    Makansi, J.

    1994-02-01

    This article examines the effect cycling capability has on a power systems plants and the tradeoffs in performance that may occur. The topics of this article include cycling capability, control and training tools, combined cycles, steam turbine selection, protection against water induction, plant staffing, boiler/steam turbines, full turbine bypasses, cycling of CFB boilers, generators, and environmental control system uses to monitor performance.

  20. Stellar magnetic cycles

    NASA Astrophysics Data System (ADS)

    Baliunas, S. L.

    2004-05-01

    Is hope for understanding the solar magnetic cycle to be found in stars? Observations of stars with significant sub-surface convective zones -- masses smaller than about 1.5 solar masses on the lower main sequence and many types of cool, post-main-sequence stars -- indicate the presence of surface and atmospheric inhomogeneities analogous to solar magnetic features, making stellar magnetic activity a cosmically widespread phenomenon. Observations have been made primarily in visible wavelengths, and important information has also been derived from the ultraviolet and x-ray spectrum regions. Interannual to interdecadal variability of spectrum indicators of stellar magnetic features is common, and in some cases similar in appearance to the 11-year sunspot cycle. Successful models of the physical processes responsible for stellar magnetic cycles, typically cast as a magnetohydrodynamic dynamo, require advances in understanding not only convection but also the magnetic field's interaction with it. The observed facts that underpin the hope for models will be summarized. Properties of stellar magnetic cycles will be compared and contrasted with those of the sun, including inferences from paleo-environmental reservoirs that contain information on solar century- to millennial-scale magnetic variability. Partial support of this research came from NASA NAG5-7635, NRC COBASE, CRDF 322, MIT-MSG 5710001241, JPL 1236821, AF 49620-02-1-0194, Richard Lounsberry Foundation, Langley-Abbot, Rollins, Scholarly Studies and James Arthur Funds (Smithsonian Institution) and several generous individuals.

  1. The Science of Cycling

    ERIC Educational Resources Information Center

    Crompton, Zoe; Daniels, Shelley

    2014-01-01

    Children are engaged by finding out about science in the real world (Harlen, 2010). Many children will be cyclists or will have seen or heard about the success of British cyclists in the Olympics and the Tour de France. This makes cycling a good hook to draw children into learning science. It is also a good cross-curricular topic, with strong…

  2. Assisted Cycling Tours

    ERIC Educational Resources Information Center

    Hollingsworth, Jan Carter

    2008-01-01

    This article discusses Assisted Cycling Tours (ACT), a Westminster, Colorado based 501(c)3, non-profit that is offering the joy of bicycle tours in breathtaking, scenic locations to children and adults with developmental and physical disabilities and their families. ACT was founded by Bob Matter and his son David with a goal of opening up the…

  3. 90-Day Cycle Handbook

    ERIC Educational Resources Information Center

    Park, Sandra; Takahashi, Sola

    2013-01-01

    90-Day Cycles are a disciplined and structured form of inquiry designed to produce and test knowledge syntheses, prototyped processes, or products in support of improvement work. With any type of activity, organizations inevitably encounter roadblocks to improving performance and outcomes. These barriers might include intractable problems at…

  4. The Learning Cycle.

    ERIC Educational Resources Information Center

    Beisenherz, Paul C.; Dantonio, Marylou; Richardson, Lon

    2000-01-01

    The Learning Cycle contains three phases. In the exploration phase, students construct shared understanding of critical characteristics of a concept. The teacher introduces a concept in the concept introduction phase. The application phase introduces activities to extend the concept. Includes five concept activities. (SAH)

  5. Re-Cycling

    ERIC Educational Resources Information Center

    Brown, Robert W.; Covault, Corbin E.

    2015-01-01

    An old comedy routine on Saturday Night Live by Father Guido Sarducci introduced a "Five-Minute University," because five minutes is all that's remembered after graduation anyway. In counterpoint, we discuss "cycling," a teaching method for memory enhancement. Our principal implementation consists of offering a simple version…

  6. LIFE-CYCLE ASSESSMENT

    EPA Science Inventory

    Life Cycle Assessment, or LCA, is an environmental accounting and mangement approach that consider all the aspects of resource use and environmental releases associated with an industrial system from cradle-to-grave. Specifically, it is a holistic view of environmental interacti...

  7. Rapid cycling superconducting magnets

    NASA Astrophysics Data System (ADS)

    Fabbricatore, P.; Farinon, S.; Gambardella, U.; Greco, M.; Volpini, G.

    2006-04-01

    The paper deals with the general problematic related to the development of fast cycled superconducting magnets for application in particle accelerator machines. Starting from the requirements of SIS300 synchrotron under design at GSI and an envisaged future Super-SPS injector at CERN, it is shown which developments are mandatory in the superconducting wire technology and in the magnet design field.

  8. Stirling cycle piston engine

    SciTech Connect

    Morgan, G. R.

    1985-02-12

    This device is an improvement over the conventional type of Stirling cycle engine where the expander piston is connected to a crankshaft and the displacer piston is connected to the same or another crankshaft for operation. The improvement is based on both the expansion and displacer pistons being an integral unit having regenerating means which eliminate the mechanisms that synchronize the regeneration mode.

  9. The Geologic Nitrogen Cycle

    NASA Astrophysics Data System (ADS)

    Johnson, B. W.; Goldblatt, C.

    2013-12-01

    N2 is the dominant gas in Earth's atmosphere, and has been so through the majority of the planet's history. Originally thought to only be cycled in significant amounts through the biosphere, it is becoming increasingly clear that a large degree of geologic cycling can occur as well. N is present in crustal rocks at 10s to 100s of ppm and in the mantle at 1s to perhaps 10s of ppm. In light of new data, we present an Earth-system perspective of the modern N cycle, an updated N budget for the silicate Earth, and venture to explain the evolution of the N cycle over time. In an fashion similar to C, N has a fast, biologically mediated cycle and a slower cycle driven by plate tectonics. Bacteria fix N2 from the atmosphere into bioavailable forms. N is then cycled through the food chain, either by direct consumption of N-fixing bacteria, as NH4+ (the primary waste form), or NO3- (the most common inorganic species in the modern ocean). Some organic material settles as sediment on the ocean floor. In anoxic sediments, NH4+ dominates; due to similar ionic radii, it can readily substitute for K+ in mineral lattices, both in sedimentary rocks and in oceanic lithosphere. Once it enters a subduction zone, N may either be volatilized and returned to the atmosphere at arc volcanoes as N2 or N2O, sequestered into intrusive igneous rocks (as NH4+?), or subducted deep into the mantle, likely as NH4+. Mounting evidence indicates that a significant amount of N may be sequestered into the solid Earth, where it may remain for long periods (100s m.y.) before being returned to the atmosphere/biosphere by volcanism or weathering. The magnitude fluxes into the solid Earth and size of geologic N reservoirs are poorly constrained. The size of the N reservoirs contained in the solid Earth directly affects the evolution of Earth's atmosphere. It is possible that N now sequestered in the solid Earth was once in the atmosphere, which would have resulted in a higher atmospheric pressure, and

  10. Gene expression during the first 28 days of axolotl limb regeneration I: Experimental design and global analysis of gene expression

    PubMed Central

    Palumbo, Alex; Nagarajan, Radha; Gardiner, David M.; Muneoka, Ken; Stromberg, Arnold J.; Athippozhy, Antony T.

    2015-01-01

    Abstract While it is appreciated that global gene expression analyses can provide novel insights about complex biological processes, experiments are generally insufficiently powered to achieve this goal. Here we report the results of a robust microarray experiment of axolotl forelimb regeneration. At each of 20 post‐amputation time points, we estimated gene expression for 10 replicate RNA samples that were isolated from 1 mm of heterogeneous tissue collected from the distal limb tip. We show that the limb transcription program diverges progressively with time from the non‐injured state, and divergence among time adjacent samples is mostly gradual. However, punctuated episodes of transcription were identified for five intervals of time, with four of these coinciding with well‐described stages of limb regeneration—amputation, early bud, late bud, and pallet. The results suggest that regeneration is highly temporally structured and regulated by mechanisms that function within narrow windows of time to coordinate transcription within and across cell types of the regenerating limb. Our results provide an integrative framework for hypothesis generation using this complex and highly informative data set. PMID:27168937

  11. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

    PubMed

    Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

    2012-04-10

    Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  12. Survival and growth of freshwater pulmonate and nonpulmonate snails in 28-day exposures to copper, ammonia, and pentachlorophenol

    USGS Publications Warehouse

    Besser, John M.; Dorman, Rebecca A.; Hardesty, Douglas K.; Ingersoll, Christopher G.

    2016-01-01

    We performed toxicity tests with two species of pulmonate snails (Lymnaea stagnalis and Physa gyrina) and four taxa of nonpulmonate snails in the family Hydrobiidae (Pyrgulopsis robusta,Taylorconcha serpenticola, Fluminicola sp., and Fontigens aldrichi). Snails were maintained in static-renewal or recirculating culture systems with adults removed periodically to isolate cohorts of offspring for toxicity testing. This method successfully produced offspring for both species of pulmonate snails and for two hydrobiid species, P. robusta and Fluminicola sp. Toxicity tests were performed for 28 days with copper, ammonia, and pentachlorophenol in hard reconstituted water with endpoints of survival and growth. Tests were started with 1-week-old L. stagnalis, 2-week-old P. gyrina, 5- to 13-week-old P. robusta and Fluminicola sp., and older juveniles and adults of several hydrobiid species. For all three chemicals, chronic toxicity values for pulmonate snails were consistently greater than those for hydrobiid snails, and hydrobiids were among the most sensitive taxa in species sensitivity distributions for all three chemicals. These results suggest that the toxicant sensitivity of nonpulmonate snails in the family Hydrobiidae would not be adequately represented by results of toxicity testing with pulmonate snails.

  13. Digestible Lysine Requirements of Male Broilers From 14 to 28 Days of Age Subjected to Different Environmental Conditions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary amino acid requirements are influenced by environmental conditions. Two experiments examined growth responses of Ross × Ross TP 16 male broilers fed diets varying in digestible (dig) Lys concentrations from 14 to 28 d of age under different environmental conditions. Experiment 1 was conduc...

  14. 29 CFR 553.230 - Maximum hours standards for work periods of 7 to 28 days-section 7(k).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-section 7(k). 553.230 Section 553.230 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR... Compensation Rules § 553.230 Maximum hours standards for work periods of 7 to 28 days—section 7(k). (a) For... 28 consecutive days, no overtime compensation is required under section 7(k) until the number...

  15. Presepsin is an early monitoring biomarker for predicting clinical outcome in patients with sepsis.

    PubMed

    Ali, Fahmy T; Ali, Mohamed A M; Elnakeeb, Mostafa M; Bendary, Heba N M

    2016-09-01

    Despite their undoubted helpfulness in diagnosing sepsis, increased blood C-reactive protein (CRP) and procalcitonin (PCT) levels have been described in many noninfectious conditions. Presepsin is a soluble fragment of the cluster of differentiation 14 involved in pathogen recognition by innate immunity. We aimed to investigate the diagnostic and prognostic performance of presepsin in comparison to PCT and CRP in patients presenting with systemic inflammatory response syndrome (SIRS) and suspected sepsis. Seventy-six subjects were enrolled in this study, including 51 patients with SIRS as well as 25 healthy subjects. Plasma presepsin, PCT and CRP levels were serially measured on admission and at days 1, 3, 7 and 15. Presepsin and PCT yielded similar diagnostic accuracy, whereas presepsin performed significantly better than CRP. Presepsin and PCT showed comparable performance for predicting 28-day mortality, and both biomarkers performed significantly better than CRP. In septic patients, presepsin revealed earlier concentration changes over time when compared to PCT and CRP. Presepsin and PCT could differentiate between septic and non-septic patients with comparable accuracy and both biomarkers showed similar performance for predicting 28-day mortality. Early changes in presepsin concentrations might reflect the appropriateness of the therapeutic modality and could be useful for making effective treatment decisions. PMID:27353646

  16. New puzzles for the use of non-invasive ventilation for immunosuppressed patients.

    PubMed

    Barbas, Carmen Sílvia Valente; Serpa Neto, Ary

    2016-01-01

    On October 27, 2015, Lemile and colleagues published an article in JAMA entitled "Effect of Noninvasive Ventilation vs. Oxygen Therapy on Mortality among Immunocompromised Patients with Acute Respiratory Failure: A Randomized Clinical Trial", which investigated the effects of non-invasive ventilation (NIV) in 28-day mortality of 374 critically ill immunosuppressed patients. The authors found that among immunosuppressed patients admitted to the intensive care unit (ICU) with hypoxemic acute respiratory failure, early NIV compared with oxygen therapy alone did not reduce 28-day mortality. Furthermore, different from the previous publications, there were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. The study power was limited, median oxygen flow used was higher than used before or 9 L/min, NIV settings provided tidal volumes higher than what is considered protective nowadays or from 7 to 10 mL/kg of ideal body weight and the hypoxemic respiratory failure was moderate to severe (median PaO2/FIO2 was around 140), a group prone to failure in noninvasive ventilatory support. Doubts arose regarding the early use of NIV in immunosuppressed critically ill patients with non-hypercapnic hypoxemic respiratory failure that need to be solved in the near future. PMID:26904233

  17. The global water cycle

    NASA Astrophysics Data System (ADS)

    Oki, Taikan; Entekhabi, Dara; Harrold, Timothy Ives

    The global water cycle consists of the oceans, water in the atmosphere, and water in the landscape. The cycle is closed by the fluxes between these reservoirs. Although the amounts of water in the atmosphere and river channels are relatively small, the fluxes are high, and this water plays a critical role in society, which is dependent on water as a renewable resource. On a global scale, the meridional component of river runoff is shown to be about 10% of the corresponding atmospheric and oceanic meridional fluxes. Artificial storages and water withdrawals for irrigation have significant impacts on river runoff and hence on the overall global water cycle. Fully coupled atmosphere-land-river-ocean models of the world's climate are essential to assess the future water resources and scarcities in relation to climate change. An assessment of future water scarcity suggests that water shortages will worsen, with a very significant increase in water stress in Africa. The impact of population growth on water stress is shown to be higher than that of climate change. The virtual water trade, which should be taken into account when discussing the global water cycle and water scarcity, is also considered. The movement of virtual water from North America, Oceania, and Europe to the Middle East, North West Africa, and East Asia represents significant global savings of water. The anticipated world water crisis widens the opportunities for the study of the global water cycle to contribute to the development of sustainability within society and to the solution of practical social problems.

  18. Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open-Label Trial

    PubMed Central

    Zhang, Xinchao; Lin, Peihong; Wei, Jie; Cao, Yu; Pan, Shuming; Walline, Joseph; Qian, Chuanyun; Shan, Zhigang

    2016-01-01

    The effect of Shenfu on biochemical parameters and survival during resuscitation in patients with septic shock was examined. This was a multicenter, controlled, randomized, open-label trial carried out in 210 patients with septic shock from seven medical centers in China. They were randomized to Shenfu or saline. The primary outcome was lactate clearance. The secondary outcomes were shock index normalization, dose of vasopressors, ICU stay, hospital stay, and mortality. A total of 199 patients completed the trial. Blood pressure, heart rate, and other routine lab tests showed no difference between the groups. Lactate levels and lactate clearance were similar between the two groups. Hospital and ICU stay were similar between the two groups. When considering all patients, the 7- and 28-day mortality were similar between the two groups, but when considering only patients with lactate levels ≥4.5 mmol/L, the Shenfu group showed a better 7-day survival than the control group (7 days: 83.3% versus 54.5%, P = 0.034; 28 days: 72.7% versus 47.6%, P = 0.092). Shenfu may improve the 7-day survival in patients with impaired lactate clearance (≥4.5 mmol/L), but the mechanism for this effect is unclear. Additional studies are necessary to characterize the hemodynamic changes after Shenfu infusion. This trial is registered with ChiCTR-TRC-11001369. PMID:27446222

  19. The microbial nitrogen cycle.

    PubMed

    Jetten, Mike S M

    2008-11-01

    This special issue highlights several recent discoveries in the microbial nitrogen cycle including the diversity of nitrogen-fixing bacteria in special habitats, distribution and contribution of aerobic ammonium oxidation by bacteria and crenarchaea in various aquatic and terrestrial ecosystems, regulation of metabolism in nitrifying bacteria, the molecular diversity of denitrifying microorganisms and their enzymes, the functional diversity of freshwater and marine anammox bacteria, the physiology of nitrite-dependent anaerobic methane oxidation and the degradation of recalcitrant organic nitrogen compounds. Simultaneously the articles in this issue show that many questions still need to be addressed, and that the microbes involved in catalyzing the nitrogen conversions still harbour many secrets that need to be disclosed to fully understand the biogeochemical nitrogen cycle, and make future predictions and global modelling possible.

  20. Stirling cycle cryogenic cooler

    NASA Astrophysics Data System (ADS)

    Gasser, M. G.; Sherman, A.; Studer, P. A.; Daniels, A.; Goldowsky, M. P.

    1983-06-01

    A long lifetime Stirling cycle cryogenic cooler particularly adapted for space applications is described. It consists of a compressor section centrally aligned end to end with an expansion section, and respectively includes a reciprocating compressor piston and displacer radially suspended in interconnecting cylindrical housings by active magnetic bearings and has adjacent reduced clearance regions so as to be in noncontacting relationship therewith and wherein one or more of these regions operate as clearance seals. The piston and displacer are reciprocated in their housings by linear drive motors to vary the volume of respectively adjacent compression and expansion spaces which contain a gaseous working fluid and a thermal regenerator to effect Stirling cycle cryogenic cooling.

  1. Archaea in biogeochemical cycles.

    PubMed

    Offre, Pierre; Spang, Anja; Schleper, Christa

    2013-01-01

    Archaea constitute a considerable fraction of the microbial biomass on Earth. Like Bacteria they have evolved a variety of energy metabolisms using organic and/or inorganic electron donors and acceptors, and many of them are able to fix carbon from inorganic sources. Archaea thus play crucial roles in the Earth's global geochemical cycles and influence greenhouse gas emissions. Methanogenesis and anaerobic methane oxidation are important steps in the carbon cycle; both are performed exclusively by anaerobic archaea. Oxidation of ammonia to nitrite is performed by Thaumarchaeota. They represent the only archaeal group that resides in large numbers in the global aerobic terrestrial and marine environments on Earth. Sulfur-dependent archaea are confined mostly to hot environments, but metal leaching by acidophiles and reduction of sulfate by anaerobic, nonthermophilic methane oxidizers have a potential impact on the environment. The metabolisms of a large number of archaea, in particular those dominating the subsurface, remain to be explored.

  2. Gondwanaland's seasonal cycle

    NASA Technical Reports Server (NTRS)

    Crowley, Thomas J.; Short, David A.; Mengel, John G.

    1987-01-01

    A two-dimensional energy balance climate model has been used to simulate the seasonal temperature cycle on a supercontinent-sized land mass. Experiments with idealized and realistic geography indicate that the land-sea configuration in high latitudes exerts a strong influence on the magnitude of summer warming. These simulations provide significant insight into the evolution of climate during the Palaeozoic, and raise questions about the presumed pre-eminent role of carbon dioxide in explaining long-term climate change.

  3. Nuclear Fuel Cycle

    SciTech Connect

    Dale, Deborah J.

    2014-10-28

    These slides will be presented at the training course “International Training Course on Implementing State Systems of Accounting for and Control (SSAC) of Nuclear Material for States with Small Quantity Protocols (SQP),” on November 3-7, 2014 in Santa Fe, New Mexico. The slides provide a basic overview of the Nuclear Fuel Cycle. This is a joint training course provided by NNSA and IAEA.

  4. Stirling cycle engine

    DOEpatents

    Lundholm, Gunnar

    1983-01-01

    In a Stirling cycle engine having a plurality of working gas charges separated by pistons reciprocating in cylinders, the total gas content is minimized and the mean pressure equalization among the serial cylinders is improved by using two piston rings axially spaced at least as much as the piston stroke and by providing a duct in the cylinder wall opening in the space between the two piston rings and leading to a source of minimum or maximum working gas pressure.

  5. The carbon dioxide cycle

    USGS Publications Warehouse

    James, P.B.; Hansen, G.B.; Titus, T.N.

    2005-01-01

    The seasonal CO2 cycle on Mars refers to the exchange of carbon dioxide between dry ice in the seasonal polar caps and gaseous carbon dioxide in the atmosphere. This review focuses on breakthroughs in understanding the process involving seasonal carbon dioxide phase changes that have occurred as a result of observations by Mars Global Surveyor. ?? 2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  6. [Microbial geochemical calcium cycle].

    PubMed

    Zavarzin, G A

    2002-01-01

    The participation of microorganisms in the geochemical calcium cycle is the most important factor maintaining neutral conditions on the Earth. This cycle has profound influence on the fate of inorganic carbon, and, thereby, on the removal of CO2 from the atmosphere. The major part of calcium deposits was formed in the Precambrian, when prokaryotic biosphere predominated. After that, calcium recycling based on biogenic deposition by skeletal organisms became the main process. Among prokaryotes, only a few representatives, e.g., cyanobacteria, exhibit a special calcium function. The geochemical calcium cycle is made possible by the universal features of bacteria involved in biologically mediated reactions and is determined by the activities of microbial communities. In the prokaryotic system, the calcium cycle begins with the leaching of igneous rock predominantly through the action of the community of organotrophic organisms. The release of carbon dioxide to the soil air by organotrophic aerobes leads to leaching with carbonic acid and soda salinization. Under anoxic conditions, of major importance is the organic acid production by primary anaerobes (fermentative microorganisms). Calcium carbonate is precipitated by secondary anaerobes (sulfate reducers) and to a smaller degree by methanogens. The role of the cyanobacterial community in carbonate deposition is exposed by stromatolites, which are the most common organo-sedimentary Precambrian structures. Deposition of carbonates in cyanobacterial mats as a consequence of photoassimilation of CO2 does not appear to be a significant process. It is argued that carbonates were deposited at the boundary between the "soda continent", which emerged as a result of subaerial leaching with carbonic acid, and the ocean containing Ca2+. Such ecotones provided favorable conditions for the development of the benthic cyanobacterial community, which was a precursor of stromatolites.

  7. The papillomavirus life cycle.

    PubMed

    Doorbar, John

    2005-03-01

    Papillomaviruses infect epithelial cells, and depend on epithelial differentiation for completion of their life cycle. The expression of viral gene products is closely regulated as the infected basal cell migrates towards the epithelial surface. Expression of E6 and E7 in the lower epithelial layers drives cells into S-phase, which creates an environment that is conducive for viral genome replication and cell proliferation. Genome amplification, which is necessary for the production of infectious virions, is prevented until the levels of viral replication proteins rise, and depends on the co-expression of several viral proteins. Virus capsid proteins are expressed in cells that also express E4 as the infected cell enters the upper epithelial layers. The timing of these events varies depending on the infecting papillomavirus, and in the case of the high-risk human papillomaviruses (HPVs), on the severity of neoplasia. Viruses that are evolutionarily related, such as HPV1 and canine oral papillomavirus (COPV), generally organize their productive cycle in a similar way, despite infecting different hosts and epithelial sites. In some instances, such as following HPV16 infection of the cervix or cottontail rabbit papillomavirus (CRPV) infection of domestic rabbits, papillomaviruses can undergo abortive infections in which the productive cycle of the virus is not completed. As with other DNA tumour viruses, such abortive infections can predispose to cancer. PMID:15753007

  8. Gap Cycling for SWIFT

    PubMed Central

    Corum, Curtis A.; Idiyatullin, Djaudat; Snyder, Carl J.; Garwood, Michael

    2014-01-01

    Purpose SWIFT (SWeep Imaging with Fourier Transformation) is a non-Cartesian MRI method with unique features and capabilities. In SWIFT, radiofrequency (RF) excitation and reception are performed nearly simultaneously, by rapidly switching between transmit and receive during a frequency-swept RF pulse. Because both the transmitted pulse and data acquisition are simultaneously amplitude-modulated in SWIFT (in contrast to continuous RF excitation and uninterrupted data acquisition in more familiar MRI sequences), crosstalk between different frequency bands occurs in the data. This crosstalk leads to a “bulls-eye” artifact in SWIFT images. We present a method to cancel this inter-band crosstalk by cycling the pulse and receive gap positions relative to the un-gapped pulse shape. We call this strategy “gap cycling.” Methods We carry out theoretical analysis, simulation and experiments to characterize the signal chain, resulting artifacts, and their elimination for SWIFT. Results Theoretical analysis reveals the mechanism for gap-cycling’s effectiveness in canceling inter-band crosstalk in the received data. We show phantom and in-vivo results demonstrating bulls-eye artifact free images. Conclusion Gap cycling is an effective method to remove bulls-eye artifact resulting from inter-band crosstalk in SWIFT data. PMID:24604286

  9. Episodic Tremor and Slip: Cycles Within Cycles

    NASA Astrophysics Data System (ADS)

    Creager, K. C.; Wech, A.; Vidale, J. E.

    2009-12-01

    Episodic tremor and slip (ETS) events, each with geodetically determined moment magnitudes in the mid-6 range, repeat about every 15 months under the Olympic Peninsula/southern Vancouver Island region. We have automatically searched for non-volcanic tremor in all 5-minute time windows both during the past five ETS events and during the two inter-ETS periods from February, 2007 through April, 2008 and June 2008 through April 2009. Inter-ETS tremor was detected in 5000 windows, which overlap by 50%, so tremor was seen 2% of the time. The catalog of 5-minute tremor locations cluster in time and space into groups we call tremor swarms, revealing 50 inter-ETS tremor swarms. The number of hours of tremor per swarm ranged from about 1 to 68, totaling 374 hours. The inter-ETS tremor swarms generally locate along the downdip side of the major ETS events, and account for approximately 45% of the time that tremor has been detected during the last two entire ETS cycles. Many of the inter-ETS events are near-carbon copies in duration, spatial extent and propagation direction, as is seen for the larger 15-month-interval events. These 50 inter-ETS swarms plus two major ETS episodes follow a power law relationship such that the number of swarms, N, exceeding duration τ is given by N ˜ τ-0.7. If we assume that seismic moment is proportional to τ as proposed by Ide et al. [Nature, 2007], we find that the tremor swarms follow a standard Gutenberg-Richter logarithmic frequency-magnitude relation, N ˜ 10-bMw, with b = 1.0, which lies in the range for normal earthquake catalogs. Furthermore, the major ETS events fall on the curve defined by the inter-ETS swarms, suggesting that the inter-ETS swarms are just smaller versions of the major 15-month ETS events. Only the largest events coincide with geodetically observed slip, suggesting that current geodetic observations may be missing nearly half of the total slip. Finally, crude estimates of the spatial dimensions of tremor swarms L

  10. Terrestrial Carbon Cycle Variability

    PubMed Central

    Baldocchi, Dennis; Ryu, Youngryel; Keenan, Trevor

    2016-01-01

    A growing literature is reporting on how the terrestrial carbon cycle is experiencing year-to-year variability because of climate anomalies and trends caused by global change. As CO 2 concentration records in the atmosphere exceed 50 years and as satellite records reach over 30 years in length, we are becoming better able to address carbon cycle variability and trends. Here we review how variable the carbon cycle is, how large the trends in its gross and net fluxes are, and how well the signal can be separated from noise. We explore mechanisms that explain year-to-year variability and trends by deconstructing the global carbon budget. The CO 2 concentration record is detecting a significant increase in the seasonal amplitude between 1958 and now. Inferential methods provide a variety of explanations for this result, but a conclusive attribution remains elusive. Scientists have reported that this trend is a consequence of the greening of the biosphere, stronger northern latitude photosynthesis, more photosynthesis by semi-arid ecosystems, agriculture and the green revolution, tropical temperature anomalies, or increased winter respiration. At the global scale, variability in the terrestrial carbon cycle can be due to changes in constituent fluxes, gross primary productivity, plant respiration and heterotrophic (microbial) respiration, and losses due to fire, land use change, soil erosion, or harvesting. It remains controversial whether or not there is a significant trend in global primary productivity (due to rising CO 2, temperature, nitrogen deposition, changing land use, and preponderance of wet and dry regions). The degree to which year-to-year variability in temperature and precipitation anomalies affect global primary productivity also remains uncertain. For perspective, interannual variability in global gross primary productivity is relatively small (on the order of 2 Pg-C y -1) with respect to a large and uncertain background (123 +/- 4 Pg-C y -1), and

  11. The Contemporary Carbon Cycle

    NASA Astrophysics Data System (ADS)

    Houghton, R. A.

    2003-12-01

    The global carbon cycle refers to the exchanges of carbon within and between four major reservoirs: the atmosphere, the oceans, land, and fossil fuels. Carbon may be transferred from one reservoir to another in seconds (e.g., the fixation of atmospheric CO2 into sugar through photosynthesis) or over millennia (e.g., the accumulation of fossil carbon (coal, oil, gas) through deposition and diagenesis of organic matter). This chapter emphasizes the exchanges that are important over years to decades and includes those occurring over the scale of months to a few centuries. The focus will be on the years 1980-2000 but our considerations will broadly include the years ˜1850-2100. Chapter 8.09, deals with longer-term processes that involve rates of carbon exchange that are small on an annual timescale (weathering, vulcanism, sedimentation, and diagenesis).The carbon cycle is important for at least three reasons. First, carbon forms the structure of all life on the planet, making up ˜50% of the dry weight of living things. Second, the cycling of carbon approximates the flows of energy around the Earth, the metabolism of natural, human, and industrial systems. Plants transform radiant energy into chemical energy in the form of sugars, starches, and other forms of organic matter; this energy, whether in living organisms or dead organic matter, supports food chains in natural ecosystems as well as human ecosystems, not the least of which are industrial societies habituated (addicted?) to fossil forms of energy for heating, transportation, and generation of electricity. The increased use of fossil fuels has led to a third reason for interest in the carbon cycle. Carbon, in the form of carbon dioxide (CO2) and methane (CH4), forms two of the most important greenhouse gases. These gases contribute to a natural greenhouse effect that has kept the planet warm enough to evolve and support life (without the greenhouse effect the Earth's average temperature would be -33

  12. Intensive Multiagent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide, Irinotecan, and Radiation, in Patients With High-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group

    PubMed Central

    Weigel, Brenda J.; Lyden, Elizabeth; Anderson, James R.; Meyer, William H.; Parham, David M.; Rodeberg, David A.; Michalski, Jeff M.; Hawkins, Douglas S.

    2016-01-01

    Purpose Patients with metastatic rhabdomyosarcoma (RMS), except those younger than 10 years with embryonal RMS, have an estimated long-term event-free survival (EFS) of less than 20%. The main goal of this study was to improve outcome of patients with metastatic RMS by dose intensification with interval compression, use of the most active agents determined in phase II window studies, and use of irinotecan as a radiation sensitizer. Patients and Methods Patients with metastatic RMS received 54 weeks of therapy: blocks of therapy with vincristine/irinotecan (weeks 1 to 6, 20 to 25, and 47 to 52), interval compression with vincristine/doxorubicin/cyclophosphamide alternating with etoposide/ifosfamide (weeks 7 to 19 and 26 to 34), and vincristine/dactinomycin/cyclophosphamide (weeks 38 to 46). Radiation therapy occurred at weeks 20 to 25 (primary) but was also permitted at weeks 1 to 6 (for intracranial or paraspinal extension) and weeks 47 to 52 (for extensive metastatic sites). Results One hundred nine eligible patients were enrolled, with a median follow-up of surviving patients of 3.8 years (3-year EFS for all patients, 38% [95% CI, 29% to 48%]; survival, 56% [95% CI, 46% to 66%]). Patients with one or no Oberlin risk factor (age > 10 years or < 1 year, unfavorable primary site of disease, ≥ three metastatic sites, and bone or bone marrow involvement) had a 3-year EFS of 69% (95% CI, 52% to 82%); high-risk patients with two or more risk factors had a 3-year EFS of 20% (95% CI, 11% to 30%). Toxicity was similar to that on prior RMS studies. Conclusion Patients with metastatic RMS with one or no Oberlin risk factor had an improved 3-year EFS of 69% on ARST0431 compared with an historical cohort from pooled European and US studies; those with two or more risk factors have a dismal prognosis, and new approaches are needed for this very-high-risk group. PMID:26503200

  13. Batch desorption studies and multiple sorption-regeneration cycles in a fixed-bed column for Cd(II) elimination by protonated Sargassum muticum.

    PubMed

    Lodeiro, P; Herrero, R; Sastre de Vicente, M E

    2006-10-11

    The protonated alga Sargassum muticum was employed in batch desorption studies to find the most appropriate eluting agent for Cd(II)-laden biomass regeneration. Eleven types of eluting solutions at different concentrations were tested, finding elution efficiencies higher than 90% for most of the desorbents studied. Total organic carbon and biomass weight loss measurements were made. The reusability of the protonated alga was also studied using a fixed-bed column. Eleven consecutive sorption-regeneration cycles at a flow rate of 10 mL min(-1) were carried out for the removal of 50 mg L(-1) Cd(II) solution. A 0.1M HNO(3) solution was employed as desorbing agent. The column was operated during 605 h for sorption and 66 h for desorption, equivalent to a continuous use during 28 days, with no apparent loss of sorption performance. In these cycles, no diminution of the breakthrough time was found; although, a relative loss of sorption capacity, regarding the found in the first cycle, was observed. The slope of the breakthrough curves experiments a gradual increase reaching its maximum value for the last cycle tested (40% greater than for the first one). The maximum Cd(II) concentration elution peak was achieved in 5 min or less, and the metal effluent concentration was always lower than 0.9 mg L(-1) after 1 h of elution. The maximum concentration factor was determined to be between 55 and 109. PMID:16759799

  14. The life cycle of Australapatemon magnacetabulum (Digenea: Strigeidae) from Northwestern Argentina.

    PubMed

    Davies, Dora; de Núñez, Margarita Ostrowski

    2012-08-01

    The life cycle of Australapatemon magnacetabulum Dubois, 1988 was resolved experimentally. Planorbid snails Biomphalaria tenagophila (d'Orbigny, 1835) collected in a small pond at the confluence of the San Lorenzo and Arias Rivers, near Salta City, Province of Salta, Argentina, were found to be shedding furcocercous cercariae possessing 4 pairs of penetration glands, 1 pair of unpigmented eyespots, 6 pairs of flame cells in the body, and 1 pair in the tail stem. Metacercariae were found encysted in naturally, and experimentally, exposed leeches Helobdella adiastola Ringuelet, 1972, Helobdella triserialis (Blanchard, 1849), Haementeria eichhorniae Ringuelet 1978, and Haementeria sp., and within their sporocysts in naturally infected planorbid intermediate hosts. Sexually mature adults were recovered from domestic chicks and a duck 8-28 days postexposure by metacercariae from leeches. The identification of the species was based upon the characteristic large ventral sucker and a genital cone, crossed by a hermaphroditic duct with internal folds, occupying approximately a 1/4 to 1/5 of the hindbody. PMID:22475196

  15. Long-term course of schizoaffective disorders. Part II: Length of cycles, episodes, and intervals.

    PubMed

    Marneros, A; Rohde, A; Deister, A; Jünemann, H; Fimmers, R

    1988-01-01

    Length of cycles, intervals, and episodes of 72 schizoaffective patients were investigated (duration of the follow-up means = 25.6 years, minimum 10, maximum 59 years). The average cycle length (time between beginning of an episode and next relapse) was found to be 37.5 months (median). Patients with a schizodepressive initial episode, unipolar course, and without precipitating factors relapsed much later than patients with schizomanic onset, bipolar course, and precipitating factors. The older the patient at onset the shorter the first cycle. The length of cycle decreased with increasing cycle number. Patients with schizodepressive onset, asthenic personality, and monomorphous course stayed in hospital longer or needed longer inpatient-like treatment than others. Length of cycles and intervals were characterized by an extraordinary intraindividual and interindividual variation.

  16. Four Different Regimens of Farnesyltransferase Inhibitor Tipifarnib in Older, Untreated Acute Myeloid Leukemia Patients: North American Intergroup Phase II Study SWOG S0432

    PubMed Central

    Erba, Harry P.; Othus, Megan; Walter, Roland B.; Kirschbaum, Mark H.; Tallman, Martin S.; Larson, Richard A.; Slovak, Marilyn L.; Kopecky, Kenneth J.; Gundacker, Holly M.; Appelbaum, Frederick R.

    2014-01-01

    We report on 348 patients ≥ 70 years (median age 78 years) with acute myeloid leukemia (> 50% with secondary AML) randomized to receive either 600 mg or 300 mg of tipifarnib orally twice daily on days 1–21 or days 1–7 and 15–21, repeated every 28 days (4 treatment regimens). Responses were seen in all regimens, with overall response rate (CR + CRi + PR) highest (20%) among patients receiving tipifarnib 300 mg twice daily on days 1–21. Toxicities were acceptable. Unless predictors of response to tipifarnib are identified, further study as a single agent in this population is unwarranted. PMID:24411921

  17. The nutritional management of urea cycle disorders.

    PubMed

    Leonard, J V

    2001-01-01

    Diet is one of the mainstays of the treatment of patients with urea cycle disorders. The protein intake should be adjusted to take account of the inborn error and its severity and the patient's age, growth rate, and individual preferences. Currently, the widely used standards for protein intake are probably more generous than necessary, particularly for those with the more severe variants. Most patients, except those with arginase deficiency, will need supplements of arginine, but the value of other supplements including citrate and carnitine is unclear. Any patient on a low-protein diet should be monitored clinically and with appropriate laboratory tests. All should have an emergency (crisis) regimen to prevent decompensation during periods of metabolic stress.

  18. Rapid Cycling and Its Treatment

    MedlinePlus

    ... may be rapid, ultra-rapid or ultradian cycling. Biological rhythm disturbances: This theory proposes that people with rapid cycling have daily biological rhythms that are out of sync with typical “ ...

  19. Fictitious Supercontinent Cycles

    NASA Astrophysics Data System (ADS)

    Marvin Herndon, J.

    2014-05-01

    "Supercontinent cycles" or "Wilson cycles" is the idea that before Pangaea there were a series of supercontinents that each formed and then broke apart and separated before colliding again, re-aggregating, and suturing into a new supercontinent in a continuing sequence. I suggest that "supercontinent cycles" are artificial constructs, like planetary orbit epicycles, attempts to describe geological phenomena within the framework of problematic paradigms, namely, planetesimal Earth formation and plate tectonics' mantle convection. The so-called 'standard model of solar system formation' is problematic as it would lead to insufficiently massive planetary cores and necessitates additional ad hoc hypotheses such as the 'frost line' between Mars and Jupiter to explain planetary differences and whole-planet melting to explain core formation from essentially undifferentiated matter. The assumption of mantle convection is crucial for plate tectonics, not only for seafloor spreading, but also for continental movement; continent masses are assumed to ride atop convection cells. In plate tectonics, plate collisions are thought to be the sole mechanism for fold-mountain formation. Indeed, the occurrence of mountain chains characterized by folding which significantly predate the breakup of Pangaea is the primary basis for assuming the existence of supercontinent cycles with their respective periods of ancient mountain-forming plate collisions. Mantle convection is physically impossible. Rayleigh Number justification has been misapplied. The mantle bottom is too dense to float to the surface by thermal expansion. Sometimes attempts are made to obviate the 'bottom heavy' prohibition by adopting the tacit assumption that the mantle behaves as an ideal gas with no viscous losses, i.e., 'adiabatic'. But the mantle is a solid that does not behave as an ideal gas as evidenced by earthquakes occurring at depths as great as 660 km. Absent mantle convection, plate tectonics is not valid

  20. GEOSS Water Cycle Integrator

    NASA Astrophysics Data System (ADS)

    Koike, Toshio; Lawford, Richard; Cripe, Douglas

    2013-04-01

    It is critically important to recognize and co-manage the fundamental linkages across the water-dependent domains; land use, including deforestation; ecosystem services; and food-, energy- and health-securities. Sharing coordinated, comprehensive and sustained observations and information for sound decision-making is a first step; however, to take full advantage of these opportunities, we need to develop an effective collaboration mechanism for working together across different disciplines, sectors and agencies, and thereby gain a holistic view of the continuity between environmentally sustainable development, climate change adaptation and enhanced resilience. To promote effective multi-sectoral, interdisciplinary collaboration based on coordinated and integrated efforts, the intergovernmental Group on Earth Observations (GEO) is implementing the Global Earth Observation System of Systems (GEOSS). A component of GEOSS now under development is the "GEOSS Water Cycle Integrator (WCI)", which integrates Earth observations, modeling, data and information, management systems and education systems. GEOSS/WCI sets up "work benches" by which partners can share data, information and applications in an interoperable way, exchange knowledge and experiences, deepen mutual understanding and work together effectively to ultimately respond to issues of both mitigation and adaptation. (A work bench is a virtual geographical or phenomenological space where experts and managers collaborate to use information to address a problem within that space). GEOSS/WCI enhances the coordination of efforts to strengthen individual, institutional and infrastructure capacities, especially for effective interdisciplinary coordination and integration. GEO has established the GEOSS Asian Water Cycle Initiative (AWCI) and GEOSS African Water Cycle Coordination Initiative (AfWCCI). Through regional, inter-disciplinary, multi-sectoral integration and inter-agency coordination in Asia and Africa, GEOSS

  1. GEOSS Water Cycle Integrator

    NASA Astrophysics Data System (ADS)

    Koike, T.; Lawford, R. G.; Cripe, D.

    2012-12-01

    It is critically important to recognize and co-manage the fundamental linkages across the water-dependent domains; land use, including deforestation; ecosystem services; and food-, energy- and health-securities. Sharing coordinated, comprehensive and sustained observations and information for sound decision-making is a first step; however, to take full advantage of these opportunities, we need to develop an effective collaboration mechanism for working together across different disciplines, sectors and agencies, and thereby gain a holistic view of the continuity between environmentally sustainable development, climate change adaptation and enhanced resilience. To promote effective multi-sectoral, interdisciplinary collaboration based on coordinated and integrated efforts, the Global Earth Observation System of Systems (GEOSS) is now developing a "GEOSS Water Cycle Integrator (WCI)", which integrates "Earth observations", "modeling", "data and information", "management systems" and "education systems". GEOSS/WCI sets up "work benches" by which partners can share data, information and applications in an interoperable way, exchange knowledge and experiences, deepen mutual understanding and work together effectively to ultimately respond to issues of both mitigation and adaptation. (A work bench is a virtual geographical or phenomenological space where experts and managers collaborate to use information to address a problem within that space). GEOSS/WCI enhances the coordination of efforts to strengthen individual, institutional and infrastructure capacities, especially for effective interdisciplinary coordination and integration. GEO has established the GEOSS Asian Water Cycle Initiative (AWCI) and GEOSS African Water Cycle Coordination Initiative (AfWCCI). Through regional, inter-disciplinary, multi-sectoral integration and inter-agency coordination in Asia and Africa, GEOSS/WCI is now leading to effective actions and public awareness in support of water security and

  2. The Global Phosphorus Cycle

    NASA Astrophysics Data System (ADS)

    Ruttenberg, K. C.

    2003-12-01

    Phosphorus is an essential nutrient for all life forms. It is a key player in fundamental biochemical reactions (Westheimer, 1987) involving genetic material (DNA, RNA) and energy transfer (ATP), and in structural support of organisms provided by membranes (phospholipids) and bone (the biomineral hydroxyapatite). Photosynthetic organisms utilize dissolved phosphorus, carbon, and other essential nutrients to build their tissues using energy from the Sun. Biological productivity is contingent upon the availability of phosphorus to these simple organisms that constitute the base of the food web in both terrestrial and aquatic systems. (For reviews of P-utilization, P-biochemicals, and pathways in aquatic plants, see Fogg (1973), Bieleski and Ferguson (1983), and Cembella et al. (1984a, 1984b).)Phosphorus locked up in bedrock, soils, and sediments is not directly available to organisms. Conversion of unavailable forms to dissolved orthophosphate, which can be directly assimilated, occurs through geochemical and biochemical reactions at various stages in the global phosphorus cycle. Production of biomass fueled by P-bioavailability results in the deposition of organic matter in soils and sediments, where it acts as a source of fuel and nutrients to microbial communities. Microbial activity in soils and sediments, in turn, strongly influences the concentration and chemical form of phosphorus incorporated into the geological record.The global phosphorus cycle has four major components: (i) tectonic uplift and exposure of phosphorus-bearing rocks to the forces of weathering; (ii) physical erosion and chemical weathering of rocks producing soils and providing dissolved and particulate phosphorus to rivers; (iii) riverine transport of phosphorus to lakes and the ocean; and (iv) sedimentation of phosphorus associated with organic and mineral matter and burial in sediments (Figure 1). The cycle begins anew with uplift of sediments into the weathering regime.

  3. On the Importance of Cycle Minimum in Sunspot Cycle Prediction

    NASA Technical Reports Server (NTRS)

    Wilson, Robert M.; Hathaway, David H.; Reichmann, Edwin J.

    1996-01-01

    The characteristics of the minima between sunspot cycles are found to provide important information for predicting the amplitude and timing of the following cycle. For example, the time of the occurrence of sunspot minimum sets the length of the previous cycle, which is correlated by the amplitude-period effect to the amplitude of the next cycle, with cycles of shorter (longer) than average length usually being followed by cycles of larger (smaller) than average size (true for 16 of 21 sunspot cycles). Likewise, the size of the minimum at cycle onset is correlated with the size of the cycle's maximum amplitude, with cycles of larger (smaller) than average size minima usually being associated with larger (smaller) than average size maxima (true for 16 of 22 sunspot cycles). Also, it was found that the size of the previous cycle's minimum and maximum relates to the size of the following cycle's minimum and maximum with an even-odd cycle number dependency. The latter effect suggests that cycle 23 will have a minimum and maximum amplitude probably larger than average in size (in particular, minimum smoothed sunspot number Rm = 12.3 +/- 7.5 and maximum smoothed sunspot number RM = 198.8 +/- 36.5, at the 95-percent level of confidence), further suggesting (by the Waldmeier effect) that it will have a faster than average rise to maximum (fast-rising cycles have ascent durations of about 41 +/- 7 months). Thus, if, as expected, onset for cycle 23 will be December 1996 +/- 3 months, based on smoothed sunspot number, then the length of cycle 22 will be about 123 +/- 3 months, inferring that it is a short-period cycle and that cycle 23 maximum amplitude probably will be larger than average in size (from the amplitude-period effect), having an RM of about 133 +/- 39 (based on the usual +/- 30 percent spread that has been seen between observed and predicted values), with maximum amplitude occurrence likely sometime between July 1999 and October 2000.

  4. Re-Cycling

    NASA Astrophysics Data System (ADS)

    Brown, Robert W.; Covault, Corbin E.

    2015-11-01

    An old comedy routine on Saturday Night Live by Father Guido Sarducci introduced a "Five-Minute University," because five minutes is all that's remembered after graduation anyway. In counterpoint, we discuss "cycling," a teaching method for memory enhancement. Our principal implementation consists of offering a simple version of a given course in the first third of the semester, a deeper and more integrated version in the second third, and the final, targeted version in the last third. We describe the benefits and challenges in this tale from the trenches.

  5. Geomicrobiological cycling of antimony

    NASA Astrophysics Data System (ADS)

    Kulp, T. R.; Terry, L.; Dovick, M. A.; Braiotta, F.

    2013-12-01

    Microbiologically catalyzed oxidation and reduction of toxic metalloids (e.g., As, Se, and Te) generally proceeds much faster than corresponding abiotic reactions. These microbial transformations constitute biogeochemical cycles that control chemical speciation and environmental behavior of metalloids in aqueous environments. Particular progress has been made over the past two decades in documenting microbiological biotransformations of As, which include anaerobic respiratory reduction of As(V) to As(III), oxidation of As(III) to As(V) linked to chemoautotrophy or photoautotrophy, and cellular detoxification pathways. By contrast, microbial interactions with Sb, As's group 15 neighbor and a toxic element of emerging global concern, are poorly understood. Our work with sediment microcosms, enrichment cultures, and bacterial isolates suggests that prokaryotic metabolisms may be similarly important to environmental Sb cycling. Enrichment cultures and isolates from a Sb-contaminated mine site in Idaho exhibited Sb(V)-dependent heterotrophic respiration under anaerobic conditions and Sb(III)-dependent autotrophic growth in the presence of air. Live, anoxic cultures reduced 2 mM Sb(V) to Sb(III) within 5 d, while no activity occurred in killed controls. Sb(V) reduction was stimulated by lactate or acetate and was quantitatively coupled to the oxidation of lactate. The oxidation of radiolabeled 14C-acetate (monitored by GC-GPC) demonstrated Sb(V)-dependent oxidation to 14CO2, suggesting a dissimilatory process. Sb(V) dependent growth in cultures was demonstrated by direct counting. Microbiological reduction of Sb(V) also occurred in anerobic sediment microcosms from an uncontaminated suburban lake, but did not appear to be linked to growth and is interpreted as a mechanism of biological detoxification. Aerobic microcosms and cultures from the Idaho mine oxidized 2 mM Sb(III) to Sb(V) within 7 d and coupled this reaction to cell growth quantified by direct counting. An

  6. Natural Cycles, Gases

    NASA Technical Reports Server (NTRS)

    Douglass, Anne R.; Jackman, Charles H.; Rood, R. B.; Aikin, A. C.; Stolarski, R. S.; Mccormick, M. P.; Fahey, David W.

    1992-01-01

    The major gaseous components of the exhaust of stratospheric aircraft are expected to be the products of combustion (CO2 and H2O), odd nitrogen (NO, NO2 HNO3), and products indicating combustion inefficiencies (CO and total unburned hydrocarbons). The species distributions are produced by a balance of photochemical and transport processes. A necessary element in evaluating the impact of aircraft exhaust on the lower stratospheric composition is to place the aircraft emissions in perspective within the natural cycles of stratospheric species. Following are a description of mass transport in the lower stratosphere and a discussion of the natural behavior of the major gaseous components of the stratospheric aircraft exhaust.

  7. Geothermal Life Cycle Calculator

    DOE Data Explorer

    Sullivan, John

    2014-03-11

    This calculator is a handy tool for interested parties to estimate two key life cycle metrics, fossil energy consumption (Etot) and greenhouse gas emission (ghgtot) ratios, for geothermal electric power production. It is based solely on data developed by Argonne National Laboratory for DOE’s Geothermal Technologies office. The calculator permits the user to explore the impact of a range of key geothermal power production parameters, including plant capacity, lifetime, capacity factor, geothermal technology, well numbers and depths, field exploration, and others on the two metrics just mentioned. Estimates of variations in the results are also available to the user.

  8. Liquid air cycle engines

    NASA Technical Reports Server (NTRS)

    Rosevear, Jerry

    1992-01-01

    Given here is a definition of Liquid Air Cycle Engines (LACE) and existing relevant technologies. Heat exchanger design and fabrication techniques, the handling of liquid hydrogen to achieve the greatest heat sink capabilities, and air decontamination to prevent heat exchanger fouling are discussed. It was concluded that technology needs to be extended in the areas of design and fabrication of heat exchangers to improve reliability along with weight and volume reductions. Catalysts need to be improved so that conversion can be achieved with lower quantities and lower volumes. Packaging studies need to be investigated both analytically and experimentally. Recycling with slush hydrogen needs further evaluation with experimental testing.

  9. Cell cycle effects of drugs

    SciTech Connect

    Dethlefsen, L.A.

    1986-01-01

    This book contains 11 chapters. Some of the chapter titles are: Cell Growth and Division Cycle; Cell Cycle Effects of Alkylating Agents; Biological Effects of Folic Acid Antagonists with Antineoplastic Activity; and Bleomycin-Mode of Action with Particular Reference to the Cell Cycle.

  10. Developing a Safe Cycling Course.

    ERIC Educational Resources Information Center

    Riddle, Amy Backus

    1983-01-01

    A cycling course can take advantage of students' interests, teach safe cycling, and give students a fuller appreciation of a lifetime sport. Suggestions for planning and scheduling a cycling course, covering safety procedures, and considering other elements necessary for a successful course are given. (PP)

  11. Sometimes "Newton's Method" Always "Cycles"

    ERIC Educational Resources Information Center

    Latulippe, Joe; Switkes, Jennifer

    2012-01-01

    Are there functions for which Newton's method cycles for all non-trivial initial guesses? We construct and solve a differential equation whose solution is a real-valued function that two-cycles under Newton iteration. Higher-order cycles of Newton's method iterates are explored in the complex plane using complex powers of "x." We find a class of…

  12. Culture in cycles: considering H.T. Odum's 'information cycle'

    NASA Astrophysics Data System (ADS)

    Abel, Thomas

    2014-01-01

    'Culture' remains a conundrum in anthropology. When recast in the mold of 'information cycles,' culture is transformed. New fault lines appear. Information is splintered into parallel or nested forms. Dynamics becomes cycling. Energy is essential. And culture has function in a directional universe. The 'information cycle' is the crowning component of H.T. Odum's theory of general systems. What follows is an application of the information cycle to the cultural domains of discourse, social media, ritual, education, journalism, technology, academia, and law, which were never attempted by Odum. In information cycles, cultural information is perpetuated - maintained against Second Law depreciation. Conclusions are that culture is in fact a nested hierarchy of cultural forms. Each scale of information production is semi-autonomous, with its own evolutionary dynamics of production and selection in an information cycle. Simultaneously, each information cycle is channeled or entrained by its larger scale of information and ultimately human-ecosystem structuring.

  13. Long-term responses of snails exposed to cadmium-contaminated soils in a partial life-cycle experiment.

    PubMed

    Gimbert, Frédéric; de Vaufleury, Annette; Douay, Francis; Coeurdassier, Michaël; Scheifler, Renaud; Badot, Pierre-Marie

    2008-05-01

    Juvenile snails were exposed during their growth period to Cd-contaminated field and artificial soils and then transferred to uncontaminated soil to assess the sequels of previous exposure on adult reproduction. Growth modelling highlighted growth inhibitions of 5% and 10% after 70 and 84 days of exposure to 20 and 100 mg Cd kg(-1) in artificial soils, respectively. Growth disruption was accompanied by a decrease in the clutch number and a 4-week delay in the egg-laying cycle. Although it was also contaminated at 20 mg Cd kg(-1), the contaminated field soil did not lead to detectable effects in snails, suggesting a lower Cd bioavailability confirmed by the bioaccumulation analysis. We demonstrated that the 28-day growth test, as advised by the ISO-guideline, may not be sufficient to assess sublethal toxic effects of realistically contaminated soils. For this purpose, a life cycle experimental set-up is proposed, allowing a thorough assessment of toxicity during successive life stages.

  14. Compound cycle engine program

    NASA Technical Reports Server (NTRS)

    Bobula, G. A.; Wintucky, W. T.; Castor, J. G.

    1987-01-01

    The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded power plant which combines the lightweight pressure rise capability of a gas turbine with the high efficiency of a diesel. When optimized for a rotorcraft, the CCE will reduce fuel burn for a typical 2 hr (plus 30 min reserve) mission by 30 to 40 percent when compared to a conventional advanced technology gas turbine. The CCE can provide a 50 percent increase in range-payload product on this mission. A program to establish the technology base for a Compound Cycle Engine is presented. The goal of this program is to research and develop those technologies which are barriers to demonstrating a multicylinder diesel core in the early 1990's. The major activity underway is a three-phased contract with the Garrett Turbine Engine Company to perform: (1) a light helicopter feasibility study, (2) component technology development, and (3) lubricant and material research and development. Other related activities are also presented.

  15. Compound cycle engine program

    NASA Technical Reports Server (NTRS)

    Bobula, G. A.; Wintucky, W. T.; Castor, J. G.

    1986-01-01

    The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded power plant which combines the lightweight pressure rise capability of a gas turbine with the high efficiency of a diesel. When optimized for a rotorcraft, the CCE will reduce fuel burned for a typical 2 hr (plus 30 min reserve) mission by 30 to 40 percent when compared to a conventional advanced technology gas turbine. The CCE can provide a 50 percent increase in range-payload product on this mission. A program to establish the technology base for a Compound Cycle Engine is presented. The goal of this program is to research and develop those technologies which are barriers to demonstrating a multicylinder diesel core in the early 1990's. The major activity underway is a three-phased contract with the Garrett Turbine Engine Company to perform: (1) a light helicopter feasibility study, (2) component technology development, and (3) lubricant and material research and development. Other related activities are also presented.

  16. The centriole duplication cycle.

    PubMed

    Fırat-Karalar, Elif Nur; Stearns, Tim

    2014-09-01

    Centrosomes are the main microtubule-organizing centre of animal cells and are important for many critical cellular and developmental processes from cell polarization to cell division. At the core of the centrosome are centrioles, which recruit pericentriolar material to form the centrosome and act as basal bodies to nucleate formation of cilia and flagella. Defects in centriole structure, function and number are associated with a variety of human diseases, including cancer, brain diseases and ciliopathies. In this review, we discuss recent advances in our understanding of how new centrioles are assembled and how centriole number is controlled. We propose a general model for centriole duplication control in which cooperative binding of duplication factors defines a centriole 'origin of duplication' that initiates duplication, and passage through mitosis effects changes that license the centriole for a new round of duplication in the next cell cycle. We also focus on variations on the general theme in which many centrioles are created in a single cell cycle, including the specialized structures associated with these variations, the deuterosome in animal cells and the blepharoplast in lower plant cells.

  17. The centriole duplication cycle

    PubMed Central

    Fırat-Karalar, Elif Nur; Stearns, Tim

    2014-01-01

    Centrosomes are the main microtubule-organizing centre of animal cells and are important for many critical cellular and developmental processes from cell polarization to cell division. At the core of the centrosome are centrioles, which recruit pericentriolar material to form the centrosome and act as basal bodies to nucleate formation of cilia and flagella. Defects in centriole structure, function and number are associated with a variety of human diseases, including cancer, brain diseases and ciliopathies. In this review, we discuss recent advances in our understanding of how new centrioles are assembled and how centriole number is controlled. We propose a general model for centriole duplication control in which cooperative binding of duplication factors defines a centriole ‘origin of duplication’ that initiates duplication, and passage through mitosis effects changes that license the centriole for a new round of duplication in the next cell cycle. We also focus on variations on the general theme in which many centrioles are created in a single cell cycle, including the specialized structures associated with these variations, the deuterosome in animal cells and the blepharoplast in lower plant cells. PMID:25047614

  18. Phase 1 results from a study of romidepsin in combination with gemcitabine in patients with advanced solid tumors.

    PubMed

    Jones, Suzanne F; Infante, Jeffrey R; Spigel, David R; Peacock, Nancy W; Thompson, Dana S; Greco, F Anthony; McCulloch, William; Burris, Howard A

    2012-07-01

    Romidepsin is a potent histone deacetylase inhibitor; preclinical studies showed potential synergy with the nucleoside analog gemcitabine. This phase 1 trial was conducted to determine the maximum tolerated dose for two schedules of romidepsin plus gemcitabine in patients with advanced solid tumors in which gemcitabine had previously demonstrated clinical activity. The recommended phase 2 dose was 12 mg/m(2) romidepsin plus 800 mg/m(2) gemcitabine on days 1 and 15 every 28 days. Results suggest additive hematologic toxicities of romidepsin plus gemcitabine, but the level of antitumor activity observed warrants more formal trials of this combination to further assess safety and efficacy.

  19. Effect of desipramine treatment on /sup 3/H-imipramine binding in the blood platelets of depressed patients

    SciTech Connect

    Arora, R.C.; Meltzer, H.Y.

    1988-02-15

    Platelet imipramine binding (IB) was studied in depressed patients before and after treatment with desipramine for 17-28 days. Administration of desipramine was associated with a significant increase in Bmax. There was a trend for an increase in Kd, but it did not reach statistical significance. The net result of the changes in Bmax and Kd was an increase in IB. There were significant correlations between the change in depression ratings and pretreatment Kd, as well as the change in Kd during treatment. These results suggest that decreased IB is not a trait-dependent marker, but a state-dependent marker for depression. 46 references.

  20. Hypothermia as a predictor for mortality in trauma patients at admittance to the Intensive Care Unit

    PubMed Central

    Balvers, Kirsten; Van der Horst, Marjolein; Graumans, Maarten; Boer, Christa; Binnekade, Jan M.; Goslings, J. Carel; Juffermans, Nicole P.

    2016-01-01

    Aims: To study the impact of hypothermia upon admission to the Intensive Care Unit (ICU) on early and late mortality and to develop a prediction model for late mortality in severely injured trauma patients. Materials and Methods: A multicenter retrospective cohort study was performed in adult trauma patients admitted to the ICU of two Level-1 trauma centers between 2007 and 2012. Hypothermia was defined as a core body temperature of ≤35° Celsius. Logistic regression analyses were performed to quantify the effect of hypothermia on 24-hour and 28-day mortality and to develop a prediction model. Results: A total of 953 patients were included, of which 354 patients had hypothermia (37%) upon ICU admission. Patients were divided into a normothermic or hypothermic group. Hypothermia was associated with a significantly increased mortality at 24 hours and 28 days (OR 2.72 (1.18-6.29 and OR 2.82 (1.83-4.35) resp.). The variables included in the final prediction model were hypothermia, age, APACHE II score (corrected for temperature), INR, platelet count, traumatic brain injury and Injury Severity Score. The final prediction model discriminated between survivors and non-survivors with high accuracy (AUC = 0.871, 95% CI 0.844-0.898). Conclusions: Hypothermia, defined as a temperature ≤35° Celsius, is common in critically ill trauma patients and is one of the most important physiological predictors for early and late mortality in trauma patients. Trauma patients admitted to the ICU may be at high risk for late mortality if the patient is hypothermic, coagulopathic, severely injured and has traumatic brain injury or an advanced age. PMID:27512330

  1. Safety of plasma-derived protein C for treating disseminated intravascular coagulation in adult patients with active cancer.

    PubMed

    Malato, Alessandra; Saccullo, Giorgia; Coco, Lucio Lo; Caracciolo, Clementina; Raso, Simona; Santoro, Marco; Zammit, Valentina; Siragusa, Sergio

    2012-02-01

    Cancer-related disseminated intravascular coagulation (DIC) is a life-threatening condition for which no effective treatment is currently available. Protein C (PC), a modulator of coagulation as well as the inflammatory system, has been successfully tested (in its activated recombinant form [a-rPC]) in sepsis-related coagulopathy, but with an increased risk for major bleeding. Plasma-derived PC (pd-PC) is more suitable than a-rPC in patients at high risk from bleeding due to its self-limiting process. We carried out a single-arm study evaluating the role of pd-PC in adult cancer patients with overt DIC. Over a period of 3 years, we treated 19 patients with overt DIC and a PC plasma concentration <50%; all received PC concentrate (Ceprotin(®), Baxter) for 72 hr in adjusted doses to restore normal PC values (70-120%). Blood coagulation, haematological tests, and the DIC score were recorded after 12, 24, 48 hr, 7 and 10 days, while clinical outcomes (bleeding, thrombosis and mortality) were recorded up to 28 days. Within 48 hr of starting pd-PC therapy, laboratory tests as well as the DIC score improved in all patients. At 28-days follow-up, no bleeding or thrombosis was observed. This is the first study to investigate the use of pd- PC for treatment of cancer-related overt DIC.

  2. Open cycle thermoacoustics

    SciTech Connect

    Reid, Robert Stowers

    2000-01-01

    A new type of thermodynamic device combining a thermodynamic cycle with the externally applied steady flow of an open thermodynamic process is discussed and experimentally demonstrated. The gas flowing through this device can be heated or cooled in a series of semi-open cyclic steps. The combination of open and cyclic flows makes possible the elimination of some or all of the heat exchangers (with their associated irreversibility). Heat is directly exchanged with the process fluid as it flows through the device when operating as a refrigerator, producing a staging effect that tends to increase First Law thermodynamic efficiency. An open-flow thermoacoustic refrigerator was built to demonstrate this concept. Several approaches are presented that describe the physical characteristics of this device. Tests have been conducted on this refrigerator with good agreement with a proposed theory.

  3. Sulphur geodynamic cycle

    PubMed Central

    Kagoshima, Takanori; Sano, Yuji; Takahata, Naoto; Maruoka, Teruyuki; Fischer, Tobias P.; Hattori, Keiko

    2015-01-01

    Evaluation of volcanic and hydrothermal fluxes to the surface environments is important to elucidate the geochemical cycle of sulphur and the evolution of ocean chemistry. This paper presents S/3He ratios of vesicles in mid-ocean ridge (MOR) basalt glass together with the ratios of high-temperature hydrothermal fluids to calculate the sulphur flux of 100 Gmol/y at MOR. The S/3He ratios of high-temperature volcanic gases show sulphur flux of 720 Gmol/y at arc volcanoes (ARC) with a contribution from the mantle of 2.9%, which is calculated as 21 Gmol/y. The C/S flux ratio of 12 from the mantle at MOR and ARC is comparable to the C/S ratio in the surface inventory, which suggests that these elements in the surface environments originated from the upper mantle. PMID:25660256

  4. Deep sulfur cycle

    NASA Astrophysics Data System (ADS)

    Shimizu, N.; Mandeville, C. W.

    2009-12-01

    Geochemical cycle of sulfur in near-surface reservoirs has been a subject of intense studies for decades. It has been shown that sulfur isotopic compositions of sedimentary sulfides and sulfates record interactions of the atmosphere, hydrosphere, biosphere and lithosphere, with δ34S of sedimentary sulfides continuously decreasing from 0‰ toward present-day values of ~-30 to -40‰ over the Phanerozoic (e.g., Canfield, 2004). It has also been shown that microbial reduction of the present-day seawater sulfate (δ34S=+21‰) results in large shifts in isotopic compositions of secondary pyrites in altered oceanic crust (to δ34S=-70‰: Rouxel et al., 2009). How much of these near surface isotopic variations survive during deep geochemical cycle of sulfur interacting with the mantle infinite reservoir with δ34S=0‰? Could extent of their survival be used as a tracer of processes and dynamics involved in deep geochemical cycle? As a first step toward answering these questions, δ34S was determined in-situ using a Cameca IMS 1280 ion microprobe at Woods Hole Oceanographic Institution in materials representing various domains of deep geochemical cycle. They include pyrites in altered MORB as potential subducting materials and pyrites in UHP eclogites as samples that have experienced subduction zone processes, and mantle-derived melts are represented by olivine-hosted melt inclusions in MORB and those in IAB, and undegassed submarine OIB glasses. Salient features of the results include: (1) pyrites in altered MORB (with O. Rouxel; from ODP site 801 and ODP Hole 1301B) range from -70 to +19‰, (2) pyrites in UHP eclogites from the Western Gneiss Region, Norway (with B. Hacker and A. Kylander-Clark) show a limited overall range from -3.4 to + 2.8‰ among five samples, with one of them covering almost the entire range, indicating limited scale lengths of isotopic equilibration during subduction, (3) olivine-hosted melt inclusions in arc basalts from Galunggung (-2

  5. The supercontinent cycle

    SciTech Connect

    Nance, R.D.; Worsley, T.R.; Moody, J.B.

    1988-07-01

    This paper discusses a new theory of plate tectonics which proposes that Pangaea was only the most recent in a series of supercontinents that have been breaking up and reassembling every 500 million years or so. The cycle, driven by heat percolating up from the mantle, splits continents and drives interrelated processes that shape the earth's geology and climate and play a role in biological evolution. The framework of the supercontinent theory makes it possible to understand the timing of changes in sea level that have taken place in the past 570 million years, and also helps to explain periods of intense mountain building, episodes of glaciation, and changes in the nature of life on the earth.

  6. The Pyrogenic Carbon Cycle

    NASA Astrophysics Data System (ADS)

    Bird, Michael I.; Wynn, Jonathan G.; Saiz, Gustavo; Wurster, Christopher M.; McBeath, Anna

    2015-05-01

    Pyrogenic carbon (PyC; includes soot, char, black carbon, and biochar) is produced by the incomplete combustion of organic matter accompanying biomass burning and fossil fuel consumption. PyC is pervasive in the environment, distributed throughout the atmosphere as well as soils, sediments, and water in both the marine and terrestrial environment. The physicochemical characteristics of PyC are complex and highly variable, dependent on the organic precursor and the conditions of formation. A component of PyC is highly recalcitrant and persists in the environment for millennia. However, it is now clear that a significant proportion of PyC undergoes transformation, translocation, and remineralization by a range of biotic and abiotic processes on comparatively short timescales. Here we synthesize current knowledge of the production, stocks, and fluxes of PyC as well as the physical and chemical processes through which it interacts as a dynamic component of the global carbon cycle.

  7. Nutrient Cycling Study

    SciTech Connect

    Peter A. Pryfogle

    2005-09-01

    The particular goal of this study is to develop measurement techniques for understanding how consortia of organisms from geothermal facilities utilize sulfur and iron for metabolic activity; and in turn, what role that activity plays in initiating or promoting the development of a biofilm on plant substrates. Sulfur cycling is of interest because sulfur is produced in the resource. Iron is found in some of the steel formulations used in plant components and is also added as chemical treatment for reducing sulfide emissions from the plants. This report describes the set-up and operation of a bioreactor for evaluating the response of colonies of geothermal organisms to changes in nutrient and environmental conditions. Data from initial experiments are presented and plans for future testing is discussed.

  8. Sulphur geodynamic cycle.

    PubMed

    Kagoshima, Takanori; Sano, Yuji; Takahata, Naoto; Maruoka, Teruyuki; Fischer, Tobias P; Hattori, Keiko

    2015-01-01

    Evaluation of volcanic and hydrothermal fluxes to the surface environments is important to elucidate the geochemical cycle of sulphur and the evolution of ocean chemistry. This paper presents S/(3)He ratios of vesicles in mid-ocean ridge (MOR) basalt glass together with the ratios of high-temperature hydrothermal fluids to calculate the sulphur flux of 100 Gmol/y at MOR. The S/(3)He ratios of high-temperature volcanic gases show sulphur flux of 720 Gmol/y at arc volcanoes (ARC) with a contribution from the mantle of 2.9%, which is calculated as 21 Gmol/y. The C/S flux ratio of 12 from the mantle at MOR and ARC is comparable to the C/S ratio in the surface inventory, which suggests that these elements in the surface environments originated from the upper mantle. PMID:25660256

  9. Coupled quantum Otto cycle.

    PubMed

    Thomas, George; Johal, Ramandeep S

    2011-03-01

    We study the one-dimensional isotropic Heisenberg model of two spin-1/2 systems as a quantum heat engine. The engine undergoes a four-step Otto cycle where the two adiabatic branches involve changing the external magnetic field at a fixed value of the coupling constant. We find conditions for the engine efficiency to be higher than in the uncoupled model; in particular, we find an upper bound which is tighter than the Carnot bound. A domain of parameter values is pointed out which was not feasible in the interaction-free model. Locally, each spin seems to cause a flow of heat in a direction opposite to the global temperature gradient. This feature is explained by an analysis of the local effective temperature of the spins.

  10. Krebs Cycle Wordsearch

    NASA Astrophysics Data System (ADS)

    Helser, Terry L.

    2001-04-01

    This puzzle embeds 46 names, terms, abbreviations, and acronyms about the citric acid (Krebs) cycle in a 14- x 17-letter matrix. A descriptive narrative beside it describes important features of the pathway. All the terms a student needs to find are embedded there with the first letter followed by underlined blanks to be completed. Therefore, the students usually must find the terms to know how to spell them, correctly fill in the blanks in the narrative with the terms, and then find and highlight the terms in the letter matrix. When all are found, the 24 unused letters complete a sentence that describes a major feature of this central pathway. The puzzle may be used as homework, an extra-credit project, or a group project in the classroom in any course where basic metabolism is learned. It disguises as fun the hard work needed to learn the names of the intermediates, enzymes, and cofactors.

  11. Quantitative culture of endotracheal aspirate and BAL fluid samples in the management of patients with ventilator-associated pneumonia: a randomized clinical trial* **

    PubMed Central

    Corrêa, Ricardo de Amorim; Luna, Carlos Michel; dos Anjos, José Carlos Fernandez Versiani; Barbosa, Eurípedes Alvarenga; de Rezende, Cláudia Juliana; Rezende, Adriano Pereira; Pereira, Fernando Henrique; Rocha, Manoel Otávio da Costa

    2014-01-01

    OBJECTIVE: To compare 28-day mortality rates and clinical outcomes in ICU patients with ventilator-associated pneumonia according to the diagnostic strategy used. METHODS: This was a prospective randomized clinical trial. Of the 73 patients included in the study, 36 and 37 were randomized to undergo BAL or endotracheal aspiration (EA), respectively. Antibiotic therapy was based on guidelines and was adjusted according to the results of quantitative cultures. RESULTS: The 28-day mortality rate was similar in the BAL and EA groups (25.0% and 37.8%, respectively; p = 0.353). There were no differences between the groups regarding the duration of mechanical ventilation, antibiotic therapy, secondary complications, VAP recurrence, or length of ICU and hospital stay. Initial antibiotic therapy was deemed appropriate in 28 (77.8%) and 30 (83.3%) of the patients in the BAL and EA groups, respectively (p = 0.551). The 28-day mortality rate was not associated with the appropriateness of initial therapy in the BAL and EA groups (appropriate therapy: 35.7% vs. 43.3%; p = 0.553; and inappropriate therapy: 62.5% vs. 50.0%; p = 1.000). Previous use of antibiotics did not affect the culture yield in the EA or BAL group (p = 0.130 and p = 0.484, respectively). CONCLUSIONS: In the context of this study, the management of VAP patients, based on the results of quantitative endotracheal aspirate cultures, led to similar clinical outcomes to those obtained with the results of quantitative BAL fluid cultures. PMID:25610505

  12. 78 FR 48691 - Food and Drug Administration Patient Network Annual Meeting; Demystifying Food and Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-09

    ... Drug Development Life Cycle We believe that enhancing patients' understanding of the drug development... clarify where patient input can be most meaningful in the drug development life cycle. Patients who...

  13. Breaking the cycle: extending the persistent pain cycle diagram using an affective pictorial metaphor.

    PubMed

    Stones, Catherine; Cole, Frances

    2014-01-01

    The persistent pain cycle diagram is a common feature of pain management literature. but how is it designed and is it fulfilling its potential in terms of providing information to motivate behavioral change? This article examines on-line persistent pain diagrams and critically discusses their purpose and design approach. By using broad information design theories by Karabeg and particular approaches to dialogic visual communications in business, this article argues the need for motivational as well as cognitive diagrams. It also outlines the design of a new persistent pain cycle that is currently being used with chronic pain patients in NHS Bradford, UK. This new cycle adopts and then visually extends an established verbal metaphor within acceptance and commitment therapy (ACT) in an attempt to increase the motivational aspects of the vicious circle diagram format.

  14. Prediction of Solar Cycle Maximum Using Solar Cycle Lengths

    NASA Astrophysics Data System (ADS)

    Kane, R. P.

    2008-03-01

    If the rise time RT, fall time FT, and total time TT ( i.e., RT+FT) of a solar cycle are compared against the maximum amplitude Rz(max ) for the following cycle, then only the association between TT and Rz(max ) is inferred to be well anticorrelated, inferring that the larger (smaller) the value of Rz(max ) for the following cycle, the shorter (longer) the TT of the preceding cycle. Although the inferred correlation (-0.68) is statistically significant, the inferred standard error of estimate is quite large, so predictions using the inferred correlation are not very precise. Removal of cycle pairs 15/16, 19/20, and 20/21 (statistical outliers) yields a regression that is highly statistically significant (-0.85) and reduces the standard error of estimate by 18%. On the basis of the adjusted regression and presuming TT=140 months for cycle 23, the present ongoing cycle, cycle 24’s 90% prediction interval for Rz(max ) is estimated to be about 94±44, inferring only a 5% probability that its Rz(max ) will be larger than about 140, unless of course cycle pair 23/24 is a statistical outlier.

  15. A silicon cell cycle in a bacterial model of calcium phosphate mineralogenesis.

    PubMed

    Linton, Kathryn M; Tapping, Charles R; Adams, David G; CarterR, D Howard; Shore, Roger C; Aaron, Jean E

    2013-01-01

    The prokaryote Corynebacterium matruchotii produces calcium phosphate (bone salt) and may serve as a convenient model for examining individual factors relevant to vertebrate calcification. A factor of current clinical uncertainty is silicon. To investigate its possible role in biomineralisation advanced optical (digital deconvolution and 3D fluorescent image rendering) and electron microscopy (EDX microanalysis and elemental mapping) were applied to calcifying microbial colonies grown in graded Si concentrations (0-60mM). Cell viability was confirmed throughout by TO-PRO-3-iodide and SYTO-9 nucleic acid staining. It was observed that calcium accumulated in dense intracellular microspherical objects (types i-iii) as nanoparticles (5 nm, type i), nanospheres (30-50 nm, type ii) and filamentous clusters (0.1-0.5 μm, type iii), with a regular transitory Si content evident. With bacterial colony development (7-28 days) the P content increased from 5 to 60%, while Si was displaced from 60 to 5%, distinguishing the phenomenon from random contamination, and with a significant relationship (p<0.001) found between calcified object number and Si supplementation (optimum 0.01mM). The Si-containing, intracellular calcified objects (also positive for Mg and negative with Lysensor blue DND-167 for acidocalcisomes) were extruded naturally in bubble-like chains to complete the cycle by coating the cell surface with discrete mineral particles. These could be harvested by lysis, French press and density fractionation when Si was confirmed in a proportion. It was concluded that the unexplained orthopaedic activity of Si may derive from its special property to facilitate calcium phosphorylation in biological systems, thereby recapitulating an ancient and conserved bacterial cycle of calcification via silicification. PMID:23098642

  16. Reproductive cycles of buffalo.

    PubMed

    Perera, B M A O

    2011-04-01

    The domestic water buffalo (Bubalus bubalis) has an important role in the agricultural economy of many developing countries in Asia, providing milk, meat and draught power. It is also used in some Mediterranean and Latin American countries as a source of milk and meat for specialized markets. Although the buffalo can adapt to harsh environments and live on poor quality forage, reproductive efficiency is often compromised by such conditions, resulting in late sexual maturity, long postpartum anoestrus, poor expression of oestrus, poor conception rates and long calving intervals. The age at puberty is influenced by genotype, nutrition, management and climate, and under favourable conditions occurs at 15-18 months in river buffalo and 21-24 months in swamp buffalo. The ovaries are smaller than in cattle and contain fewer primordial follicles. Buffalo are capable of breeding throughout the year, but in many countries a seasonal pattern of ovarian activity occurs. This is attributed in tropical regions to changes in rainfall resulting in feed availability or to temperature stress resulting in elevated prolactin secretion, and in temperate regions to changes in photoperiod and melatonin secretion. The mean length of the oestrous cycle is 21 days, with greater variation than observed in cattle. The signs of oestrus in buffalo are less overt than in cattle and homosexual behaviour between females is rare. The duration of oestrus is 5-27 h, with ovulation occurring 24-48 h (mean 34 h) after the onset of oestrus. The hormonal changes occurring in peripheral circulation are similar to those observed in cattle, but the peak concentrations of progesterone and oestradiol-17β are less. The number of follicular waves during an oestrous cycle varies from one to three and influences the length of the luteal phase as well as the inter-ovulatory interval. Under optimal conditions, dairy types managed with limited or no suckling resume oestrus cyclicity by 30-60 days after calving

  17. Reproductive cycles of buffalo.

    PubMed

    Perera, B M A O

    2011-04-01

    The domestic water buffalo (Bubalus bubalis) has an important role in the agricultural economy of many developing countries in Asia, providing milk, meat and draught power. It is also used in some Mediterranean and Latin American countries as a source of milk and meat for specialized markets. Although the buffalo can adapt to harsh environments and live on poor quality forage, reproductive efficiency is often compromised by such conditions, resulting in late sexual maturity, long postpartum anoestrus, poor expression of oestrus, poor conception rates and long calving intervals. The age at puberty is influenced by genotype, nutrition, management and climate, and under favourable conditions occurs at 15-18 months in river buffalo and 21-24 months in swamp buffalo. The ovaries are smaller than in cattle and contain fewer primordial follicles. Buffalo are capable of breeding throughout the year, but in many countries a seasonal pattern of ovarian activity occurs. This is attributed in tropical regions to changes in rainfall resulting in feed availability or to temperature stress resulting in elevated prolactin secretion, and in temperate regions to changes in photoperiod and melatonin secretion. The mean length of the oestrous cycle is 21 days, with greater variation than observed in cattle. The signs of oestrus in buffalo are less overt than in cattle and homosexual behaviour between females is rare. The duration of oestrus is 5-27 h, with ovulation occurring 24-48 h (mean 34 h) after the onset of oestrus. The hormonal changes occurring in peripheral circulation are similar to those observed in cattle, but the peak concentrations of progesterone and oestradiol-17β are less. The number of follicular waves during an oestrous cycle varies from one to three and influences the length of the luteal phase as well as the inter-ovulatory interval. Under optimal conditions, dairy types managed with limited or no suckling resume oestrus cyclicity by 30-60 days after calving

  18. The Global Nitrogen Cycle

    NASA Astrophysics Data System (ADS)

    Galloway, J. N.

    2003-12-01

    Once upon a time nitrogen did not exist. Today it does. In the intervening time the universe was formed, nitrogen was created, the Earth came into existence, and its atmosphere and oceans were formed! In this analysis of the Earth's nitrogen cycle, I start with an overview of these important events relative to nitrogen and then move on to the more traditional analysis of the nitrogen cycle itself and the role of humans in its alteration.The universe is ˜15 Gyr old. Even after its formation, there was still a period when nitrogen did not exist. It took ˜300 thousand years after the big bang for the Universe to cool enough to create atoms; hydrogen and helium formed first. Nitrogen was formed in the stars through the process of nucleosynthesis. When a star's helium mass becomes great enough to reach the necessary pressure and temperature, helium begins to fuse into still heavier elements, including nitrogen.Approximately 10 Gyr elapsed before Earth was formed (˜4.5 Ga (billion years ago)) by the accumulation of pre-assembled materials in a multistage process. Assuming that N2 was the predominate nitrogen species in these materials and given that the temperature of space is -270 °C, N2 was probably a solid when the Earth was formed since its boiling point (b.p.) and melting point (m.p.) are -196 °C and -210 °C, respectively. Towards the end of the accumulation period, temperatures were probably high enough for significant melting of some of the accumulated material. The volcanic gases emitted by the resulting volcanism strongly influenced the surface environment. Nitrogen was converted from a solid to a gas and emitted as N2. Carbon and sulfur were probably emitted as CO and H2S (Holland, 1984). N2 is still the most common nitrogen volcanic gas emitted today at a rate of ˜2 TgN yr-1 (Jaffee, 1992).Once emitted, the gases either remained in the atmosphere or were deposited to the Earth's surface, thus continuing the process of biogeochemical cycling. The rate of

  19. Advanced regenerative absorption refrigeration cycles

    DOEpatents

    Dao, Kim

    1990-01-01

    Multi-effect regenerative absorption cycles which provide a high coefficient of performance (COP) at relatively high input temperatures. An absorber-coupled double-effect regenerative cycle (ADR cycle) (10) is provided having a single-effect absorption cycle (SEA cycle) (11) as a topping subcycle and a single-effect regenerative absorption cycle (1R cycle) (12) as a bottoming subcycle. The SEA cycle (11) includes a boiler (13), a condenser (21), an expansion device (28), an evaporator (31), and an absorber (40), all operatively connected together. The 1R cycle (12) includes a multistage boiler (48), a multi-stage resorber (51), a multisection regenerator (49) and also uses the condenser (21), expansion device (28) and evaporator (31) of the SEA topping subcycle (11), all operatively connected together. External heat is applied to the SEA boiler (13) for operation up to about 500 degrees F., with most of the high pressure vapor going to the condenser (21) and evaporator (31) being generated by the regenerator (49). The substantially adiabatic and isothermal functioning of the SER subcycle (12) provides a high COP. For higher input temperatures of up to 700 degrees F., another SEA cycle (111) is used as a topping subcycle, with the absorber (140) of the topping subcycle being heat coupled to the boiler (13) of an ADR cycle (10). The 1R cycle (12) itself is an improvement in that all resorber stages (50b-f) have a portion of their output pumped to boiling conduits (71a-f) through the regenerator (49), which conduits are connected to and at the same pressure as the highest pressure stage (48a) of the 1R multistage boiler (48).

  20. The Cycles of Math and Science.

    ERIC Educational Resources Information Center

    Sumrall, William J.; Rock, David

    2002-01-01

    Introduces lesson plans on cycles designed for middle school students. Activities include: (1) "Boiling and Evaporation"; (2) "Experimenting with Evaporation"; (3) "Condensation and the Water Cycle"; and (4) "Understanding Cycles". Explains the mathematical applications of cycles. (YDS)

  1. How do prokaryotic cells cycle?

    PubMed

    Margolin, William; Bernander, Rolf

    2004-09-21

    This issue of Current Biology features five reviews covering various key aspects of the eukaryotic cell cycle. The topics include initiation of chromosome replication, assembly of the mitotic spindle, cytokinesis, the regulation of cell-cycle progression, and cell-cycle modeling, focusing mainly on budding yeast, fission yeast and animal cell model systems. The reviews underscore common themes as well as key differences in the way these processes are carried out and regulated among the different model organisms. Consequently, an important question is how cell-cycle mechanisms and controls have evolved, particularly in the broader perspective of the three domains of life.

  2. Regenerative superheated steam turbine cycles

    NASA Technical Reports Server (NTRS)

    Fuller, L. C.; Stovall, T. K.

    1980-01-01

    PRESTO computer program was developed to analyze performance of wide range of steam turbine cycles with special attention given to regenerative superheated steam turbine cycles. It can be used to model standard turbine cycles, including such features as process steam extraction, induction and feedwater heating by external sources, peaking, and high back pressure. Expansion line efficiencies, exhaust loss, leakages, mechanical losses, and generator losses are used to calculate cycle heat rate and generator output. Program provides power engineer with flexible aid for design and analysis of steam turbine systems.

  3. Self-organizing biochemical cycles

    NASA Technical Reports Server (NTRS)

    Orgel, L. E.; Bada, J. L. (Principal Investigator)

    2000-01-01

    I examine the plausibility of theories that postulate the development of complex chemical organization without requiring the replication of genetic polymers such as RNA. One conclusion is that theories that involve the organization of complex, small-molecule metabolic cycles such as the reductive citric acid cycle on mineral surfaces make unreasonable assumptions about the catalytic properties of minerals and the ability of minerals to organize sequences of disparate reactions. Another conclusion is that data in the Beilstein Handbook of Organic Chemistry that have been claimed to support the hypothesis that the reductive citric acid cycle originated as a self-organized cycle can more plausibly be interpreted in a different way.

  4. The Learning Cycle: A Reintroduction

    NASA Astrophysics Data System (ADS)

    Maier, Steven J.; Marek, Edmund A.

    2006-02-01

    The learning cycle is an inquiry approach to instruction that continues to demonstrate significant effectiveness in the classroom.1-3 Rooted in Piaget's theory of intellectual development, learning cycles provide a structured means for students to construct concepts from direct experiences with science phenomena. Learning cycles have been the subject of numerous articles in science practitioner periodicals as well as the focus of much research in science education journals.4 This paper reintroduces the learning cycle by giving a brief description, followed by an example suitable for a range of physics classrooms.

  5. Glacial cycles and astronomical forcing

    SciTech Connect

    Muller, R.A.; MacDonald, G.J.

    1997-07-11

    Narrow spectral features in ocean sediment records offer strong evidence that the cycles of glaciation were driven by astronomical forces. Two million years ago, the cycles match the 41,000-year period of Earth`s obliquity. This supports the Croll/Milankovitch theory, which attributes the cycles to variations in insolation. But for the past million years, the spectrum is dominated by a single 100,000-year feature and is a poor match to the predictions of insolation models. The spectrum can be accounted for by a theory that derives the cycles of glaciation from variations in the inclination of Earth`s orbital plane.

  6. The nitrogen cycle.

    PubMed

    Stein, Lisa Y; Klotz, Martin G

    2016-02-01

    Nitrogen is the fourth most abundant element in cellular biomass, and it comprises the majority of Earth's atmosphere. The interchange between inert dinitrogen gas (N2) in the extant atmosphere and 'reactive nitrogen' (those nitrogen compounds that support, or are products of, cellular metabolism and growth) is entirely controlled by microbial activities. This was not the case, however, in the primordial atmosphere, when abiotic reactions likely played a significant role in the inter-transformation of nitrogen oxides. Although such abiotic reactions are still important, the extant nitrogen cycle is driven by reductive fixation of dinitrogen and an enzyme inventory that facilitates dinitrogen-producing reactions. Prior to the advent of the Haber-Bosch process (the industrial fixation of N2 into ammonia, NH3) in 1909, nearly all of the reactive nitrogen in the biosphere was generated and recycled by microorganisms. Although the Haber-Bosch process more than quadrupled the productivity of agricultural crops, chemical fertilizers and other anthropogenic sources of fixed nitrogen now far exceed natural contributions, leading to unprecedented environmental degradation.

  7. The closed fuel cycle

    SciTech Connect

    Froment, Antoine; Gillet, Philippe

    2007-07-01

    Available in abstract form only. Full text of publication follows: The fast growth of the world's economy coupled with the need for optimizing use of natural resources, for energy security and for climate change mitigation make energy supply one of the 21. century most daring challenges. The high reliability and efficiency of nuclear energy, its competitiveness in an energy market undergoing a new oil shock are as many factors in favor of the 'renaissance' of this greenhouse gas free energy. Over 160,000 tHM of LWR1 and AGR2 Used Nuclear Fuel (UNF) have already been unloaded from the reactor cores corresponding to 7,000 tons discharged per year worldwide. By 2030, this amount could exceed 400,000 tHM and annual unloading 14,000 tHM/year. AREVA believes that closing the nuclear fuel cycle through the treatment and recycling of Used Nuclear Fuel sustains the worldwide nuclear power expansion. It is an economically sound and environmentally responsible choice, based on the preservation of natural resources through the recycling of used fuel. It furthermore provides a safe and secure management of wastes while significantly minimizing the burden left to future generations. (authors)

  8. Wilson Cycle studies

    NASA Technical Reports Server (NTRS)

    Burke, Kevin

    1987-01-01

    The main activity relating to the study during this half year was a three week field trip to study Chinese sedimentary basins (June 10 to July 3, 1986) at no cost to the project. This study, while of a reconnaissance character, permitted progress in understanding how the processes of island arc-collision and micro-continental collision operated during the Paleozoic in far western China (especially the Junggar and Tarim basins and in the intervening Tien Shan Mountains). These effects of the continuing collision of India and Asia on the area were also studied. Most specifically, these result in the elevation of the Tien Shan to more than 4 km above sea level and the depression of Turfan to move 150m below sea level. Both thrusting and large-scale strike-slip motion are important in producing these elevation changes. Some effort during the half year was also devoted to the study of greenstone-belts in terms of the Wilson Cycle.

  9. Biomass Gasification Combined Cycle

    SciTech Connect

    Judith A. Kieffer

    2000-07-01

    Gasification combined cycle continues to represent an important defining technology area for the forest products industry. The ''Forest Products Gasification Initiative'', organized under the Industry's Agenda 2020 technology vision and supported by the DOE ''Industries of the Future'' program, is well positioned to guide these technologies to commercial success within a five-to ten-year timeframe given supportive federal budgets and public policy. Commercial success will result in significant environmental and renewable energy goals that are shared by the Industry and the Nation. The Battelle/FERCO LIVG technology, which is the technology of choice for the application reported here, remains of high interest due to characteristics that make it well suited for integration with the infrastructure of a pulp production facility. The capital cost, operating economics and long-term demonstration of this technology area key input to future economically sustainable projects and must be verified by the 200 BDT/day demonstration facility currently operating in Burlington, Vermont. The New Bern application that was the initial objective of this project is not currently economically viable and will not be implemented at this time due to several changes at and around the mill which have occurred since the inception of the project in 1995. The analysis shows that for this technology, and likely other gasification technologies as well, the first few installations will require unique circumstances, or supportive public policies, or both to attract host sites and investors.

  10. Organic rankine cycle fluid

    DOEpatents

    Brasz, Joost J.; Jonsson, Ulf J.

    2006-09-05

    A method of operating an organic rankine cycle system wherein a liquid refrigerant is circulated to an evaporator where heat is introduced to the refrigerant to convert it to vapor. The vapor is then passed through a turbine, with the resulting cooled vapor then passing through a condenser for condensing the vapor to a liquid. The refrigerant is one of CF.sub.3CF.sub.2C(O)CF(CF.sub.3).sub.2, (CF.sub.3).sub.2 CFC(O)CF(CF.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.2C(O)CF(CF.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.3C(O)CF(CG.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.5C(O)CF.sub.3, CF.sub.3CF.sub.2C(O)CF.sub.2CF.sub.2CF.sub.3, CF.sub.3C(O)CF(CF.sub.3).sub.2.

  11. The Photosynthetic Cycle

    DOE R&D Accomplishments Database

    Calvin, Melvin

    1955-03-21

    A cyclic sequence of transformations, including the carboxylation of RuDP (ribulose diphosphate) and its re-formation, has been deduced as the route for the creation of reduced carbon compounds in photosynthetic organisms. With the demonstration of RuDP as substrate for the carboxylation in a cell-free system, each of the reactions has now been carried out independently in vitro. Further purification of this last enzyme system has confirmed the deduction that the carboxylation of RuDP leads directly to the two molecules of PGA (phosphoglyceric acid) involving an internal dismutation and suggesting the name "carboxydismutase" for the enzyme. As a consequence of this knowledge of each of the steps in the photosynthetic CO{sub 2} reduction cycle, it is possible to define the reagent requirements to maintain it. The net requirement for the reduction of one molecule of CO{sub 2} is four equivalents of [H]and three molecules of ATP (adenine triphosphate). These must ultimately be supplied by the photochemical reaction. Some possible ways in which this may be accomplished are discussed.

  12. The nitrogen cycle.

    PubMed

    Stein, Lisa Y; Klotz, Martin G

    2016-02-01

    Nitrogen is the fourth most abundant element in cellular biomass, and it comprises the majority of Earth's atmosphere. The interchange between inert dinitrogen gas (N2) in the extant atmosphere and 'reactive nitrogen' (those nitrogen compounds that support, or are products of, cellular metabolism and growth) is entirely controlled by microbial activities. This was not the case, however, in the primordial atmosphere, when abiotic reactions likely played a significant role in the inter-transformation of nitrogen oxides. Although such abiotic reactions are still important, the extant nitrogen cycle is driven by reductive fixation of dinitrogen and an enzyme inventory that facilitates dinitrogen-producing reactions. Prior to the advent of the Haber-Bosch process (the industrial fixation of N2 into ammonia, NH3) in 1909, nearly all of the reactive nitrogen in the biosphere was generated and recycled by microorganisms. Although the Haber-Bosch process more than quadrupled the productivity of agricultural crops, chemical fertilizers and other anthropogenic sources of fixed nitrogen now far exceed natural contributions, leading to unprecedented environmental degradation. PMID:26859274

  13. Specific cell cycle synchronization with butyrate and cell cycle analysis.

    PubMed

    Li, Congjun

    2011-01-01

    Synchronized cells have been invaluable in many kinds of cell cycle and cell proliferation studies. Butyrate induces cell cycle arrest and apoptosis in Madin Darby Bovine Kidney (MDBK) cells. We explore the possibility of using butyrate-blocked cells to obtain synchronized cells and we characterize the properties of butyrate-induced cell cycle arrest. The site of growth inhibition and cell cycle arrest was analyzed using 5-bromo-2'-deoxyuridine (BrdU) incorporation and flow cytometry analyses. Exposure of MDBK cells to 10 mM butyrate caused growth inhibition and cell cycle arrest in a reversible manner. Butyrate affected the cell cycle at a specific point both immediately after mitosis and at a very early stage of the G1 phase. After release from butyrate arrest, MDBK cells underwent synchronous cycles of DNA synthesis and transited through the S phase. It takes at least 8 h for butyrate-induced G1-synchronized cells to begin the progression into the S phase. One cycle of cell division for MDBK cells is about 20 h. By combining BrdU incorporation and DNA content analysis, not only can the overlapping of different cell populations be eliminated, but the frequency and nature of individual cells that have synthesized DNA can also be determined.

  14. Improving long term outcomes in urea cycle disorders-report from the Urea Cycle Disorders Consortium.

    PubMed

    Waisbren, Susan E; Gropman, Andrea L; Batshaw, Mark L

    2016-07-01

    The Urea Cycle Disorders Consortium (UCDC) has conducted, beginning in 2006, a longitudinal study (LS) of eight enzyme deficiencies/transporter defects associated with the urea cycle. These include N-acetylglutamate synthase deficiency (NAGSD); Carbamyl phosphate synthetase 1 deficiency (CPS1D); Ornithine transcarbamylase deficiency (OTCD); Argininosuccinate synthetase deficiency (ASSD) (Citrullinemia); Argininosuccinate lyase deficiency (ASLD) (Argininosuccinic aciduria); Arginase deficiency (ARGD, Argininemia); Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome (or mitochondrial ornithine transporter 1 deficiency [ORNT1D]); and Citrullinemia type II (mitochondrial aspartate/glutamate carrier deficiency [CITRIN]). There were 678 UCD patients enrolled in 14 sites in the U.S., Canada, and Europe at the writing of this paper. This review summarizes findings of the consortium related to outcome, focusing primarily on neuroimaging findings and neurocognitive function. Neuroimaging studies in late onset OTCD offered evidence that brain injury caused by biochemical dysregulation may impact functional neuroanatomy serving working memory processes, an important component of executive function and regulation. Additionally, there were alteration in white mater microstructure and functional connectivity at rest. Intellectual deficits in OTCD and other urea cycle disorders (UCD) vary. However, when neuropsychological deficits occur, they tend to be more prominent in motor/performance areas on both intelligence tests and other measures. In some disorders, adults performed significantly less well than younger patients. Further longitudinal follow-up will reveal whether this is due to declines throughout life or to improvements in diagnostics (especially newborn screening) and treatments in the younger generation of patients.

  15. Improving long term outcomes in urea cycle disorders-report from the Urea Cycle Disorders Consortium.

    PubMed

    Waisbren, Susan E; Gropman, Andrea L; Batshaw, Mark L

    2016-07-01

    The Urea Cycle Disorders Consortium (UCDC) has conducted, beginning in 2006, a longitudinal study (LS) of eight enzyme deficiencies/transporter defects associated with the urea cycle. These include N-acetylglutamate synthase deficiency (NAGSD); Carbamyl phosphate synthetase 1 deficiency (CPS1D); Ornithine transcarbamylase deficiency (OTCD); Argininosuccinate synthetase deficiency (ASSD) (Citrullinemia); Argininosuccinate lyase deficiency (ASLD) (Argininosuccinic aciduria); Arginase deficiency (ARGD, Argininemia); Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome (or mitochondrial ornithine transporter 1 deficiency [ORNT1D]); and Citrullinemia type II (mitochondrial aspartate/glutamate carrier deficiency [CITRIN]). There were 678 UCD patients enrolled in 14 sites in the U.S., Canada, and Europe at the writing of this paper. This review summarizes findings of the consortium related to outcome, focusing primarily on neuroimaging findings and neurocognitive function. Neuroimaging studies in late onset OTCD offered evidence that brain injury caused by biochemical dysregulation may impact functional neuroanatomy serving working memory processes, an important component of executive function and regulation. Additionally, there were alteration in white mater microstructure and functional connectivity at rest. Intellectual deficits in OTCD and other urea cycle disorders (UCD) vary. However, when neuropsychological deficits occur, they tend to be more prominent in motor/performance areas on both intelligence tests and other measures. In some disorders, adults performed significantly less well than younger patients. Further longitudinal follow-up will reveal whether this is due to declines throughout life or to improvements in diagnostics (especially newborn screening) and treatments in the younger generation of patients. PMID:27215558

  16. Long-Term Results of a Prospective, Phase II Study of Long-Term Androgen Ablation, Pelvic Radiotherapy, Brachytherapy Boost, and Adjuvant Docetaxel in Patients With High-Risk Prostate Cancer

    SciTech Connect

    DiBiase, Steven J.; Hussain, Arif; Kataria, Ritesh; Amin, Pradip; Bassi, Sunakshi; Dawson, Nancy; Kwok, Young

    2011-11-01

    Purpose: We report the long-term results of a prospective, Phase II study of long-term androgen deprivation (AD), pelvic radiotherapy (EBRT), permanent transperineal prostate brachytherapy boost (PB), and adjuvant docetaxel in patients with high-risk prostate cancer. Methods and Materials: Eligibility included biopsy-proven prostate adenocarcinoma with the following: prostate-specific antigen (PSA) > 20 ng/ml; or Gleason score of 7 and a PSA >10 ng/ml; or any Gleason score of 8 to 10; or stage T2b to T3 irrespective of Gleason score or PSA. Treatment consisted of 45 Gy of pelvic EBRT, followed 1 month later by PB with either iodine-125 or Pd-103. One month after PB, patients received three cycles of docetaxel chemotherapy (35 mg/m{sup 2} per week, Days 1, 8, and 15 every 28 days). All patients received 2 years of AD. Biochemical failure was defined as per the Phoenix definition (PSA nadir + 2). Results: From August 2000 to March 2004, 42 patients were enrolled. The median overall and active follow-ups were 5.6 years (range, 0.9-7.8 years) and 6.3 years (range, 4-7.8 years), respectively. Grade 2 and 3 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 50.0% and 14.2%, respectively, with no Grade 4 toxicities noted. Grade 3 and 4 acute hematologic toxicities were 19% and 2.4%, respectively. Of the patients, 85.7% were able to complete the planned multimodality treatment. The 5- and 7-year actuarial freedom from biochemical failures rates were 89.6% and 86.5%, and corresponding rates for disease-free survival were 76.2% and 70.4%, respectively. The 5- and 7-year actuarial overall survival rates were 83.3% and 80.1%, respectively. The 5- and 7-year actuarial rates of late Grade 2 GI/GU toxicity (no Grade 3-5) was 7.7%. Conclusions: The trimodality approach of using 2 years of AD, external radiation, brachytherapy, and upfront docetaxel in high-risk prostate cancer is well tolerated, produces encouraging long-term results, and should be validated in a

  17. Life Cycle of Stars

    NASA Technical Reports Server (NTRS)

    1999-01-01

    In this stunning picture of the giant galactic nebula NGC 3603, the crisp resolution of NASA's Hubble Space Telescope captures various stages of the life cycle of stars in one single view. To the upper left of center is the evolved blue supergiant called Sher 25. The star has a unique circumstellar ring of glowing gas that is a galactic twin to the famous ring around the supernova 1987A. The grayish-bluish color of the ring and the bipolar outflows (blobs to the upper right and lower left of the star) indicates the presence of processed (chemically enriched) material. Near the center of the view is a so-called starburst cluster dominated by young, hot Wolf-Rayet stars and early O-type stars. A torrent of ionizing radiation and fast stellar winds from these massive stars has blown a large cavity around the cluster. The most spectacular evidence for the interaction of ionizing radiation with cold molecular-hydrogen cloud material are the giant gaseous pillars to the right of the cluster. These pillars are sculptured by the same physical processes as the famous pillars Hubble photographed in the M16 Eagle Nebula. Dark clouds at the upper right are so-called Bok globules, which are probably in an earlier stage of star formation. To the lower left of the cluster are two compact, tadpole-shaped emission nebulae. Similar structures were found by Hubble in Orion, and have been interpreted as gas and dust evaporation from possibly protoplanetary disks (proplyds). This true-color picture was taken on March 5, 1999 with the Wide Field Planetary Camera 2.

  18. The water cycle for kids

    USGS Publications Warehouse

    Neno, Stephanie; Morgan, Jim; Zonolli, Gabriele; Perlman, Howard; Gonthier, Gerard

    2013-01-01

    The U.S. Geological Survey (USGS) and the Food and Agriculture Organization of the United Nations (FAO) have created a water-cycle diagram for use in elementary and middle schools. The diagram is available in many languages. This diagram is part of the USGS's Water Science School, in which the water cycle is described in detail.

  19. Reducing Life-Cycle Costs.

    ERIC Educational Resources Information Center

    Roodvoets, David L.

    2003-01-01

    Presents factors to consider when determining roofing life-cycle costs, explaining that costs do not tell the whole story; discussing components that should go into the decision (cost, maintenance, energy use, and environmental costs); and concluding that important elements in reducing life-cycle costs include energy savings through increased…

  20. Variations on the Zilch Cycle

    ERIC Educational Resources Information Center

    Binder, P.-M.; Tanoue, C. K. S.

    2013-01-01

    Thermo dynamic cycles in introductory physics courses are usually made up from a small number of permutations of isothermal, adiabatic, and constant-pressure and volume quasistatic strokes, with the working fluid usually being an ideal gas. Among them we find the Carnot, Stirling, Otto, Diesel, and Joule-Brayton cycles; in more advanced courses,…

  1. Life Cycle of a Pencil.

    ERIC Educational Resources Information Center

    Reeske, Mike

    2000-01-01

    Explains a project called "Life Cycle of a Pencil" which was developed by the National Science Teachers Association (NSTA) and the U.S. Environmental Protection Agency (USEPA). Describes the life cycle of a pencil in stages starting from the first stage of design to the sixth stage of product disposal. (YDS)

  2. Fuel cycle cost uncertainty from nuclear fuel cycle comparison

    SciTech Connect

    Li, J.; McNelis, D.; Yim, M.S.

    2013-07-01

    This paper examined the uncertainty in fuel cycle cost (FCC) calculation by considering both model and parameter uncertainty. Four different fuel cycle options were compared in the analysis including the once-through cycle (OT), the DUPIC cycle, the MOX cycle and a closed fuel cycle with fast reactors (FR). The model uncertainty was addressed by using three different FCC modeling approaches with and without the time value of money consideration. The relative ratios of FCC in comparison to OT did not change much by using different modeling approaches. This observation was consistent with the results of the sensitivity study for the discount rate. Two different sets of data with uncertainty range of unit costs were used to address the parameter uncertainty of the FCC calculation. The sensitivity study showed that the dominating contributor to the total variance of FCC is the uranium price. In general, the FCC of OT was found to be the lowest followed by FR, MOX, and DUPIC. But depending on the uranium price, the FR cycle was found to have lower FCC over OT. The reprocessing cost was also found to have a major impact on FCC.

  3. A case report of a 19-week gravid patient with a dehisced abdominal wound and treated with V.A.C. ATS(®) Therapy System.

    PubMed

    Asukai, Kei; Kashiwazaki, Masaki; Koizumi, Kaori; Nobunaga, Toshikatsu; Yano, Hiroshi

    2016-10-01

    Negative pressure wound therapy (NPWT) is an effective treatment for various non-healing wounds, and V.A.C.(®) Therapy was the first-approved NPWT device by the Japanese government in 2009. We report the case of a 19-week pregnant patient where V.A.C.(®) Therapy was applied to her dehisced laparotomy wound with satisfactory results. The patient was a 30-year-old female who was referred to our hospital from her previous doctor because of the presence of an ovarian cyst on the left ovary. The patient presented at 14 weeks into her pregnancy, and surgery was considered because of no reduction in the size of the cyst. An oophorocystectomy was performed, and then the surgical incision was re-opened at postoperative day (POD) 10 due to a surgical site infection. V.A.C.(®) Therapy was initiated on POD 26 (20 weeks of pregnancy) and continued for 28 days. After 28 days of V.A.C.(®) Therapy (POD 54), the wound was sutured for complete closure. The foetus did not experience any adverse affects from the surgery and, subsequently, normal vaginal delivery was achieved. This case is the first report of the use of V.A.C.(®) Therapy over a dehisced abdominal wound on a pregnant patient in our country.

  4. The selenium-75-homocholic acid taurine test reevaluated: combined measurement of fecal selenium-75 activity and 3 alpha-hydroxy bile acids in 211 patients

    SciTech Connect

    van Tilburg, A.J.; de Rooij, F.W.; van den Berg, J.W.; Kooij, P.P.; van Blankenstein, M. )

    1991-06-01

    The recommended reference values for the selenium-75-homocholic acid taurine (75SeHCAT) test, used in the analysis of chronic diarrhea, were evaluated in 211 patients by comparing simultaneous measurements of 3 alpha-hydroxy bile acids and 75Se activity in daily collected stools. An initial evaluation in 11 patients showed that the fecal collection method, which allows inspection and additional analysis of stools, was equivalent to the abdominal retention method. Selenium-75-HCAT whole-body retention half-life (WBR50) was greater than 2.8 days in less than 10% of the patients with bile acid malabsorption and less than 1.7 days in less than 10% of the normals. We recommend that a 75SeHCAT WBR50 less than 1.7 days is abnormal, a WBR50 greater than 2.8 days is normal, and a WBR50 in the range 1.7-2.8 days is equivocal, which was the case in 48% (94/195) of the patients in this study.

  5. [Clinical pilot study to evaluate the efficacy of a preservative-free hypertonic ophthalmic solution for patients with symptomatic corneal edema].

    PubMed

    Rouland, J-F

    2015-11-01

    This exploratory clinical trial aims to assess the effect on visual acuity and central corneal thickness of an unpreserved hypertonic ophthalmic solution containing sodium chloride (5%) and sodium hyaluronate, in patients with chronic corneal edema caused by endothelial disease reducing their visual acuity. Twenty patients were enrolled and treated with the hypertonic solution (1 to 2 drops per eye, 4 times a day over 28 days). Progression of visual acuity (ETDRS score) and corneal thickness (ultrasonic pachymetry) was measured from baseline (without treatment) through the treatment period (Day 7 and Day 28). The analyses were performed on 18 patients (Full Analysis Set [FAS] population). The causes of corneal edema were Fuchs endothelial dystrophy in 10 cases and post-cataract surgery endothelial decompensation in 8 patients. The mean visual acuity values for the FAS population compared between baseline (Day-7) and one week of treatment (Day+7) show a significant 5-point VA improvement (P<0.001 paired Wilcoxon test). For corneal thickness, there was also a significant decrease (P=0.033 paired Wilcoxon test). Functional improvement was observed at 28 days of instillation. No adverse events were recorded during the clinical study. In conclusion, the unpreserved hyperosmolar solution containing sodium chloride and sodium hyaluronate significantly improved ETDRS visual acuity after one week of use. In this clinical trial, the solution also showed excellent tolerability results.

  6. Readmission patterns in patients with chronic obstructive pulmonary disease, chronic heart failure and diabetes mellitus: an administrative dataset analysis.

    PubMed

    Brand, C; Sundararajan, V; Jones, C; Hutchinson, A; Campbell, D

    2005-05-01

    Comprehensive disease management programmes for chronic disease aim to improve patient outcomes and reduce health-care utilization. Readmission rates are often used as an outcome measure of effectiveness. This study aimed to document readmission rates, and risk for early and late readmission, for patients discharged from the Royal Melbourne Hospital with a disease diagnosis of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) or diabetes mellitus compared to those with other general medical conditions. Eighty five (8.6%) of patients were readmitted within 28 days and 183 (20.8%) were readmitted between 29 and 180 days. No risk factors for early readmission were identified. Patients with a primary disease diagnosis of CHF and COPD are at increased risk of late readmissions (29-180 days).

  7. Cheng Cycle reporting high availability

    SciTech Connect

    Not Available

    1986-02-01

    Operating results from the Cheng Cycle cogeneration plants at San Jose State University and at Sunkist Growers in Ontario, California look very good so far, according to officials of International Power Technology (IPT). Both plants contain IPT's Cheng Cycle Series 7-Cogen system, which produces between 3 and 6 MW of electricity and up to 45,000 pounds of steam per hour. The company is developing the patented technology as an improved combined cycle system which can produce steam and electricity under widely varying load demands.

  8. Comparing the Environmental Impacts of Alkali Activated Mortar and Traditional Portland Cement Mortar using Life Cycle Assessment

    NASA Astrophysics Data System (ADS)

    Matheu, P. S.; Ellis, K.; Varela, B.

    2015-11-01

    Since the year 1908 there has been research into the use alkali activated materials (AAM) in order to develop cementitious materials with similar properties to Ordinary Portland Cement. AAMs are considered green materials since their production and synthesis is not energy intensive. Even though AAMs have a high compressive strength, the average cost of production among other issues limits its feasibility. Previous research by the authors yielded a low cost AAM that uses mine tailings, wollastonite and ground granulated blast furnace slag (GGBFS). This mortar has an average compressive strength of 50MPa after 28 days of curing. In this paper the software SimaPro was used to create a product base cradle to gate Life Cycle Assessment (LCA). This compared the environmental impact of the AAM mortar to an Ordinary Portland Cement mortar (PCHM) with similar compressive strength. The main motivation for this research is the environmental impact of producing Ordinary Portland Cement as compared to alkali activated slag materials. The results of this LCA show that the Alkali Activated Material has a lower environmental impact than traditional Portland cement hydraulic mortar, in 10 out of 12 categories including Global Warming Potential, Ecotoxicity, and Smog. Areas of improvement and possible future work were also discovered with this analysis.

  9. The Transient Role for Calcium and Vitamin D during the Developmental Hair Follicle Cycle.

    PubMed

    Mady, Leila J; Ajibade, Dare V; Hsaio, Connie; Teichert, Arnaud; Fong, Chak; Wang, Yongmei; Christakos, Sylvia; Bikle, Daniel D

    2016-07-01

    The role for 1,25-dihydroxyvitamin D3 and/or calcium in hair follicle cycling is not clear despite their impact on keratinocyte differentiation. We found that calbindin-D9k null (knockout) pups generated from calbindin-D9k knockout females fed a vitamin D-deficient, low-calcium (0.47%) diet develop transient alopecia. The pups appear phenotypically normal until 13 days of age, after which the hair progressively sheds in a caudocephalic direction, resulting in truncal alopecia totalis by 20-23 days, with spontaneous recovery by 28 days. Histological studies showed markedly dystrophic hair follicles, loss of hair shafts with increased apoptosis, and hyperplastic epidermis during this time. Ha1 expression is lost during catagen in all mice but recovers more slowly in the knockout pups on the vitamin D-deficient, low-calcium diet. Keratin 1 expression is reduced throughout days 19-28. The expressions of involucrin, loricrin, and cathepsin L is initially increased by day 19 but subsequently falls below those of controls by day 23, as does that of desmoglein 3. Feeding the mothers a high-vitamin D/high-calcium (2%)/lactose (20%) diet lessens the phenotype, and knockout pups fostered to mothers fed a normal diet do not develop alopecia. Our results show that in calbindin-D9k knockout pups, a maternal vitamin D-deficient/low-calcium diet leads to transient noncicatricial alopecia. PMID:26994969

  10. Ochratoxin A induces karyomegaly and cell cycle aberrations in renal tubular cells without relation to induction of oxidative stress responses in rats.

    PubMed

    Taniai, Eriko; Yafune, Atsunori; Nakajima, Masahiro; Hayashi, Shim-Mo; Nakane, Fumiyuki; Itahashi, Megu; Shibutani, Makoto

    2014-01-01

    Ochratoxin A (OTA) is a renal carcinogen that induces karyomegaly in target renal tubular cells of the outer stripe of the outer medulla (OSOM). This study was performed to clarify the relationship between oxidative stress and the karyomegaly-inducing potential involving cell cycle aberration of OTA in the OSOM. Rats were treated with OTA for 28 days in combination with enzymatically modified isoquercitrin (EMIQ) or α-lipoic acid (ALA) as antioxidants. OTA increased the mRNA levels of the antioxidant enzyme-related genes Gpx1, Gpx2, Gstm1 and Nfe2l2, but did not increase the levels of Gsta5, Keap1, Nqo1, Hmox1, Aldh1a1, Por, Prdx1 and Txn1. OTA also did not change the levels of thiobarbituric acid-reactive substances, glutathione disulfide/reduced glutathione, and the immunoreactive tubular cell distribution of nuclear factor erythroid 2-related factor 2 in the OSOM. Co-treatment with EMIQ or ALA did not cause any changes in these parameters. As previously reported, OTA increased cell proliferation activity, apoptosis and immunohistochemical cellular distributions of molecules suggestive of induction of DNA damage and cell cycle aberrations involving spindle checkpoint disruption and cell cycle arrest. However, co-treatment with EMIQ or ALA did not suppress these changes, and ALA co-treatment increased the cell proliferation activity induced by OTA. These results suggest that OTA facilitates cell cycling involving cell cycle aberrations and apoptosis as a basis of the mechanism behind the development of karyomegaly and subsequent carcinogenicity targeting the OSOM, without relation to induction of oxidative stress. On the other hand, ALA may promote the OTA-induced proliferation of carcinogenic target cells.

  11. The effect of continuous blood purification on the prognosis of cardiorenal syndrome patients.

    PubMed

    Jia, Fengyu; Rong, Peng; Li, Dandan; Wang, Suxia; Jing, Ying; Ge, Yanming; Meng, Jianzhong

    2015-03-01

    To discuss the effect of continuous blood purification (CBP) on the prognosis of cardiorenal syndrome (CRS) patients. Twenty-seven patients were selected for this study, who had previously been treated at the Blood Purification Center of the General Hospital of Jinan Military Region from May 2007 to October 2010. All patients suffered from chronic heart failure and acute kidney injury. Using a non-invasive hemodynamics monitoring system, we observed the dynamic changes in their cardiac output (CO), systemic vascular resistance (SVR), thoracic fluid capacity (TFC), central venous pressure (CVP), urinary volume, and Acute Physiology and Chronic Health Evaluation II system (APACHEII) score. Individual measurements were obtained at 24 h, 48 h, 72 h, 96 h, and 120 h after CBP treatment. At the same time, levels of serum creatinine (Scr), cysteine proteinase inhibitor Cystatin C (CysC), high sensitivity C-reactive protein (hs-CRP), and serum sodium were observed. The fatality rate at 28 days was also recorded. After 24 h of CBP treatment, acidosis, CO, and disturbances in water and electrolyte levels were all improved. As well, concentrations of Scr and CysC were significantly decreased, and the levels of SVR, TFC, and CVP were also decreased. After 72 h of CBP treatment, hs-CRP levels and APACHE II scores were significantly lower (P < 0.01). From 72 to 120 h of CBP treatment, oliguria was resolved in 24 patients, with improved sensitivity to diuretics. The fatality rate at 28 days was 11.12 %. CBP treatment could improve myocardial function, shorten the oliguria period, decrease the fatality rate, and improve the prognosis of CRS patients. PMID:25304742

  12. [Forest carbon cycle model: a review].

    PubMed

    Wang, Ping

    2009-06-01

    Forest carbon cycle is one of the important items in the research of terrestrial carbon cycle, while carbon cycle model is an important means in studying the carbon cycle mechanisms of forest ecosystem and in estimating carbon fluxes. Based on the sum-up of main carbon cycle models, this paper classified the forest carbon cycle models into two categories, i.e., patch scale forest carbon cycle models and regional scale terrestrial carbon cycle models, with their features commented. The future development trend in the research of forest carbon cycle models in China was discussed.

  13. Revenue cycle management, Part II.

    PubMed

    Crew, Matt

    2007-01-01

    The proper management of your revenue cycle requires the application of "best practices" and the continual monitoring and measuring of the entire cycle. The correct technology will enable you to gain the insight and efficiencies needed in the ever-changing healthcare economy. The revenue cycle is a process that begins when you negotiate payor contracts, set fees, and schedule appointments and continues until claims are paid in full. Every single step in the cycle carries equal importance. Monitoring all phases and a commitment to continually communicating the results will allow you to achieve unparalleled success. In part I of this article, we explored the importance of contracting, scheduling, and case management as well as coding and clinical documentation. We will now take a closer look at the benefits charge capture, claim submission, payment posting, accounts receivable follow-up, and reporting can mean to your practice.

  14. Our World: The Rock Cycle

    NASA Video Gallery

    Find out how rocks brought to Earth by the Apollo astronauts have helped NASA learn more about the rock cycle. Compare igneous, sedimentary and metamorphic rocks found on Earth to three types of ro...

  15. Self-organizing biochemical cycles

    PubMed Central

    Orgel, Leslie E.

    2000-01-01

    I examine the plausibility of theories that postulate the development of complex chemical organization without requiring the replication of genetic polymers such as RNA. One conclusion is that theories that involve the organization of complex, small-molecule metabolic cycles such as the reductive citric acid cycle on mineral surfaces make unreasonable assumptions about the catalytic properties of minerals and the ability of minerals to organize sequences of disparate reactions. Another conclusion is that data in the Beilstein Handbook of Organic Chemistry that have been claimed to support the hypothesis that the reductive citric acid cycle originated as a self-organized cycle can more plausibly be interpreted in a different way. PMID:11058157

  16. The pattern of deep-vein thrombosis and clinical course of a group of Hong Kong Chinese patients following hip surgery for fracture of the proximal femur.

    PubMed

    Mok, C K; Hoaglund, F T; Rogoff, S M; Chow, S P; Yau, A C

    1980-01-01

    In a prospective study of deep-vein thrombosis following hip surgery for fractures of the proximal femur, 45 Hong Kong Chinese patients were examined by bilateral functional ascending phlebography 7 to 28 days postfracture and 5 to 15 days post-surgery. In 14 patients, the phlebography was repeated 10 to 32 days later. The patients were followed for 27 to 32 months. The phlebographic pattern of the venous thrombi were analyzed, and the clinical course of the patients was presented. Despite the fact that the overall incidence of deep-vein thrombosis in this group of Chinese patients was similar to that reported in the West, clinical pulmonary embolism was not observed. The study suggested a difference in the distribution, pattern and probably the natural history of the venous thrombi among the Chinese when compared with the Western series.

  17. Detonation Jet Engine. Part 1--Thermodynamic Cycle

    ERIC Educational Resources Information Center

    Bulat, Pavel V.; Volkov, Konstantin N.

    2016-01-01

    We present the most relevant works on jet engine design that utilize thermodynamic cycle of detonative combustion. The efficiency advantages of thermodynamic detonative combustion cycle over Humphrey combustion cycle at constant volume and Brayton combustion cycle at constant pressure were demonstrated. An ideal Ficket-Jacobs detonation cycle, and…

  18. Physiologic responses during indoor cycling.

    PubMed

    Battista, Rebecca A; Foster, Carl; Andrew, Jessica; Wright, Glenn; Lucia, Alejandro; Porcari, John P

    2008-07-01

    During the last decade, there has been active interest in indoor cycling (e.g., spinning) as a method of choreographed group exercise. Recent studies have suggested that exercise intensity during indoor cycling may be quite high and may transiently exceed Vo2max. This study sought to confirm these findings, as the apparent high intensity of indoor cycling has implications for both the efficacy and the risk of indoor cycling as an exercise method. Twenty healthy female students performed an incremental exercise test to define Vo2max and performed 2 videotaped indoor exercise classes lasting 45 minutes and 35 minutes. Vo2, heart rate (HR), and rating of perceived exertion (RPE) were measured during the indoor cycling classes, with Vo2 data integrated in 30-second intervals. The mean %Vo2max during the indoor cycling classes was modest (74 +/- 14% Vo2max and 66 +/- 14%Vo2max, respectively). However, 52% and 35% of the time during the 45- and 35-minute classes was spent at intensities greater than the ventilatory threshold (VT). The HR response indicated that 35% and 38% of the session time was above the HR associated with VT. In 10 of the 40 exercise sessions, there were segments in which the momentary Vo2 exceeded Vo2max observed during incremental testing, and the cumulative time with exercise intensity greater than Vo2max ranged from 0.5 to 14.0 minutes. It can be concluded that although the intensity of indoor cycling in healthy, physically active women is moderate, there are frequent observations of transient values of Vo2 exceeding Vo2max, and a substantial portion of the exercise bouts at intensities greater than VT. As such, the data suggest that indoor cycling must be considered a high-intensity exercise mode of exercise training, which has implications for both efficacy and risk. PMID:18545183

  19. Equipment life cycle costs minimised.

    PubMed

    Kuligowski, Sharon

    2004-11-01

    With the cost of energy now a major component of building operating costs, NHS Trust managers increasingly focus on estimating total life cycle costs of equipment such as boiler room and heat, steam and incineration plant. "Life cycle costing" is a broad term and encompasses a wide range of techniques that take into account both initial and future costs as well as the savings of an investment over a period of time. PMID:15575554

  20. Ecology of the nitrogen cycle

    SciTech Connect

    Sprent, J.J.

    1987-01-01

    This book consists of two parts, approximately equal in size. The first part covers the general features of the nitrogen cycle, while the second part consists of case histories from particular environments. These include arid and semi-arid areas, tundras, peat soils, lakes, marshes, and such saline systems as salt marshes, coral reefs, intertidal zones, and the open sea. The last chapter discusses the human impact on the cycle through agriculture, forestry, and acidification.

  1. Limit cycle vibrations in turbomachinery

    NASA Technical Reports Server (NTRS)

    Ryan, S. G.

    1991-01-01

    The focus is on an examination of rotordynamic systems which are simultaneously susceptible to limit cycle instability and subharmonic response. Characteristics of each phenomenon are determined as well as their interrelationship. A normalized, single mass rotor model is examined as well as a complex model of the high pressure fuel turbopump and the Space Shuttle Main Engine. Entrainment of limit cycle instability by subharmonic response is demonstrated for both models. The nonuniqueness of the solution is also demonstrated.

  2. Equipment life cycle costs minimised.

    PubMed

    Kuligowski, Sharon

    2004-11-01

    With the cost of energy now a major component of building operating costs, NHS Trust managers increasingly focus on estimating total life cycle costs of equipment such as boiler room and heat, steam and incineration plant. "Life cycle costing" is a broad term and encompasses a wide range of techniques that take into account both initial and future costs as well as the savings of an investment over a period of time.

  3. The chromosome cycle of prokaryotes.

    PubMed

    Kuzminov, Andrei

    2013-10-01

    In both eukaryotes and prokaryotes, chromosomal DNA undergoes replication, condensation-decondensation and segregation, sequentially, in some fixed order. Other conditions, like sister-chromatid cohesion (SCC), may span several chromosomal events. One set of these chromosomal transactions within a single cell cycle constitutes the 'chromosome cycle'. For many years it was generally assumed that the prokaryotic chromosome cycle follows major phases of the eukaryotic one: -replication-condensation-segregation-(cell division)-decondensation-, with SCC of unspecified length. Eventually it became evident that, in contrast to the strictly consecutive chromosome cycle of eukaryotes, all stages of the prokaryotic chromosome cycle run concurrently. Thus, prokaryotes practice 'progressive' chromosome segregation separated from replication by a brief SCC, and all three transactions move along the chromosome at the same fast rate. In other words, in addition to replication forks, there are 'segregation forks' in prokaryotic chromosomes. Moreover, the bulk of prokaryotic DNA outside the replication-segregation transition stays compacted. I consider possible origins of this concurrent replication-segregation and outline the 'nucleoid administration' system that organizes the dynamic part of the prokaryotic chromosome cycle.

  4. The NEWS Water Cycle Climatology

    NASA Technical Reports Server (NTRS)

    Rodell, Matthew; Beaudoing, Hiroko Kato; L'Ecuyer, Tristan; William, Olson

    2012-01-01

    NASA's Energy and Water Cycle Study (NEWS) program fosters collaborative research towards improved quantification and prediction of water and energy cycle consequences of climate change. In order to measure change, it is first necessary to describe current conditions. The goal of the first phase of the NEWS Water and Energy Cycle Climatology project was to develop "state of the global water cycle" and "state of the global energy cycle" assessments based on data from modern ground and space based observing systems and data integrating models. The project was a multi-institutional collaboration with more than 20 active contributors. This presentation will describe the results of the water cycle component of the first phase of the project, which include seasonal (monthly) climatologies of water fluxes over land, ocean, and atmosphere at continental and ocean basin scales. The requirement of closure of the water budget (i.e., mass conservation) at various scales was exploited to constrain the flux estimates via an optimization approach that will also be described. Further, error assessments were included with the input datasets, and we examine these in relation to inferred uncertainty in the optimized flux estimates in order to gauge our current ability to close the water budget within an expected uncertainty range.

  5. The NEWS Water Cycle Climatology

    NASA Astrophysics Data System (ADS)

    Rodell, M.; Beaudoing, H. K.; L'Ecuyer, T.; Olson, W. S.

    2012-12-01

    NASA's Energy and Water Cycle Study (NEWS) program fosters collaborative research towards improved quantification and prediction of water and energy cycle consequences of climate change. In order to measure change, it is first necessary to describe current conditions. The goal of the first phase of the NEWS Water and Energy Cycle Climatology project was to develop "state of the global water cycle" and "state of the global energy cycle" assessments based on data from modern ground and space based observing systems and data integrating models. The project was a multi-institutional collaboration with more than 20 active contributors. This presentation will describe the results of the water cycle component of the first phase of the project, which include seasonal (monthly) climatologies of water fluxes over land, ocean, and atmosphere at continental and ocean basin scales. The requirement of closure of the water budget (i.e., mass conservation) at various scales was exploited to constrain the flux estimates via an optimization approach that will also be described. Further, error assessments were included with the input datasets, and we examine these in relation to inferred uncertainty in the optimized flux estimates in order to gauge our current ability to close the water budget within an expected uncertainty range.

  6. A biogeochemical cycle for aluminium?

    PubMed

    Exley, Christopher

    2003-09-15

    The elaboration of biogeochemical cycles for elements which are known to be essential for life has enabled a broad appreciation of the homeostatic mechanisms which underlie element essentiality. In particular they can be used effectively to identify any part played by human activities in element cycling and to predict how such activities might impact upon the lithospheric and biospheric availability of an element in the future. The same criteria were the driving force behind the construction of a biogeochemical cycle for aluminium, a non-essential element which is a known ecotoxicant and a suspected health risk in humans. The purpose of this exercise was to examine the concept of a biogeochemical cycle for aluminium and not to review the biogeochemistry of this element. The cycle as presented is rudimentary and qualitative though, even in this nascent form, it is informative and predictive and, for these reasons alone, it is deserving of future quantification. A fully fledged biogeochemical cycle for aluminium should explain the biospheric abundance of this element and whether we should expect its (continued) active involvement in biochemical evolution.

  7. Impact of early methadone initiation in critically injured burn patients: a pilot study.

    PubMed

    Jones, G Morgan; Porter, Kyle; Coffey, Rebecca; Miller, Sidney F; Cook, Charles H; Whitmill, Melissa L; Murphy, Claire V

    2013-01-01

    Numerous studies have identified strategies to reduce mechanical ventilation duration by targeting appropriate sedation levels. However, applicability of these strategies to critically injured patients with burn injury has not been established. At our medical center, methadone is commonly used early in the care of burn patients to treat background pain and limit the development of opioid tolerance. The aim of this study is to evaluate the effect of early methadone initiation in critically injured burn patients requiring mechanical ventilation. This retrospective study compared patients who received early methadone with patients who did not while mechanically ventilated with the primary outcome of ventilator-free days in a 28-day period. Those who received methadone within 4 days of intubation and remained ventilated for 2 days after the first dose were included in the methadone group. Propensity scores were used to match up to three control patients to each methadone patient. Seventy patients (18 methadone and 52 matched control patients) were included in the final evaluation. Patients in the methadone group averaged 16.5 ventilator-free days compared with 11.5 in the control group (P = .03). There was no statistical difference in the duration of intensive care unit or hospital length of stay between groups. Our results suggest that early methadone initiation may have a significant effect on ventilator outcomes in critically injured patients with burn injury. However, further research is warranted.

  8. AVS regulation of cadmium bioavailability in a life-cycle sediment toxicity test using Leptocheirus plumulosus

    SciTech Connect

    DeWitt, T.H.; Swartz, R.C.; Hansen, D.J.; McGovern, D.; Berry, W.J.

    1995-12-31

    Numerous studies have shown the utility of interstitial water concentrations of metals and simultaneously extracted metals:acid volatile sulfide ratios (SEM:AVS) in explaining the acute toxicity of sediment-associated metals to benthic organisms, but no full life-cycle chronic tests have been conducted for this purpose. In this study, cohorts of newborn amphipods, Leptocheirus plumulosus, were exposed to cadmium-spiked estuarine sediment for 28 days to determine effects on mortality, growth, and reproduction relative to interstitial water and SEM:AVS normalizations. Seven treatments of Cd were tested: control, 0.35, 0.87, 1.32, 1.53, 2.22, and 5.10 molar SEM:AVS ratios. Overlying water, interstitial water and sediment concentrations of SEM Cd and AVS were monitored periodically and by depth during the exposure. When sediments SEM:AVS ratios were < 1.53, interstitial water concentrations of Cd were less than the 10-day water-only Cd LC50, and mortality, growth and reproduction were not affected. When SEM:AVS ratios were > 2.22, interstitial water Cd concentrations were greater than 100 times the 10-day water-only Cd LC50, and all amphipods died. These results are consistent with predictions of metal bioavailability from acute tests with metals-spiked sediments, i.e. that sediments with SEM:AVS ratios less than 1.0 and less than 0.5 interstitial water toxic units are not toxic, while sediments with SEM:AVS ratios greater than 1.0 and interstitial water toxic units (IWTUS) greater than 0.5 may be toxic.

  9. Predictive factors of short-term survival from acute myocardial infarction in early and late patients in Isfahan and Najafabad, Iran

    PubMed Central

    Abdolazimi, Mohammad; Khosravi, Alireza; Sadeghi, Masoumeh; Mohammadian-Hafshejani, Abdollah; Sarrafzadegan, Nizal; Salehiniya, Hamid; Golshahi, Jafar

    2016-01-01

    BACKGROUND Cardiovascular disease (CVD) is the primary cause of mortality in the world and Iran. The aim of this study was to determine the prognostic factors of short-term survival from acute myocardial infarction (AMI) in early and late patients in the Najafabad and Isfahan County, Iran. METHODS This hospital-based cohort study was conducted using the hospital registry of 1999-2009 in Iran. All patients (n = 14426) with an AMI referred to hospitals of Isfahan and Najafabad were investigated. To determine prognostic factors of short-term (28-days) survival in early and late patients, unadjusted and adjusted hazard ratio (HR) was calculated using univariate and multivariate Cox regression. RESULTS The short-term (28-day) survival rate of early and late patients was 96.64% and 89.42% (P < 0.001), respectively. In 80% of early and 79.3% of late patients, mortality occurred during the first 7 days of disease occurrence. HR of death was higher in women in the two groups; it was 1.97 in early patients was (CI95%: 1.32-2.92) and 1.35 in late patients (CI95%: 1.19-1.53) compared to men. HR of death had a rising trend with the increasing of age in the two groups. CONCLUSION Short-term survival rate was higher in early patients than in late patients. In addition, case fatality rate (CFR) of AMI in women was higher than in men. In both groups, sex, age, an atomic location of myocardial infarction based on the International Classification of Disease, Revision 10 (ICD10), cardiac enzymes, and clinical symptoms were significant predictors of survival in early and late patients following AMI. PMID:27429625

  10. Preliminary Tests of a Practical Fuzzy FES Controller Based on Cycle-to-Cycle Control in the Knee Flexion and Extension Control

    NASA Astrophysics Data System (ADS)

    Watanabe, Takashi; Masuko, Tomoya; Arifin, Achmad

    The fuzzy controller based on cycle-to-cycle control with output value adjustment factors (OAF) was developed for restoring gait of paralyzed subjects by using functional electrical stimulation (FES). Results of maximum knee flexion and extension controls with neurologically intact subjects suggested that the OAFs would be effective in reaching the target within small number of cycles and in reducing the error after reaching the target. Oscillating responses between cycles were also suppressed. The fuzzy controller was expected to be examined to optimize the OAFs with more subjects including paralyzed patients for clinical application.

  11. The Sphinx's Riddle: Life and Career Cycles.

    ERIC Educational Resources Information Center

    Burack, Elmer H.

    1984-01-01

    Career cycles should be considered apart from life cycles, even though the two are interrelated. This essay examines five theories about life and career cycles, and offers insights into their limitations and potential uses. (JB)

  12. Thermodynamic Cycles--One More Time.

    ERIC Educational Resources Information Center

    Nolan, Michael J.

    1995-01-01

    Discusses interesting aspects of the Carnot cycle and other thermodynamic cycles that are generally not dealt with in elementary physics texts. Presents examples that challenge the student to think about the extraction of net work from a cycle. (JRH)

  13. Physiological responses and perceived exertion during cycling with superimposed electromyostimulation.

    PubMed

    Wahl, Patrick; Schaerk, Jonas; Achtzehn, Silvia; Kleinöder, Heinz; Bloch, Wilhelm; Mester, Joachim

    2012-09-01

    The goal of the study was to evaluate and to quantify the effects of local electromyostimulation (EMS) during cycling on the cardiorespiratory system, muscle metabolism, and perceived exertion compared with cycling with no EMS. Ten healthy men (age: 24.6 ± 3.2 years, V[Combining Dot Above]O2max: 54.1 ± 6.0 ml·min·kg) performed 3 incremental cycle ergometer step tests, 1 without and 2 with EMS (30 and 85 Hz) until volitional exhaustion. Lactate values and respiratory exchange ratio were significantly higher at intensities ≥75% peak power output (PPO) when EMS was applied. Bicarbonate concentration, base excess (BE), and Pco2 were significantly lower when EMS was applied compared with the control at intensities ≥75% PPO. Saliva cortisol levels increased because of the exercise but were unaffected by EMS. Furthermore, EMS showed greater effects on CK levels 24 hours postexercise than normal cycling did. Rating of perceived exertion was significantly higher at 100% PPO with EMS. No statistical differences were found for heart rate, pH, and Po2 between the tested cycling modes. The main findings of this study are greater metabolic changes (lactate, respiratory exchange ratio, BE, (Equation is included in full-text article.), Pco2) during cycling with EMS compared with normal cycling independent of frequency, mainly visible at higher work rates. Because metabolic alterations are important for the induction of cellular signaling cascades and adaptations, these results lead to the hypothesis that applied EMS stimulations during cycling exercise might be an enhancing stimulus for skeletal muscle metabolism and related adaptations. Thus, superimposed EMS application during cycling could be beneficial to aerobic performance enhancements in athletes and in patients who cannot perform high workloads. However, the higher demand on skeletal muscles involved must be considered. PMID:22067251

  14. Enhanced absorption cycle computer model

    NASA Astrophysics Data System (ADS)

    Grossman, G.; Wilk, M.

    1993-09-01

    Absorption heat pumps have received renewed and increasing attention in the past two decades. The rising cost of electricity has made the particular features of this heat-powered cycle attractive for both residential and industrial applications. Solar-powered absorption chillers, gas-fired domestic heat pumps, and waste-heat-powered industrial temperature boosters are a few of the applications recently subjected to intensive research and development. The absorption heat pump research community has begun to search for both advanced cycles in various multistage configurations and new working fluid combinations with potential for enhanced performance and reliability. The development of working absorption systems has created a need for reliable and effective system simulations. A computer code has been developed for simulation of absorption systems at steady state in a flexible and modular form, making it possible to investigate various cycle configurations with different working fluids. The code is based on unit subroutines containing the governing equations for the system's components and property subroutines containing thermodynamic properties of the working fluids. The user conveys to the computer an image of his cycle by specifying the different subunits and their interconnections. Based on this information, the program calculates the temperature, flow rate, concentration, pressure, and vapor fraction at each state point in the system, and the heat duty at each unit, from which the coefficient of performance (COP) may be determined. This report describes the code and its operation, including improvements introduced into the present version. Simulation results are described for LiBr-H2O triple-effect cycles, LiCl-H2O solar-powered open absorption cycles, and NH3-H2O single-effect and generator-absorber heat exchange cycles. An appendix contains the user's manual.

  15. Final Report - The Xanthophyll Cycle

    SciTech Connect

    Harry Yamamato

    2005-04-21

    The xanthophyll cycle is a ubiquitous activity in higher plants. A major function of the cycle is to protect the photosynthetic system from the potentially damaging effects of high light by dissipating excess energy that might otherwise damage the photosynthetic apparatus harmlessly as heat by a process termed non-photochemical quenching (NFQ). This research focused on investigating the dynamics of the relationship between PsbS, subunit PSII protein required for NPQ, and zeaxanthin by perturbing the natural relationship of these components by overexpression of PsbS, violaxanthin de-epoxidase (VDE), and PsbS-VDE in tobacco. The effects of these treatments showed that the relationship between NPQ and zeaxanthin formation is more complex than previously indicated from studies carried out under high light. It is postulated that the xanthophyll cycle functions as a type of signal-transduction system within the thylakoid membrane. Recent studies in model lipid systems demonstrated that zeaxanthin exerts feedback inhibition on violaxanthin de-epoxidase. This feedback inhibition is consistent with the lipid phase functioning as a modulating factor in the dynamics of the cycle's operation. While this research and those in other laboratories have defined both the biochemistry and molecular mechanism of the cycle's operation, especially for violaxanthin de-epoxidase, there is yet insufficient knowledge that explains the ubiquitous presence of the cycle in all higher plants and a related cycle in diatoms. Antisense VDE tobacco plants (work carried out under another grant) withstood the high-light environment in Hawaii over one generation. Thus, it is speculated that the protective system was essential for survival in earth's high-light earth environment over multiple generations. The proposed signal transduction protective system, however, may explain the ability of the protective system to modulate or adapt to a range of environments.

  16. The Water Cycle Solutions Network

    NASA Astrophysics Data System (ADS)

    Houser, P.; Belvedere, D.; Imam, B.; Schiffer, R.; Schlosser, C.; Gupta, H.; Welty, C.; Vörösmarty, C.; Matthews, D.; Lawford, R.

    2006-12-01

    The goal of the Water cycle Solutions Network is to improve and optimize the sustained ability of water cycle researchers, stakeholders, organizations and networks to interact, identify, harness, and extend research results to augment decision support tools and meet national needs. WaterNet will engage relevant NASA water cycle research resources and community-of-practice organizations, to develop what we term an "actionable database" that can be used to communicate and connect water cycle research results (WCRs) towards the improvement of water-related Decision Support Tools (DSTs). An actionable database includes enough sufficient knowledge about its nodes and their heritage so that connections between these nodes are identifiable and robust. Recognizing the many existing highly valuable water-related science and application networks, we will focus the balance of our efforts on enabling their interoperability in a solutions network context. We will initially focus on identification, collection, and analysis of the two end points, these being the WCRs and water related DSTs. We will then develop strategies to connect these two end points via innovative communication strategies, improved user access to NASA resources, improved water cycle research community appreciation for DST requirements, improved policymaker, management and stakeholder knowledge of NASA research and application products, and improved identification of pathways for progress. Finally, we will develop relevant benchmarking and metrics, to understand the network's characteristics, to optimize its performance, and to establish sustainability. The WaterNet will deliver numerous pre-evaluation reports that will identify the pathways for improving the collective ability of the water cycle community to routinely harness WCRs that address crosscutting water cycle challenges.

  17. 42 CFR 494.70 - Condition: Patients' rights.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., transplantation, home dialysis modalities (home hemodialysis, intermittent peritoneal dialysis, continuous ambulatory peritoneal dialysis, continuous cycling peritoneal dialysis),and in-facility hemodialysis. The... Patient Care § 494.70 Condition: Patients' rights. The dialysis facility must inform patients (or...

  18. Treatment-induced cell cycle kinetics dictate tumor response to chemotherapy

    PubMed Central

    Hallett, Robin M.; Huang, Cheng; Motazedian, Ali; Auf der Mauer, Stefanie; Pond, Gregory R.; Hassell, John A.; Nordon, Robert E.; Draper, Jonathan S.

    2015-01-01

    Chemotherapy fails to provide durable cure for the majority of cancer patients. To identify mechanisms associated with chemotherapy resistance, we identified genes differentially expressed before and after chemotherapeutic treatment of breast cancer patients. Treatment response resulted in either increased or decreased cell cycle gene expression. Tumors in which cell cycle gene expression was increased by chemotherapy were likely to be chemotherapy sensitive, whereas tumors in which cell cycle gene transcripts were decreased by chemotherapy were resistant to these agents. A gene expression signature that predicted these changes proved to be a robust and novel index that predicted the response of patients with breast, ovarian, and colon tumors to chemotherapy. Investigations in tumor cell lines supported these findings, and linked treatment induced cell cycle changes with p53 signaling and G1/G0 arrest. Hence, chemotherapy resistance, which can be predicted based on dynamics in cell cycle gene expression, is associated with TP53 integrity. PMID:25749523

  19. Focused training boosts revenue cycle skills, accountability.

    PubMed

    Richmond, Craig

    2011-09-01

    In 2009, the MetroHealth System took its first steps toward creating a comprehensive revenue cycle university, with the goal of developing revenue cycle staff talent and achieving best-in-class revenue cycle operations. MetroHealth became a beta site for HFMA's online Credentialed Revenue Cycle Representative (CRCR) program, and asked its revenue cycle leaders to present classes on key revenue cycle issues. As of June 2011, 62 percent of 122 revenue cycle employees who had taken the CRCR course passed the exam. The CRCR designation is now a prerequisite for career advancement in certain revenue cycle areas at MetroHealth.

  20. A comparative look at sunspot cycles

    NASA Technical Reports Server (NTRS)

    Wilson, R. M.

    1984-01-01

    On the basis of cycles 8 through 20, spanning about 143 years, observations of sunspot number, smoothed sunspot number, and their temporal properties were used to compute means, standard deviations, ranges, and frequency of occurrence histograms for a number of sunspot cycle parameters. The resultant schematic sunspot cycle was contrasted with the mean sunspot cycle, obtained by averaging smoothed sunspot number as a function of time, tying all cycles (8 through 20) to their minimum occurence date. A relatively good approximation of the time variation of smoothed sunspot number for a given cycle is possible if sunspot cycles are regarded in terms of being either HIGH- or LOW-R(MAX) cycles or LONG- or SHORT-PERIOD cycles, especially the latter. Linear regression analyses were performed comparing late cycle parameters with early cycle parameters and solar cycle number. The early occurring cycle parameters can be used to estimate later occurring cycle parameters with relatively good success, based on cycle 21 as an example. The sunspot cycle record clearly shows that the trend for both R(MIN) and R(MAX) was toward decreasing value between cycles 8 through 14 and toward increasing value between cycles 14 through 20. Linear regression equations were also obtained for several measures of solar activity.

  1. Immunotoxin Therapy for Relapsed Hairy Cell Leukemia

    Cancer.gov

    In this trial, patients with hairy cell leukemia who have relapsed multiple times or not responded to prior chemotherapy will be treated with an experimental immunotoxin called moxetumomab pasudotox given intravenously on days 1, 3, and 5 of 28-day cycles

  2. Answering Key Fuel Cycle Questions

    SciTech Connect

    Piet, S.J.; Dixon, B.W.; Bennett, R.G.; Smith, J.D.; Hill, R.N.

    2004-10-03

    Given the range of fuel cycle goals and criteria, and the wide range of fuel cycle options, how can the set of options eventually be narrowed in a transparent and justifiable fashion? It is impractical to develop all options. We suggest an approach that starts by considering a range of goals for the Advanced Fuel Cycle Initiative (AFCI) and then posits seven questions, such as whether Cs and Sr isotopes should be separated from spent fuel and, if so, what should be done with them. For each question, we consider which of the goals may be relevant to eventually providing answers. The AFCI program has both ''outcome'' and ''process'' goals because it must address both waste already accumulating as well as completing the fuel cycle in connection with advanced nuclear power plant concepts. The outcome objectives are waste geologic repository capacity and cost, energy security and sustainability, proliferation resistance, fuel cycle economics, and safety. The process objectives are rea diness to proceed and adaptability and robustness in the face of uncertainties.

  3. A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia

    PubMed Central

    2013-01-01

    Introduction Endothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN. Methods This was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome. Results A total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality. Conclusions A high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia. PMID:23915833

  4. Thermodynamics of combined cycle plant

    NASA Astrophysics Data System (ADS)

    Crane, R. I.

    The fundamental thermodynamics of power plants including definitions of performance criteria and an introduction to exergy are reviewed, and treatments of simplified performance calculations for the components which form the major building blocks and a gas/steam combined cycle plant are given: the gas turbine, the heat recovery steam generator, and the remainder of the steam plant. Efficiency relationships and energy and exergy analyses of combined cycle plant are presented, with examples. Among the aspects considered are gas turbine performance characteristics and fuels, temperature differences for heat recovery, multiple steam pressures and reheat, supplementary firing and feed water heating. Attention is drawn to points of thermodynamic interest arising from applications of combined cycle plant to repowering of existing steam plant and to combined heat and power (cogeneration); some advances, including coal firing, are also introduced.

  5. Measuring risky adolescent cycling behaviour.

    PubMed

    Feenstra, Hans; Ruiter, Robert A C; Schepers, Jan; Peters, Gjalt-Jorn; Kok, Gerjo

    2011-09-01

    Adolescents are at a greater risk of being involved in traffic accidents than most other age groups, even before they start driving cars. This article aims to determine the factor structure of a self-report questionnaire measuring adolescent risky cycling behaviour, the ACBQ (Adolescent Cycling Behaviour Questionnaire). The questionnaire's structure was based on the widely used Driver Behaviour Questionnaire (DBQ). A sample of secondary school students (N = 1749; age range: 13-18 years) filled out the questionnaire. Factor analysis revealed a three-factor structure underlying the questionnaire, which was confirmed on two equally large portions of the entire sample. These three underlying factors were identified as errors, common violations and exceptional violations. The ACBQ is a useful instrument for measuring adolescents' risky cycling behaviour.

  6. ALMA Cycle 0 Publication Statistics

    NASA Astrophysics Data System (ADS)

    Stoehr, F.; Grothkopf, U.; Meakins, S.; Bishop, M.; Uchida, A.; Testi, L.; Iono, D.; Tatematsu, K.; Wootten, A.

    2015-12-01

    The scientific impact of a facility is the most important measure of its success. Monitoring and analysing the scientific return can help to modify and optimise operations and adapt to the changing needs of scientific research. The methodology that we have developed to monitor the scientific productivity of the ALMA Observatory, as well as the first results, are described. We focus on the outcome of the first cycle (Cycle 0) of ALMA Early Science operations. Despite the fact that only two years have passed since the completion of Cycle 0 and operations have already changed substantially, this analysis confirms the effectiveness of the underlying concepts. We fin