Does Maternal Buprenorphine Dose Affect Severity or Incidence of Neonatal Abstinence Syndrome?

PubMed

Wong, Jacqueline; Saver, Barry; Scanlan, James M; Gianutsos, Louis Paul; Bhakta, Yachana; Walsh, James; Plawman, Abigail; Sapienza, David; Rudolf, Vania

2018-06-13

To measure the incidence, onset, duration, and severity of neonatal abstinence syndrome (NAS) in infants born to mothers receiving buprenorphine and to assess the association between buprenorphine dose and NAS outcomes. We reviewed charts of all mother-infant pairs maintained on buprenorphine who delivered in our hospital from January 1, 2000 to April 1, 2016. In 89 infants, NAS incidence requiring morphine was 43.8%. Means for morphine-treated infants included: 55.2 hours to morphine start, 15.9 days on morphine, and 20 days hospital stay. NAS requiring morphine treatment occurred in 48.5% and 41.4% of infants of mothers receiving ≤8 mg/d buprenorphine versus >8 mg/d, respectively (P = 0.39). We found no significant associations of maternal buprenorphine dose with peak NAS score, NAS severity requiring morphine, time to morphine start, peak morphine dose, or days on morphine. Among the other factors examined, only exclusive breastfeeding was significantly associated with neonatal outcomes, specifically lower odds of morphine treatment (odds ratio 0.24, P = 0.003). These findings suggest higher buprenorphine doses can be prescribed to pregnant women receiving medication therapy for addiction without increasing NAS severity. Our finding of reduced risk of NAS requiring morphine treatment also suggests breastfeeding is both safe and beneficial for these infants and should be encouraged.

Dose-response meta-analysis of poultry intake and colorectal cancer incidence and mortality.

PubMed

Shi, Yan; Yu, Pei-Wu; Zeng, Dong-Zhu

2015-03-01

Poultry intake has been inconsistently associated with incidence or mortality of colorectal cancer (CRC) in epidemiologic studies. The purpose of this study was to assess their relationships by performing a dose-response meta-analysis. We conducted a search of PubMed database between January 1966 and July 2013 for prospective studies that reported relative risks (RRs) with 95 % confidence interval (CIs) of CRC for at least three categories of poultry intake. Dose-response relationships were examined with the generalized least-squares trend estimation. Study-specific results were pooled with a random-effects model. Subgroup, sensitivity, and meta-regression analyses were also conducted to explore heterogeneity. Sixteen studies on poultry intake and CRC incidence, and four studies regarding poultry intake and CRC mortality were identified. These studies involved a total of 13,949 incident CRC cases and 983 CRC deaths. The RRs of CRC for higher compared with lower intake of poultry were reported in these studies, and the reported levels of poultry intake varied substantially. Results of the dose-response meta-analysis conferred a RR of 0.89 (95 % CI 0.81-0.97) for an increase in poultry intake of 50 g/day. The results were not sensitive to any individual studies and were similar for colon and rectal cancer. Poultry intake was not associated with CRC mortality (RR for 50 g/day = 0.97, 95 % CI 0.79-1.20). This meta-analysis indicates that poultry intake may be moderately associated with reduced incidence of CRC.

Dexmedetomidine reduces pain associated with rocuronium injection without causing a decrease in BIS values: a dose-response study.

PubMed

Joo, Jin; Baek, Jungwon; Lee, Jaemin

2014-09-01

To examine whether dexmedetomidine reduces the injection pain of propofol and rocuronium and to investigate whether the decrease in injection pain is associated with the known sedative action of dexmedetomidine. Randomized, double-blind, placebo-controlled clinical comparison study. Patients undergoing general anesthesia with intubation received 40 mg of 1% lidocaine (lidocaine group; n = 28), 0.25 μg/kg of dexmedetomidine (low-dose group; n = 27), 0.5 μg/kg of dexmedetomidine (subclinical dose group; n = 28), 1.0 μg/kg of dexmedetomidine (clinical dose group, n = 27), or normal saline (saline group; n = 28) before anesthetic induction. Pain associated with propofol and rocuronium injection was assessed using a 10-point verbal analog scale (VAS) and a 4-point withdrawal movement scale, respectively. The BIS value was measured 60 seconds after administration of the study drug, and at the time of rocuronium injection and intubation. The overall incidence of withdrawal movements due to rocuronium decreased significantly as the dose of dexmedetomidine increased (92.8%, 85.2%, 78.6%, and 51.9% in the saline, low-dose, subclinical dose, and clinical dose groups, respectively; P = 0.001). There was no significant difference in BIS values among the groups 60 seconds after study drug administration or at the time of rocuronium injection. Dexmedetomidine reduced pain associated with rocuronium injection in a dose-dependent manner. This effect was not associated with the decrease in BIS value. Copyright © 2014 Elsevier Inc. All rights reserved.

Neutron equivalent doses and associated lifetime cancer incidence risks for head & neck and spinal proton therapy

NASA Astrophysics Data System (ADS)

Athar, Basit S.; Paganetti, Harald

2009-08-01

In this work we have simulated the absorbed equivalent doses to various organs distant to the field edge assuming proton therapy treatments of brain or spine lesions. We have used computational whole-body (gender-specific and age-dependent) voxel phantoms and considered six treatment fields with varying treatment volumes and depths. The maximum neutron equivalent dose to organs near the field edge was found to be approximately 8 mSv Gy-1. We were able to clearly demonstrate that organ-specific neutron equivalent doses are age (stature) dependent. For example, assuming an 8-year-old patient, the dose to brain from the spinal fields ranged from 0.04 to 0.10 mSv Gy-1, whereas the dose to the brain assuming a 9-month-old patient ranged from 0.5 to 1.0 mSv Gy-1. Further, as the field aperture opening increases, the secondary neutron equivalent dose caused by the treatment head decreases, while the secondary neutron equivalent dose caused by the patient itself increases. To interpret the dosimetric data, we analyzed second cancer incidence risks for various organs as a function of patient age and field size based on two risk models. The results show that, for example, in an 8-year-old female patient treated with a spinal proton therapy field, breasts, lungs and rectum have the highest radiation-induced lifetime cancer incidence risks. These are estimated to be 0.71%, 1.05% and 0.60%, respectively. For an 11-year-old male patient treated with a spinal field, bronchi and rectum show the highest risks of 0.32% and 0.43%, respectively. Risks for male and female patients increase as their age at treatment time decreases.

Reduced lung-cancer mortality with low-dose computed tomographic screening.

PubMed

Aberle, Denise R; Adams, Amanda M; Berg, Christine D; Black, William C; Clapp, Jonathan D; Fagerstrom, Richard M; Gareen, Ilana F; Gatsonis, Constantine; Marcus, Pamela M; Sicks, JoRean D

2011-08-04

The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer

SU-E-T-44: Angular Dependence of Surface Dose Enhancement Measured On Several Inhomogeneities Using Radiochromic EBT3 Films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jansen, A; Schoenfeld, A; Poppinga, D

Purpose: The quantification of the relative surface dose enhancement in dependence on the angle of incidence and the atomic number Z of the surface material. Methods: Experiments were performed with slabs made of aluminum, titanium, copper, silver, dental gold and lead. The metal slabs with equal sizes of 1.0×8.0×8.8mm{sup 3} were embedded in an Octavius 4D phantom (PTW Freiburg, Germany). Radiochromic EBT3 films were used to measure the surface dose for angles of incidence ranging from 0° to 90°. The setup with the metals slabs at the isocenter was irradiated with acceleration voltages of 6MV and 10MV. Water reference measurementsmore » were taken under equal conditions. Results: The surface dose enhancement is highest for angles of incidence below 30° and drops significantly for higher. The surface dose enhancement produced by lead and dental gold at 6MV showed a peak of 65%. At 90°, the surface dose enhancement dropped to 15% for both materials. The surface dose enhancements for silver, copper, titanium and aluminum were 45%, 32%, 22% and 12% at 0°, respectively. At an angle of incidence of 80°, the values dropped to 22%, 18%, 12% und 6%. The values for 10MV were very similar. Lead and dental gold showed peaks of 65% und 60%. Their values dropped to 18% at an angle of 90°. The surface dose enhancements for silver, copper, titanium and aluminum were 45%, 30%, 20% and 8% at 0°. At 80° the values dropped to 30%, 20%, 12% and 5%. A dependence of the magnitude of the surface dose enhancement on the atomic number of the surface material can be seen, which is in consistence with literature. Conclusion: The results show that the surface dose enhancements near implant materials with high Z-values should be taken into consideration in radio therapy, even when the angle of incidence is flat.« less

Leuco-crystal-violet micelle gel dosimeters: Component effects on dose-rate dependence

NASA Astrophysics Data System (ADS)

Xie, J. C.; Katz, E. A. B.; Alexander, K. M.; Schreiner, L. J.; McAuley, K. B.

2017-05-01

Designed experiments were performed to produce empirical models for the dose sensitivity, initial absorbance, and dose-rate dependence respectively for leucocrystal violet (LCV) micelle gel dosimeters containing cetyltrimethylammonium bromide (CTAB) and 2,2,2-trichloroethanol (TCE). Previous gels of this type showed dose-rate dependent behaviour, producing an ˜18% increase in dose sensitivity between dose rates of 100 and 600 cGy min-1. Our models predict that the dose rate dependence can be reduced by increasing the concentration of TCE, CTAB and LCV. Increasing concentrations of LCV and CTAB produces a significant increase in dose sensitivity with a corresponding increase in initial absorbance. An optimization procedure was used to determine a nearly dose-rate independent gel which maintained high sensitivity and low initial absorbance. This gel which contains 33 mM CTAB, 1.25 mM LCV, and 96 mM TCE in 25 mM trichloroacetic acid and 4 wt% gelatin showed an increase in dose sensitivity of only 4% between dose rates of 100 and 600 cGy min-1, and provides an 80% greater dose sensitivity compared to Jordan’s standard gels with similar initial absorbance.

Incidence of colorectal cancer in new users and non-users of low-dose aspirin without existing cardiovascular disease: A cohort study using The Health Improvement Network.

PubMed

Cea Soriano, Lucía; Soriano-Gabarró, Montse; García Rodríguez, Luis A

2017-12-01

Evidence regarding the chemo-protective effects of aspirin has influenced expert opinion in favour of low-dose aspirin use in certain patient populations without cardiovascular disease (CVD). The effects of aspirin in reducing the incidence of colorectal cancer (CRC) may be a large contributor to this favourable risk-benefit profile of low-dose aspirin in primary CVD prevention. Using The Health Improvement Network, we estimated the incidence of CRC in individuals free of CVD and either prescribed or not prescribed prophylactic low-dose aspirin. Two cohorts - new-users of low-dose aspirin (N=109,426) and a comparator cohort of non-users (N=154,056) at start of follow-up - were followed (maximum 13years) to identify incident CRC cases. Individuals with a record of CVD, cancer or low-dose aspirin prescription before start of follow-up were excluded. 2330 incident cases of CRC occurred; 885 in the aspirin cohort and 1445 in the comparator cohort, after mean follow-ups of 5.43years and 5.17years, respectively. Incidence rates of CRC per 10,000 person-years (95% confidence interval) were 14.90 (13.95-15.92) in the aspirin cohort and 18.15 (17.24-19.12) in the comparator cohort; incidence rate ratio 0.82 (0.76-0.89) adjusted for age, sex and primary care practitioner (PCP) visits in the previous year. Lower incidence rates were seen in the aspirin cohort for all strata evaluated (gender, age group and number of PCP visits in the previous year) except those aged ≥80years. Among most individuals without established CVD, initiation of low-dose aspirin is associated with a reduced incidence of CRC. Copyright © 2017 Elsevier B.V. All rights reserved.

Medication Incidents Involving Antiepileptic Drugs in Canadian Hospitals: A Multi-Incident Analysis.

PubMed

Cheng, Roger; Yang, Yu Daisy; Chan, Matthew; Patel, Tejal

2017-01-01

Medication errors involving antiepileptic drugs (AEDs) are not well studied but have the potential to cause significant harm. We investigated the occurrence of medication incidents in Canadian hospitals that involve AEDs, their severity and contributing factors by analyzing data from two national databases. Our multi-incident analysis revealed that while medication errors were rarely fatal, errors do occur of which some are serious. Medication incidents were most commonly caused by dose omissions, the dose or its frequency being incorrect and the wrong AED being given. Our analysis could augment quality-improvement initiatives by medication safety administrators to reduce AED medication incidents in hospitals.

Direct imaging of small scatterers using reduced time dependent data

NASA Astrophysics Data System (ADS)

Cakoni, Fioralba; Rezac, Jacob D.

2017-06-01

We introduce qualitative methods for locating small objects using time dependent acoustic near field waves. These methods have reduced data collection requirements compared to typical qualitative imaging techniques. In particular, we only collect scattered field data in a small region surrounding the location from which an incident field was transmitted. The new methods are partially theoretically justified and numerical simulations demonstrate their efficacy. We show that these reduced data techniques give comparable results to methods which require full multistatic data and that these time dependent methods require less scattered field data than their time harmonic analogs.

Dose-dependent protective effect of breast-feeding against breast cancer among ever-lactated women in Korea.

PubMed

Kim, Yeonju; Choi, Ji-Yeob; Lee, Kyoung-Mu; Park, Sue Kyung; Ahn, Sei-Hyun; Noh, Dong-Young; Hong, Yun-Chul; Kang, Daehee; Yoo, Keun-Young

2007-04-01

Lactation might have a crucial role in an extraordinary increase in breast cancer incidence in Korea, as the proportion of mothers who practised breast-feeding fell dramatically. This hospital-based case-control analysis has been carried out since 1997 to evaluate whether lactation is associated with breast cancer risk in Korean women. Among the eligible study participants, a total of 753 histologically confirmed incident cases and an equal number of controls were included in the analysis. The risk was estimated using unconditional logistic regression models. Family history, older at menopause, more full-term pregnancies increased the risk of breast cancer. Breast cancer risk decreased according to the total months of breast-feeding (P for trend=0.03). Average duration of breast-feeding of 11-12 months reduced risk of breast cancer by 54% compared with the duration of 1-4 months (odds ratio, 0.46; 95% confidence interval, 0.30-0.70). The decreasing risk trend according to average months of breast-feeding was also statistically significant (P for trend=0.02). Moreover, a reduced risk of breast cancer was apparent when analysis was restricted to the first breast-fed child (P for trend=0.006). This study confirms that lactation has an apparent dose-dependent protective effect against breast cancer in Korean women.

Hypoglycemia in glyburide-treated gestational diabetes: is it dose-dependent?

PubMed

Brustman, Lois; Langer, Oded; Scarpelli, Sophia; El Daouk, Manal; Fuchs, Anna; Rosenn, Barak

2011-02-01

To estimate whether there is a relationship between glyburide dose and the rate of hypoglycemic episodes in women with gestational diabetes mellitus (GDM). We studied 674 women with GDM who were treated with glyburide and diagnosed from 2000 to 2009. Glucose data were downloaded from memory-based meters at each visit and analyzed to estimate the incidence of recorded episodes of hypoglycemia and the association with concurrent dose of glyburide therapy (2.5, 5, 10, 15, or 20 mg). Hypoglycemia was defined as a blood glucose of less than 50 mg/dL, further classified as "severe hypoglycemia" if the event required the assistance of another person for resuscitation, "symptomatic hypoglycemia" if it was associated with typical neurogenic symptoms, or "asymptomatic hypoglycemia" if the biochemical reading was less than 50 mg/dL with no symptoms or accompanied by mild symptoms that did not impair the patient's ability to function. Patients recorded a mean of 272 glucose values. Sixty-seven percent of the patients experienced no blood glucose values in the hypoglycemic range. 33% had 1-7% of their total blood glucose values within the hypoglycemic range. All recordings of hypoglycemic episodes were asymptomatic; no patient reported a severe or symptomatic hypoglycemic episode. A significant association was found between the incidence of asymptomatic hypoglycemia and mean blood glucose (P<.001). No association was found between glyburide dose and incidence of asymptomatic hypoglycemia. No association between glyburide dose or mean blood glucose value and the incidence of neonatal hypoglycemia was found. Incremental increases in glyburide dose are not associated with an increase in the incidence of hypoglycemic episodes. II.

A spectrum of exercise training reduces soluble Aβ in a dose-dependent manner in a mouse model of Alzheimer's disease.

PubMed

Moore, Kaitlin M; Girens, Renee E; Larson, Sara K; Jones, Maria R; Restivo, Jessica L; Holtzman, David M; Cirrito, John R; Yuede, Carla M; Zimmerman, Scott D; Timson, Benjamin F

2016-01-01

Physical activity has long been hypothesized to influence the risk and pathology of Alzheimer's disease. However, the amount of physical activity necessary for these benefits is unclear. We examined the effects of three months of low and high intensity exercise training on soluble Aβ40 and Aβ42 levels in extracellular enriched fractions from the cortex and hippocampus of young Tg2576 mice. Low (LOW) and high (HI) intensity exercise training animals ran at speeds of 15m/min on a level treadmill and 32 m/min at a 10% grade, respectively for 60 min per day, five days per week, from three to six months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. Soleus muscle citrate synthase activity increased by 39% in the LOW group relative to SED, and by 71% in the HI group relative to LOW, indicating an exercise training effect in these mice. Soluble Aβ40 concentrations decreased significantly in an exercise training dose-dependent manner in the cortex. In the hippocampus, concentrations were decreased significantly in the HI group relative to LOW and SED. Soluble Aβ42 levels also decreased significantly in an exercise training dose-dependent manner in both the cortex and hippocampus. Five proteins involved in Aβ clearance (neprilysin, IDE, MMP9, LRP1 and HSP70) were elevated by exercise training with its intensity playing a role in each case. Our data demonstrate that exercise training reduces extracellular soluble Aβ in the brains of Tg2576 mice in a dose-dependent manner through an up-regulation of Aβ clearance. Copyright © 2015 Elsevier Inc. All rights reserved.

Blockade of hyperpolarizing currents produces a dose-dependent effect on heart rate.

PubMed

Ziyatdinova, N I; Giniatullin, R A; Svyatova, N V; Zefirov, T L

2001-03-01

Intravenous injection of ZD 7288, a new specific hyperpolarizing current blocker, dose-dependently reduces heart rate in adult rats. The autonomic nervous system modulates changes in heart rate caused by hyperpolarizing currents.

Incidence of Hyponatremia with High-Dose Trimethoprim-Sulfamethoxazole Exposure.

PubMed

Tsapepas, Demetra; Chiles, Mariana; Babayev, Revekka; Rao, Maya K; Jaitly, Manasvi; Salerno, David; Mohan, Sumit

2016-12-01

Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly prescribed antibiotic used at high doses for treatment of pneumocystis pneumonia and other infections. Trimethoprim is structurally related to the potassium-sparing diuretic amiloride and has been associated with hyperkalemia and hyponatremia through blocking of epithelial sodium channels in the distal nephron. The incidence of hyponatremia in hospitalized patients treated with high-dose TMP-SMX is unknown. We performed a single-center retrospective chart review of all hospitalized patients who received high-dose TMP-SMX (n = 235) from January 2012 to July 2014. Patients with congestive heart failure, cirrhosis, estimated glomerular filtration rate <30 mL/min/1.73 m 2 , baseline hyponatremia, and those on other medications associated with hyponatremia were excluded. Hyponatremia was defined as a serum sodium level <136 mEq/L. Analysis was restricted to 76 unique patients who received more than 8 mg/kg/d of TMP for ≥3 days. Mean starting serum sodium at time of TMP-SMX initiation was 138.4 ± 2.1 mEq/L. Fifty-five patients (72.3%) developed hyponatremia while on therapy, of which 43.6% (n = 24) were cases of serum sodium <130 mEq/L. Mean sodium at the time of nadir was 131.6 ± 5.1 mEq/L. Hyponatremia was noted, on average, 5.5 days after initiation of therapy, with more severe hyponatremia development among African American patients. Urine sodium concentrations were available for 40.0% (22/55) of incident hyponatremia cases, with mean urinary sodium of 104.8 ± 55.9 mEq/L. Hyponatremia often resolved within 3 weeks of drug discontinuation. There is a high incidence (72.3%) of hyponatremia associated with the use of high-dose TMP-SMX among hospitalized patients. This is an overlooked and potentially reversible cause of hyponatremia. Copyright © 2016 Elsevier Inc. All rights reserved.

Tigecycline Reduces Ethanol Intake in Dependent and Non-Dependent Male and Female C57BL/6J Mice

PubMed Central

Bergeson, Susan E.; Nipper, Michelle A.; Jensen, Jeremiah; Helms, Melinda L.; Finn, Deborah A.

2016-01-01

Background The chronic intermittent ethanol (CIE) paradigm is valuable for screening compounds for efficacy to reduce drinking traits related to alcohol use disorder (AUD), as it measures alcohol consumption and preference under physical dependence conditions. Air control treated animals allow simultaneous testing of similarly treated, non-dependent animals. As a consequence, we used CIE to test the hypothesis that tigecycline, a semi-synthetic tetracycline similar to minocycline and doxycycline, would reduce alcohol consumption regardless of dependence status. Methods Adult C57BL/6J female and male mice were tested for tigecycline efficacy to reduce ethanol consumption using a standard CIE paradigm. The ability of tigecycline to decrease 2-bottle choice of 15% ethanol (15E) versus water intake in dependent (CIE-vapor) and non-dependent (air-treated) male and female mice was tested after four cycles of CIE vapor or air exposure using a within-subjects design and a dose response. Drug doses of 0, 40, 60, 80, 100 mg/kg in saline were administered intraperitoneally (0.01 mL/g body weight) and in random order, with a 1 hr pretreatment time. Baseline 15E intake was re-established prior to administration of subsequent injections, with a maximum of two drug injections tested per week. Results Tigecycline was found to effectively reduce high alcohol consumption in both dependent and non-dependent female and male mice. Conclusions Our data suggest that tigecycline may be a promising drug with novel pharmacotherapeutic characteristics for the treatment of mild to severe AUD in both sexes. PMID:27859429

Incidence of oral thrush in patients with COPD prescribed inhaled corticosteroids: Effect of drug, dose, and device.

PubMed

Dekhuijzen, P N Richard; Batsiou, Maria; Bjermer, Leif; Bosnic-Anticevich, Sinthia; Chrystyn, Henry; Papi, Alberto; Rodríguez-Roisin, Roberto; Fletcher, Monica; Wood, Lucy; Cifra, Alessandra; Soriano, Joan B; Price, David B

2016-11-01

Little information is available on real-life occurrence of oral thrush in COPD patients treated with ICS. We investigated oral thrush incidence in COPD patients prescribed FDC ICS/LABA therapies and assessed whether it is modulated by the ICS type, dose, and delivery device. We conducted a historical, observational, matched cohort study (one baseline year before and one outcome year after initiation of therapy) using data from the UK Optimum Patient Care Research Database. We assessed oral thrush incidence in patients initiating long-acting bronchodilators or FDC ICS/LABA therapy. We then compared different combination therapies (budesonide/formoterol fumarate dihydrate [BUD/FOR] and fluticasone propionate/salmeterol xinafoate [FP/SAL]) and devices (DPI and pMDI). Patients prescribed FDC ICS/LABA had significantly greater odds of experiencing oral thrush than those prescribed long-acting bronchodilators alone (adjusted OR 2.18 [95% CI 1.84-2.59]). Significantly fewer patients prescribed BUD/FOR DPI developed oral thrush compared with FP/SAL DPI (OR 0.77 [0.63-0.94]) when allowing for differences in prescribed doses between the drugs. A significantly smaller proportion of patients developed oral thrush in the FP/SAL pMDI arm than in the FP/SAL DPI arm (OR 0.67 [0.55-0.82]). Additionally, in the FP/SAL cohort (both DPI and pMDI), increased risk of oral thrush was significantly associated with high ICS daily dose (OR 1.97 [1.22-3.17] vs low daily dose). ICS use increases oral thrush incidence in COPD and this effect is dose-dependent for FP/SAL therapies. Of the therapies assessed, FP/SAL pMDI and BUD/FOR DPI may be more protective against oral thrush. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharyngeal and cervical cancer incidences significantly correlate with personal UV doses among whites in the United States.

PubMed

Godar, Dianne E; Tang, Rong; Merrill, Stephen J

2014-09-01

Because we found UV-exposed oral tissue cells have reduced DNA repair and apoptotic cell death compared with skin tissue cells, we asked if a correlation existed between personal UV dose and the incidences of oral and pharyngeal cancer in the United States. We analyzed the International Agency for Research on Cancer's incidence data for oral and pharyngeal cancers by race (white and black) and sex using each state's average annual personal UV dose. We refer to our data as 'white' rather than 'Caucasian,' which is a specific subgroup of whites, and 'black' rather than African-American because blacks from other countries around the world reside in the U.S. Most oropharyngeal carcinomas harboured human papilloma virus (HPV), so we included cervical cancer as a control for direct UV activation. We found significant correlations between increasing UV dose and pharyngeal cancer in white males (p=0.000808) and females (p=0.0031) but not in blacks. Shockingly, we also found cervical cancer in whites to significantly correlate with increasing UV dose (p=0.0154). Thus, because pharyngeal and cervical cancer correlate significantly with increasing personal UV dose in only the white population, both direct (DNA damage) and indirect (soluble factors) effects may increase the risk of HPV-associated cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Angular dependence of dose sensitivity of nanoDot optically stimulated luminescent dosimeters in different radiation geometries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jursinic, Paul A., E-mail: pjursinic@wmcc.org

2015-10-15

Purpose: A type of in vivo dosimeter, an optically stimulated luminescent dosimeter, OSLD, may have dose sensitivity that depends on the angle of incidence of radiation. This work measures how angular dependence of a nanoDot changes with the geometry of the phantom in which irradiation occurs and with the intrinsic structure of the nanoDot. Methods: The OSLDs used in this work were nanoDot dosimeters (Landauer, Inc., Glenwood, IL), which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). Dose to the OSLDs was delivered by 6 MV x-rays. NanoDots with various intrinsic sensitivities were irradiated in numerous phantoms thatmore » had geometric shapes of cylinders, rectangles, and a cube. Results: No angular dependence was seen in cylindrical phantoms, cubic phantoms, or rectangular phantoms with a thickness to width ratio of 0.3 or 1.5. An angular dependence of 1% was observed in rectangular phantoms with a thickness to width of 0.433–0.633. A group of nanoDots had sensitive layers with mass density of 2.42–2.58 g/cm{sup 3} and relative sensitivity of 0.92–1.09 and no difference in their angular dependence. Within experimental uncertainty, nanoDot measurements agree with a parallel-plate ion chamber at a depth of maximum dose. Conclusions: When irradiated in cylindrical, rectangular, and cubic phantoms, nanoDots show a maximum angular dependence of 1% or less at an incidence angle of 90°. For a sample of 78 new nanoDots, the range of their relative intrinsic sensitivity is 0.92–1.09. For a sample of ten nanoDots, on average, the mass in the sensitive layer is 73.1% Al{sub 2}O{sub 3}:C and 26.9% polyester. The mass density of the sensitive layer of a nanoDot disc is between 2.42 and 2.58 g/cm{sup 3}. The angular dependence is not related to Al{sub 2}O{sub 3}:C loading of the nanoDot disc. The nanoDot at the depth of maximum dose has no more angular dependence than a parallel-plate ion chamber.« less

Multiple-, But Not Single-, Dose of Parecoxib Reduces Shoulder Pain after Gynecologic Laparoscopy

PubMed Central

Zhang, Hufei; Shu, Haihua; Yang, Lu; Cao, Minghui; Zhang, Jingjun; Liu, Kexuan; Xiao, Liangcan; Zhang, Xuyu

2012-01-01

Background: The aim of this study was to investigate effect of single- and multiple-dose of parecoxib on shoulder pain after gynecologic laparoscopy. Methods: 126 patients requiring elective gynecologic laparoscopy were randomly allocated to three groups. Group M (multiple-dose): receiving parecoxib 40mg at 30min before the end of surgery, at 8 and 20hr after surgery, respectively; Group S (single-dose): receiving parecoxib 40mg at 30min before the end of surgery and normal saline at the corresponding time points; Group C (control): receiving normal saline at the same three time points. The shoulder pain was evaluated, both at rest and with motion, at postoperative 6, 24 and 48hr. The impact of shoulder pain on patients' recovery (activity, mood, walking and sleep) was also evaluated. Meanwhile, rescue analgesics and complications were recorded. Results: The overall incidence of shoulder pain in group M (37.5%) was lower than that in group C (61.9%) (difference=-24.4%; 95% CI: 3.4~45.4%; P=0.023). Whereas, single-dose regimen (61.0%) showed no significant reduction (difference with control=-0.9%; 95% CI: -21.9~20.0%; P=0.931). Moreover, multiple-dose regimen reduced the maximal intensity of shoulder pain and the impact for activity and mood in comparison to the control. Multiple-dose of parecoxib decreased the consumption of rescue analgesics. The complications were similar among all groups and no severe complications were observed. Conclusions: Multiple-, but not single-, dose of parecoxib may attenuate the incidence and intensity of shoulder pain and thereby improve patients' quality of recovery following gynecologic laparoscopy. PMID:23136538

Local Control With Reduced-Dose Radiotherapy for Low-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group D9602 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breneman, John, E-mail: john.breneman@uchealth.com; Meza, Jane; Donaldson, Sarah S.

2012-06-01

Purpose: To analyze the effect of reduced-dose radiotherapy on local control in children with low-risk rhabdomyosarcoma (RMS) treated in the Children's Oncology Group D9602 study. Methods and Materials: Patients with low-risk RMS were nonrandomly assigned to receive radiotherapy doses dependent on the completeness of surgical resection of the primary tumor (clinical group) and the presence of involved regional lymph nodes. After resection, most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide addedmore » for patient subsets with a higher risk of relapse in Intergroup Rhabdomyosarcoma Study Group III and IV studies. Results: Three hundred forty-two patients were eligible for analysis; 172 received radiotherapy as part of their treatment. The cumulative incidence of local/regional failure was 15% in patients with microscopic involved margins when cyclophosphamide was not part of the treatment regimen and 0% when cyclophosphamide was included. The cumulative incidence of local/regional failure was 14% in patients with orbital tumors. Protocol-specified omission of radiotherapy in girls with Group IIA vaginal tumors (n = 5) resulted in three failures for this group. Conclusions: In comparison with Intergroup Rhabdomyosarcoma Study Group III and IV results, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or with orbital primary tumors when cyclophosphamide is added to the treatment program. Girls with unresected nonbladder genitourinary tumors require radiotherapy for postsurgical residual tumor for optimal local control to be achieved.« less

First-principles X-ray absorption dose calculation for time-dependent mass and optical density.

PubMed

Berejnov, Viatcheslav; Rubinstein, Boris; Melo, Lis G A; Hitchcock, Adam P

2018-05-01

A dose integral of time-dependent X-ray absorption under conditions of variable photon energy and changing sample mass is derived from first principles starting with the Beer-Lambert (BL) absorption model. For a given photon energy the BL dose integral D(e, t) reduces to the product of an effective time integral T(t) and a dose rate R(e). Two approximations of the time-dependent optical density, i.e. exponential A(t) = c + aexp(-bt) for first-order kinetics and hyperbolic A(t) = c + a/(b + t) for second-order kinetics, were considered for BL dose evaluation. For both models three methods of evaluating the effective time integral are considered: analytical integration, approximation by a function, and calculation of the asymptotic behaviour at large times. Data for poly(methyl methacrylate) and perfluorosulfonic acid polymers measured by scanning transmission soft X-ray microscopy were used to test the BL dose calculation. It was found that a previous method to calculate time-dependent dose underestimates the dose in mass loss situations, depending on the applied exposure time. All these methods here show that the BL dose is proportional to the exposure time D(e, t) ≃ K(e)t.

Dose-Response Association Between Physical Activity and Incident Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies.

PubMed

Liu, Xuejiao; Zhang, Dongdong; Liu, Yu; Sun, Xizhuo; Han, Chengyi; Wang, Bingyuan; Ren, Yongcheng; Zhou, Junmei; Zhao, Yang; Shi, Yuanyuan; Hu, Dongsheng; Zhang, Ming

2017-05-01

Despite the inverse association between physical activity (PA) and incident hypertension, a comprehensive assessment of the quantitative dose-response association between PA and hypertension has not been reported. We performed a meta-analysis, including dose-response analysis, to quantitatively evaluate this association. We searched PubMed and Embase databases for articles published up to November 1, 2016. Random effects generalized least squares regression models were used to assess the quantitative association between PA and hypertension risk across studies. Restricted cubic splines were used to model the dose-response association. We identified 22 articles (29 studies) investigating the risk of hypertension with leisure-time PA or total PA, including 330 222 individuals and 67 698 incident cases of hypertension. The risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.96) with each 10 metabolic equivalent of task h/wk increment of leisure-time PA. We found no evidence of a nonlinear dose-response association of PA and hypertension ( P nonlinearity =0.094 for leisure-time PA and 0.771 for total PA). With the linear cubic spline model, when compared with inactive individuals, for those who met the guidelines recommended minimum level of moderate PA (10 metabolic equivalent of task h/wk), the risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.97). This meta-analysis suggests that additional benefits for hypertension prevention occur as the amount of PA increases. © 2017 American Heart Association, Inc.

Radiation dose and cataract surgery incidence in atomic bomb survivors, 1986-2005.

PubMed

Neriishi, Kazuo; Nakashima, Eiji; Akahoshi, Masazumi; Hida, Ayumi; Grant, Eric J; Masunari, Naomi; Funamoto, Sachiyo; Minamoto, Atsushi; Fujiwara, Saeko; Shore, Roy E

2012-10-01

To examine the incidence of clinically important cataracts in relation to lens radiation doses between 0 and approximately 3 Gy to address risks at relatively low brief doses. Informed consent was obtained, and human subjects procedures were approved by the ethical committee at the Radiation Effects Research Foundation. Cataract surgery incidence was documented for 6066 atomic bomb survivors during 1986-2005. Sixteen risk factors for cataract, such as smoking, hypertension, and corticosteroid use, were not confounders of the radiation effect on the basis of Cox regression analysis. Radiation dose-response analyses were performed for cataract surgery incidence by using Poisson regression analysis, adjusting for demographic variables and diabetes mellitus, and results were expressed as the excess relative risk (ERR) and the excess absolute risk (EAR) (ie, measures of how much radiation multiplies [ERR] or adds to [EAR] the risk in the unexposed group). Of 6066 atomic bomb survivors, 1028 underwent a first cataract surgery during 1986-2005. The estimated threshold dose was 0.50 Gy (95% confidence interval [CI]: 0.10 Gy, 0.95 Gy) for the ERR model and 0.45 Gy (95% CI: 0.10 Gy, 1.05 Gy) for the EAR model. A linear-quadratic test for upward curvature did not show a significant quadratic effect for either the ERR or EAR model. The linear ERR model for a 70-year-old individual, exposed at age 20 years, showed a 0.32 (95% CI: 0.09, 0.53) [corrected] excess risk at 1 Gy. The ERR was highest for those who were young at exposure. These data indicate a radiation effect for vision-impairing cataracts at doses less than 1 Gy. The evidence suggests that dose standards for protection of the eye from brief radiation exposures should be 0.5 Gy or less. © RSNA, 2012.

Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention

PubMed Central

Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

2016-01-01

Abstract Background: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. Methods: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. Results: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P < 0.00001) and an 18% reduction in RR (RR 0.82, 95% CI [0.73, 0.93], P = 0.002) in the subgroup without renal transplant recipients and patients undergoing regular hemodialysis separately. For the fatal stroke incidences, intensive-dose statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. Conclusion: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences. PMID:27684837

Influenza vaccine oculorespiratory syndrome incidence is reduced in HIV.

PubMed

Cooper, Curtis; Thorne, Anona

2011-10-19

Clinical experience suggests Oculorespiratory Syndrome (ORS) following influenza vaccination is rare in HIV but this is not well evaluated. We assessed ORS incidence in a randomized influenza vaccine trial of HIV participants. The overall incidence was 0.8% suggesting that influenza vaccine ORS incidence is reduced in HIV. Copyright © 2011 Elsevier Ltd. All rights reserved.

Quality of life in a cohort of high-dose benzodiazepine dependent patients.

PubMed

Lugoboni, Fabio; Mirijello, Antonio; Faccini, Marco; Casari, Rebecca; Cossari, Anthony; Musi, Gessica; Bissoli, Giorgia; Quaglio, Gianluca; Addolorato, Giovanni

2014-09-01

Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria.

PubMed

Wong, Phillip; Polkinghorne, Kevan; Kerr, Peter G; Doery, James C G; Gillespie, Matthew T; Larmour, I; Fuller, Peter J; Bowden, Donald K; Milat, Frances

2016-04-01

Deferasirox is an oral iron chelator used widely in the treatment of thalassemia major and other transfusion-dependent hemoglobinopathies. Whilst initial long-term studies established the renal safety of deferasirox, there are now increasing reports of hypercalciuria and renal tubular dysfunction. In addition, urolithiasis with rapid loss of bone density in patients with β thalassemia major has been reported. We conducted a cross-sectional cohort study enrolling 152 adult patients comprising of β thalassemia major (81.5%), sickle cell disease (8%), thalassemia intermedia (2%), HbH disease (6.5%) and E/β thalassemia (2%). Cases were matched with normal control subjects on age, gender and serum creatinine. Iron chelator use was documented and urine calcium to creatinine ratios measured. At the time of analysis, 88.8% of patients were receiving deferasirox and 11.2% were on deferoxamine. Hypercalciuria was present in 91.9% of subjects on deferasirox in a positive dose-dependent relationship. This was not seen with subjects receiving deferoxamine. At a mean dose of 30.2±8.8mg/kg/day, deferasirox was associated with an almost 4 fold increase in urine calcium to creatinine ratio (UCa/Cr). Hypercalciuria was present at therapeutic doses of deferasirox in a dose-dependent manner and warrants further investigation and vigilance for osteoporosis, urolithiasis and other markers of renal dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

Propofol dose and incidence of dreaming during sedation.

PubMed

Eer, Audrey Singyi; Padmanabhan, Usha; Leslie, Kate

2009-10-01

Dreaming is commonly reported after propofol-based sedation. We measured the incidence of dreaming and bispectral index (BIS) values in colonoscopy patients sedated with combinations of propofol, midazolam and fentanyl. Two hundred patients presenting for elective outpatient colonoscopy were sedated with combinations of propofol, midazolam and fentanyl. BIS was monitored throughout the procedure. Patients were interviewed immediately after they emerged from sedation. The primary end point was a report of dreaming during sedation. Ninety-seven patients were administered propofol alone, 44 were administered propofol and fentanyl, 16 were administered propofol and midazolam and 43 were administered propofol, midazolam and fentanyl. Dreaming was reported by 19% of patients. Dreamers received higher doses of propofol and had lower BIS values during sedation. Age of 50 years or less, preoperative quality of recovery score of less than 14, higher home dream recall, propofol dose of more than 300 mg and time to Observers' Assessment of Alertness/Sedation score equalling 5 of 8 min or less were independent predictors of dreaming. Dreaming during sedation is associated with higher propofol dose and lower BIS values.

The effects of recombinant activated factor VII dose on the incidence of thromboembolic events in patients with coagulopathic bleeding.

PubMed

Bucklin, Mason H; Acquisto, Nicole M; Nelson, Catherine

2014-05-01

Previous studies have suggested the used of off-label recombinant factor VII (rFVIIa) increases the risk of thromboembolic events, but the effect of the dose of rFVIIa is not well described in the literature. All adult patients that received off-label rFVIIa from 2005-2012 were included in this single-center, retrospective cohort study. The primary endpoint was the incidence of a thromboembolic event in the low dose (<50 mcg/kg) compared to the high dose (≥50 mcg/kg) cohort. Secondary endpoints compared time to thromboembolic event, incidence of arterial compared to venous events, and mortality. There were 152 patients that received rFVIIa during the study period with 66 in the low dose cohort and 86 in the high dose cohort. Mean total dose of rFVIIa was 30.2 mcg/kg (SD ± 9.5 mcg/kg) in the low dose and 99.8 mcg/kg (SD ± 64.7 mcg/kg) in the high dose cohort (p=0.0001). The overall incidence of thromboembolic events was 12.5%. There were 12 (14%) events in the low dose cohort and seven (10.6%) in the high dose cohort, RR=0.76 (95% CI 0.31-1.82). There were no differences in any of the secondary outcomes. A higher incidence of thromboembolic events in cardiothoracic surgery (20.8%) and penetrating trauma patients (21.4%) was seen compared to the remaining cohort (6.7%). No significant difference in the incidence of thromboembolic events was seen between low dose versus high dose rFVIIa over a seven year period at our institution. However, due to the relatively low overall incidence and a small sample size, type II error may be present. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial.

PubMed

Cengiz, Pelin; Gokcinar, Derya; Karabeyoglu, Isil; Topcu, Hulya; Cicek, Gizem Selen; Gogus, Nermin

2014-05-01

To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. A randomized, double-blind comparative study. Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6 μg/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects.

Angular dependence of the MOSFET dosimeter and its impact on in vivo surface dose measurement in breast cancer treatment.

PubMed

Qin, S; Chen, T; Wang, L; Tu, Y; Yue, N; Zhou, J

2014-08-01

The focus of this study is the angular dependence of two types of Metal Oxide Semiconductor Field Effect Transistor (MOSFET) dosimeters (MOSFET20 and OneDose/OneDosePlus) when used for surface dose measurements. External beam radiationat different gantry angles were delivered to a cubic solid water phantom with a MOSFET placed on the top surface at CAX. The long axis of the MOSFET was oriented along the gantry axis of rotation, with the dosimeter (bubble side) facing the radiation source. MOSFET-measured surface doses were compared against calibrated radiochromic film readings. It was found that both types of MOSFET dosimeters exhibited larger than previously reported angular dependence when measuring surface dose in beams at large oblique angles. For the MOSFET20 dosimeter the measured surface dose deviation against film readings was as high as 17% when the incident angle was 72 degrees to the norm of the phantom surface. It is concluded that some MOSFET dosimeters may have a strong angular dependence when placed on the surface of water-equivalent material, even though they may have an isotropic angular response when surrounded by uniform medium. Extra on-surface calibration maybe necessary before using MOSFET dosimeters for skin dose measurement in tangential fields.

Dosimetric evaluation of the OneDoseTM MOSFET for measuring kilovoltage imaging dose from image-guided radiotherapy procedures.

PubMed

Ding, George X; Coffey, Charles W

2010-09-01

The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.

Gold Nanoparticle Hyperthermia Reduces Radiotherapy Dose

PubMed Central

Lin, Lynn; Slatkin, Daniel N.; Dilmanian, F. Avraham; Vadas, Timothy M.; Smilowitz, Henry M.

2014-01-01

Gold nanoparticles can absorb near infrared light, resulting in heating and ablation of tumors. Gold nanoparticles have also been used for enhancing the dose of X-rays in tumors during radiotherapy. The combination of hyperthermia and radiotherapy is synergistic, importantly allowing a reduction in X-ray dose with improved therapeutic results. Here we intratumorally infused small 15 nm gold nanoparticles engineered to be transformed from infrared-transparent to infrared-absorptive by the tumor, which were then heated by infrared followed by X-ray treatment. Synergy was studied using a very radioresistant subcutaneous squamous cell carcinoma (SCCVII) in mice. It was found that the dose required to control 50% of the tumors, normally 55 Gy, could be reduced to <15 Gy (a factor of >3.7). Gold nanoparticles therefore provide a method to combine hyperthermia and radiotherapy to drastically reduce the X-ray radiation needed, thus sparing normal tissue, reducing the side effects, and making radiotherapy more effective. PMID:24990355

Ionizing radiation sensitivity of the ocular lens and its dose rate dependence.

PubMed

Hamada, Nobuyuki

2017-10-01

In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such a threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures. Such a change was made predicated on epidemiological evidence suggesting that a threshold for fractionated/protracted exposures is not higher than an acute threshold, and that a chronic threshold is uncertain. Thus, the dose rate dependence is still unclear. This paper therefore reviews the current knowledge on the radiosensitivity of the lens and the dose rate dependence of radiation cataractogenesis, and discusses its mechanisms. Mounting biological evidence indicates that the lens cells are not necessarily radiosensitive to cell killing, and the high radiosensitivity of the lens thus appears to be attributable to other mechanisms (e.g., excessive proliferation, abnormal differentiation, a slow repair of DNA double-strand breaks, telomere, senescence, crystallin changes, non-targeted effects and inflammation). Both biological and epidemiological evidence generally supports the lack of dose rate effects. However, there is also biological evidence for the tissue sparing dose rate (or fractionation) effect of low-LET radiation and an enhancing inverse dose fractionation effect of high-LET radiation at a limited range of LET. Emerging epidemiological evidence in chronically exposed individuals implies the inverse dose rate effect. Further biological and epidemiological studies are warranted to gain deeper knowledge on the radiosensitivity of the lens and dose rate dependence of radiation cataractogenesis.

High-dose naltrexone therapy for cocaine-alcohol dependence.

PubMed

Schmitz, Joy M; Lindsay, Jan A; Green, Charles E; Herin, David V; Stotts, Angela L; Moeller, F Gerard

2009-01-01

This randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence.

Use of remifentanil to reduce propofol injection pain and the required propofol dose in upper digestive tract endoscopy diagnostic tests.

PubMed

Uliana, Gustavo Nadal; Tambara, Elizabeth Milla; Baretta, Giorgio Alfredo Pedroso

2015-01-01

The introduction of propofol (2,6-diisopropylphenol) as a sedative agent has transformed the area of sedation for endoscopic procedures. However, a major drawback of sedation with the use of propofol is its high incidence of injection pain. The most widely used technique in reducing propofol injection pain is through the association of other drugs. The aim of this study was to evaluate the effect of remifentanil-propofol combination on the incidence of propofol injection pain and its influence on the total dose of propofol required for sedation in upper digestive tract endoscopy (UDE) diagnostic tests. One hundred and five patients undergoing upper digestive tract endoscopy were evaluated and randomly divided into 3 groups of 35 patients each. The Control Group received propofol alone; Study-group 1 received remifentanil at a fixed dose of 0.2mg/kg combined with propofol; Study-group 2 received remifentanil at a fixed dose of 0.3mg/kg combined with propofol. The incidence of propofol injection pain and the total dose of propofol required for the test were evaluated. The sample was very similar regarding age, weight, height, sex, and physical status. Statistical analysis was performed according to the nature of the evaluated data. Student's t-test was used to compare the mean of age, weight, height (cm), and dose (mg/kg) variables between groups. The χ(2) test was used to compare sex, physical status, and propofol injection pain between groups. The significance level was α<0.05. There was significant statistical difference between the study groups and the control group regarding the parameters of propofol injection pain and total dose of propofol (mg/kg) used. However, there were no statistical differences between the two study groups for these parameters. We conclude that the use of remifentanil at doses of 0.2mg/kg and 0.3mg/kg was effective for reducing both the propofol injection pain and the total dose of propofol used. Copyright © 2015 Sociedade Brasileira

Sibutramine-induced anorexia: potent, dose-dependent and behaviourally-selective profile in male rats.

PubMed

Tallett, A J; Blundell, J E; Rodgers, R J

2009-03-17

The serotonin and noradrenaline reuptake inhibitor sibutramine has been licensed as an anti-obesity treatment for more than a decade. However, while inhibitory effects on food intake and weight gain are well documented, surprisingly little published detail exists regarding its influence on feeding and related behaviours. The present study was therefore designed to assess the effects of acute sibutramine treatment on food intake, the behavioural satiety sequence (BSS) and post-treatment weight gain. Subjects were 10 non-deprived adult male Lister hooded rats, tested with 0.5-3.0 mg/kg sibutramine hydrochloride during 1-h DVD-recorded test sessions with palatable mash. Our results show that sibutramine dose-dependently reduced food intake, an effect significant at all doses tested. Ethological analysis revealed very few behavioural effects, except for a dose-dependent reduction in time spent feeding and an increase in the frequency of resting. Behavioural specificity was further supported by time-bin analysis which confirmed both the structural integrity and dose-dependent acceleration of the BSS. Single dosing with sibutramine (3.0 mg/kg) also suppressed daily weight gain over the 24-72 h period post-dosing. Current data support the conclusion that the acute anorectic and weight loss efficacy of sibutramine in adult male rats is not secondary to behavioural disruption but, instead, is due largely to an acceleration in behavioural satiety.

Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention: A meta-analysis.

PubMed

Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

2016-09-01

Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P < 0.00001) and an 18% reduction in RR (RR 0.82, 95% CI [0.73, 0.93], P = 0.002) in the subgroup without renal transplant recipients and patients undergoing regular hemodialysis separately. For the fatal stroke incidences, intensive-dose statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences.

Cryoradiolytic reduction of heme proteins: Maximizing dose-dependent yield

NASA Astrophysics Data System (ADS)

Denisov, Ilia G.; Victoria, Doreen C.; Sligar, Stephen G.

2007-04-01

Radiolytic reduction in frozen solutions and crystals is a useful method for generation of trapped intermediates in protein-based radical reactions. In this communication we define the conditions which provide the maximum yield of one electron-reduced myoglobin at 77 K using 60Co γ-irradiation in aqueous glycerol glass. The yield reached 50% after 20 kGy, was almost complete at ˜160 kGy total dose, and does not depend on the protein concentration in the range 0.01-5 mM.

Incidence of adrenal insufficiency and impact of corticosteroid supplementation in critically ill children with systemic inflammatory syndrome and vasopressor-dependent shock.

PubMed

Hebbar, Kiran B; Stockwell, Jana A; Leong, Traci; Fortenberry, James D

2011-05-01

Adrenal insufficiency may be common in adults and children with vasopressor-resistant shock. We developed a protocolized approach to low-dose adrenocorticotropin testing and empirical low-dose glucocorticoid/mineralocorticoid supplementation in children with systemic inflammatory response syndrome and persistent hypotension following fluid resuscitation and vasopressor infusion. We hypothesized that absolute and relative adrenal insufficiency was common in children with systemic inflammatory response syndrome requiring vasopressor support and that steroid administration would be associated with decreased vasopressor need. Retrospective review of pediatric patients with systemic inflammatory response syndrome and vasopressor-dependent shock receiving protocol-based adrenocorticotropin testing and low-dose steroid supplementation. The incidence of absolute and relative adrenal insufficiency was determined using several definitions. Vasopressor dose requirements were evaluated before, and following, initiation of corticosteroids. Seventy-eight patients met inclusion criteria for systemic inflammatory response syndrome and shock; 40 had septic shock. Median age was 84 months (range, 0.5-295). By adrenocorticotropin testing, 44 (56%) had absolute adrenal insufficiency, 39 (50%) had relative adrenal insufficiency, and 69 (88%) had either form of adrenal insufficiency. Adrenal insufficiency incidence was significantly higher in children >2 yrs (p = .0209). Therapeutic interventions included median 80-mL/kg fluid resuscitation; 65% of patients required dopamine, 58% norepinephrine, and 49% dopamine plus norepinephrine. With steroid supplementation, median dopamine dose decreased from 10 to 4 μg/kg/min at 4 hrs (p = .0001), and median dose of norepinephrine decreased from 0.175 μg/kg/min to 0.05 μg/kg/min at 4 hrs (p = .039). Absolute and relative adrenal insufficiency was prevalent in this cohort of children with systemic inflammatory response syndrome and vasopressor-dependent

Dose dependency of time of onset of radiation-induced growth hormone deficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clayton, P.E.; Shalet, S.M.

1991-02-01

Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showedmore » that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis.« less

Dose-dependent effects of hydrocortisone infusion on autobiographical memory recall

PubMed Central

Young, Kymberly; Drevets, Wayne C.; Schulkin, Jay; Erickson, Kristine

2011-01-01

The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n=66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n=33) or high-dose (0.45 mg/kg IV; n=33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p = 0.04), increased the percent of categorical (nonspecific) memories recalled, and slowed response times for categorical memories (p <0.001), compared to placebo performance (p < 0.001). Under moderate-dose hydrocortisone the autobiographical memory performance did not change significantly with respect to percent of specific or categorical memories recalled or reaction times. Performance on the CVLT was not affected by hydrocortisone. These findings suggest that cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories. PMID:21942435

Bupropion Dose-Dependently Reverses Nicotine Withdrawal Deficits in Contextual Fear Conditioning

PubMed Central

Portugal, George S.; Gould, Thomas J.

2007-01-01

Bupropion, a norepinephrine and dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist, facilitates smoking cessation and reduces some symptoms of nicotine withdrawal. However, the effects of bupropion on nicotine withdrawal-associated deficits in learning remain unclear. The present study investigated whether bupropion has effects on contextual and cued fear conditioning following withdrawal from chronic nicotine or when administered alone. Bupropion was administered alone for a range of doses (2.5, 5, 10, 20 or 40 mg/kg), and dose-dependent impairments in contextual and cued fear conditioning were observed (20 or 40 mg/kg). Follow-up studies investigated if bupropion disrupted acquisition or expression of fear conditioning. Bupropion (40 mg/kg) administration on training day only produced deficits in contextual fear conditioning. Alternatively, bupropion (20 or 40 mg/kg) administration during testing dose-dependently produced deficits in contextual and cued fear conditioning. To test the effect of bupropion on nicotine withdrawal, mice were withdrawn from 12 days of chronic nicotine (6.3 mg/kg/day) or saline treatment. Withdrawal from chronic nicotine disrupted contextual fear conditioning; however, 5 mg/kg bupropion reversed this deficit. Overall, these results indicate that a low dose of bupropion can reverse nicotine withdrawal deficits in contextual fear conditioning, but that high doses of bupropion produce deficits in fear conditioning. PMID:17868796

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

PubMed Central

Johnson, Matthew W.; Sewell, R. Andrew; Griffiths, Roland R.

2011-01-01

Background Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. Methods This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Results Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Conclusions Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. PMID:22129843

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers.

PubMed

Johnson, Matthew W; Sewell, R Andrew; Griffiths, Roland R

2012-06-01

Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Incidence of intracranial bleeds in new users of low-dose aspirin: a cohort study using The Health Improvement Network.

PubMed

Cea Soriano, L; Gaist, D; Soriano-Gabarró, M; García Rodríguez, L A

2017-06-01

Essentials Intracranial bleeds (ICB) are serious clinical events that have been associated with aspirin use. Incidence rates of ICB were calculated among new-users of low-dose aspirin in the UK (2000-2012). Over a median follow-up of 5.58 years, the incidence of ICB was 0.08 per 100 person-years. Our estimates are valuable for inclusion in risk-benefit assessments of low-dose aspirin use. Background Low-dose aspirin protects against both ischemic cardiovascular (CV) events and colorectal cancer (CRC). However, low-dose aspirin may be associated with a slightly increased risk of intracranial bleeds (ICBs). Objectives To obtain the incidence rates of ICBs overall and by patient subgroups among new users of low-dose aspirin. Patients/Methods Using The Health Improvement Network (THIN) UK primary-care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N = 199 079; mean age at start of follow-up, 63.9 years) and followed them for up to 14 years (median 5.58 years). Incident ICB cases were identified and validated through linkage to hospitalization data and/or review of THIN records with free-text comments. Incidence rates with 95% confidence intervals (CIs) were calculated. Results Eight hundred and eighty-one incident ICBs cases were identified: 407 cases of intracerebral hemorrhage (ICH), 283 cases of subdural hematoma (SDH), and 191 cases of subarachnoid hemorrhage (SAH). Incidence rates per 100 person-years were 0.08 (95% CI 0.07-0.08) for all ICBs, 0.04 (95% CI 0.03-0.04) for ICH, 0.03 (95% CI 0.02-0.03) for SDH, and 0.02 (95% CI 0.01-0.02) for SAH. The ICB incidence rates per 100 person-years for individuals with an indication of primary CV disease prevention were 0.07 (95% CI 0.06-0.07) and 0.09 (95% CI 0.08-0.10) for secondary CV disease prevention. Incidence rates were higher in men for SDH, and higher in women for ICH and SAH. Conclusions Our results provide valuable estimates of the absolute ICB risk for

Obtaining the Optimal Dose in Alcohol Dependence Studies

PubMed Central

Wages, Nolan A.; Liu, Lei; O’Quigley, John; Johnson, Bankole A.

2012-01-01

In alcohol dependence studies, the treatment effect at different dose levels remains to be ascertained. Establishing this effect would aid us in identifying the best dose that has satisfactory efficacy while minimizing the rate of adverse events. We advocate the use of dose-finding methodology that has been successfully implemented in the cancer and HIV settings to identify the optimal dose in a cost-effective way. Specifically, we describe the continual reassessment method (CRM), an adaptive design proposed for cancer trials to reconcile the needs of dose-finding experiments with the ethical demands of established medical practice. We are applying adaptive designs for identifying the optimal dose of medications for the first time in the context of pharmacotherapy research in alcoholism. We provide an example of a topiramate trial as an illustration of how adaptive designs can be used to locate the optimal dose in alcohol treatment trials. It is believed that the introduction of adaptive design methods will enable the development of medications for the treatment of alcohol dependence to be accelerated. PMID:23189064

Leisure-Time Physical Activity Reduces Total and Cardiovascular Mortality and Cardiovascular Disease Incidence in Older Adults.

PubMed

Barengo, Noël C; Antikainen, Riitta; Borodulin, Katja; Harald, Kennet; Jousilahti, Pekka

2017-03-01

To determine whether leisure-time physical activity (LTPA) is independently associated with all-cause and cardiovascular mortality and with incidence of cardiovascular disease (CVD) and stroke in older adults. Population-based cohort study (median follow-up 11.8 years). Community, five Finnish provinces. Men and women aged 65 to 74 who participated in a baseline risk factor survey between 1997 and 2007 in Finland (N = 2,456). The study protocol included a self-administered questionnaire, health examination at the study site, and blood sample for laboratory analysis. LTPA was classified into three levels: low, moderate, high. Mortality data were obtained from the National Causes of Death Register and data on incident CVD (coronary heart disease, stroke) events from the National Hospital Discharge Register. Multifactorial-adjusted (age, area, study year, sex, smoking, body mass index, systolic blood pressure, serum cholesterol, education, marital status) risks of total mortality (moderate: hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.50-0.74; high: HR = 0.47, 95% CI = 0.34-0.63, P for trend <.001), CVD mortality (moderate: HR = 0.46, 95% CI = 0.33-0.64; high: HR = 0.34, 95% CI = 0.20-0.59, P for trend <.001), and an incident CVD event (moderate HR = 0.69, 95% CI = 0.54-0.88; high: HR = 0.55, 95% CI = 0.38-0.79, P for trend <.001) were lower for those with moderate or high LTPA levels than for those with low LTPA levels. Further adjustment for self-reported inability to perform LTPA did not change the associations remarkably. Baseline LTPA reduces the risk of total and CVD mortality and incident CVD events in older adults independently of the major known CVD risk factors. The protective effect of LTPA is dose dependent. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Time-dependent radiation dose estimations during interplanetary space flights

NASA Astrophysics Data System (ADS)

Dobynde, M. I.; Shprits, Y.; Drozdov, A.

2015-12-01

Time-dependent radiation dose estimations during interplanetary space flights 1,2Dobynde M.I., 2,3Drozdov A.Y., 2,4Shprits Y.Y.1Skolkovo institute of science and technology, Moscow, Russia 2University of California Los Angeles, Los Angeles, USA 3Lomonosov Moscow State University Skobeltsyn Institute of Nuclear Physics, Moscow, Russia4Massachusetts Institute of Technology, Cambridge, USASpace radiation is the main restriction for long-term interplanetary space missions. It induces degradation of external components and propagates inside providing damage to internal environment. Space radiation particles and induced secondary particle showers can lead to variety of damage to astronauts in short- and long- term perspective. Contribution of two main sources of space radiation- Sun and out-of-heliosphere space varies in time in opposite phase due to the solar activity state. Currently the only habituated mission is the international interplanetary station that flights on the low Earth orbit. Besides station shell astronauts are protected with the Earth magnetosphere- a natural shield that prevents significant damage for all humanity. Current progress in space exploration tends to lead humanity out of magnetosphere bounds. With the current study we make estimations of spacecraft parameters and astronauts damage for long-term interplanetary flights. Applying time dependent model of GCR spectra and data on SEP spectra we show the time dependence of the radiation in a human phantom inside the shielding capsule. We pay attention to the shielding capsule design, looking for an optimal geometry parameters and materials. Different types of particles affect differently on the human providing more or less harm to the tissues. Incident particles provide a large amount of secondary particles while propagating through the shielding capsule. We make an attempt to find an optimal combination of shielding capsule parameters, namely material and thickness, that will effectively decrease

Dose-dependent effects of prenatal ethanol exposure in the guinea pig.

PubMed

Catlin, M C; Abdollah, S; Brien, J F

1993-01-01

The guinea pig is an appropriate animal for studying ethanol central nervous system (CNS) teratogenesis due to its extensive prenatal CNS development. In order to establish an ethanol dosage regimen that produces CNS teratogenesis, the objective of this study was to characterize the dose-dependent effects of chronic ethanol administration on pregnancy outcome and locomotor activity of the offspring. Pregnant guinea pigs received one of the following oral treatments, via intubation into the oral cavity, throughout gestation: 3, 4, 5 or 6 g ethanol/kg maternal body weight/day; isocaloric sucrose and pair feeding; or water. The 5 and 6 g ethanol/kg/day regimens produced maternal death, spontaneous abortion, and perinatal death with at least 75% incidence; the 3 and 4 g ethanol/kg/day regimens produced little or no maternal, embryonic/fetal, or perinatal lethality. The 3 and 4 g ethanol/kg/day regimens did not affect other indices of pregnancy outcome compared with the respective isocaloric-sucrose pair-fed control animals and water-treated animals. The 3, 4, and 5 g ethanol/kg/day regimens increased spontaneous locomotor activity in the offspring, and there was a direct relationship between the magnitude of hyperactivity at days 10 and 60 of age and each of the ethanol dosage regimens and the maternal blood ethanol concentration on day 56 of gestation. The data demonstrate that, in the guinea pig, chronic oral administration of ethanol produces: (a) dose-dependent effects on pregnancy outcome, (b) hyperactivity in the offspring that is dose- (and maternal blood ethanol concentration-) and age-related, and (c) persistent hyperactivity into adulthood with minimal toxicity on pregnancy outcome for the 4 g ethanol/kg/day regimen.

Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach.

PubMed

Varas, Javier; Ramos, Rosa; Aljama, Pedro; Pérez-García, Rafael; Moreso, Francesc; Pinedo, Miguel; Ignacio Merello, José; Stuard, Stefano; Canaud, Bernard; Martín-Malo, Alejandro

2018-01-01

Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization. This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month. Kaplan-Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses  >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population. Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection-related hospitalizations. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Incident Energy Dependence of p t Correlations at RHIC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, J.; Aggarwal, M. M.; Ahammed, Z.

2005-10-01

We present results for two-particle transverse momentum correlations, Δp t,iΔ t,j, as a function of event centrality for Au+Au collisions at √( sNN) = 20, 62, 130, and 200 GeV at the Relativistic Heavy Ion Collider. We observe correlations decreasing with centrality that are similar at all four incident energies. The correlations multiplied by the multiplicity density increase with incident energy and the centrality dependence may show evidence of processes such as thermalization, jet production, or the saturation of transverse flow. The square root of the correlations divided by the event-wise average transverse momentum per event shows little or nomore » beam energy dependence and generally agrees with previous measurements at the Super Proton Synchrotron.« less

Dietary resistant starch dose-dependently reduces adiposity in obesity-prone and obesity-resistant male rats.

PubMed

Belobrajdic, Damien P; King, Roger A; Christophersen, Claus T; Bird, Anthony R

2012-10-25

Animal studies show that diets containing resistant starch (RS) at levels not achievable in the human diet result in lower body weight and/or adiposity in rodents. We aimed to determine whether RS dose-dependently reduces adiposity in obesity-prone (OP) and obesity-resistant (OR) rats. Male Sprague-Dawley rats (n=120) were fed a moderate-fat, high-energy diet for 4 wk. Rats that gained the most weight (40%) were classified as obesity-prone (OP) and obesity-resistant (OR) rats were the 40% that gained the least weight. OP and OR rats were randomly allocated to one of six groups (n=8 for each phenotype). One group was killed for baseline measurements, the other five groups were allocated to AIN-93 based diets that contained 0, 4, 8, 12 and 16% RS (as high amylose maize starch) for 4 wk. These diets were matched for total carbohydrate content. At 0, 4 and 7 wk from the start of the study insulin sensitivity was calculated by homeostasis model assessment of insulin resistance (HOMA-IR) and adiposity was determined by dual-energy X-ray absorptiometry (DXA). At 8 wk, rats were euthanized and fat pad weights, intestinal digesta short chain fatty acid (SCFA) pools and plasma gut hormone levels were determined. Obesity prone rats gained less weight with 4, 12 and 16% RS compared to 0% RS, but the effect in OR animals was significant only at 16% RS. Irrespective of phenotype, diets containing ≥8% RS reduced adiposity compared to 0% RS. Energy intake decreased by 9.8 kJ/d for every 4% increase in RS. All diets containing RS increased total SCFA pools in the caecum and lowered plasma GIP concentrations compared to the 0% RS, whereas plasma GLP-1 and PYY were increased when the diet contained at least 8% RS. Insulin sensitivity was not affected by RS. RS in amounts that could be potentially consumed by humans were effective in reducing adiposity and weight gain in OP and OR rats, due in part to a reduction in energy intake, and changes in gut hormones and large bowel

A Polarization-Dependent Normal Incident Quantum Cascade Detector Enhanced Via Metamaterial Resonators.

PubMed

Wang, Lei; Zhai, Shen-Qiang; Wang, Feng-Jiao; Liu, Jun-Qi; Liu, Shu-Man; Zhuo, Ning; Zhang, Chuan-Jin; Wang, Li-Jun; Liu, Feng-Qi; Wang, Zhan-Guo

2016-12-01

The design, fabrication, and characterization of a polarization-dependent normal incident quantum cascade detector coupled via complementary split-ring metamaterial resonators in the infrared regime are presented. The metamaterial structure is designed through three-dimensional finite-difference time-domain method and fabricated on the top metal contact, which forms a double-metal waveguide together with the metallic ground plane. With normal incidence, significant enhancements of photocurrent response are obtained at the metamaterial resonances compared with the 45° polished edge coupling device. The photocurrent response enhancements exhibit clearly polarization dependence, and the largest response enhancement factor of 165% is gained for the incident light polarized parallel to the split-ring gap.

Suppository naproxen reduces incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial.

PubMed

Mansour-Ghanaei, Fariborz; Joukar, Farahnaz; Taherzadeh, Zahra; Sokhanvar, Homayoon; Hasandokht, Tolou

2016-06-07

significantly lower than that in the placebo (6 patients vs 23 patients, P < 0.01, RRR = 12%, AR = 0.3, 95%CI: 0.2-0.6). Naproxen reduced the PEP in patients with ≥ 3 pancreatic cannulations (P < 0.01, RRR = 25%, AR = 0.1, 95%CI: 0.1-0.4) and an ERCP duration > 40 min (P < 0.01, RRR = 20%, AR = 0.9, 95%CI: 0.4-1.2). Single dose of suppository naproxen administered immediately before ERCP reduces the incidence of PEP.

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

PubMed

Yang, Yi-Sun; Kornelius, Edy; Chiou, Jeng-Yuan; Lai, Yung-Rung; Lo, Shih-Chang; Peng, Chiung-Huei; Huang, Chien-Ning

2017-12-01

Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (<8,600 mg) and medium (8,600-88,900 mg) cumulative doses of aspirin did not reduce the risk of breast cancer. Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

MO-E-17A-06: Organ Dose in Abdomen-Pelvis CT: Does TG 111 Equilibrium Dose Concept Better Accounts for KVp Dependence Than Conventional CTDI?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, X; Morgan, A; Davros, W

Purpose: In CT imaging, a desirable quality assurance (QA) dose quantity should account for the dose variability across scan parameters and scanner models. Recently, AAPM TG 111 proposed to use equilibrium dose-pitch product, in place of CT dose index (CTDI100), for scan modes involving table translation. The purpose of this work is to investigate whether this new concept better accounts for the kVp dependence of organ dose than the conventional CTDI concept. Methods: The adult reference female extended cardiac-torso (XCAT) phantom was used for this study. A Monte Carlo program developed and validated for a 128-slice CT system (Definition Flash,more » Siemens Healthcare) was used to simulate organ dose for abdomenpelvis scans at five tube voltages (70, 80, 100, 120, 140 kVp) with a pitch of 0.8 and a detector configuration of 2x64x0.6 mm. The same Monte Carlo program was used to simulate CTDI100 and equilibrium dose-pitch product. For both metrics, the central and peripheral values were used together with helical pitch to calculate a volume-weighted average, i.e., CTDIvol and (Deq)vol, respectively. Results: While other scan parameters were kept constant, organ dose depended strongly on kVp; the coefficient of variation (COV) across the five kVp values ranged between 70–75% for liver, spleen, stomach, pancreas, kidneys, colon, small intestine, bladder, and ovaries, all of which were inside the primary radiation beam. One-way analysis of variance (ANOVA) for the effect of kVp was highly significant (p=3e−30). When organ dose was normalized by CTDIvol, the COV across the five kVp values reduced to 7–16%. The effect of kVp was still highly significant (p=4e−4). When organ dose was normalized by (Deq)vol, the COV further reduced to 4−12%. The effect of kVp was borderline significant (p=0.04). Conclusion: In abdomen-pelvis CT, TG 111 equilibrium dose concept better accounts for kVp dependence than the conventional CTDI. This work is supported by a faculty

Bedtime Routines for Young Children: A Dose-Dependent Association with Sleep Outcomes

PubMed Central

Mindell, Jodi A.; Li, Albert M.; Sadeh, Avi; Kwon, Robert; Goh, Daniel Y.T.

2015-01-01

Background: Establishment of a consistent bedtime routine (the activities that occur right before lights out) is often recommended as part of healthy sleep habits. However, no studies have investigated the dose-dependent association of a bedtime routine with sleep outcomes, especially in young children for whom they are particularly recommended. Thus, the aim of this study was to examine the associations of a consistent bedtime routine with sleep outcomes in young children (ages 0 through 5 y) in a large global sample and assess whether there is a dose-dependent relationship between the frequency of a bedtime routine both concurrently and retrospectively with sleep outcomes. Participants: Mothers of 10,085 children (Australia-New Zealand, Canada, China, Hong Kong, India, Japan, Korea, Malaysia, Philippines, Singapore, Thailand, United Kingdom, United States) completed the Brief Infant/Child Sleep Questionnaire. Results: A consistent bedtime routine was associated with better sleep outcomes, including earlier bedtimes, shorter sleep onset latency, reduced night wakings, and increased sleep duration. Decreased parent-perceived sleep problems and daytime behavior problems were also related to institution of a regular bedtime routine. Furthermore, there was a dose-dependent relationship, with better outcomes associated with increased “doses” of having a bedtime routine, both currently and retrospectively, and was found within both predominantly Asian and predominantly Caucasian cultural regions. Conclusions: These results indicate that having a regular nightly bedtime routine is associated with improved sleep in young children, and suggests that the more consistently a bedtime routine is instituted and the younger started the better. Citation: Mindell JA, Li AM, Sadeh A, Kwon R, Goh DY. Bedtime routines for young children: a dose-dependent association with sleep outcomes. SLEEP 2015;38(5):717–722. PMID:25325483

Is the incidence of constant esotropia in childhood reducing?

PubMed

Carney, C V; Lysons, D A; Tapley, J V

1995-01-01

Episodes of strabismus surgery in the under-14 year age group in West Berkshire have reduced by 42%, from 22.7 to 13.2 per 10,000 population, between 1968 and 1985. Clinical audit of patterns of referral shows that the incidence of constant esotropia has reduced by 55%, from 28.3 to 12.8 per 10,000 population, between 1971 and 1991.

Leisure-time physical activity and incident metabolic syndrome: a systematic review and dose-response meta-analysis of cohort studies.

PubMed

Zhang, Dongdong; Liu, Xuejiao; Liu, Yu; Sun, Xizhuo; Wang, Bingyuan; Ren, Yongcheng; Zhao, Yang; Zhou, Junmei; Han, Chengyi; Yin, Lei; Zhao, Jingzhi; Shi, Yuanyuan; Zhang, Ming; Hu, Dongsheng

2017-10-01

Leisure-time physical activity (LTPA) has been suggested to reduce risk of metabolic syndrome (MetS). However, a quantitative comprehensive assessment of the dose-response association between LTPA and incident MetS has not been reported. We performed a meta-analysis of studies assessing the risk of MetS with LTPA. MEDLINE via PubMed and EMBase databases were searched for relevant articles published up to March 13, 2017. Random-effects models were used to estimate the summary relative risk (RR) of MetS with LTPA. Restricted cubic splines were used to model the dose-response association. We identified 16 articles (18 studies including 76,699 participants and 13,871 cases of MetS). We found a negative linear association between LTPA and incident MetS, with a reduction of 8% in MetS risk per 10 metabolic equivalent of task (MET) h/week increment. According to the restricted cubic splines model, risk of MetS was reduced 10% with LTPA performed according to the basic guideline-recommended level of 150min of moderate PA (MPA) per week (10METh/week) versus inactivity (RR=0.90, 95% CI 0.86-0.94). It was reduced 20% and 53% with LTPA at twice (20METh/week) and seven times (70METh/week) the basic recommended level (RR=0.80, 95% CI 0.74-0.88 and 0.47, 95% CI 0.34-0.64, respectively). Our findings provide quantitative data suggesting that any amount of LTPA is better than none and that LTPA substantially exceeding the current LTPA guidelines is associated with an additional reduction in MetS risk. Copyright © 2017. Published by Elsevier Inc.

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

PubMed

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

Dose-Dependent Associations between Wine Drinking and Breast Cancer Risk - Meta-Analysis Findings.

PubMed

Chen, Jia-Yan; Zhu, Hong-Cheng; Guo, Qing; Shu, Zheng; Bao, Xu-Hui; Sun, Feng; Qin, Qin; Yang, Xi; Zhang, Chi; Cheng, Hong-Yan; Sun, Xin-Chen

2016-01-01

To investigate any potential association between wine and breast cancer risk. We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

SU-F-303-15: Ion Chamber Dose Response in Magnetic Fields as a Function of Incident Photon Energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malkov, V. N.; Rogers, D. W. O.

2015-06-15

Purpose: In considering the continued development of synergetic MRI-radiation therapy machines, we seek to quantify the variability of ion chamber response per unit dose in the presence of magnetic fields of varying strength as a function of incident photon beam quality and geometric configuration. Methods: To account for the effect of magnetic fields on the trajectory of charged particles a new algorithm was introduced into the EGSnrc Monte Carlo code. In the egs-chamber user code the dose to the cavity of an NE2571 ion chamber is calculated in two configurations, in 0 to 2 T magnetic fields, with an incomingmore » parallel 10×10 cm{sup 2} photon beam with energies ranging between 0.5 MeV and 8 MeV. In the first, the photon beam is incident on the long-axis of the ion chamber (config-1), and in the second the beam is parallel to the long-axis and incident from the conical end of the chamber (config-2). For both, the magnetic field is perpendicular to the direction of the beam and the long axis of the chamber. Results: The ion chamber response per unit dose to water at the same point is determined as a function of magnetic field and is normalized to the 0T case for each of incoming photon energies. For both configurations, accurate modeling of the ion chamber yielded closer agreement with the experimental results obtained by Meijsing et. al (2009). Config-1 yields a gradual increase in response with increasing field strength to a maximum of 13.4% and 1.4% for 1 MeV and 8 MeV photon beams, respectively. Config-2 produced a decrease in response of up to 6% and 13% for 0.5 MeV and 8 MeV beams, respectively. Conclusion: These results provide further support for ion chamber calibration in MRI-radiotherapy coupled systems and demonstrates noticeable energy dependence for clinically relevant fields.« less

Space-Time Dependent Transport, Activation, and Dose Rates for Radioactivated Fluids.

NASA Astrophysics Data System (ADS)

Gavazza, Sergio

Two methods are developed to calculate the space - and time-dependent mass transport of radionuclides, their production and decay, and the associated dose rates generated from the radioactivated fluids flowing through pipes. The work couples space- and time-dependent phenomena, treated as only space- or time-dependent in the open literature. The transport and activation methodology (TAM) is used to numerically calculate space- and time-dependent transport and activation of radionuclides in fluids flowing through pipes exposed to radiation fields, and volumetric radioactive sources created by radionuclide motions. The computer program Radionuclide Activation and Transport in Pipe (RNATPA1) performs the numerical calculations required in TAM. The gamma ray dose methodology (GAM) is used to numerically calculate space- and time-dependent gamma ray dose equivalent rates from the volumetric radioactive sources determined by TAM. The computer program Gamma Ray Dose Equivalent Rate (GRDOSER) performs the numerical calculations required in GAM. The scope of conditions considered by TAM and GAM herein include (a) laminar flow in straight pipe, (b)recirculating flow schemes, (c) time-independent fluid velocity distributions, (d) space-dependent monoenergetic neutron flux distribution, (e) space- and time-dependent activation process of a single parent nuclide and transport and decay of a single daughter radionuclide, and (f) assessment of space- and time-dependent gamma ray dose rates, outside the pipe, generated by the space- and time-dependent source term distributions inside of it. The methodologies, however, can be easily extended to include all the situations of interest for solving the phenomena addressed in this dissertation. A comparison is made from results obtained by the described calculational procedures with analytical expressions. The physics of the problems addressed by the new technique and the increased accuracy versus non -space and time-dependent methods

Pasteurization of mother's own milk for preterm infants does not reduce the incidence of late-onset sepsis.

PubMed

Cossey, Veerle; Vanhole, Chris; Eerdekens, An; Rayyan, Maissa; Fieuws, Steffen; Schuermans, Annette

2013-01-01

Feeding preterm infants human milk has a beneficial effect on the risk of late-onset sepsis (LOS). Due to lack of microbiological standards, practices such as pasteurization of mother's own milk differ widely among neonatal intensive care units worldwide. To investigate whether pasteurization of mother's own milk for very-low-birth-weight (VLBW) infants influences the incidence and severity of infection-related outcomes. In this randomized controlled trial, preterm infants (gestational age <32 weeks and/or birth weight <1,500 g) received either raw or pasteurized mother's own milk during the first 8 weeks of life. The primary outcome was the incidence of proven LOS. A dose-response relation was verified, i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother's own milk. This study included 303 VLBW infants (mean birth weight: 1,276 g; mean gestational age: 29 weeks) whose baseline and nutritional characteristics were similar. The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk: 22/151 (0.15, CI: 0.08-0.20) and 31/152 (0.20, CI: 0.14-0.27), respectively (RR: 0.71; 95% CI: 0.43-1.17). A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS, regardless of the type of feeding. For preterm infants, pasteurization of mother's own milk shows a trend towards an increase in infectious morbidity, although no statistical significance was reached. Practices should focus on collection, storage and labeling procedures to ensure the safety and quality of expressed milk. Copyright © 2012 S. Karger AG, Basel.

Incidence of hypothyroidism following small doses of /sup 131/I in the treatment of Graves' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCullagh, F.P.; Jelden, G.L.; Rodriguez-Antunez, A.

1976-09-01

In a group of 147 patients treated with /sup 131/I in doses of 3.0 millicuries or less for Graves' disease, the incidence of hypothyroidism was calculated 10 to 17 years after treatment. This paper emphasizes the frequency of hypothyroidism after treatment with /sup 131/I in small doses, if sufficient time lapse is considered.

Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease

PubMed Central

Ng, William; Wong, Wai-Man; Chen, Wai-Hong; Tse, Hung-Fat; Lee, Pui-Yin; Lai, Kam-Chuen; Li, Sheung-Wai; Ng, Matthew; Lam, Kwok-Fai; Cheng, Xi; Lau, Chu-Pak

2006-01-01

AIM: The use of low-dose aspirin to prevent cardiovascular disease events is well established. However, the incidence and predictors of upper gastrointestinal bleeding (UGIB) with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users. METHODS: A total of 991 patients with coronary artery disease (CAD) on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB. RESULTS: UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension (OR = 4.6, 95%CI 1.5 - 14.7, P = 0.009), history of peptic ulceration (OR = 3.1, 95%CI 1.1 - 9.0, P = 0.039), tertiary education (OR = 3.08, 95%CI 1.1 - 9.0, P = 0.039) and higher lean body mass (P = 0.016) were independent factors associated with UGIB. Use of nitrate did not reduce UGIB. CONCLUSION: The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy. PMID:16718820

Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study.

PubMed

Miner, Philip B; Silberg, Debra G; Ruth, Magnus; Miller, Frank; Pandolfino, John

2014-11-18

The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose-response effect of lesogaberan on reflux episodes in partial responders. In this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance-pH measurements were taken. Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment. Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events. ClinicalTrials.gov identifier: NCT01043185.

Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

PubMed

Elhennawy, Mai Gamal; Lin, Hai-Shu

2018-06-15

Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

Analysis of incident-energy dependence of delayed neutron yields in actinides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nasir, Mohamad Nasrun bin Mohd, E-mail: monasr211@gmail.com; Metorima, Kouhei, E-mail: kohei.m2420@hotmail.co.jp; Ohsawa, Takaaki, E-mail: ohsawa@mvg.biglobe.ne.jp

The changes of delayed neutron yields (ν{sub d}) of Actinides have been analyzed for incident energy up to 20MeV using realized data of precursor after prompt neutron emission, from semi-empirical model, and delayed neutron emission probability data (P{sub n}) to carry out a summation method. The evaluated nuclear data of the delayed neutron yields of actinide nuclides are still uncertain at the present and the cause of the energy dependence has not been fully understood. In this study, the fission yields of precursor were calculated considering the change of the fission fragment mass yield based on the superposition of fivesmore » Gaussian distribution; and the change of the prompt neutrons number associated with the incident energy dependence. Thus, the incident energy dependent behavior of delayed neutron was analyzed.The total number of delayed neutron is expressed as ν{sub d}=∑Y{sub i} • P{sub ni} in the summation method, where Y{sub i} is the mass yields of precursor i and P{sub ni} is the delayed neutron emission probability of precursor i. The value of Y{sub i} is derived from calculation of post neutron emission mass distribution using 5 Gaussian equations with the consideration of large distribution of the fission fragments. The prompt neutron emission ν{sub p} increases at higher incident-energy but there are two different models; one model says that the fission fragment mass dependence that prompt neutron emission increases uniformly regardless of the fission fragments mass; and the other says that the major increases occur at heavy fission fragments area. In this study, the changes of delayed neutron yields by the two models have been investigated.« less

Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and Inflammatory Response: A Randomized Controlled Trial.

PubMed

Zeng, Wei-Nan; Liu, Jun-Li; Wang, Fu-You; Chen, Cheng; Zhou, Qiang; Yang, Liu

2018-02-21

differences were observed in the incidence of thromboembolic complications, wound score, range of motion, and HSS score among the 3 groups (p > 0.05). The combined administration of low-dose epinephrine and tranexamic acid demonstrated an increased effect in reducing perioperative blood loss and the inflammatory response compared with tranexamic acid alone, with no apparent increased incidence of thromboembolic and other complications. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Psychosis induced by the interaction between disulfiram and methylphenidate may be dose dependent.

PubMed

Grau-López, Lara; Roncero, Carlos; Navarro, Maria C; Casas, Miquel

2012-01-01

There are few studies describing psychiatric symptoms occurring when methylphenidate and disulfiram are used together. The authors report a case of disulfiram and methylphenidate interaction in which psychotic symptoms could be dose dependent. The patient, diagnosed of alcohol and cocaine dependence and attention deficit hyperactivity disorder (ADHD), started treatment with methylphenidate increasing doses and disulfiram 250 mg/day over 4 weeks. During the first 2 weeks at doses of 36 mg/day of methylphenidate and maintaining disulfiram, side effects were not observed. However, by increasing to 54 mg/day, psychotic symptoms were detected. The authors reported that the effects are dose dependent. This is the first report about dose-dependent side effects in substance use disorder with ADHD.

Fasting Reduces the Incidence of Delayed-Type Vomiting Associated with Doxorubicin Treatment in Dogs with Lymphoma.

PubMed

Withers, Sita S; Kass, Philip H; Rodriguez, Carlos O; Skorupski, Katherine A; O'Brien, Danielle; Guerrero, Teri A; Sein, Kristen D; Rebhun, Robert B

2014-05-12

Fasting reduces gastrointestinal cellular proliferation rates through G 1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effects of fasting on delayed-type chemotherapy-induced nausea and vomiting in dogs receiving doxorubicin. This prospective randomized crossover study involved intended administration of two doses of doxorubicin. Cancer-bearing dogs were randomized to be fasted for 24 hours beginning at 6 P.M. the night before the first or second doxorubicin administration, and all treatments were administered within an hour before or after 12 P.M. Dogs were fed normally before the alternate dose. Circulating IGF-1 concentrations were determined from serum samples obtained immediately before each doxorubicin treatment. Data from 35 doses were available from 20 dogs enrolled. Dogs that were fasted exhibited a significantly lower incidence of vomiting, when compared to fed dogs (10% compared to 67%, P = .020). Furthermore, among the 15 dogs that completed crossover dosing, vomiting was abrogated in four of five dogs that experienced doxorubicin-induced vomiting when fed normally (P = .050). No differences in other gastrointestinal, constitutional, or bone marrow toxicities or serum IGF-1 levels were observed. Copyright © 2014 Elsevier Inc. All rights reserved.

Swimming reduces the severity of physical and psychological dependence and voluntary morphine consumption in morphine dependent rats.

PubMed

Fadaei, Atefeh; Gorji, Hossein Miladi; Hosseini, Shahrokh Makvand

2015-01-15

Previous studies have indicated that voluntary exercise decreases the severity of the anxiogenic-like behaviors in both morphine-dependent and withdrawn rats. This study examined the effects of regular swimming exercise during the development of dependency and spontaneous morphine withdrawal on the anxiety-depression profile and voluntary morphine consumption in morphine dependent rats. The rats were chronically treated with bi-daily doses (10 mg/kg, at 12h intervals) of morphine over a period of 14 days. The exercising rats were allowed to swim (45 min/d, five days per a week, for 14 or 21 days) during the development of morphine dependence and withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice paradigm in animal models of craving. The results showed that withdrawal signs were decreased in swimmer morphine dependent rats than sedentary rats (P<0.05). Also, the swimmer morphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries (P<0.05), higher levels of sucrose preference (P<0.001) than sedentary rats. Voluntary consumption of oral morphine was less in the swimmer morphine-withdrawn rats than the sedentary groups during four periods of the intake of drug (P<0.01). We conclude that regular swimming exercise reduces the severity of morphine dependence and voluntary morphine consumption with reducing anxiety and depression in morphine-dependent and withdrawn rats. Thus, swimming exercise may be a potential method to ameliorate some of the deleterious behavioral consequences of morphine dependence. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact and cost-effectiveness of a second tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine dose to prevent pertussis in the United States.

PubMed

Kamiya, Hajime; Cho, Bo-Hyun; Messonnier, Mark L; Clark, Thomas A; Liang, Jennifer L

2016-04-04

The United States experienced a substantial increase in reported pertussis cases over the last decade. Since 2005, persons 11 years and older have been routinely recommended to receive a single dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine. The objective of this analysis was to evaluate the potential impact and cost-effectiveness of recommending a second dose of Tdap. A static cohort model was used to calculate the epidemiologic and economic impact of adding a second dose of Tdap at age 16 or 21 years. Projected costs and outcomes were examined from a societal perspective over a 20-year period. Quality-adjusted Life Years (QALY) saved were calculated. Using baseline pertussis incidence from the National Notifiable Diseases Surveillance System, Tdap revaccination at either age 16 or 21 years would reduce outpatient visits by 433 (5%) and 285 (4%), and hospitalization cases by 7 (7%) and 5 (5%), respectively. The costs per QALY saved with a second dose of Tdap were approximately US $19.7 million (16 years) and $26.2 million (21 years). In sensitivity analyses, incidence most influenced the model; as incidence increased, the costs per QALY decreased. To a lesser degree, initial vaccine effectiveness and waning of effectiveness also affected cost outcomes. Multivariate sensitivity analyses showed that under a set of optimistic assumptions, the cost per QALY saved would be approximately $163,361 (16 years) and $204,556 (21 years). A second dose of Tdap resulted in a slight decrease in the number of cases and other outcomes, and that trend is more apparent when revaccinating at age 16 years than at age 21 years. Both revaccination strategies had high dollar per QALY saved even under optimistic assumptions in a multivariate sensitivity analysis. Published by Elsevier Ltd.

A single dose of erythropoietin reduces perioperative transfusions in cardiac surgery: results of a prospective single-blind randomized controlled trial.

PubMed

Weltert, Luca; Rondinelli, Beatrice; Bello, Ricardo; Falco, Mauro; Bellisario, Alessandro; Maselli, Daniele; Turani, Franco; De Paulis, Ruggero; Pierelli, Luca

2015-07-01

We conducted a prospective single-blind randomized study to assess whether a single 80,000 IU dose of human recombinant erythropoietin (HRE), given just 2 days before cardiac surgery, could be effective in reducing perioperative allogeneic red blood cell transfusion (aRBCt). Six-hundred patients presenting with preoperative hemoglobin (Hb) level of not more than 14.5 g/dL were randomly assigned to either HRE or control. The primary endpoint was the incidence of perioperative aRBCt. The secondary endpoints were mortality and the incidence of adverse events in the first 45 days after surgery, Hb level on Postoperative Day 4, and number of units of RBC transfusions in the first 4 days after surgery. A total of 17% (HRE) versus 39% (control) required transfusion (relative risk, 0.436; p<0.0005). After baseline Hb was controlled for, there was no difference in the incidence of aRBCt between HRE (0%) and control (3.5%) among the patients with baseline Hb of 13.0 g/dL or more, which included the nonanemic fraction of the study population. The mean (range) Hb level on Postoperative Day 4 was 10.2 (9.9-10.6) g/dL (HRE) versus 8.7 (8.5-9.2) g/dL (control; p<0.0005). The distribution of number of units transfused was shifted toward fewer units in HRE (p<0.0005). The all-cause mortality at 45 days was 3.00% (HRE) versus 3.33% (control). The 45-day adverse event rate was 4.33% (HRE) versus 5.67% (control; both p=NS). In anemic patients (Hb<13 g/dL), a single high dose of HRE administered 2 days before cardiac surgery is effective in reducing the incidence of aRBCt without increasing adverse events. © 2015 AABB.

Time-dependent radiation dose simulations during interplanetary space flights

NASA Astrophysics Data System (ADS)

Dobynde, Mikhail; Shprits, Yuri; Drozdov, Alexander; Hoffman, Jeffrey; Li, Ju

2016-07-01

Space radiation is one of the main concerns in planning long-term interplanetary human space missions. There are two main types of hazardous radiation - Solar Energetic Particles (SEP) and Galactic Cosmic Rays (GCR). Their intensities and evolution depend on the solar activity. GCR activity is most enhanced during solar minimum, while the most intense SEPs usually occur during the solar maximum. SEPs are better shielded with thick shields, while GCR dose is less behind think shields. Time and thickness dependences of the intensity of these two components encourage looking for a time window of flight, when radiation intensity and dose of SEP and GCR would be minimized. In this study we combine state-of-the-art space environment models with GEANT4 simulations to determine the optimal shielding, geometry of the spacecraft, and launch time with respect to the phase of the solar cycle. The radiation environment was described by the time-dependent GCR model, and the SEP spectra that were measured during the period from 1990 to 2010. We included gamma rays, electrons, neutrons and 27 fully ionized elements from hydrogen to nickel. We calculated the astronaut's radiation doses during interplanetary flights using the Monte-Carlo code that accounts for the primary and the secondary radiation. We also performed sensitivity simulations for the assumed spacecraft size and thickness to find an optimal shielding. In conclusion, we present the dependences of the radiation dose as a function of launch date from 1990 to 2010, for flight durations of up to 3 years.

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

PubMed

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

The effects of incidence angle on film dosimetry and their consequences in IMRT dose verification.

PubMed

Srivastava, R P; De Wagter, C

2012-10-01

The dosimetric accuracy of EDR2 radiographic film has been rigorously assessed in regular and intensity modulated beams for various incidence angles, including the parallel and perpendicular orientation. There clearly exists confusion in literature regarding the effect of film orientation. The primary aim is to clarify potential sources of the confusion and to gain physical insight into the film orientation effect with a link to radiochromic film as well. An inverse pyramid IMRT field, consisting of six regular and elongated 3 × 20 cm(2) field segments, was studied in perpendicular and parallel orientation. Assessment of film self-perturbation and intrinsic directional sensitivity were also included in the experiments. Finally, the authors investigated the orientational effect in composite beams in the two extreme orientations, i.e., perpendicular and parallel. The study of an inverse pyramid dose profile revealed good agreement between the perpendicular film and the diamond detector within 0.5% in the low-scatter regions for both 6 and 18 MV. The parallel oriented film demonstrated a 3% under-response at 5-cm (6 MV) depth against the perpendicular orientation, but both orientations over responded equally in the central region, which received only scattered dose, at both 5- and 20-cm depths. In a regular 6-MV 5 × 5 cm(2) field, a 4.1% lower film response was observed in the parallel orientation compared to perpendicular orientation. The under response gradually increased to 6% when reducing the field size to 0.5 × 5 cm(2). On the other hand, the film showed a 1.7% lower response in parallel orientation for the large field size of 20 × 20 cm(2) at 5-cm depth but the difference disappeared at 10 cm. At 18 MV, similar but somewhat lower differences were found between the two orientations. The directional sensitivity of the film diminishes with increasing field size and depth. Surprisingly a composite IMRT beam consisting of 20 adjacent strip segments also

Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated with mycophenolate mofetil combined with low cyclosporine and steroid doses.

PubMed

Moreso, F; Serón, D; Morales, J M; Cruzado, J M; Gil-Vernet, S; Pérez, J L; Fulladosa, X; Andrés, A; Grinyó, J M

1998-06-01

Mycophenolate mofetil (MMF) combined with conventional cyclosporine and steroids doses efficiently prevents acute rejection in kidney transplants. However, this regimen has been associated with an increased incidence of cytomegalovirus (CMV) disease and leukopenia, specially in patients receiving MMF at 3 g/d, suggesting that the combination of two powerful immunosuppressants carries the risk of overimmunosuppression. For this reason, we treated a group of patients with MMF 3 g/d combined with low cyclosporine and steroids doses. Eighty-two kidney transplants performed at two centers and enrolled in the European Mycophenolate Mofetil Cooperative Study were randomized to receive: A) placebo (n = 27); B) MMF 2 g/d (n = 27); and C) MMF 3 g/d (n = 28). In this double blind study all patients received cyclosporine and steroids at conventional doses. Fifteen kidney transplants enrolled in an MMF open pharmacokinetic study were treated with MMF 3 g/day combined with low cyclosporine and steroid doses (group D). Efficacy was evaluated as the incidence of biopsy proven acute rejection, and safety focused on CMV disease and leukopenia. Patients receiving MMF showed a low incidence of biopsy proven rejection (B) 18.5%; C) 10.7%; and D) 13.3%). Patients of group C had a high incidence of CMV disease (35.7%) when compared with the other groups (lower than 8%). Incidence of leukopenia was higher in patients treated with MMF (B) 25.9%; C) 39.3%; and D) 40%) than in placebo treated patients (7.4%). Patients in group (C) displayed leukopenia mainly in the context of CMV disease, while patients of group (D) had leukopenia not related to CMV infection. All patients of group (D) who presented leukopenia recovered after MMF reduction dose, while in group (C) there were 5 out of 28 patients who required MMF withdrawal. We propose that a reasonable approach to take advantage of a powerful non-nephrotoxic immunosuppressant such as MMF, could be the administration of this drug at 3 g

Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats.

PubMed

Kotronoulas, Aristotelis; Pizarro, Nieves; Serra, Aida; Robledo, Patricia; Joglar, Jesús; Rubió, Laura; Hernaéz, Alvaro; Tormos, Carmen; Motilva, Ma José; Fitó, Montserrat; Covas, Maria-Isabel; Solà, Rosa; Farré, Magí; Saez, Guillermo; de la Torre, Rafael

2013-11-01

Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone-quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were evaluated within the dose range tested. Following HT administration, dose-dependent effects were observed for the recovery of all the metabolites studied. At the lowest dose of 1 mg/kg, the glucuronidation pathway was the most relevant (25-30%), with lower recoveries for sulfation (14%), while at the highest dose of 100 mg/kg, sulfation was the most prevalent (75%). In addition, we report for the first time the formation of the mercapturate conjugate of HT in a dose-dependent manner. The biochemical data did not reveal significant toxic effects of HT at any of the doses studied. An increase in the GSH/GSSG ratio at the highest dose was observed indicating that the products of HT autoxidation are counteracted by glutathione, resulting in their detoxification. These results indicate that the metabolic disposition of HT is highly dependent on the dose ingested. Copyright © 2013. Published by Elsevier Ltd.

Finasteride Reduces the Risk of Incident Clinical Benign Prostatic Hyperplasia

PubMed Central

Parsons, J. Kellogg; Schenk, Jeannette M.; Arnold, Kathryn B.; Messer, Karen; Till, Cathee; Thompson, Ian M.; Kristal, Alan R.

2014-01-01

Background Despite the high prevalence of clinical benign prostatic hyperplasia (BPH) among older men, there remains a notable absence of studies focused on BPH prevention. Objective To determine if finasteride prevents incident clinical BPH in healthy older men. Design, setting, and participants Data for this study are from the Prostate Cancer Prevention Trial. After excluding those with a history of BPH diagnosis or treatment, or an International Prostate Symptom Score (IPSS) ≥8 at study entry, 9253 men were available for analysis. Outcome measurements and statistical analysis The primary outcome was incident clinical BPH, defined as the initiation of medical treatment, surgery, or sustained, clinically significant urinary symptoms (IPSS >14). Finasteride efficacy was estimated using Cox proportional regression models to generate hazards ratios (HRs). Results and limitations Mean length of follow-up was 5.3 yr. The rate of clinical BPH was 19 per 1000 person-years in the placebo arm and 11 per 1000 person-years in the finasteride arm (p < 0.001). In a covariate-adjusted model, finasteride reduced the risk of incident clinical BPH by 40% (HR: 0.60; 95% confidence interval, 0.51–0.69; p < 0.001). The effect of finasteride on incident clinical BPH was attenuated in men with a body mass index ≥30 kg/m2 (pinteraction = 0.04) but otherwise did not differ significantly by physical activity, age, race, current diabetes, or current smoking. The post hoc nature of the analysis is a potential study limitation. Conclusions Finasteride substantially reduces the risk of incident clinical BPH in healthy older men. These results should be considered in formulating recommendations for the use of finasteride to prevent prostate diseases in asymptomatic older men. PMID:22459892

Time and dose-response effects of honokiol on UVB-induced skin cancer development.

PubMed

Guillermo, Ruth F; Chilampalli, Chandeshwari; Zhang, Xiaoying; Zeman, David; Fahmy, Hesham; Dwivedi, Chandradhar

2012-06-01

Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 μg), and then the effects of different honokiol doses (30, 45, and 60 μg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 μg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 μg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 μg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 μg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 μg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 μg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.

Accuracy of Reduced-Dose Computed Tomography for Ureteral Stones in Emergency Department Patients

PubMed Central

Moore, Christopher L.; Daniels, Brock; Ghita, Monica; Gunabushanam, Gowthaman; Luty, Seth; Molinaro, Annette M.; Singh, Dinesh; Gross, Cary P.

2016-01-01

Study objective Reduced-dose computed tomography (CT) scans have been recommended for diagnosis of kidney stone but are rarely used in the emergency department (ED) setting. Test characteristics are incompletely characterized, particularly in obese patients. Our primary outcome is to determine the sensitivity and specificity of a reduced-dose CT protocol for symptomatic ureteral stones, particularly those large enough to require intervention, using a protocol stratified by patient size. Methods This was a prospective, blinded observational study of 201 patients at an academic medical center. Consenting subjects underwent both regular- and reduced-dose CT, stratified into a high and low body mass index (BMI) protocol based on effective abdominal diameter. Reduced-dose CT scans were interpreted by radiologists blinded to regular-dose interpretations. Follow-up for outcome and intervention was performed at 90 days. Results CT scans with both regular and reduced doses were conducted for 201 patients, with 63% receiving the high BMI reduced-dose protocol. Ureteral stone was identified in 102 patients (50.7%) of those receiving regular-dose CT, with a ureteral stone greater than 5 mm identified in 26 subjects (12.9%). Sensitivity of the reduced-dose CT for any ureteral stone was 90.2% (95% confidence interval [CI] 82.3% to 95.0%), with a specificity of 99.0% (95% CI 93.7% to 100.0%). For stones greater than 5 mm, sensitivity was 100% (95% CI 85.0% to 100.0%). Reduced-dose CT identified 96% of patients who required intervention for ureteral stone within 90 days. Mean reduction in size-specific dose estimate was 18.6 milligray (mGy), from 21.7 mGy (SD 9.7) to 3.4 mGy (SD 0.9). Conclusion CT with substantial dose reduction was 90.2% (95% CI 82.3% to 95.0%) sensitive and 98.9% (95% CI 85.0% to 100.0%) specific for ureteral stones in ED patients with a wide range of BMIs. Reduced-dose CT was 96.0% (95% CI 80.5% to 99.3%) sensitive for ureteral stones requiring intervention

Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study.

PubMed

van der Pol, Peggy; Liebregts, Nienke; Brunt, Tibor; van Amsterdam, Jan; de Graaf, Ron; Korf, Dirk J; van den Brink, Wim; van Laar, Margriet

2014-07-01

Increased delta-9-tetrahydrocannabinol (THC) concentrations in cannabis may lead to higher THC exposure, cannabis dependence and treatment need, but users may also adapt the actual intake of THC through reduced inhalation of THC containing smoke (titration). We investigated whether consumers of stronger cannabis use less cannabis per joint or inhale less smoke than those using less potent cannabis and whether these factors predict cannabis dependence severity. Heavy cannabis users (n = 98) brought their own cannabis, rolled a joint and smoked it ad libitum in a naturalistic setting. We analysed the content of the joint, its association with smoking behaviour and the cross-sectional and prospective (1.5-year follow-up) relations between smoking behaviour and cannabis dependence severity (total number of DSM-IV dependence symptoms). THC concentration in cannabis (range 1.10-24.70%) was correlated positively with cannabis dose per joint (b = 0.008, P = 0.01), but the resulting THC concentration per joint (range 0.24-15.72%) was associated negatively with inhalation volume (b = -0.05, P = 0.03). Smoking behaviour measures (number of puffs, inhaled volume, reduction of puff volume and puff duration while smoking) predicted follow-up dependence severity, independently of baseline dependence severity and monthly THC dose (number of joints × cannabis dose × cannabis THC concentration). Monthly THC dose only predicted follow-up dependence severity when unadjusted for baseline severity. Cannabis users titrate their delta-9-tetrahydrocannabinol intake by inhaling lower volumes of smoke when smoking strong joints, but this does not fully compensate for the higher cannabis doses per joint when using strong cannabis. Thus, users of more potent cannabis are generally exposed to more delta-9-tetrahydrocannabinol. Smoking behaviour appears to be a stronger predictor for cannabis dependence severity than monthly delta-9-tetrahydrocannabinol dose. �

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats

PubMed Central

2013-01-01

Introduction The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Methods Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. Results We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality

Mechanisms of carcinogensis: dose response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gehring, P.J.; Blau, G.E.

There is great controversy whether the carcinogenicity of chemicals is dose-dependent and whether a threshold dose exists below which cancer will not be induced by exposure. Evidence for dose-dependency exists and is believed to be accepted generally if extricated as it should be from the threshold concept. The threshold concept conflict is not likely to be resolved in the foreseeable future; proponents and opponents argue their case in a manner similar to those arguing religion. In this paper the various arguments are reviewed. Subsequently, a chemical process model for carcinogenesis is developed based on the generally accepted evidence that themore » carcinogenic activity of many chemicals can be related to electrophilic alkylation of DNA. Using this model, some incidence of cancer, albeit negligible, will be predicted regardless how low the dose. However, the model revelas that the incidence of cancer induced by real-life exposures is likely to be greatly overestimated by currently used stochastic statistical extrapolations. Even more important, modeling of the chemical processes involved in the fate of a carcinogenic chemical in the body reveals experimental approaches to elucidating the mechanism(s) of carcinogenesis and ultimately a more scientifically sound basis for assessing the hazard of low-level exposure to a chemical carcinogen.« less

Reduced-dose C-arm computed tomography applications at a pediatric institution.

PubMed

Acord, Michael; Shellikeri, Sphoorti; Vatsky, Seth; Srinivasan, Abhay; Krishnamurthy, Ganesh; Keller, Marc S; Cahill, Anne Marie

2017-12-01

Reduced-dose C-arm computed tomography (CT) uses flat-panel detectors to acquire real-time 3-D images in the interventional radiology suite to assist with anatomical localization and procedure planning. To describe dose-reduction techniques for C-arm CT at a pediatric institution and to provide guidance for implementation. We conducted a 5-year retrospective study on procedures using an institution-specific reduced-dose protocol: 5 or 8 s Dyna Rotation, 248/396 projection images/acquisition and 0.1-0.17 μGy/projection dose at the detector with 0.3/0.6/0.9-mm copper (Cu) filtration. We categorized cases by procedure type and average patient age and calculated C-arm CT and total dose area product (DAP). Two hundred twenty-two C-arm CT-guided procedures were performed with a dose-reduction protocol. The most common procedures were temporomandibular and sacroiliac joint injections (48.6%) and sclerotherapy (34.2%). C-arm CT was utilized in cases of difficult percutaneous access in less common applications such as cecostomy and gastrostomy placement, foreign body retrieval and thoracentesis. C-arm CT accounted for between 9.9% and 80.7% of the total procedural DAP. Dose-reducing techniques can preserve image quality for intervention while reducing radiation exposure to the child. This technology has multiple applications within pediatric interventional radiology and can be considered as an adjunctive imaging tool in a variety of procedures, particularly when percutaneous access is challenging despite routine fluoroscopic or ultrasound guidance.

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

PubMed Central

Conover, Christine F.; Beggs, Luke A.; Beck, Darren T.; Otzel, Dana M.; Balaez, Alexander; Combs, Sarah M.; Miller, Julie R.; Ye, Fan; Aguirre, J. Ignacio; Neuville, Kathleen G.; Williams, Alyssa A.; Conrad, Bryan P.; Gregory, Chris M.; Wronski, Thomas J.; Bose, Prodip K.; Borst, Stephen E.

2014-01-01

Abstract Androgen administration protects against musculoskeletal deficits in models of sex-steroid deficiency and injury/disuse. It remains unknown, however, whether testosterone prevents bone loss accompanying spinal cord injury (SCI), a condition that results in a near universal occurrence of osteoporosis. Our primary purpose was to determine whether testosterone-enanthate (TE) attenuates hindlimb bone loss in a rodent moderate/severe contusion SCI model. Forty (n=10/group), 14 week old male Sprague-Dawley rats were randomized to receive: (1) Sham surgery (T9 laminectomy), (2) moderate/severe (250 kdyne) SCI, (3) SCI+Low-dose TE (2.0 mg/week), or (4) SCI+High-dose TE (7.0 mg/week). Twenty-one days post-injury, SCI animals exhibited a 77–85% reduction in hindlimb cancellous bone volume at the distal femur (measured via μCT) and proximal tibia (measured via histomorphometry), characterized by a >70% reduction in trabecular number, 13–27% reduction in trabecular thickness, and increased trabecular separation. A 57% reduction in cancellous volumetric bone mineral density (vBMD) at the distal femur and a 20% reduction in vBMD at the femoral neck were also observed. TE dose dependently prevented hindlimb bone loss after SCI, with high-dose TE fully preserving cancellous bone structural characteristics and vBMD at all skeletal sites examined. Animals receiving SCI also exhibited a 35% reduction in hindlimb weight bearing (triceps surae) muscle mass and a 22% reduction in sublesional non-weight bearing (levator ani/bulbocavernosus [LABC]) muscle mass, and reduced prostate mass. Both TE doses fully preserved LABC mass, while only high-dose TE ameliorated hindlimb muscle losses. TE also dose dependently increased prostate mass. Our findings provide the first evidence indicating that high-dose TE fully prevents hindlimb cancellous bone loss and concomitantly ameliorates muscle loss after SCI, while low-dose TE produces much less profound musculoskeletal benefit

Prophylactic Diclectin reduces the incidence of postoperative vomiting.

PubMed

Reeve, Brenda K; Cook, Deborah J; Babineau, Denise; Scholes, L Cory; Buckley, D Norman

2005-01-01

Diclectin(R) (DCL) is an effective antiemetic used for relief of nausea and vomiting in pregnancy. It is unknown whether DCL is effective in the prevention of postoperative nausea and vomiting (PONV). We conducted a randomized, stratified, double-blind placebo-controlled trial to examine the incidence of PONV in women undergoing elective laparoscopic tubal ligation in the day surgery setting. DCL (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) was administered orally the night before surgery, the morning of surgery, and upon hospital discharge. We enrolled 146 women in the trial, 127 of whom were included in the effectiveness analysis and 102 of whom were included in the efficacy analysis. We did not detect a difference in the incidence of nausea and vomiting in the first six hours postoperatively after adjusting for additional antiemetics administered. Patients receiving DCL as compared with placebo were significantly less likely to experience vomiting six to 24 hr postoperatively [5/59 (8.5%) vs 14/55 (25.4%), P < 0.017]. Treated patients tended to return to work earlier than those who received placebo (1.74 vs 3.7 days P = NS). Perioperative oral DCL reduces the incidence of postoperative vomiting in women undergoing elective laparoscopic tubal ligation, and may accelerate return to work.

Verbenone: Dose-Dependent Interruption of Pheromone-Based Attraction of Three Sympatric Species of Pine Bark Beetles (Coleoptera: Scolytidae)

Treesearch

Daniel R. Miller; John H. Borden; B. Staffan Lindgren

1995-01-01

Verbenone significantly reduced catches of Ips latidens (LeConte), I. pini (Say), and Dendroctonus ponderosae Hopkins in multiple-funnel traps, baited with aggregation pheromones, in stands of lodgepole pine in southern British Columbia. Interruption of attraction was dose dependent for all three species. There...

Reduced Incidence of Invasive Breast Cancer With Raloxifene Among Women at Increased Coronary Risk

PubMed Central

Grady, Deborah; Cauley, Jane A.; Geiger, Mary Jane; Kornitzer, Marcel; Mosca, Lori; Collins, Peter; Wenger, Nanette K.; Song, Jingli; Mershon, John; Barrett-Connor, Elizabeth

2013-01-01

Background In the Raloxifene Use for The Heart trial, 10 101 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors were randomly assigned to 60 mg/d raloxifene or to placebo and followed for a median of 5.6 years. Raloxifene, a selective estrogen receptor modulator, was found to reduce the risk of invasive breast cancer and vertebral fractures but not the risk of cardiovascular events. Here, we provide further details about breast cancer incidence by tumor characteristics, duration of treatment, and subgroup. Methods Reported breast cancer was adjudicated by an independent committee based on medical records and pathology reports. The primary analyses used Cox proportional hazards models with time to first breast cancer as the outcome. Subgroup effects were analyzed using similar models with terms for treatment by subgroup. All statistical tests were two-sided. Results As previously reported, raloxifene reduced the incidence of invasive breast cancer by 44% (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.38 to 0.83; absolute risk reduction = 1.2 invasive breast cancers per 1000 women treated for 1 year). The lower incidence of invasive breast cancer reflected a 55% lower incidence of invasive estrogen receptor (ER)–positive tumors (HR = 0.45; 95% CI = 0.28 to 0.72). However, raloxifene treatment did not reduce the incidence of noninvasive breast cancer or of invasive ER-negative breast cancer. The reduced incidence of invasive breast cancer was similar across subgroups, including those defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and 5-year estimated risk of invasive breast cancer. Conclusion Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman's baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers. These results confirm those of the Multiple Outcomes of Raloxifene Evaluation, a previous

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

PTW-diamond detector: dose rate and particle type dependence.

PubMed

Fidanzio, A; Azario, L; Miceli, R; Russo, A; Piermattei, A

2000-11-01

In this paper the suitability of a PTW natural diamond detector (DD) for relative and reference dosimetry of photon and electron beams, with dose per pulse between 0.068 mGy and 0.472 mGy, was studied and the results were compared with those obtained by a stereotactic silicon detector (SFD). The results show that, in the range of the examined dose per pulse the DD sensitivity changes up to 1.8% while the SFD sensitivity changes up to 4.5%. The fitting parameter, delta, used to correct the dose per pulse dependence of solid state detectors, was delta = 0.993 +/- 0.002 and delta = 1.025 +/- 0.002 for the diamond detector and for the silicon diode, respectively. The delta values were found to be independent of particle type of two conventional beams (a 10 MV x-ray beam and a 21 MeV electron beam). So if delta is determined for a radiotherapy beam, it can be used to correct relative dosimetry for other conventional radiotherapy beams. Moreover the diamond detector shows a calibration factor which is independent of beam quality and particle type, so an empirical dosimetric formalism is proposed here to obtain the reference dosimetry. This formalism is based on a dose-to-water calibration factor and on an empirical coefficient, that takes into account the reading dependence on the dose per pulse.

Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seibert, Tyler M.; Karunamuni, Roshan; Kaifi, Samar

Purpose and Objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Methods and Materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex formore » each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical

Increased dose near the skin due to electromagnetic surface beacon transponder.

PubMed

Ahn, Kang-Hyun; Manger, Ryan; Halpern, Howard J; Aydogan, Bulent

2015-05-08

The purpose of this study was to evaluate the increased dose near the skin from an electromagnetic surface beacon transponder, which is used for localization and tracking organ motion. The bolus effect due to the copper coil surface beacon was evaluated with radiographic film measurements and Monte Carlo simulations. Various beam incidence angles were evaluated for both 6 MV and 18 MV experimentally. We performed simulations using a general-purpose Monte Carlo code MCNPX (Monte Carlo N-Particle) to supplement the experimental data. We modeled the surface beacon geometry using the actual mass of the glass vial and copper coil placed in its L-shaped polyethylene terephthalate tubing casing. Film dosimetry measured factors of 2.2 and 3.0 enhancement in the surface dose for normally incident 6 MV and 18 MV beams, respectively. Although surface dose further increased with incidence angle, the relative contribution from the bolus effect was reduced at the oblique incidence. The enhancement factors were 1.5 and 1.8 for 6 MV and 18 MV, respectively, at an incidence angle of 60°. Monte Carlo simulation confirmed the experimental results and indicated that the epidermal skin dose can reach approximately 50% of the dose at dmax at normal incidence. The overall effect could be acceptable considering the skin dose enhancement is confined to a small area (~ 1 cm2), and can be further reduced by using an opposite beam technique. Further clinical studies are justified in order to study the dosimetric benefit versus possible cosmetic effects of the surface beacon. One such clinical situation would be intact breast radiation therapy, especially large-breasted women.

Assessing patient dose in interventional fluoroscopy using patient-dependent hybrid phantoms

NASA Astrophysics Data System (ADS)

Johnson, Perry Barnett

Interventional fluoroscopy uses ionizing radiation to guide small instruments through blood vessels or other body pathways to sites of clinical interest. The technique represents a tremendous advantage over invasive surgical procedures, as it requires only a small incision, thus reducing the risk of infection and providing for shorter recovery times. The growing use and increasing complexity of interventional procedures, however, has resulted in public health concerns regarding radiation exposures, particularly with respect to localized skin dose. Tracking and documenting patient-specific skin and internal organ dose has been specifically identified for interventional fluoroscopy where extended irradiation times, multiple projections, and repeat procedures can lead to some of the largest doses encountered in radiology. Furthermore, inprocedure knowledge of localized skin doses can be of significant clinical importance to managing patient risk and in training radiology residents. In this dissertation, a framework is presented for monitoring the radiation dose delivered to patients undergoing interventional procedures. The framework is built around two key points, developing better anthropomorphic models, and designing clinically relevant software systems for dose estimation. To begin, a library of 50 hybrid patient-dependent computational phantoms was developed based on the UF hybrid male and female reference phantoms. These phantoms represent a different type of anthropomorphic model whereby anthropometric parameters from an individual patient are used during phantom selection. The patient-dependent library was first validated and then used in two patient-phantom matching studies focused on cumulative organ and local skin dose. In terms of organ dose, patient-phantom matching was shown most beneficial for estimating the dose to large patients where error associated with soft tissue attenuation differences could be minimized. For small patients, inherent difference

Dose-dependent effect of aspirin on the level of sphingolipids in human blood.

PubMed

Knapp, M; Lisowska, A; Knapp, P; Baranowski, M

2013-01-01

Aspirin is an antiplatelet drug which is commonly used in secondary prevention in ischemic heart disease and cerebrovascular events, and in newly diagnosed myocardial infarction. The aim of the present study was to examine effect of aspirin on the level of selected sphingolipid intermediates in plasma, erythrocytes and platelets. Forty two healthy volunteers participated in the study. They were divided into two groups. In one group aspirin was given orally, daily, for one week in a dose of 75 mg (n=25). The subjects from the second group received one 300 mg dose of the drug (n=17). In both groups the blood was taken 4h after the last dose of aspirin. The following sphingolipid intermediates were quantified using high-pressure liquid chromatography: sphinganine, sphingosine, sphingosine-1-phosphate (S1P), sphinganine-1-phosphate (SA1P) and ceramide. It was found that lower dose of aspirin increased the level of S1P and ceramide in erythrocytes (by 23 and 37%, respectively) having no effect on plasma and platelet sphingolipid levels. Higher dose of the drug reduced S1P and SA1P concentration in the plasma (by 16 and 10%, respectively). We conclude that aspirin interferes with sphingolipid metabolism in blood and that this effect depends on a dose of the drug. Since S1P is a potent cardioprotectant, the reduction in its plasma concentration after the loading dose of aspirin could be undesired side effect of the drug.

Reducing the Incidence of Plagiarism in an Undergraduate Course: The Role of Education

ERIC Educational Resources Information Center

Breen, Lauren; Maassen, Margaret

2005-01-01

Plagiarism by students is an increasing problem at higher education institutions. However, the development of academic misconduct policies has done little to reduce the incidence of plagiarism as many incidents result from ignorance and poor skill development rather than intentional misconduct. Our purpose in embarking on this research project was…

Novel high dose rate lip brachytherapy technique to improve dose homogeneity and reduce toxicity by customized mold.

PubMed

Feldman, Jon; Appelbaum, Limor; Sela, Mordechay; Voskoboinik, Ninel; Kadouri, Sarit; Weinberger, Jeffrey; Orion, Itzhak; Meirovitz, Amichay

2014-12-23

The purpose of this study is to describe a novel brachytherapy technique for lip Squamous Cell Carcinoma, utilizing a customized mold with embedded brachytherapy sleeves, which separates the lip from the mandible, and improves dose homogeneity. Seven patients with T2 lip cancer treated with a "sandwich" technique of High Dose Rate (HDR) brachytherapy to the lip, consisting of interstitial catheters and a customized mold with embedded catheters, were reviewed for dosimetry and outcome using 3D planning. Dosimetric comparison was made between the "sandwich" technique to "classic" - interstitial catheters only plan. We compared dose volume histograms for Clinical Tumor Volume (CTV), normal tissue "hot spots" and mandible dose. We are reporting according to the ICRU 58 and calculated the Conformal Index (COIN) to show the advantage of our technique. The seven patients (ages 36-81 years, male) had median follow-up of 47 months. Four patients received Brachytherapy and External Beam Radiation Therapy, 3 patients received brachytherapy alone. All achieved local control, with excellent esthetic and functional results. All patients are disease free. The Customized Mold Sandwich technique (CMS) reduced the high dose region receiving 150% (V150) by an average of 20% (range 1-47%), The low dose region (les then 90% of the prescribed dose) improved by 73% in average by using the CMS technique. The COIN value for the CMS was in average 0.92 as opposed to 0.88 for the interstitial catheter only. All differences (excluding the low dose region) were statistically significant. The CMS technique significantly reduces the high dose volume and increases treatment homogeneity. This may reduce the potential toxicity to the lip and adjacent mandible, and results in excellent tumor control, cosmetic and functionality.

Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer.

PubMed

Miao, Junjie; Yan, Hui; Tian, Yuan; Ma, Pan; Liu, Zhiqiang; Li, Minghui; Ren, Wenting; Chen, Jiayun; Zhang, Ye; Dai, Jianrong

2017-11-01

It is important to minimize lung dose during intensity-modulated radiation therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach was proposed to reduce lung dose by relaxing the constraint of target dose homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor on the right side were selected. The total dose for planning target volume (PTV) was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were created in Pinnacle treatment planning system. The dose homogeneity of target was controlled by constraints on the maximum and uniform doses of target volume. One IMRT plan was made with homogeneous target dose (the resulting target dose was within 95%-107% of the prescribed dose), while another IMRT plan was made with inhomogeneous target dose (the resulting target dose was more than 95% of the prescribed dose). During plan optimization, the dose of cord and heart in two types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs at risk (OARs) between two types of IMRT plans were compared and analyzed quantitatively. For all patients, the lung dose was decreased in the IMRT plans with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to normal tissue was also reduced. These reductions in DVH values were all statistically significant (P < 0.05). There were no significant differences between the two IMRT plans on V25, V30, V40, V50 and mean dose for heart. The maximum doses of cords in two type IMRT plans were nearly the same. IMRT plans with inhomogeneous target dose could protect lungs better and may be considered as a choice for treating NSCLC. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Impact of high-dose atorvastatin therapy and clinical risk factors on incident aortic valve stenosis in patients with cardiovascular disease (from TNT, IDEAL, and SPARCL).

PubMed

Arsenault, Benoit J; Boekholdt, S Matthijs; Mora, Samia; DeMicco, David A; Bao, Weihang; Tardif, Jean-Claude; Amarenco, Pierre; Pedersen, Terje; Barter, Philip; Waters, David D

2014-04-15

Clinical trials have not provided evidence for a role of statin therapy in reducing aortic valve stenosis (AVS) severity in patients with documented AVS. However, whether statin therapy could prevent the onset of AVS is unknown. Our objectives were (1) to compare the incidence rates of AVS among patients treated with high-dose versus usual-dose statin or placebo and (2) to identify clinical risk factors associated with the development of AVS. We conducted post hoc analyses in 23,508 participants from 3 large-scale multicenter atorvastatin randomized blinded clinical trials: Treating to New Targets, the Incremental Decrease in End Points Through Aggressive Lipid Lowering, and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels. The main outcome measure was the incidence of clinical AVS over a median follow-up of 4.9 years (82 cases). Among patients who developed AVS, 39 (47.6%) were treated with atorvastatin 80 mg and 43 (52.4%) were treated with lower dose statin (atorvastatin 10 mg in Treating to New Targets, simvastatin 20 to 40 mg in Incremental Decrease in End Points Through Aggressive Lipid Lowering, or placebo in Stroke Prevention by Aggressive Reduction in Cholesterol Levels; hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.59 to 1.41, p=0.67). In multivariate analyses forcing treatment, sex, and race into the model, factors that were significantly associated with AVS included age (HR 2.17, 95% CI 1.61 to 2.93, p<0.0001 per 1-SD increment), diabetes (HR 1.67, 95% CI 1.00 to 2.80, p=0.05), vitamin K antagonist use (HR 3.25, 95% CI 2.06 to 5.16, p<0.0001), and previous statin use (HR 2.65, 95% CI 1.54 to 4.60, p=0.0008). In conclusion, random allocation to high-dose versus usual-dose statin therapy or placebo did not impact the incidence of AVS among patients without known AVS. Age, diabetes, vitamin K antagonists, and previous statin use were significant predictors of incident AVS in these high-risk patients. Copyright © 2014 Elsevier

Dose-Dependent Model of Caffeine Effects on Human Vigilance during Total Sleep Deprivation

DTIC Science & Technology

2014-05-20

does not consider the absorption of caffeine . This is a reasonable approximation for caffeine when ingested via coffee , tea, energy drinks, and most...Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation Sridhar Ramakrishnan a, Srinivas Laxminarayan a, Nancy J...We modeled the dose-dependent effects of caffeine on human vigilance. The model predicted the effects of both single and repeated caffeine doses

Rivastigmine reduces "Likely to use methamphetamine" in methamphetamine-dependent volunteers.

PubMed

De La Garza, R; Newton, T F; Haile, C N; Yoon, J H; Nerumalla, C S; Mahoney, J J; Aziziyeh, A

2012-04-27

We previously reported that treatment with the cholinesterase inhibitor rivastigmine (3mg, PO for 5days) significantly attenuated "Desire for METH". Given that higher dosages of rivastigmine produce greater increases in synaptic ACh, we predicted that 6mg should have more pronounced effects on craving and other subjective measures. In the current study, we sought to characterize the effects of short-term exposure to rivastigmine (0, 3 or 6mg) on the subjective and reinforcing effects produced by administration of methamphetamine (METH) in non-treatment-seeking, METH-dependent volunteers. This was a double-blind, placebo-controlled, crossover study. Participants received METH on day 1, and were then randomized to placebo or rivastigmine on day 2 in the morning and treatment continued through day 8. METH dosing was repeated on day 6. The data indicate that METH (15 and 30mg), but not saline, increased several positive subjective effects, including "Any Drug Effect", "High", "Stimulated", "Desire METH", and "Likely to Use METH" (all p's<0.0001). In addition, during self-administration sessions, participants were significantly more likely to choose METH over saline (p<0.0001). Evaluating outcomes as peak effects, there was a trend for rivastigmine to reduce "Desire METH" (p=0.27), and rivastigmine significantly attenuated "Likely to Use METH" (p=0.01). These effects were most prominent for rivastigmine 6mg when participants were exposed to the low dose (15mg, IV), but not high dose (30mg, IV), of METH. The self-administration data reveal that rivastigmine did not alter total choices for METH (5mg, IV/choice). Overall, the results indicate some efficacy for rivastigmine in attenuating key subjective effects produced by METH, though additional research using higher doses and longer treatment periods is likely needed. These data extend previous findings and indicate that cholinesterase inhibitors, and other drugs that target acetylcholine systems, warrant continued

[Reducing the Incidence of Phlebitis Related to Intravenous Injection in Pediatric Patients].

PubMed

Cho, Yen-Hua; Yen, Li-Ling; Yu, Kai-Ling; Chang, Chun-Chu; Chen, Hsuen-Ling

2015-06-01

Peripheral venous catheter (PVC) is commonly used to provide nutrition and medicine to pediatric inpatients. Phlebitis is a common side effect of PVC insertion. Over 90% of pediatric patients in the paedi-atric medical ward at the Chang Gung Memorial Hospital (CGMH) receive PVC insertion, with an incident rate of phlebitis of 5.07%. Common cause factors of phlebitis are: insufficient sterilization time, inappropriate methods used to fix the PVC, the use of fixtures that loosen easily, high re-fix rates, and inadequate wound care after catheter removal. The purpose of this project was to reduce the incidence rate of PVC-insertion-related phlebitis in children from 5.07% to 2.5%. A one-week clinical observation identified the re-inserting / re-fixing of existing PVCs as the principal cause of phlebitis in the CGMH paediatric ward. Therefore, the researchers modified the catheter care bundle based on a review of the literature and the suggestions of clinical pediatric experts. Modifications included applying 2% chlorhexidine to sterilize the insertion site; using a new, non-woven fabric splint to fix the PVC site; providing cartoon-themed waterproof dressings for the first bath after the removal of the PVC; and setting standard operating procedures (SOPs) for PVC insertion and catheter removal. After applying these modifications, the incident rate of phlebitis in children with PVC insertions decreased from 5.07% to 2.08%. The application of 2% chlorhexidine reduces the waiting time for sterilization; the purpose-designed splint strengthens the fixation of the PVC; and the development of the SOPs for PVC insertion and post-removal catheter care reduces the risk of phlebitis. The combination of these strategies effectively reduces the incidence of phlebitis and improves the nursing care quality.

Medication incidents related to automated dose dispensing in community pharmacies and hospitals--a reporting system study.

PubMed

Cheung, Ka-Chun; van den Bemt, Patricia M L A; Bouvy, Marcel L; Wensing, Michel; De Smet, Peter A G M

2014-01-01

Automated dose dispensing (ADD) is being introduced in several countries and the use of this technology is expected to increase as a growing number of elderly people need to manage their medication at home. ADD aims to improve medication safety and treatment adherence, but it may introduce new safety issues. This descriptive study provides insight into the nature and consequences of medication incidents related to ADD, as reported by healthcare professionals in community pharmacies and hospitals. The medication incidents that were submitted to the Dutch Central Medication incidents Registration (CMR) reporting system were selected and characterized independently by two researchers. Person discovering the incident, phase of the medication process in which the incident occurred, immediate cause of the incident, nature of incident from the healthcare provider's perspective, nature of incident from the patient's perspective, and consequent harm to the patient caused by the incident. From January 2012 to February 2013 the CMR received 15,113 incidents: 3,685 (24.4%) incidents from community pharmacies and 11,428 (75.6%) incidents from hospitals. Eventually 1 of 50 reported incidents (268/15,113 = 1.8%) were related to ADD; in community pharmacies more incidents (227/3,685 = 6.2%) were related to ADD than in hospitals (41/11,428 = 0.4%). The immediate cause of an incident was often a change in the patient's medicine regimen or relocation. Most reported incidents occurred in two phases: entering the prescription into the pharmacy information system and filling the ADD bag. A proportion of incidents was related to ADD and is reported regularly, especially by community pharmacies. In two phases, entering the prescription into the pharmacy information system and filling the ADD bag, most incidents occurred. A change in the patient's medicine regimen or relocation was the immediate causes of an incident.

Dose-Rate Dependence of High-Dose Health Effects in Humans from Photon Radiation with Application to Radiological Terrorism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strom, Daniel J.

2005-01-14

In 1981, as part of a symposium entitled ''The Control of Exposure of the Public to Ionizing Radiation in the Event of Accident or Attack,'' Lushbaugh, H?bner, and Fry published a paper examining ''radiation tolerance'' of various human health endpoints as a function of dose rate. This paper may not have received the notice it warrants. The health endpoints examined by Lushbaugh et al. were the lethal dose that will kill 50% of people within 60 days of exposure without medical care (LD50/60); severe bone marrow damage in healthy men; severe bone marrow damage in leukemia patients; temporary sterility (azoospermia);more » reduced male fertility; and late effects such as cancer. Their analysis was grounded in extensive clinical experience and anchored to a few selected data points, and based on the 1968 dose-rate dependence theory of J.L. Bateman. The Lushbaugh et al. paper did not give predictive equations for the relationships, although they were implied in the text, and the relationships were presented in a non-intuitive way. This work derives the parameters needed in Bateman's equation for each health endpoint, tabulates the results, and plots them in a more conventional manner on logarithmic scales. The results give a quantitative indication of how the human organism can tolerate more radiation dose when it is delivered at lower dose rates. For example, the LD50/60 increases from about 3 grays (300 rads) when given at very high dose rates to over 10 grays (1,000 rads) when given at much lower dose rates over periods of several months. The latter figure is borne out by the case of an individual who survived for at least 19 years after receiving doses in the range of 9 to 17 grays (900-1700 rads) over 106 days. The Lushbaugh et al. work shows the importance of sheltering when confronted with long-term exposure to radiological contamination such as would be expected from a radiological dispersion event, reactor accident, or ground-level nuclear explosion.« less

Duration of skin photosensitivity and incidence of photosensitivity reactions after administration of verteporfin.

PubMed

Houle, Jean-Marie; Strong, H Andrew

2002-12-01

Verteporfin (Visudyne, Novartis AG) is a light-activated drug that reduces the risk of vision loss in patients with certain types of choroidal neovascularization (CNV). Because photosensitivity can occur with photosensitizers, it is important for ophthalmologists providing verteporfin therapy to understand its time course and duration, as well as the incidence of photosensitivity reactions. Data were obtained from three sources: 1) the time course of skin photosensitivity in 17 volunteers by measuring erythema/edema over time after verteporfin, using red light exposure; 2) the duration of skin photosensitivity in 30 patients with skin cancer by exposing skin to simulated solar light and calculating the daily minimal erythematous dose; and 3) the incidences of photosensitivity reactions as recorded in three phase III trials in patients with CNV secondary to age-related macular degeneration or pathologic myopia who received the regimen of verteporfin therapy currently approved by regulatory authorities (infusion of 6 mg/m(2) body surface area). 1) Skin photosensitivity was high at the first timepoint of 1.5 hours after dosing and decreased rapidly thereafter; 2) the duration of skin photosensitivity was dose dependent, ranging from 2.0 to 6.7 days at 6 to 20 mg/m(2), respectively (mean of 2 days at a dose of 6 mg/m(2)); and 3) photosensitivity reactions occurred in only 2.2% of patients in the phase III trials, including two severe events, one secondary to extravasation. All treatment-related reactions in the phase III trials occurred within the first 2 days after dosing, with the exception of two mild reactions and one moderate reaction that occurred 3 days after treatment. Verteporfin is associated with short-lived photosensitivity and a low incidence of photosensitivity reactions in clinical trials, most of which could probably have been avoided by adherence to protocol instructions for skin protection.

Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.

PubMed

Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; di Giosia, Paolo; Barnabei, Remo; Allegaert, Leen; Bernaert, Herwig; Ferri, Claudio

2015-02-01

Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose-response effects. We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P < 0.0001). Compared with the control, even 80  mg cocoa flavonoids per day increased FMD (P < 0.0001). Cocoa dose-dependently decreased PWV (P < 0.0001). Cocoa intake decreased office blood pressure (BP) (SBP: -4.8 ± 1.03  mmHg, P < 0.0001; DBP: -3.03 ± 1.07 mmHg, P = 0.0011). With respect to control, cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment <0.05)]. Compared with the control, significant changes were observed for all doses of flavonoids (ET-1; P < 0.05). Our study showed for the first time that cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary

Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs

PubMed Central

Burr, David B.; Liu, Ziyue; Allen, Matthew R.

2014-01-01

Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than bone’s material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1 ml/kg/day) or alendronate (ALN) at a clinical dose (0.2 mg/kg/day). Treatment duration ranged from 3 months to 3 years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of femoral

Low-Dose Dextromethorphan, a NADPH Oxidase Inhibitor, Reduces Blood Pressure and Enhances Vascular Protection in Experimental Hypertension

PubMed Central

Wu, Tao-Cheng; Chao, Chih-Yu; Lin, Shing-Jong; Chen, Jaw-Wen

2012-01-01

Background Vascular oxidative stress may be increased with age and aggravate endothelial dysfunction and vascular injury in hypertension. This study aimed to investigate the effects of dextromethorphan (DM), a NADPH oxidase inhibitor, either alone or in combination treatment, on blood pressure (BP) and vascular protection in aged spontaneous hypertensive rats (SHRs). Methodology/Principal Findings Eighteen-week-old WKY rats and SHRs were housed for 2 weeks. SHRs were randomly assigned to one of the 12 groups: untreated; DM monotherapy with 1, 5 or 25 mg/kg/day; amlodipine (AM, a calcium channel blocker) monotherapy with 1 or 5 mg/kg/day; and combination therapy of DM 1, 5 or 25 mg/kg/day with AM 1 or 5 mg/kg/day individually for 4 weeks. The in vitro effects of DM were also examined. In SHRs, AM monotherapy dose-dependently reduced arterial systolic BP. DM in various doses significantly and similarly reduced arterial systolic BP. Combination of DM with AM gave additive effects on BP reduction. DM, either alone or in combination with AM, improved aortic endothelial function indicated by ex vivo acetylcholine-induced relaxation. The combination of low-dose DM with AM gave most significant inhibition on aortic wall thickness in SHRs. Plasma total antioxidant status was significantly increased by all the therapies except for the combination of high-dose DM with high-dose AM. Serum nitrite and nitrate level was significantly reduced by AM but not by DM or the combination of DM with AM. Furthermore, in vitro treatment with DM reduced angiotensin II-induced reactive oxygen species and NADPH oxidase activation in human aortic endothelial cells. Conclusions/Significance Treatment of DM reduced BP and enhanced vascular protection probably by inhibiting vascular NADPH oxidase in aged hypertensive animals with or without AM treatment. It provides the potential rationale to a novel combination treatment with low-dose DM and AM in clinical hypertension. PMID:23049937

Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.

PubMed

Quelch, Darren R; Mick, Inge; McGonigle, John; Ramos, Anna C; Flechais, Remy S A; Bolstridge, Mark; Rabiner, Eugenii; Wall, Matthew B; Newbould, Rexford D; Steiniger-Brach, Björn; van den Berg, Franz; Boyce, Malcolm; Østergaard Nilausen, Dorrit; Breuning Sluth, Lasse; Meulien, Didier; von der Goltz, Christoph; Nutt, David; Lingford-Hughes, Anne

2017-06-01

Nalmefene is a µ and δ opioid receptor antagonist, κ opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with "high-risk drinking levels" to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge. Twenty-two currently heavy-drinking, non-treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL). Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal region of interest compared with placebo. Nalmefene did not alter brain perfusion. Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene's actions on opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery.

PubMed

Johnson, Daniel J; Johnson, Christine C; Goobie, Susan M; Nami, Nina; Wetzler, Joshua A; Sponseller, Paul D; Frank, Steven M

2017-12-01

Our objective was to quantify blood loss and transfusion requirements for high-dose and low-dose tranexamic acid (TXA) dosing regimens in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis. Previous investigators have established the efficacy of TXA in pediatric scoliosis surgery; however, the dosing regimens vary widely and the optimal dose has not been established. We retrospectively analyzed electronic medical records for 116 patients who underwent spinal fusion surgery for idiopathic scoliosis by a single surgeon and were treated with TXA. In total, 72 patients received a 10 mg/kg loading dose with a 1 mg/kg/h maintenance dose (low-dose) and 44 patients received 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose (high-dose). Estimated blood loss and transfusion requirements were compared between dosing groups. Patient characteristics were nearly identical between the 2 groups. Compared with the low-dose TXA group, the high-dose TXA group had decreased estimated blood loss (695 vs. 968 mL, P=0.01), and a decrease in both intraoperative (0.3 vs. 0.9 units, P=0.01) and whole hospitalization (0.4 vs. 1.0 units, P=0.04) red blood cell transfusion requirements. The higher-dose TXA was associated with decreased intraoperative (P=0.01), and whole hospital transfusion (P=0.01) requirements, even after risk-adjustment for potential confounding variables. High-dose TXA is more effective than low-dose TXA in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. Level-III, retrospective cohort study.

Continuing evaluation of bipolar linear devices for total dose bias dependency and ELDRS effects

NASA Technical Reports Server (NTRS)

McClure, Steven S.; Gorelick, Jerry L.; Yui, Candice; Rax, Bernard G.; Wiedeman, Michael D.

2003-01-01

We present results of continuing efforts to evaluate total dose bias dependency and ELDRS effects in bipolar linear microcircuits. Several devices were evaluated, each exhibiting moderate to significant bias and/or dose rate dependency.

Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.

PubMed Central

Selby, P. J.; Lopes, N.; Mundy, J.; Crofts, M.; Millar, J. L.; McElwain, T. J.

1987-01-01

A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre-treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan. PMID:3111515

Dependence of pentobarbital kinetics upon the dose of the drug and its pharmacodynamic effects.

PubMed

Kozlowski, K H; Szaykowski, A; Danysz, A

1977-01-01

Pentobarbital (PB), at dose range of 20--50 mg/kg, displays in rabbits non-linear, dose-dependent kinetics. Pharmacokinetics parameters of drug elimination depend largely upon the dose, while the distribution phase is dose-independent. The rate of disappearance of PB from the central compartment (plasma) decreases with the increase of the dose. The analysis of pharmacodynamic parameters has shown that this dose-dependent retardation of PB elimination is probably caused by an impairment of metabolic processes, resulting from disturbance of the circulatory system. A close correlation has been found between the hypotensive effect of PB and the elimination constant, k13, and also between the hypotensive effect and beta.Vd(extrap), a coefficient proportional to the rate of metabolism of PB [23, 29]. The results indicate the necessity of considering the changes in the functional state of the organism, related to the action of a drug, in pharmacokinetic studies.

Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

PubMed

McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

2018-04-25

Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

Ibogaine for treating drug dependence. What is a safe dose?

PubMed

Schep, L J; Slaughter, R J; Galea, S; Newcombe, D

2016-09-01

The indole alkaloid ibogaine, present in the root bark of the West African rain forest shrub Tabernanthe iboga, has been adopted in the West as a treatment for drug dependence. Treatment of patients requires large doses of the alkaloid to cause hallucinations, an alleged integral part of the patient's treatment regime. However, case reports and case series continue to describe evidences of ataxia, gastrointestinal distress, ventricular arrhythmias and sudden and unexplained deaths of patients undergoing treatment for drug dependence. High doses of ibogaine act on several classes of neurological receptors and transporters to achieve pharmacological responses associated with drug aversion; limited toxicology research suggests that intraperitoneal doses used to successfully treat rodents, for example, have also been shown to cause neuronal injury (purkinje cells) in the rat cerebellum. Limited research suggests lethality in rodents by the oral route can be achieved at approximately 263mg/kg body weight. To consider an appropriate and safe initial dose for humans, necessary safety factors need to be applied to the animal data; these would include factors such as intra- and inter-species variability and for susceptible people in a population (such as drug users). A calculated initial dose to treat patients could be approximated at 0.87mg/kg body weight, substantially lower than those presently being administered to treat drug users. Morbidities and mortalities will continue to occur unless practitioners reconsider doses being administered to their susceptible patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reducing Interprocessor Dependence in Recoverable Distributed Shared Memory

NASA Technical Reports Server (NTRS)

Janssens, Bob; Fuchs, W. Kent

1994-01-01

Checkpointing techniques in parallel systems use dependency tracking and/or message logging to ensure that a system rolls back to a consistent state. Traditional dependency tracking in distributed shared memory (DSM) systems is expensive because of high communication frequency. In this paper we show that, if designed correctly, a DSM system only needs to consider dependencies due to the transfer of blocks of data, resulting in reduced dependency tracking overhead and reduced potential for rollback propagation. We develop an ownership timestamp scheme to tolerate the loss of block state information and develop a passive server model of execution where interactions between processors are considered atomic. With our scheme, dependencies are significantly reduced compared to the traditional message-passing model.

Febuxostat protects rats against lipopolysaccharide-induced lung inflammation in a dose-dependent manner.

PubMed

Fahmi, Alaa N A; Shehatou, George S G; Shebl, Abdelhadi M; Salem, Hatem A

2016-03-01

The aim of the present work was to investigate possible protective effects of febuxostat, a highly potent xanthine oxidase inhibitor, against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. Male Sprague Dawley rats were randomly divided into six groups, as follows: (i) vehicle control group; (ii) and (iii) febuxostat 10 and febuxostat 15 groups, drug-treated controls; (iv) LPS group, receiving an intraperitoneal injection of LPS (7.5 mg/kg); (v) and (vi) febuxostat 10-LPS and febuxostat 15-LPS groups, receiving oral treatment of febuxostat (10 and 15 mg/kg/day, respectively) for 7 days before LPS. After 18 h administration of LPS, blood was collected for C-reactive protein (CRP) measurement. Bronchoalveolar lavage fluid (BALF) was examined for leukocyte infiltration, lactate dehydrogenase (LDH) activity, protein content, and total nitrate/nitrite. Lung weight gain was determined, and lung tissue homogenate was prepared and evaluated for oxidative stress. Tumor necrosis factor-α (TNF-α) was assessed in BALF and lung homogenate. Moreover, histological changes of lung tissues were evaluated. LPS elicited lung injury characterized by increased lung water content (by 1.2 fold), leukocyte infiltration (by 13 fold), inflammation and oxidative stress (indicated by increased malondialdehyde (MDA), by 3.4 fold), and reduced superoxide dismutase (SOD) activity (by 34 %). Febuxostat dose-dependently decreased LPS-induced lung edema and elevations in BALF protein content, infiltration of leukocytes, and LDH activity. Moreover, the elevated levels of TNF-α in BALF and lung tissue of LPS-treated rats were attenuated by febuxostat pretreatment. Febuxostat also displayed a potent antioxidant activity by decreasing lung tissue levels of MDA and enhancing SOD activity. Histological analysis of lung tissue further demonstrated that febuxostat dose-dependently reversed LPS-induced histopathological changes. These findings demonstrate a significant dose-dependent

Medication Incidents Related to Automated Dose Dispensing in Community Pharmacies and Hospitals - A Reporting System Study

PubMed Central

Cheung, Ka-Chun; van den Bemt, Patricia M. L. A.; Bouvy, Marcel L.; Wensing, Michel; De Smet, Peter A. G. M.

2014-01-01

Introduction Automated dose dispensing (ADD) is being introduced in several countries and the use of this technology is expected to increase as a growing number of elderly people need to manage their medication at home. ADD aims to improve medication safety and treatment adherence, but it may introduce new safety issues. This descriptive study provides insight into the nature and consequences of medication incidents related to ADD, as reported by healthcare professionals in community pharmacies and hospitals. Methods The medication incidents that were submitted to the Dutch Central Medication incidents Registration (CMR) reporting system were selected and characterized independently by two researchers. Main Outcome Measures Person discovering the incident, phase of the medication process in which the incident occurred, immediate cause of the incident, nature of incident from the healthcare provider's perspective, nature of incident from the patient's perspective, and consequent harm to the patient caused by the incident. Results From January 2012 to February 2013 the CMR received 15,113 incidents: 3,685 (24.4%) incidents from community pharmacies and 11,428 (75.6%) incidents from hospitals. Eventually 1 of 50 reported incidents (268/15,113 = 1.8%) were related to ADD; in community pharmacies more incidents (227/3,685 = 6.2%) were related to ADD than in hospitals (41/11,428 = 0.4%). The immediate cause of an incident was often a change in the patient's medicine regimen or relocation. Most reported incidents occurred in two phases: entering the prescription into the pharmacy information system and filling the ADD bag. Conclusion A proportion of incidents was related to ADD and is reported regularly, especially by community pharmacies. In two phases, entering the prescription into the pharmacy information system and filling the ADD bag, most incidents occurred. A change in the patient's medicine regimen or relocation was the immediate causes of an incident

SEMICONDUCTOR PHYSICS Dose-rate dependence of optically stimulated luminescence signal

NASA Astrophysics Data System (ADS)

Pingqiang, Wei; Zhaoyang, Chen; Yanwei, Fan; Yurun, Sun; Yun, Zhao

2010-10-01

Optically stimulated luminescence (OSL) is the luminescence emitted from a semiconductor during its exposure to light. The OSL intensity is a function of the total dose absorbed by the sample. The dose-rate dependence of the OSL signal of the semiconductor CaS doped Ce and Sm was studied by numerical simulation and experiments. Based on a one-trap/one-center model, the whole OSL process was represented by a series of differential equations. The dose-rate properties of the materials were acquired theoretically by solving the equations. Good coherence was achieved between numerical simulation and experiments, both of which showed that the OSL signal was independent of dose rate. This result validates that when using OSL as a dosimetry technique, the dose-rate effect can be neglected.

Olive oil phenolics are dose-dependently absorbed in humans.

PubMed

Visioli, F; Galli, C; Bornet, F; Mattei, A; Patelli, R; Galli, G; Caruso, D

2000-02-25

Olive oil phenolic constituents have been shown, in vitro, to be endowed with potent biological activities including, but not limited to, an antioxidant action. To date, there is no information on the absorption and disposition of such compounds in humans. We report that olive oil phenolics, namely tyrosol and hydroxytyrosol, are dose-dependently absorbed in humans after ingestion and that they are excreted in the urine as glucuronide conjugates. Furthermore, an increase in the dose of phenolics administered increased the proportion of conjugation with glucuronide.

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

PubMed

Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Crockett, R S; Howes, John; Darpo, Borje; Zhou, Meijian; Weis, Holger; Friedhoff, Lawrence

2016-11-01

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C max and was slowly eliminated (mean t 1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues. © 2016, The American College of Clinical Pharmacology.

A study on quantitative analysis of exposure dose caused by patient depending on time and distance in nuclear medicine examination

NASA Astrophysics Data System (ADS)

Kim, H. S.; Cho, J. H.; Shin, S. G.; Dong, K. R.; Chung, W. K.; Chung, J. E.

2013-01-01

This study evaluated possible actions that can help protect against and reduce radiation exposure by measuring the exposure dose for each type of isotope that is used frequently in nuclear medicine before performing numerical analysis of the effective half-life based on the measurement results. From July to August in 2010, the study targeted 10, 6 and 5 people who underwent an 18F-FDG (fludeoxyglucose) positron emission tomography (PET) scan, 99mTc-HDP bone scan, and 201Tl myocardial single-photon emission computed tomography (SPECT) scan, respectively, in the nuclear medicine department. After injecting the required medicine into the subjects, a survey meter was used to measure the dose depending on the distance from the heart and time elapsed. For the 18F-FDG PET scan, the dose decreased by approximately 66% at 90 min compared to that immediately after the injection and by 78% at a distance of 1 m compared to that at 0.3 m. In the 99mTc-HDP bone scan, the dose decreased by approximately 71% in 200 min compared to that immediately after the injection and by approximately 78% at a distance of 1 m compared to that at 0.3 m. In the 201Tl myocardial SPECT scan, the dose decreased by approximately 30% in 250 min compared to that immediately after the injection and by approximately 55% at a distance of 1 m compared to that at 0.3 m. In conclusion, the dose decreases by a large margin depending on the distance and time. In conclusion, this study measured the exposure doses by isotopes, distance from the heart and exposure time, and found that the doses were reduced significantly according the distance and the time.

SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose-Range Dependency of Radio-Biological Parameters.

PubMed

Troeller, A; Soehn, M; Yan, D

2012-06-01

Introducing an extended, phenomenological, generalized equivalent uniform dose (eEUD) that incorporates multiple volume-effect parameters for different dose-ranges. The generalized EUD (gEUD) was introduced as an estimate of the EUD that incorporates a single, tissue-specific parameter - the volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its radio-biological equivalency to a given inhomogeneous dose distribution is not a priori clear and mechanistic models based on radio-biological parameters are assumed to better resemble the underlying biology. However, for normal organs mechanistic models are hard to derive, since the structural organization of the tissue plays a significant role. Consequently, phenomenological approaches might be especially useful in order to describe dose-response for normal tissues. However, the single parameter used to estimate the gEUD may not suffice in accurately representing more complex biological effects that have been discussed in the literature. For instance, radio-biological parameters and hence the effects of fractionation are known to be dose-range dependent. Therefore, we propose an extended phenomenological eEUD formula that incorporates multiple VEPs accounting for dose-range dependency. The eEUD introduced is a piecewise polynomial expansion of the gEUD formula. In general, it allows for an arbitrary number of VEPs, each valid for a certain dose-range. We proved that the formula fulfills required mathematical and physical criteria such as invertibility of the underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD as a special case, if all VEPs are equal to 'a' from the gEUD model. The eEUD is a concept that expands the gEUD such that it can theoretically represent dose-range dependent effects. Its practicality, however, remains to be shown. As a next step, this will be done by estimating the eEUD from patient data using maximum-likelihood based NTCP modelling in the same way

Reduced incidence of laryngospasm with remifentanil-midazolam anaesthesia compared to halothane-fentanyl.

PubMed

Ali, Shahriari

2008-03-01

To compare the incidence of laryngospasm by using halothane-fentanyl anaesthesia and midazolam-remifentanil anaesthesia in paediatric patients undergoing eye surgery. We enrolled 120 ASA physical status I children aged 7-12 years scheduled for eye surgery from March 2004 to February 2006 in this prospective clinical trial study. Children suffering from any medical condition that could affect airway reflexes such as active upper respiratory infection, symptomatic asthma, obesity, patients with predicted difficulty in tracheal intubation were not included in the study. Patients with prolonged or difficult intubation or those who received another drug before extubation were excluded from the study. Using a random numbers table, participants were allocated to two equal groups. After induction of anaesthesia, in one group Halothane 1% was administered for the maintenance of anaesthesia in addition with intravenous fentanyl 1.5 microg kg(-1), and for the patients of the other group midazolam with a dose of 0.1 mg kg(-1) and remifentanil infusion by a dose of 0.1 microg kg(-1) min(-1) was administered. The patients were extubated in a unique plan of anaesthesia, using the sign of swallowing as a clinical indicator for extubation of patients. The incidence of laryngospasm was lower in midazolam-remifentanil group (0%) in comparison with halothane-fentanyl group (6.6%). The results of our study suggest that remifentanil combined with midazolam in children undergoing eye surgery provided a better condition for extubation of the patients.

Human Collagen Injections to Reduce Rectal Dose During Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noyes, William R., E-mail: noyes@cancercenternd.com; Hosford, Charles C.; Schultz, Steven E.

Objectives: The continuing search for interventions, which address the incidence and grade of rectal toxicities associated with radiation treatment of prostate cancer, is a major concern. We are reporting an investigational trial using human collagen to increase the distance between the prostate and anterior rectal wall, thereby decreasing the radiation dose to the rectum. Methods: This is a pilot study evaluating the use of human collagen as a displacing agent for the rectal wall injected before starting a course of intensity-modulated radiotherapy (IMRT) for prostate cancer. Using a transperineal approach, 20 mL of human collagen was injected into the perirectalmore » space in an outpatient setting. Computerized IMRT plans were performed pre- and postcollagen injection, and after a patient completed their radiotherapy, to determine radiation dose reduction to the rectum associated with the collagen injection. Computed tomography scans were performed 6 months and 12 months after completing their radiotherapy to evaluate absorption rate of the collagen. All patients were treated with IMRT to a dose of 75.6 Gy to the prostate. Results: Eleven patients were enrolled into the study. The injection of human collagen in the outpatient setting was well tolerated. The mean separation between the prostate and anterior rectum was 12.7 mm. The mean reduction in dose to the anterior rectal wall was 50%. All men denied any rectal symptoms during the study. Conclusions: The transperineal injection of human collagen for the purpose of tissue displacement is well tolerated in the outpatient setting. The increased separation between the prostate and rectum resulted in a significant decrease in radiation dose to the rectum while receiving IMRT and was associated with no rectal toxicities.« less

Impact of the two-dose rubella vaccination regimen on incidence of rubella seronegativity in gravidae aged 25 years and younger.

PubMed

Hui, Shuk Yi Annie; Sahota, Daljit S; Lao, Terence T

2017-01-01

This study compared the incidence of rubella seronegativity among gravidae of 25 year-old and younger, between those born in Hong Kong after 1983 when the two-dose rubella vaccination was implemented, versus gravidae born before, to examine the impact of the two-dose regimen. In this retrospective cohort study, the incidence of antenatal rubella seronegativity in our parturients managed in1997-2015 was analysed by their age from ≤16 to 25 years, and the effect of year of birth was determined adjusting for confounding factors including teenage status, obstetric history, anthropometric factors, and health parameters including anaemia, thalassaemia trait and hepatitis B carrier status. Among the 12743 gravidae, the 6103 gravidae born after 1983 had overall higher rubella seronegativity (9.1% versus 4.4%, OR 2.061, 95% CI 1.797-2.364), with significant difference (p = 0.006) and inverse correlation (p<0.001) with age, in contrast to the 6640 gravidae born in/before 1983 whom there was significant difference (p = 0.027) but a positive correlation (p = 0.008) with age. For each year of age, the former had significantly higher incidence of rubella seronegativity except for those of ≤16 years. Regression analysis confirmed that birth after 1983 was independently associated with rubella seronegativity (aOR 2.207, 95% CI 1.902-2.562). There was a significant trend between rubella seronegativity with age in young gravidae, but the pattern was opposite between gravidae born after versus in/before 1983, with the former having a higher incidence of seronegativity at all ages. Young women covered by the two-dose rubella immunisation programme have a paradoxically higher incidence of rubella seronegativity.

Dose computation for therapeutic electron beams

NASA Astrophysics Data System (ADS)

Glegg, Martin Mackenzie

The accuracy of electron dose calculations performed by two commercially available treatment planning computers, Varian Cadplan and Helax TMS, has been assessed. Measured values of absorbed dose delivered by a Varian 2100C linear accelerator, under a wide variety of irradiation conditions, were compared with doses calculated by the treatment planning computers. Much of the motivation for this work was provided by a requirement to verify the accuracy of calculated electron dose distributions in situations encountered clinically at Glasgow's Beatson Oncology Centre. Calculated dose distributions are required in a significant minority of electron treatments, usually in cases involving treatment to the head and neck. Here, therapeutic electron beams are subject to factors which may cause non-uniformity in the distribution of dose, and which may complicate the calculation of dose. The beam shape is often irregular, the beam may enter the patient at an oblique angle or at an extended source to skin distance (SSD), tissue inhomogeneities can alter the dose distribution, and tissue equivalent material (such as wax) may be added to reduce dose to critical organs. Technological advances have allowed the current generation of treatment planning computers to implement dose calculation algorithms with the ability to model electron beams in these complex situations. These calculations have, however, yet to be verified by measurement. This work has assessed the accuracy of calculations in a number of specific instances. Chapter two contains a comparison of measured and calculated planar electron isodose distributions. Three situations were considered: oblique incidence, incidence on an irregular surface (such as that which would be arise from the use of wax to reduce dose to spinal cord), and incidence on a phantom containing a small air cavity. Calculations were compared with measurements made by thermoluminescent dosimetry (TLD) in a WTe electron solid water phantom. Chapter

Dose-Dependent Suppression of Gonadotropins and Ovarian Hormones by Elagolix in Healthy Premenopausal Women.

PubMed

Ng, Juki; Chwalisz, Kristof; Carter, David C; Klein, Cheri E

2017-05-01

Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone-dependent diseases in women. We evaluated the pharmacokinetics and pharmacodynamics of elagolix. This study was a randomized, double-blind, placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal women at a research unit. Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice daily (BID)] or placebo was administered for 21 days. Main outcome measures were elagolix pharmacokinetics, suppression of gonadotropics [follicle-stimulating hormone (FSH), luteinizing hormone (LH)] and ovarian hormones [estradiol (E2), progesterone (P)], and adverse events. Elagolix was rapidly absorbed after oral dosing, reaching maximum concentrations at 1.0 to 1.5 hours, with a half-life of 4 to 6 hours. FSH, LH, and E2 were suppressed within hours of elagolix administration on day 1. Dose-dependent suppression of E2 was observed, with maximum suppression achieved with elagolix 200 mg BID. Dose-dependent suppression of FSH and LH was also observed, with maximal or near-maximal suppression achieved at 300 mg BID and 200 mg BID, respectively. At elagolix doses ≥100 mg BID, P concentrations remained at anovulatory levels throughout 21 days of dosing. The most frequently reported adverse events were headache and hot flush. Elagolix administration allows for modulation of gonadotropin and ovarian hormone concentrations, from partial suppression at lower doses to nearly full suppression at higher doses. The results of this study provide a rationale for elagolix dose selection for treatment of sex hormone-dependent diseases in women. Copyright © 2017 Endocrine Society

Magnetic-field-induced dose effects in MR-guided radiotherapy systems: dependence on the magnetic field strength.

PubMed

Raaijmakers, A J E; Raaymakers, B W; Lagendijk, J J W

2008-02-21

Several institutes are currently working on the development of a radiotherapy treatment system with online MR imaging (MRI) modality. The main difference between their designs is the magnetic field strength of the MRI system. While we have chosen a 1.5 Tesla (T) magnetic field strength, the Cross Cancer Institute in Edmonton will be using a 0.2 T MRI scanner and the company Viewray aims to use 0.3 T. The magnetic field strength will affect the severity of magnetic field dose effects, such as the electron return effect (ERE): considerable dose increase at tissue air boundaries due to returning electrons. This paper has investigated how the ERE dose increase depends on the magnetic field strength. Therefore, four situations where the ERE occurs have been simulated: ERE at the distal side of the beam, the lateral ERE, ERE in cylindrical air cavities and ERE in the lungs. The magnetic field comparison values were 0.2, 0.75, 1.5 and 3 T. Results show that, in general, magnetic field dose effects are reduced at lower magnetic field strengths. At the distal side, the ERE dose increase is largest for B = 0.75 T and depends on the irradiation field size for B = 0.2 T. The lateral ERE is strongest for B = 3 T but shows no effect for B = 0.2 T. Around cylindrical air cavities, dose inhomogeneities disappear if the radius of the cavity becomes small relative to the in-air radius of the secondary electron trajectories. At larger cavities (r > 1 cm), dose inhomogeneities exist for all magnetic field strengths. In water-lung-water phantoms, the ERE dose increase takes place at the water-lung transition and the dose decreases at the lung-water transition, but these effects are minimal for B = 0.2 T. These results will contribute to evaluating the trade-off between magnetic field dose effects and image quality of MR-guided radiotherapy systems.

Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models

PubMed Central

Florova, Galina; Azghani, Ali O.; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M.; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

2016-01-01

The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP. PMID:27343192

Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models.

PubMed

Komissarov, Andrey A; Florova, Galina; Azghani, Ali O; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

2016-08-01

The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP. Copyright © 2016 the American Physiological Society.

Rivastigmine Reduces “Likely to Use Methamphetamine” in Methamphetamine-Dependent Volunteers

PubMed Central

De La Garza, R.; Newton, T.F.; Haile, C.N.; Yoon, J.H.; Nerumalla, C.S.; Mahoney, J.J.; Aziziyeh, A.

2012-01-01

We previously reported that treatment with the cholinesterase inhibitor rivastigmine (3 mg, PO for 5 days) significantly attenuated “Desire for METH”. Given that higher dosages of rivastigmine produce greater increases in synaptic ACh, we predicted that 6 mg should have more pronounced effects on craving and other subjective measures. In the current study, we sought to characterize the effects of short-term exposure to rivastigmine (0, 3 or 6 mg) on the subjective and reinforcing effects produced by administration of methamphetamine (METH) in non-treatment-seeking, METH-dependent volunteers. This was a double-blind, placebo-controlled, crossover study. Participants received METH on day 1, and were then randomized to placebo or rivastigmine on day 2 in the morning and treatment continued through day 8. METH dosing was repeated on day 6. The data indicate that METH (15 and 30 mg), but not saline, increased several positive subjective effects, including “Any Drug Effect”, “High”, “Stimulated”, “Desire METH”, and “Likely to Use METH” (all p’s<0.0001). In addition, during self-administration sessions, participants were significantly more likely to choose METH over saline (p<0.0001). Evaluating outcomes as peak effects, there was a trend for rivastigmine to reduce “Desire METH” (p=0.27), and rivastigmine significantly attenuated “Likely to Use METH” (p=0.01). These effects were most prominent for rivastigmine 6 mg when participants were exposed to the low dose (15 mg, IV), but not high dose (30 mg, IV), of METH. The self-administration data reveal that rivastigmine did not alter total choices for METH (5 mg, IV/choice). Overall, the results indicate some efficacy for rivastigmine in attenuating key subjective effects produced by METH, though additional research using higher doses and longer treatment periods is likely needed. These data extend previous findings and indicate that cholinesterase inhibitors, and other drugs that target

Postnatal glucocorticoid-induced hypomyelination, gliosis, neurologic deficits are dose-dependent, preparation-specific, and reversible

PubMed Central

Zia, Muhammad TK; Vinukonda, Govindaiah; Vose, Linnea; Bhimavarapu, Bala B.R.; Iacobas, Sanda; Pandey, Nishi K.; Beall, Ann Marie; Dohare, Preeti; LaGamma, Edmund F.; Iacobas, Dumitru A.; Ballabh, Praveen

2014-01-01

Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. Their pharmacologic use is associated with neurodevelopmental delay and cerebral palsy. However, the effect of GC dose and preparation (dexamethasone versus betamethasone) on short and long-term neurological outcomes remains undetermined, and the mechanisms of GC-induced brain injury are unclear. We hypothesized that postnatal GC would induce hypomyelination and motor impairment in a preparation- and dose-specific manner, and that GC receptor (GR) inhibition might restore myelination and neurological function in GC-treated animals. Additionally, GC-induced hypomyelination and neurological deficit might be transient. To test our hypotheses, we treated prematurely delivered rabbit pups with high (0.5 mg/kg/day) or low (0.2 mg/kg/day) doses of dexamethasone or betamethasone. Myelin basic protein (MBP), oligodendrocyte proliferation and maturation, astrocytes, transcriptomic profile, and neurobehavioral functions were evaluated. We found that high-dose GC treatment, but not low-dose, reduced MBP expression and impaired motor function at postnatal day 14. High-dose dexamethasone induced astrogliosis, betamethasone did not. Mifepristone, a GR antagonist, reversed dexamethasone-induced myelination, but not astrogliosis. Both GCs inhibited oligodendrocyte proliferation and maturation. Moreover, high-dose dexamethasone altered genes associated with myelination, cell-cycle, GR, and Mitogen-activated protein kinase. Importantly, GC-induced hypomyelination, gliosis, and motor-deficit, observed at day 14, completely recovered by day 21. Hence, high-dose, but not low-dose, postnatal GC causes reversible reductions in myelination and motor functions. GC treatment induces hypomyelination by GR-dependent genomic mechanisms, but astrogliosis by non-genomic mechanisms. GC-induced motor impairment and neurodevelopmental delay might be transient and recover spontaneously in

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors.

PubMed

Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

2015-01-01

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection.

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

PubMed Central

Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

2015-01-01

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection. PMID:26413188

Reducing ionizing radiation doses during cardiac interventions in pregnant women.

PubMed

Orchard, Elizabeth; Dix, Sarah; Wilson, Neil; Mackillop, Lucy; Ormerod, Oliver

2012-09-01

There is concern over ionizing radiation exposure in women who are pregnant or of child-bearing age. Due to the increasing prevalence of congenital and acquired heart disease, the number of women who require cardiac interventions during pregnancy has increased. We have developed protocols for cardiac interventions in pregnant women and women of child-bearing age, aimed at substantially reducing both fluoroscopy duration and radiation doses. Over five years, we performed cardiac interventions on 15 pregnant women, nine postpartum women and four as part of prepregnancy assessment. Fluoroscopy times were minimized by simultaneous use of intracardiac echocardiography, and by using very low frame rates (2/second) during fluoroscopy. The procedures most commonly undertaken were closure of atrial septal defect (ASD) or patent foramen ovale (PFO) in 16 women, coronary angiograms in seven, right and left heart catheters in three and two stent placements. The mean screening time for all patients was 2.38 minutes (range 0.48-13.7), the median radiation dose was 66 (8.9-1501) Gy/cm(2). The median radiation dose to uterus was 1.92 (0.59-5.47) μGy, and the patient estimated dose was 0.24 (0.095-0.80) mSv. Ionizing radiation can be used safely in the management of severe cardiac structural disease in pregnancy, with very low ionizing radiation dose to the mother and extremely low exposure to the fetus. With experience, ionizing radiation doses at our institution have been reduced.

Reduced radiation dose for elective nodal irradiation in node-negative anal cancer: back to the roots?

PubMed

Henkenberens, Christoph; Meinecke, Daniela; Michael, Stoll; Bremer, Michael; Christiansen, Hans

2015-11-01

Chemoradiation (CRT) is the standard of care in patients with node-positive (cN+) and node-negative (cN0) anal cancer. Depending on the tumor size (T-stage), total doses of 50-60 Gray (Gy) in daily fractions of 1.8-2.0 Gy are usually applied to the tumor site. Inguinal and iliac lymph nodes usually receive a dose of ≥ 45 Gy. Since 2010, our policy has been to apply a reduced total dose of 39.6 Gy to uninvolved nodal regions. This paper provides preliminary results of the efficacy and safety of this protocol. Overall, 30 patients with histologically confirmed and node-negative anal cancer were treated in our department from 2009-2014 with definitive CRT. Histology all cases showed squamous cell carcinoma. A total dose of 39.6 Gy [single dose (SD) 1.8 Gy] was delivered to the iliac/inguinal lymph nodes. The area of the primary tumor received 50-59.4 Gy, depending on the T-stage. In parallel with the irradiation, 5-fluorouracil (5-FU) at a dose of 1000 mg/m(2) was administered by continuous intravenous infusion over 24 h on days 1-4 and 29-32, and mitomycin C (MMC) at a dose of 10 mg/m(2) (maximum absolute dose 14 mg) was administered on days 1 and 29. The distribution of the tumor stages was as follows: T1, n = 8; T2, n = 17; T3 n = 3. Overall survival (OS), local control (LC) of the lymph nodes, colostomy-free survival (CFS), and acute and chronic toxicities were assessed. The median follow-up was 27.3 months (range 2.7-57.4 months). Three patients (10.0 %) died, 2 of cardiopulmonary diseases and one of liver failure, yielding a 3-year OS of 90.0 %. Two patients (6.7 %) relapsed early and received salvage colostomies, yielding a 3-year CFS of 93.3 %. No lymph node relapses were observed, giving a lymph node LC of 100 %. According to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE V. 4.0), there were no grade IV gastrointestinal or genitourinary acute toxicities. Seven patients showed acute grade

Finding Uncertainties that Cause the Age Dependence of Dose Limits to Be Immature

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.

2007-01-01

Space radiation permissible exposure limits (PEL) are intended to set acceptable levels of cancer risks, and avoid any clinical significant non-cancer effects. The 1989 recommendation of the National Council of Radiation Protection and Measurements (NCRP) recommended a strong age dependence of dose limits that departed drastically from the then mature 1970 dose limits recommendations from the National Academy of Science, which were independent of age. In 2000, the NCRP recommended revised limits that showed a similar trend of risk with age to the 1989 report. In this model, the cancer risk per Sv varies by more than 2-fold for ages between 30- and 50-yr. Therefore for galactic cosmic rays exposure, astronaut age has a larger influence on risk then radiation shielding mass or material composition, vehicle propulsion method, or position in the solar cycle. For considering the control of mission costs and resources, the possibility of using astronaut age as a trade variable in mission design could be considered. However, the uncertainties in describing the age dependence on risk have not been fully explored. We discuss biological factors that influence the age dependence of radiation risks, including susceptibility, expression and latency, and radiation quality. These factors depend not only on the individual s age, but also their genetic sensitivity and interaction with other environmental factors. Epidemiological data is limited in describing the age dependence on risk. The 2005, BEIR VII report recommends an age dependence for cancer risk attributable solely to the life-table disagreeing strongly with the NCRP model. However, BEIR VII also noted the limited power of human data for concomitantly describing both age and age after exposure dependences of cancer risks. Many experimental studies have shown that high LET radiation (e.g., high charge and energy (HZE) nuclei and neutrons) display reduced latency compared to low LET radiation, suggesting distinct biological

Organ doses from radionuclides on the ground. Part I. Simple time dependences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, P.; Paretzke, H.G.; Rosenbaum, H.

1988-06-01

Organ dose equivalents of mathematical, anthropomorphical phantoms ADAM and EVA for photon exposures from plane sources on the ground have been calculated by Monte Carlo photon transport codes and tabulated in this article. The calculation takes into account the air-ground interface and a typical surface roughness, the energy and angular dependence of the photon fluence impinging on the phantom and the time dependence of the contributions from daughter nuclides. Results are up to 35% higher than data reported in the literature for important radionuclides. This manuscript deals with radionuclides, for which the time dependence of dose equivalent rates and dosemore » equivalents may be approximated by a simple exponential. A companion manuscript treats radionuclides with non-trivial time dependences.« less

A comparison of single-dose dexmedetomidine or propofol on the incidence of emergence delirium in children undergoing general anaesthesia for magnetic resonance imaging.

PubMed

Bong, C L; Lim, E; Allen, J C; Choo, W L H; Siow, Y N; Teo, P B Y; Tan, J S K

2015-04-01

Emergence delirium is a significant problem in children regaining consciousness following general anaesthesia. We compared the emergence characteristics of 120 patients randomly assigned to receive a single intravenous dose of dexmedetomidine 0.3 μg.kg(-1) , propofol 1 mg.kg(-1) , or 10 ml saline 0.9% before emerging from general anaesthesia following a magnetic resonance imaging scan. Emergence delirium was diagnosed as a score of 10 or more on the Paediatric Anaesthesia Emergence Delirium scale. The incidence of emergence delirium was 42.5% in the dexmedetomidine group, 33.3% in the propofol group and 41.5% in the saline group (p = 0.671). Three patients in the dexmedetomidine group, none in the propofol group and two in the saline group required pharmacological intervention for emergence delirium (p = 0.202). Administration of neither dexmedetomidine nor propofol significantly reduced the incidence, or severity, of emergence delirium. The only significant predictor for emergence delirium was the time taken to awaken from general anaesthesia, with every minute increase in wake-up time reducing the odds of emergence delirium by 7%. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Measures of reducing obstetric emergencies hysterectomy incidence.

PubMed

Ren, Guo-ping; Wang, Bao-lian; Wang, Yan-hong

2016-03-01

To study the obstetric emergency hysterectomy which can reduce the incidence of measures. In maternity of Xinxiang Central Hospital, the total number of deliveries cases has been up to 50,526 in 20 years, of which 48 cases were retrospectively analyzed for the clinical data of Emergency uterine surgery cases. Cases underwent obstetric emergency hysterectomy accounted for 0.095% of total deliveries (48/50 526), in which 11 cases of vaginal delivery, 37 cases of cesarean section. The indications for surgery: 27 cases were cased by placental factors accounted for 56.25%; 14 cases of uterine inertia, accounting for 29.17%; uterine rupture in 4 cases, accounting for 8.33%; 3 cases of coagulopathy, accounting for 6.25%. Where the maternal placental factors hysterectomy is the most common (69.70%, 23/33) and the predominant factor is early maternal uterine inertia (60.00%, 9/15). There are 74.09% (20/27) of patients with placental abnormalities history of previous cesarean section or uterine surgery. The major risk factors leading to obstetric emergency hysterectomy is placental factors. Preventing the occurrence of placental abnormalities planting actively can effectively reduce the rate of obstetric hysterectomy.

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

PubMed Central

McCormick, Barry; Lukito, Veny; Wilson, Kirsten L.

2017-01-01

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord.

PubMed

Dickie, Allen C; McCormick, Barry; Lukito, Veny; Wilson, Kirsten L; Torsney, Carole

2017-07-05

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1-10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action

Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain.

PubMed

Van Bockstaele, Elisabeth J; Qian, Yaping; Sterling, Robert C; Page, Michelle E

2008-05-15

The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone-precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pre-treatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional 4 h. At the end of the experiment

Bacterial Dose-Dependent Role of G Protein-Coupled Receptor Kinase 5 in Escherichia coli-Induced Pneumonia.

PubMed

Packiriswamy, Nandakumar; Steury, Michael; McCabe, Ian C; Fitzgerald, Scott D; Parameswaran, Narayanan

2016-05-01

G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase previously shown to mediate polymicrobial sepsis-induced inflammation. The goal of the present study was to examine the role of GRK5 in monomicrobial pulmonary infection by using an intratracheal Escherichia coli infection model of pneumonia. We used sublethal and lethal doses of E. coli to examine the mechanistic differences between low-grade and high-grade inflammation induced by E. coli infection. With a sublethal dose of E. coli, GRK5 knockout (KO) mice exhibited higher plasma CXCL1/KC levels and enhanced lung neutrophil recruitment early after infection, and lower bacterial loads, than wild-type (WT) mice. The inflammatory response was also diminished, and resolution of inflammation advanced, in the lungs of GRK5 KO mice. In contrast to the reduced bacterial loads in GRK5 KO mice following a sublethal dose, at a lethal dose of E. coli, the bacterial burdens remained high in GRK5 KO mice relative to those in WT mice. This occurred in spite of enhanced plasma CXCL1 levels as well as neutrophil recruitment in the KO mice. But the recruited neutrophils (following high-dose infection) exhibited decreased CD11b expression and reduced reactive oxygen species production, suggesting decreased neutrophil activation or increased neutrophil exhaustion in the GRK5 KO mice. In agreement with the increased bacterial burden, KO mice showed poorer survival than WT mice following E. coli infection at a lethal dose. Overall, our data suggest that GRK5 negatively regulates CXCL1/KC levels during bacterial pneumonia but that the role of GRK5 in the clinical outcome in this model is dependent on the bacterial dose. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

PubMed

Dionet, Claude; Müller-Barthélémy, Melanie; Marceau, Geoffroy; Denis, Jean-Marc; Averbeck, Dietrich; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andrei; Chautard, Emmanuel; Verrelle, Pierre

2016-09-01

To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

Impact of the two-dose rubella vaccination regimen on incidence of rubella seronegativity in gravidae aged 25 years and younger

PubMed Central

Sahota, Daljit S.; Lao, Terence T.

2017-01-01

Objective This study compared the incidence of rubella seronegativity among gravidae of 25 year-old and younger, between those born in Hong Kong after 1983 when the two-dose rubella vaccination was implemented, versus gravidae born before, to examine the impact of the two-dose regimen. Methods In this retrospective cohort study, the incidence of antenatal rubella seronegativity in our parturients managed in1997-2015 was analysed by their age from ≤16 to 25 years, and the effect of year of birth was determined adjusting for confounding factors including teenage status, obstetric history, anthropometric factors, and health parameters including anaemia, thalassaemia trait and hepatitis B carrier status. Results Among the 12743 gravidae, the 6103 gravidae born after 1983 had overall higher rubella seronegativity (9.1% versus 4.4%, OR 2.061, 95% CI 1.797–2.364), with significant difference (p = 0.006) and inverse correlation (p<0.001) with age, in contrast to the 6640 gravidae born in/before 1983 whom there was significant difference (p = 0.027) but a positive correlation (p = 0.008) with age. For each year of age, the former had significantly higher incidence of rubella seronegativity except for those of ≤16 years. Regression analysis confirmed that birth after 1983 was independently associated with rubella seronegativity (aOR 2.207, 95% CI 1.902–2.562). Conclusion There was a significant trend between rubella seronegativity with age in young gravidae, but the pattern was opposite between gravidae born after versus in/before 1983, with the former having a higher incidence of seronegativity at all ages. Young women covered by the two-dose rubella immunisation programme have a paradoxically higher incidence of rubella seronegativity. PMID:28854204

Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation.

PubMed

Ramakrishnan, Sridhar; Laxminarayan, Srinivas; Wesensten, Nancy J; Kamimori, Gary H; Balkin, Thomas J; Reifman, Jaques

2014-10-07

Caffeine is the most widely consumed stimulant to counter sleep-loss effects. While the pharmacokinetics of caffeine in the body is well-understood, its alertness-restoring effects are still not well characterized. In fact, mathematical models capable of predicting the effects of varying doses of caffeine on objective measures of vigilance are not available. In this paper, we describe a phenomenological model of the dose-dependent effects of caffeine on psychomotor vigilance task (PVT) performance of sleep-deprived subjects. We used the two-process model of sleep regulation to quantify performance during sleep loss in the absence of caffeine and a dose-dependent multiplier factor derived from the Hill equation to model the effects of single and repeated caffeine doses. We developed and validated the model fits and predictions on PVT lapse (number of reaction times exceeding 500 ms) data from two separate laboratory studies. At the population-average level, the model captured the effects of a range of caffeine doses (50-300 mg), yielding up to a 90% improvement over the two-process model. Individual-specific caffeine models, on average, predicted the effects up to 23% better than population-average caffeine models. The proposed model serves as a useful tool for predicting the dose-dependent effects of caffeine on the PVT performance of sleep-deprived subjects and, therefore, can be used for determining caffeine doses that optimize the timing and duration of peak performance. Published by Elsevier Ltd.

Surface buildup dose dependence on photon field delivery technique for IMRT

PubMed Central

Yokoyama, Shigeru; Roberson, Peter L.; Litzenberg, Dale W.; Moran, Jean M.; Fraass, Benedick A.

2004-01-01

The more complex delivery techniques required for implementation of intensity‐modulated radiotherapy (IMRT) based on inverse planning optimization have changed the relationship between dose at depth and dose at buildup regions near the surface. Surface buildup dose is dependent on electron contamination primarily from the unblocked view of the flattening filter and secondarily from air and collimation systems. To evaluate the impact of beam segmentation on buildup dose, measurements were performed with 10×10 cm2 fields, which were delivered with 3 static 3.5×10 cm2 or 3×10 cm2 strips, 5 static 2×10 cm2 strips, 10 static 1×10 cm2 strips, and 1.1×10 cm2 dynamic delivery, compared with a 10×10 cm2 open field. Measurements were performed in water and Solid Water using parallel plate chambers, a stereotactic diode, and thermoluminescent dosimeters (TLDs) for a 6 MV X‐ray beam. Depth doses at 2 mm depth (relative to dose at 10 cm depth) were lower by 6%, 7%, 11%, and 10% for the above field delivery techniques, respectively, compared to the open field. These differences are most influenced by differences in multileaf collimator (MLC) transmission contributing to the useful beam. An example IMRT field was also studied to assess variations due to delivery technique (static vs. dynamic) and intensity level. Buildup dose is weakly dependent on the multileaf delivery technique for efficient IMRT fields. PACS numbers: 87.53.‐j, 87.53.Dq PMID:15738914

Reducing radiation dose to the female breast during conventional and dedicated breast computed tomography

NASA Astrophysics Data System (ADS)

Rupcich, Franco John

The purpose of this study was to quantify the effectiveness of techniques intended to reduce dose to the breast during CT coronary angiography (CTCA) scans with respect to task-based image quality, and to evaluate the effectiveness of optimal energy weighting in improving contrast-to-noise ratio (CNR), and thus the potential for reducing breast dose, during energy-resolved dedicated breast CT. A database quantifying organ dose for several radiosensitive organs irradiated during CTCA, including the breast, was generated using Monte Carlo simulations. This database facilitates estimation of organ-specific dose deposited during CTCA protocols using arbitrary x-ray spectra or tube-current modulation schemes without the need to run Monte Carlo simulations. The database was used to estimate breast dose for simulated CT images acquired for a reference protocol and five protocols intended to reduce breast dose. For each protocol, the performance of two tasks (detection of signals with unknown locations) was compared over a range of breast dose levels using a task-based, signal-detectability metric: the estimator of the area under the exponential free-response relative operating characteristic curve, AFE. For large-diameter/medium-contrast signals, when maintaining equivalent AFE, the 80 kV partial, 80 kV, 120 kV partial, and 120 kV tube-current modulated protocols reduced breast dose by 85%, 81%, 18%, and 6%, respectively, while the shielded protocol increased breast dose by 68%. Results for the small-diameter/high-contrast signal followed similar trends, but with smaller magnitude of the percent changes in dose. The 80 kV protocols demonstrated the greatest reduction to breast dose, however, the subsequent increase in noise may be clinically unacceptable. Tube output for these protocols can be adjusted to achieve more desirable noise levels with lesser dose reduction. The improvement in CNR of optimally projection-based and image-based weighted images relative to photon

Low-dose caffeine physical dependence in humans.

PubMed

Griffiths, R R; Evans, S M; Heishman, S J; Preston, K L; Sannerud, C A; Wolf, B; Woodson, P P

1990-12-01

This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.

Analysis of dose-incidence relationships for marrow failure in different species, in terms of radiosensitivity of tissue-rescuing units

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendry, J.H.; Roberts, S.A.

1990-05-01

The analysis of 68 published sets of dose-incidence data for marrow failure in different species, using a double-log mortality function, indicates: (a) There is more heterogeneity, i.e. greater sums-of-squares per degree of freedom, within the data sets for mouse than for larger species (monkey, dog, sheep, goat, pig). (b) For mice the curves for acute doses are characterized by a D0 of about 100 cGy for tissue-rescuing units (or target cells), which are depleted at most to about 3 x 10(-4) at LD50. (c) Larger species are much less tolerant to target-cell depletion, the corresponding level being consistently in themore » range of 10(-2)-10(-3) at LD50. Also, the D0 is often lower (approximately 55 cGy), which is compatible in the dog with such a value for hemopoietic progenitor cells. (d) With larger species there is an unexpected reduction in heterogeneity when the dose rate is lower, which gives a D0 lower than expected and a higher extrapolate. It is concluded that the position and slope of the dose-incidence curves are compatible with interpretations based primarily on target-cell number and survival characteristics, modified by additional heterogeneity factors.« less

Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity.

PubMed

Wiczer, Tracy; Dotson, Emily; Tuten, Amy; Phillips, Gary; Maddocks, Kami

2016-06-01

High-dose methotrexate (doses ≥1 g/m(2)) is a key component of several chemotherapy regimens used to treat patients with leukemia or lymphoma. Despite appropriate precautions with hydration, urine alkalinization, and leucovorin, nephrotoxicity remains a risk which can lead to significant morbidity and mortality. Current reports of risk factors for nephrotoxicity focus on patients with nephrotoxicity with a lack of comparison to those without toxicity. This study aimed to describe the incidence of high-dose methotrexate-induced nephrotoxicity at our institution and determined risk factors for high-dose methotrexate-induced nephrotoxicity by examining characteristics of patients with and without nephrotoxicity. This was a retrospective, single-center, chart review. Adult patients with a diagnosis of leukemia or lymphoma who received high-dose methotrexate were included. Serum creatinine values were used to evaluate nephrotoxicity according to Common Terminology Criteria for Adverse Events criteria v4.03. Data related to the following proposed risk factors were collected: age, sex, body mass index, methotrexate dose, number of high-dose methotrexate exposures, leucovorin administration route, baseline renal function, albumin, hydration status, Clostridium difficile infection, urine pH, and concomitant interacting and nephrotoxic medications. The primary endpoint was evaluated with exact binomial methods and risk factors were identified using multivariable random-effects logistic regression. Final analyses included 140 patients with 432 high-dose methotrexate exposures. There were no differences in baseline demographical characteristics. Fifty-four patients (38.6%) experienced nephrotoxicity of any grade: 27.9% with grade 1, 5.7% with grade 2, 3.6% grade 3, 0% with grade 4, and 1.4% with grade 5 toxicity. More patients in the toxicity group received doses of methotrexate ≥3 g/m(2) (58.3% versus 57.2%, p < 0.001), had an albumin level <3 g/dL (31.9% versus

Dose-Dependent Effects of Statins for Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Regression Analysis.

PubMed

To, Minh-Son; Prakash, Shivesh; Poonnoose, Santosh I; Bihari, Shailesh

2018-05-01

The study uses meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DIND), and mortality in aneurysmal subarachnoid hemorrhage. Prospective, retrospective observational studies, and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo). Meta-regression using inverse variance weighting and robust variance estimation was performed to assess the effect of statin dose on transformed AR in a random effects model. Dose-dependence of predicted AR with 95% confidence interval (CI) was recovered by using Miller's Freeman-Tukey inverse. The database search and study selection criteria yielded 18 studies (2594 patients) for analysis. These included 12 RCTs, 4 retrospective observational studies, and 2 prospective observational studies. Twelve studies investigated simvastatin, whereas the remaining studies investigated atorvastatin, pravastatin, or pitavastatin, with simvastatin-equivalent doses ranging from 20 to 80 mg. Meta-regression revealed dose-dependent reductions in Freeman-Tukey-transformed AR of vasospasm (slope coefficient -0.00404, 95% CI -0.00720 to -0.00087; P = 0.0321), DIND (slope coefficient -0.00316, 95% CI -0.00586 to -0.00047; P = 0.0392), and mortality (slope coefficient -0.00345, 95% CI -0.00623 to -0.00067; P = 0.0352). The present meta-regression provides weak evidence for dose-dependent reductions in vasospasm, DIND and mortality associated with acute statin use after aneurysmal subarachnoid hemorrhage. However, the analysis was limited by substantial heterogeneity among individual studies. Greater dosing strategies are a potential consideration for future RCTs. Copyright © 2018 Elsevier Inc. All rights reserved.

A method to reduce patient's eye lens dose in neuro-interventional radiology procedures

NASA Astrophysics Data System (ADS)

Safari, M. J.; Wong, J. H. D.; Kadir, K. A. A.; Sani, F. M.; Ng, K. H.

2016-08-01

Complex and prolonged neuro-interventional radiology procedures using the biplane angiography system increase the patient's risk of radiation-induced cataract. Physical collimation is the most effective way of reducing the radiation dose to the patient's eye lens, but in instances where collimation is not possible, an attenuator may be useful in protecting the eyes. In this study, an eye lens protector was designed and fabricated to reduce the radiation dose to the patients' eye lens during neuro-interventional procedures. The eye protector was characterised before being tested on its effectiveness in a simulated aneurysm procedure on an anthropomorphic phantom. Effects on the automatic dose rate control (ADRC) and image quality are also evaluated. The eye protector reduced the radiation dose by up to 62.1% at the eye lens. The eye protector is faintly visible in the fluoroscopy images and increased the tube current by a maximum of 3.7%. It is completely invisible in the acquisition mode and does not interfere with the clinical procedure. The eye protector placed within the radiation field of view was able to reduce the radiation dose to the eye lens by direct radiation beam of the lateral x-ray tube with minimal effect on the ADRC system.

Intra-patient comparison of reduced-dose model-based iterative reconstruction with standard-dose adaptive statistical iterative reconstruction in the CT diagnosis and follow-up of urolithiasis.

PubMed

Tenant, Sean; Pang, Chun Lap; Dissanayake, Prageeth; Vardhanabhuti, Varut; Stuckey, Colin; Gutteridge, Catherine; Hyde, Christopher; Roobottom, Carl

2017-10-01

To evaluate the accuracy of reduced-dose CT scans reconstructed using a new generation of model-based iterative reconstruction (MBIR) in the imaging of urinary tract stone disease, compared with a standard-dose CT using 30% adaptive statistical iterative reconstruction. This single-institution prospective study recruited 125 patients presenting either with acute renal colic or for follow-up of known urinary tract stones. They underwent two immediately consecutive scans, one at standard dose settings and one at the lowest dose (highest noise index) the scanner would allow. The reduced-dose scans were reconstructed using both ASIR 30% and MBIR algorithms and reviewed independently by two radiologists. Objective and subjective image quality measures as well as diagnostic data were obtained. The reduced-dose MBIR scan was 100% concordant with the reference standard for the assessment of ureteric stones. It was extremely accurate at identifying calculi of 3 mm and above. The algorithm allowed a dose reduction of 58% without any loss of scan quality. A reduced-dose CT scan using MBIR is accurate in acute imaging for renal colic symptoms and for urolithiasis follow-up and allows a significant reduction in dose. • MBIR allows reduced CT dose with similar diagnostic accuracy • MBIR outperforms ASIR when used for the reconstruction of reduced-dose scans • MBIR can be used to accurately assess stones 3 mm and above.

Camphor-Crataegus berry extract combination dose-dependently reduces tilt induced fall in blood pressure in orthostatic hypotension.

PubMed

Belz, G G; Butzer, R; Gaus, W; Loew, D

2002-10-01

In order to test the efficacy of a combination of natural D-camphor and an extract of fresh crataegus berries (Korodin Herz-Kreislauf-Tropfen) on orthostatic hypotension, two similar, controlled, randomized studies were carried out in a balanced crossover design in 24 patients each with orthostatic dysregulation. The camphor-crataegus berry combination (CCC) was orally administered as a single regimen in 3 different dosages of 5 drops, 20 drops and 80 drops; a placebo with 20 drops of a 60% alcoholic solution served as control. Orthostatic hypotension was assessed with the tilt table test before and after medication. Source data of both studies were pooled and meta-analytically evaluated for all 48 patients. CCC drops decreased the orthostatic fall in blood pressure versus placebo, as almost uniformly established at all times by mean arterial pressure and diastolic blood pressure. Mean arterial pressure demonstrated the very fast onset of action by a clearly dose-dependent statistically significant effect even after 1-minute orthostasis. Increase of mean arterial pressure as compared to the orthostasis test before medication was on average 4.5 mmHg. CCC affected diastolic blood pressure after 1 minute of orthostasis in all dosages as compared to placebo. A statistically significant effect of the highest dose of 80 drops on diastolic blood pressure could be demonstrated after 1-, 3-, and 5-minute orthostasis. The hemodynamic findings of a stabilizing effect on arterial pressure in orthostasis corroborate the long-term medical experience with CCC and justify the indication orthostatic hypotension.

Dose-dependency of dexamethasone on the analgesic effect of interscalene block for arthroscopic shoulder surgery using ropivacaine 0.5%: A randomised controlled trial.

PubMed

Woo, Jae Hee; Kim, Youn Jin; Kim, Dong Yeon; Cho, Sooyoung

2015-09-01

Dexamethasone prolongs the duration of single-shot interscalene brachial plexus block (SISB). However, dose-dependency of dexamethasone as an adjuvant for SISB remains insufficiently understood. The objective of this study is to evaluate the effect of different doses of dexamethasone on the duration of SISB using ropivacaine 0.5%. A randomised, double-blind controlled trial. Single university tertiary care centre. One hundred and forty-four patients scheduled for elective arthroscopic shoulder surgery were allocated randomly to one of four groups. Patients received 12 ml of ropivacaine 0.5% in 0.9% saline (control group), or containing dexamethasone 2.5, 5.0 or 7.5 mg for SISB. The primary endpoint was the time to the first analgesic request. Pain scores and adverse effects were also assessed up to 48 h postoperatively. Inclusion of dexamethasone 2.5, 5.0 and 7.5 mg resulted in significant (P < 0.001) increases in time to the first analgesic request by factors of 1.6, 2.2 and 1.8, respectively. The percentages of patients not requiring analgesics in the first 48 h postoperatively with dexamethasone 0.0, 2.5, 5.0 and 7.5 mg were 3, 22, 39 and 33%, respectively (P < 0.001). There were no significant effects on pain scores or incidences of adverse effects. Dexamethasone demonstrated significant beneficial dose-dependent effects on duration to the first analgesic request, the number of patients not requiring analgesics and analgesic use in the first 48 h after SISB for arthroscopic shoulder surgery. There were no significant effects on pain scores or incidences of adverse effects. the trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001078.

[Application of Care Bundles to Reduce Medical-Device-Related Pressure Injury (MDRPI) Incidence in a Coronary Care Unit].

PubMed

Wang, Shu-Ling; Chuang, Pao-Yu; Su, Wan-Chuan

2018-06-01

Pressure injuries increase the cost of medical care and prolong hospitalization. The incidence of pressure injury at the target coronary care unit (CCU) from January to August 2016 was 1.1%, which was significantly higher than the 0.4% defined in the 2015 Taiwan Clinical Performance Indicators (TCPI) system. Medical device related pressure injury (MDRPI) accounted for 73.1% of the pressure injuries (incidence: 0.8%). The main causes of the high incidence of MDRPI were: (1) inadequate decompression dressing and restraint equipment, (2) incomplete implementation of prevention interventions in the CCU, (3) inadequate knowledge of MDRPI prevention among nurses, (4) deficient standards for preventing MDRPI, (5) ineffective MDRPI-related education, and (6) insufficient auditing frequencies. To reduce the incidence of MDRPI in the target CCU to 0.4% or less. Promote a seed-teacher system and a care bundle that "increased skin tolerance, decompression, medical dressing, change, and removal" using education, the adoption of PE-foam binding gloves, and regular audits. The incidence of MDRPI was reduced from 0.8% to 0.3% between October 2016 and April 2017 and further reduced to 0.1% during the maintenance phase between May and July 2017. The results indicate that the improvement program effectively reduced the incidence of MDRPI and thus increased the quality of nursing care. Therefore, the use of a care bundles should be promoted in intensive care units.

DOSE-RATE DEPENDENCE OF INSTANTANEOUS PHYSIOLOGICAL RADIATION EFFECTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hug, O.

Nastic movements in Mimosa pudica were induced by x radiation. Using short radiation impulses of 10 to 30 sec and doses up to 120 kr/min, the leaflets were observed to close and the stem to bend in the main joint during the first minute. After irradiation of parts of the leaflet, the reaction spreads along the physiological pathways as in any other stimulus. When the action potential is completed, slow depolarization continues and reaches a maximum, finally returning to the initial value in about two hr. The effect was found to be dose- dependent. It is hypothesized that either amore » direct physicochemical change of the cell membrane or a damage of substances which influence the function of the cell membrane is induced by the irradiation. (H.M.G.)« less

A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence

DTIC Science & Technology

2017-07-01

12 and decided the optimal strategy would be to modify the route of drug delivery from gavage to intravenous (IV). We tested several vehicles and...the most likely reason for these negative results was either our injury model is too severe causing the animals to be moribund or the mode of drug ...Page 1 AWARD NUMBER: W81XWH-16-1-0288 TITLE: A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence PRINCIPAL INVESTIGATOR: Gary

Fruit and vegetables consumption and incident hypertension: dose-response meta-analysis of prospective cohort studies.

PubMed

Wu, L; Sun, D; He, Y

2016-10-01

The role of dietary factors on chronic diseases seems essential in the potentially adverse or preventive effects. However, no evidence of dose-response meta-analysis of prospective cohort studies has verified the association between the intake of fruit and/or vegetables and the risk of developing hypertension. The PubMed and Embase were searched for prospective cohort studies. A generic inverse-variance method with random effects model was used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs). Generalized least squares trend estimation model was used to calculate the study-specific slopes for the dose-response analyses. Seven articles comprised nine cohorts involving 185 676 participants were assessed. The highest intake of fruit or vegetables separately, and total fruit and vegetables were inversely associated with the incident risk of hypertension compared with the lowest level, and the pooled RRs and 95% CIs were 0.87 (0.79, 0.95), 0.88 (0.79, 0.99) and 0.90 (0.84, 0.98), respectively. We also found an inverse dose-response relation between the risk of developing hypertension and fruit intake, and total fruit and vegetables consumption. The incident risk of hypertension was decreased by 1.9% for each serving per day of fruit consumption, and decreased by 1.2% for each serving per day of total fruit and vegetables consumption. Our results support the recommendation to increase the consumption of fruit and vegetables with respect to preventing the risk of developing hypertension. However, further large prospective studies and long-term high-quality randomized controlled trials are still needed to confirm the observed association.

The pharmacokinetics of pyridostigmine and 3-hydroxy-N-methylpyridinium in the rat: dose-dependent effects after portal vein administration.

PubMed Central

Barber, H E; Bourne, G R; Calvey, T N; Muir, K T

1975-01-01

1 The elimination kinectis of [14C]-pyridostigmine iodine and [14-C-methyl]-3-hydroxypyridinium bromide (3-OH NMP) have been studied in the rat. 2 For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver. 3 When doses of pyridostigmine 1.25 mumol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose-dependent process is involved in the urinary excretion of 3-OH NMP. 4 This conclusion was supported by studies involving the portal and systemic venous injection of 3-OH NMP at different dose levels. After 4 h, approximately85% of the lowest dose was eliminated unchanged in ug this period. The proportion of the dose eliminated in urine was not related to the route of administration. 5 After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug. PMID:173444

An Online Tutorial vs. Pre-Recorded Lecture for Reducing Incidents of Plagiarism

ERIC Educational Resources Information Center

Henslee, Amber M.; Goldsmith, Jacob; Stone, Nancy J.; Krueger, Merilee

2015-01-01

The current study compared an online academic integrity tutorial modified from Belter & du Pre (2009) to a pre-recorded online academic integrity lecture in reducing incidents of plagiarism among undergraduate students at a science and technology university. Participants were randomized to complete either the tutorial or the pre-recorded…

Approaches to reducing photon dose calculation errors near metal implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Jessie Y.; Followill, David S.; Howell, Reb

Purpose: Dose calculation errors near metal implants are caused by limitations of the dose calculation algorithm in modeling tissue/metal interface effects as well as density assignment errors caused by imaging artifacts. The purpose of this study was to investigate two strategies for reducing dose calculation errors near metal implants: implementation of metal-based energy deposition kernels in the convolution/superposition (C/S) dose calculation method and use of metal artifact reduction methods for computed tomography (CT) imaging. Methods: Both error reduction strategies were investigated using a simple geometric slab phantom with a rectangular metal insert (composed of titanium or Cerrobend), as well asmore » two anthropomorphic phantoms (one with spinal hardware and one with dental fillings), designed to mimic relevant clinical scenarios. To assess the dosimetric impact of metal kernels, the authors implemented titanium and silver kernels in a commercial collapsed cone C/S algorithm. To assess the impact of CT metal artifact reduction methods, the authors performed dose calculations using baseline imaging techniques (uncorrected 120 kVp imaging) and three commercial metal artifact reduction methods: Philips Healthcare’s O-MAR, GE Healthcare’s monochromatic gemstone spectral imaging (GSI) using dual-energy CT, and GSI with metal artifact reduction software (MARS) applied. For the simple geometric phantom, radiochromic film was used to measure dose upstream and downstream of metal inserts. For the anthropomorphic phantoms, ion chambers and radiochromic film were used to quantify the benefit of the error reduction strategies. Results: Metal kernels did not universally improve accuracy but rather resulted in better accuracy upstream of metal implants and decreased accuracy directly downstream. For the clinical cases (spinal hardware and dental fillings), metal kernels had very little impact on the dose calculation accuracy (<1.0%). Of the commercial CT

Tea Consumption Reduces the Incidence of Neurocognitive Disorders: Findings from the Singapore Longitudinal Aging Study.

PubMed

Feng, L; Chong, M-S; Lim, W-S; Gao, Q; Nyunt, M S; Lee, T-S; Collinson, S L; Tsoi, T; Kua, E-H; Ng, T-P

2016-01-01

To examine the relationships between tea consumption habits and incident neurocognitive disorders (NCD) and explore potential effect modification by gender and the apolipoprotein E (APOE) genotype. Population-based longitudinal study. The Singapore Longitudinal Aging Study (SLAS). 957 community-living Chinese elderly who were cognitively intact at baseline. We collected tea consumption information at baseline from 2003 to 2005 and ascertained incident cases of neurocognitive disorders (NCD) from 2006 to 2010. Odds ratio (OR) of association were calculated in logistic regression models that adjusted for potential confounders. A total of 72 incident NCD cases were identified from the cohort. Tea intake was associated with lower risk of incident NCD, independent of other risk factors. Reduced NCD risk was observed for both green tea (OR=0.43) and black/oolong tea (OR=0.53) and appeared to be influenced by the changing of tea consumption habit at follow-up. Using consistent non-tea consumers as the reference, only consistent tea consumers had reduced risk of NCD (OR=0.39). Stratified analyses indicated that tea consumption was associated with reduced risk of NCD among females (OR=0.32) and APOE ε4 carriers (OR=0.14) but not males and non APOE ε4 carriers. Regular tea consumption was associated with lower risk of neurocognitive disorders among Chinese elderly. Gender and genetic factors could possibly modulate this association.

Propranolol reduces reference-dependence in intertemporal choice

PubMed Central

Lempert, Karolina M.; Lackovic, Sandra F.; Tobe, Russell H.; Glimcher, Paul W.

2017-01-01

Abstract In intertemporal choices between immediate and delayed rewards, people tend to prefer immediate rewards, often even when the delayed reward is larger. This is known as temporal discounting. It has been proposed that this tendency emerges because immediate rewards are more emotionally arousing than delayed rewards. However, in our previous research, we found no evidence for this but instead found that arousal responses (indexed with pupil dilation) in intertemporal choice are context-dependent. Specifically, arousal tracks the subjective value of the more variable reward option in the paradigm, whether it is immediate or delayed. Nevertheless, people tend to choose the less variable option in the choice task. In other words, their choices are reference-dependent and depend on variance in their recent history of offers. This suggests that there may be a causal relationship between reference-dependent choice and arousal, which we investigate here by reducing arousal pharmacologically using propranolol. Here, we show that propranolol reduces reference-dependence, leading to choices that are less influenced by recent history and more internally consistent. PMID:28992268

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long

Comparison of composite prostate radiotherapy plan doses with dependent and independent boost phases.

PubMed

Narayanasamy, Ganesh; Avila, Gabrielle; Mavroidis, Panayiotis; Papanikolaou, Niko; Gutierrez, Alonso; Baacke, Diana; Shi, Zheng; Stathakis, Sotirios

2016-09-01

Prostate cases commonly consist of dual phase planning with a primary plan followed by a boost. Traditionally, the boost phase is planned independently from the primary plan with the risk of generating hot or cold spots in the composite plan. Alternatively, boost phase can be planned taking into account the primary dose. The aim of this study was to compare the composite plans from independently and dependently planned boosts using dosimetric and radiobiological metrics. Ten consecutive prostate patients previously treated at our institution were used to conduct this study on the Raystation™ 4.0 treatment planning system. For each patient, two composite plans were developed: a primary plan with an independently planned boost and a primary plan with a dependently planned boost phase. The primary plan was prescribed to 54 Gy in 30 fractions to the primary planning target volume (PTV1) which includes prostate and seminal vesicles, while the boost phases were prescribed to 24 Gy in 12 fractions to the boost planning target volume (PTV2) that targets only the prostate. PTV coverage, max dose, median dose, target conformity, dose homogeneity, dose to OARs, and probabilities of benefit, injury, and complication-free tumor control (P+) were compared. Statistical significance was tested using either a 2-tailed Student's t-test or Wilcoxon signed-rank test. Dosimetrically, the composite plan with dependent boost phase exhibited smaller hotspots, lower maximum dose to the target without any significant change to normal tissue dose. Radiobiologically, for all but one patient, the percent difference in the P+ values between the two methods was not significant. A large percent difference in P+ value could be attributed to an inferior primary plan. The benefits of considering the dose in primary plan while planning the boost is not significant unless a poor primary plan was achieved.

Dose-dependent changes of chemical attributes in irradiated sausages.

PubMed

Nam, K C; Lee, E J; Ahn, D U; Kwon, J H

2011-05-01

To determine the effects of irradiation on the chemical attributes of sausages, TBARS values, volatile compounds, gaseous compounds, and hydrocarbons of vacuum-packaged sausages were analyzed during 60 d of refrigerated storage. A sulfur-containing volatile (dimethyl disulfide), a gas (methane), and radiation-induced hydrocarbons (1-tetradecene, pentadecane, heptadecane, 8-heptadecene, eicosane, 1, 7-hexadecadiene, hexadecane) were mainly detected in irradiated sausages and the concentrations of these compounds were irradiation dose-dependent with R(2) = 0.9585, 0.9431, and 0.9091-0.9977, respectively. Especially methane and a few hydrocarbons were detected only in irradiated sausages and their amounts were dose-dependent. On the other hand, TBARS values, other off-odor volatiles (carbon disulfide, hexanal), and gases (carbon monoxide, carbon dioxide) were found both in irradiated and nonirradiated sausages. Therefore, it is suggested that radiation-induced hydrocarbons (1-tetradecene, pentadecane, heptadecane, 8-heptadecene, eicosane, 1, 7-hexadecadiene, hexadecane), dimethyl disulfide, and methane can be used as markers for irradiated sausages. Copyright © 2010 The American Meat Science Association. Published by Elsevier Ltd. All rights reserved.

Influence of beam incidence and irradiation parameters on stray neutron doses to healthy organs of pediatric patients treated for an intracranial tumor with passive scattering proton therapy.

PubMed

Bonfrate, A; Farah, J; De Marzi, L; Delacroix, S; Hérault, J; Sayah, R; Lee, C; Bolch, W E; Clairand, I

2016-04-01

In scattering proton therapy, the beam incidence, i.e. the patient's orientation with respect to the beam axis, can significantly influence stray neutron doses although it is almost not documented in the literature. MCNPX calculations were carried out to estimate stray neutron doses to 25 healthy organs of a 10-year-old female phantom treated for an intracranial tumor. Two beam incidences were considered in this article, namely a superior (SUP) field and a right lateral (RLAT) field. For both fields, a parametric study was performed varying proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and air gap size. Using a standard beam line configuration for a craniopharyngioma treatment, neutron absorbed doses per therapeutic dose of 63μGyGy(-1) and 149μGyGy(-1) were found at the heart for the SUP and the RLAT fields, respectively. This dose discrepancy was explained by the different patient's orientations leading to changes in the distance between organs and the final collimator where external neutrons are mainly produced. Moreover, investigations on neutron spectral fluence at the heart showed that the number of neutrons was 2.5times higher for the RLAT field compared against the SUP field. Finally, the influence of some irradiation parameters on neutron doses was found to be different according to the beam incidence. Beam incidence was thus found to induce large variations in stray neutron doses, proving that this parameter could be optimized to enhance the radiation protection of the patient. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Dose-dependent bioavailability indicators for curcumin and two of its novel derivatives.

PubMed

Abd el Aziz, Mohamed; El-Asmer, Mohamed; Rezq, Ameen; Al-Malki, Abdulrahman; Kumosani, Taha; Fouad, Hanan; Ahmed, Hanan; Taha, Fatma; Hassouna, Amira; Hafez, Hafez

2014-01-01

Novel water-soluble curcumin derivatives have been developed to overcome low in vivo bioavailability of curcumin. The aim of this work is to assess the potential utility of certain downstream targets as bioavailability indicators of systemic activity of pure curcumin and two novel water-soluble curcumin derivatives (NCD) by constructing dose-dependent response curves and to prove whether this novel curcumin derivatives retained, improved, or abolished biological activity of pure curcumin when applied in vivo. Pure curcumin (CUR), curcumin-carboxy derivative (NCD-1), and curcumin protein conjugate (NCD-2) were administered orally to rats at escalating doses: 37, 74, 148, and 296 μM/kg body weight, respectively. Plasma levels of GST activity, cavernous tissue levels of cGMP, and enzymatic activity of both HO-1 and GST were assessed one and half and 24 hours after oral administration of curcumin formulae. This study showed that there was a progressive elevation of cavernous tissue levels of cGMP and enzymatic activity of both HO-1 and GST in a dose-dependent manner that was maintained for 24 h with CUR, NCD-1, and NCD-2. Plasma GST activity was decreased by the lowest doses on the curve. The three dose-dependent bioavailability indicators as surrogates of curcumin and two of its novel derivatives are valid in the studied range of concentration and extended time. The novel curcumin derivatives still conserve with improvement the biological activity of natural curcumin when applied in vivo. © 2013 International Union of Biochemistry and Molecular Biology.

Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on fetal articular cartilage development.

PubMed

Chen, Ze; Zhao, Zhe; Li, Yunzepeng; Zhang, Xingyu; Li, Bin; Chen, Liaobin; Wang, Hui

2018-04-01

Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development. Pregnant mice (C57BL/6) received subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day (GD) 15 or once a day from GD 15 to 17, or received various doses of dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy (GD 15-17). Offspring's knee joints were harvested at birth for morphological analyses and detection of gene expression. Repeated PDE significantly suppressed fetal and articular cartilage development, which were characterized by decreased body weight and body length, coarse articular cartilage surfaces, and reduced gene and protein expression of Col2a1 and aggrecan. For those newborns treated with repeated PDE at different doses, the toxic effects on fetal and articular cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on fetal and articular cartilage development, compared with PDE during the late embryonic stage. Detection of gene expression showed that the TGFβ signaling pathway in the articular cartilage was down-regulated after PDE. Taken together, PDE induces fetal developmental toxicity and articular cartilage developmental toxicity in a course-, dose-, and stage-dependent manner. Copyright © 2018 Elsevier B

Acute modafinil exposure reduces daytime sleepiness in abstinent methamphetamine-dependent volunteers

PubMed Central

Mahoney, James J.; Jackson, Brian J.; Kalechstein, Ari D.; De La Garza, Richard; Chang, Lee C.; Newton, Thomas F.

2012-01-01

The purpose of this study was to evaluate the effects of acute, oral modafinil (200 mg) exposure on daytime sleepiness in methamphetamine (Meth)-dependent individuals. Eighteen Meth-dependent subjects were enrolled in a 7-d inpatient study and were administered placebo or modafinil on day 6 and the counter-condition on day 7 (randomized) of the protocol. Subjects completed several subjective daily assessments (such as the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Beck Depression Inventory and visual analogue scale) throughout the protocol as well as objective assessments on days 5–7, when the Multiple Sleep Latency Test was performed. The results of the current study suggest that short-term abstinence from Meth is associated with increased daytime sleepiness and that a single dose of 200 mg modafinil reduces daytime somnolence in this population. In addition, a positive correlation was found between subjective reporting of the likelihood of taking a nap and craving and desire for Meth, as well as the likelihood of using Meth and whether Meth would make the participant feel better. The results of this study should be considered when investigating candidate medications for Meth-dependence, especially in those individuals who attribute their Meth use to overcoming deficits resulting from sleep abnormalities. PMID:22214752

Acute modafinil exposure reduces daytime sleepiness in abstinent methamphetamine-dependent volunteers.

PubMed

Mahoney, James J; Jackson, Brian J; Kalechstein, Ari D; De La Garza, Richard; Chang, Lee C; Newton, Thomas F

2012-10-01

The purpose of this study was to evaluate the effects of acute, oral modafinil (200 mg) exposure on daytime sleepiness in methamphetamine (Meth)-dependent individuals. Eighteen Meth-dependent subjects were enrolled in a 7-d inpatient study and were administered placebo or modafinil on day 6 and the counter-condition on day 7 (randomized) of the protocol. Subjects completed several subjective daily assessments (such as the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Beck Depression Inventory and visual analogue scale) throughout the protocol as well as objective assessments on days 5-7, when the Multiple Sleep Latency Test was performed. The results of the current study suggest that short-term abstinence from Meth is associated with increased daytime sleepiness and that a single dose of 200 mg modafinil reduces daytime somnolence in this population. In addition, a positive correlation was found between subjective reporting of the likelihood of taking a nap and craving and desire for Meth, as well as the likelihood of using Meth and whether Meth would make the participant feel better. The results of this study should be considered when investigating candidate medications for Meth-dependence, especially in those individuals who attribute their Meth use to overcoming deficits resulting from sleep abnormalities.

Annexin A5 prevents post-interventional accelerated atherosclerosis development in a dose-dependent fashion in mice.

PubMed

Ewing, M M; Karper, J C; Sampietro, M L; de Vries, M R; Pettersson, K; Jukema, J W; Quax, P H A

2012-04-01

Activated cells in atherosclerotic lesions expose phosphatidylserine (PS) on their surface. Annexin A5 (AnxA5) binds to PS and is used for imaging atherosclerotic lesions. Recently, AnxA5 was shown to inhibit vascular inflammatory processes after vein grafting. Here, we report a therapeutic role for AnxA5 in post-interventional vascular remodeling in a mouse model mimicking percutaneous coronary intervention (PCI). Associations between the rs4833229 (OR = 1.29 (CI 95%), p(allelic) = 0.011) and rs6830321 (OR = 1.35 (CI 95%), p(allelic) = 0.003) SNPs in the AnxA5 gene and increased restenosis-risk in patients undergoing PCI were found in the GENDER study. To evaluate AnxA5 effects on post-interventional vascular remodeling and accelerated atherosclerosis development in vivo, hypercholesterolemic ApoE(-/-) mice underwent femoral arterial cuff placement to induce intimal thickening. Dose-dependent effects were investigated after 3 days (effects on inflammation and leukocyte recruitment) or 14 days (effects on remodeling) after cuff placement. Systemically administered AnxA5 in doses of 0.1, 0.3 and 1.0mg/kg compared to vehicle reduced early leukocyte and macrophage adherence up to 48.3% (p = 0.001) and diminished atherosclerosis development by 71.2% (p = 0.012) with a reduction in macrophage/foam cell presence. Moreover, it reduced the expression of the endoplasmic reticulum stress marker GRP78/BiP, indicating lower inflammatory activity of the cells present. AnxA5 SNPs could serve as markers for restenosis after PCI and AnxA5 therapeutically prevents vascular remodeling in a dose-dependent fashion, together indicating clinical potential for AnxA5 against post-interventional remodeling. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia.

PubMed

Knight, Richard J; Graviss, Edward A; Nguyen, Duc T; Kuten, Samantha A; Patel, Samir J; Gaber, Lillian; Gaber, A Osama

2018-04-19

We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prophylactic administration of a combined prebiotic and probiotic, or therapeutic administration of enrofloxacin, to reduce the incidence of bacterial chondronecrosis with osteomyelitis in broilers.

PubMed

Wideman, R F; Al-Rubaye, A; Kwon, Y M; Blankenship, J; Lester, H; Mitchell, K N; Pevzner, I Y; Lohrmann, T; Schleifer, J

2015-01-01

Bacteria entering the bloodstream via translocation from the gastrointestinal tract spread hematogenously and can trigger bacterial chondronecrosis with osteomyelitis (BCO) by infecting osteochondrotic microfractures in the epiphyseal-physeal cartilage of the proximal femora and tibiae. In experiment 1, broilers were fed control feed or the same feed containing BacPack 2X, which includes the prebiotic IMW50 (a mannan oligosaccharide beta-glucan yeast cell wall product) plus the probiotic Calsporin (Bacillus subtilis C-3102). Broilers reared on wire flooring consistently developed higher incidences of BCO than hatchmates reared on wood shavings litter (≥24 vs. ≤4%, respectively; P=0.001). Adding BacPack 2X to the feed on d 1 through 56 delayed the age of onset and reduced the cumulative incidence of BCO on wire flooring when compared with broilers fed the control feed (24.0 vs. 40.7%, respectively; P=0.003). In experiment 2, broilers reared on wire flooring received tap water on d 1 through 62 (control group) or therapeutic levels of the potent fluoroquinolone antimicrobial enrofloxacin in the water on d 35 through 54 (enrofloxacin group). During enrofloxacin administration, half as many birds developed BCO in the enrofloxacin group when compared with the control group (8.1 vs. 19.5%, respectively, on d 35 through 54; P=0.001), whereas both groups had similar BCO incidences subsequent to withdrawing enrofloxacin on d 55 through 62 (14.8 vs. 18.2% for the enrofloxacin vs. control groups; P=0.386). Cumulative lameness incidences for d 1 through 62 were higher for the control group than for the enrofloxacin group (39.0 vs. 25.8%, respectively; P=0.003). These results demonstrate that wire flooring imposes a rigorous challenge that leads to high incidences of BCO that can be difficult to suppress, even with therapeutic doses of enrofloxacin. Prophylactically adding BacPack 2X to the feed reduced the incidence of BCO lameness by a proportion similar to that achieved

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.

PubMed

Ozyigit, Filiz; Kucuk, Aysegul; Akcer, Sezer; Tosun, Murat; Kocak, Fatma Emel; Kocak, Cengiz; Kocak, Ahmet; Metineren, Hasan; Genc, Osman

2015-08-26

Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (p<0.01), levels of MDA, NO, and inducible nitric oxide synthase (iNOS) positive cells (p<0.01, p<0.05, respectively), and increased SOD, GPx, and CAT activities (p<0.001, p<0.01, p<0.05, respectively) compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (p<0.01, p<0.05, p<0.001) and MDA and NO levels (p<0.05, p<0.01) and decreased SOD, GPx, and CAT activities (p<0.05) compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

Methylphenidate Exerts Dose-Dependent Effects on Glutamate Receptors and Behaviors

PubMed Central

Cheng, Jia; Xiong, Zhe; Duffney, Lara J.; Wei, Jing; Liu, Aiyi; Liu, Sihang; Chen, Guo-Jun; Yan, Zhen

2014-01-01

Background Methylphenidate (MPH), a psychostimulant drug for the treatment of attention-deficit hyperactivity disorder (ADHD), produces the effects of increasing alertness and improving attention, while its misuse has been associated with an increased risk of aggression and psychosis. In this study, we sought to determine the molecular mechanism underlying the complex actions of MPH. Methods Adolescent (4-week-old) rats were given one injection of MPH at different doses. The impact of MPH on glutamatergic signaling in pyramidal neurons of prefrontal cortex (PFC) was measured. MPH-induced behavioral changes were also examined in parallel. Results We found that administration of low-dose (0.5 mg/kg) MPH selectively potentiated NMDAR-mediated excitatory synaptic currents (EPSCs) via adrenergic receptor activation, while the high-dose (10 mg/kg) MPH suppressed both NMDAR- and AMPAR-EPSCs. The dual effects of MPH on EPSCs were associated with bi-directional changes in the surface level of glutamate receptor subunits. Behavioral tests also indicated that low-dose MPH facilitated the PFC-mediated temporal order recognition memory (TORM) and attention, while animals injected with high-dose MPH exhibited significantly elevated locomotive activity. Inhibiting the function of SNAP-25, a key SNARE proteins involved in NMDAR exocytosis, blocked the increase of NMDAR-EPSC by low-dose MPH. In animals exposed to repeated stress, administration of low-dose MPH effectively restored NMDAR function and TORM via a mechanism dependent on SNAP-25. Conclusions Our results have provided a potential mechanism underlying the cognitive enhancing effects of low-dose MPH, as well as the psychosis-inducing effects of high-dose MPH. PMID:24832867

Thermal dose dependent optical property changes of ex vivo chicken breast tissues between 500 and 1100 nm.

PubMed

Adams, Matthew T; Wang, Qi; Cleveland, Robin O; Roy, Ronald A

2014-07-07

This study examines the effectiveness of the thermal dose model in accurately predicting thermally induced optical property changes of ex vivo chicken breast between 500-1100 nm. The absorption coefficient, μa, and the reduced scattering coefficient, μ's, of samples are measured as a function of thermal dose over the range 50 °C-70 °C. Additionally, the maximum observable changes in μa and μ's are measured as a function of temperature in the range 50 °C-90 °C. Results show that the standard thermal dose model used in the majority of high-intensity focused ultrasound (HIFU) treatments is insufficient for modeling optical property changes, but that the isodose constant may be modified in order to better predict thermally induced changes. Additionally, results are presented that show a temperature dependence on changes in the two coefficients, with an apparent threshold effect occurring between 65 °C-70 °C.

New image-processing and noise-reduction software reduces radiation dose during complex endovascular procedures.

PubMed

Kirkwood, Melissa L; Guild, Jeffrey B; Arbique, Gary M; Tsai, Shirling; Modrall, J Gregory; Anderson, Jon A; Rectenwald, John; Timaran, Carlos

2016-11-01

procedures with and without Clarity were not significantly different. For all cases, procedure radiation dose to the patient and the primary and assistant operators were significantly decreased in the Clarity group by 60% compared with the non-Clarity group. By procedure type, fluorography dose rates decreased from 44% for fenestrated endovascular repair and up to 70% with lower extremity interventions. Fluoroscopy dose rates also significantly decreased, from about 37% to 47%, depending on procedure type. The AlluraClarity system reduces the patient and primary operator's radiation dose by more than half during CEPs. This feature appears to be an effective tool in lowering the radiation dose while maintaining image quality. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident

PubMed Central

Tronko, Mykola D.; Hatch, Maureen; Bogdanova, Tetyana I.; Oliynik, Valery A.; Lubin, Jay H.; Zablotska, Lydia B.; Tereschenko, Valery P.; McConnell, Robert J.; Zamotaeva, Galina A.; O’Kane, Patrick; Bouville, Andre C.; Chaykovskaya, Ludmila V.; Greenebaum, Ellen; Paster, Ihor P.; Shpak, Victor M.; Ron, Elaine

2011-01-01

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case–control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose–response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models. Results: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose–response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43–6.34], and the EAR per 104 PY/Gy was 2.21 (95% CI, 0.04–5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. Conclusions: I-131–related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies. PMID:21406336

The dose of hydroxyethyl starch 6% 130/0.4 for fluid therapy and the incidence of acute kidney injury after cardiac surgery: A retrospective matched study

PubMed Central

Nkoy Ena, Lompoli; Van Dyck, Michel; Matta, Amine; Kahn, David; Thiry, Dominique; Grégoire, André; Watremez, Christine

2017-01-01

The safety of hydroxyethyl starches (HES) is still under debate. No studies have compared different dosing regimens of HES in cardiac surgery. We analyzed whether the incidence of Acute Kidney Injury (AKI) differed taking into account a weight-adjusted cumulative dose of HES 6% 130/0.4 for perioperative fluid therapy. This retrospective cohort study included all adult patients undergoing elective or emergency cardiac surgery with or without cardiopulmonary bypass. Exclusion criteria were patients on renal replacement therapy (RRT), cardiac trauma surgery, heart transplantation, patients with ventricular assist devices, subjects who required a surgical revision for bleeding and those whose medical records were incomplete. Primary endpoint was AKI following the creatinine based RIFLE classification. Secondary endpoints were 30-day mortality and RRT. Patients were divided into 2 groups whether they had received a cumulative HES dose of < 30 mL/kg (Low HES) or ≥ 30 mL/kg (High HES) during the intra- and postoperative period. A total of 1501 patients were analyzed with 983 patients in the Low HES and 518 subjects in the High HES group. 185 (18.8%) patients in the Low HES and 119 (23.0%) patients in the High HES group developed AKI (P = 0.06). In multivariable regression analysis the dose of HES administered per weight was not associated with AKI. After case-control matching 217 patients were analyzed in each group. AKI occurred in 39 (18.0%) patients in the Low HES and 50 (23.0%) patients in the High HES group (P = 0.19). In conditional regression analysis performed on the matched groups a lower weight-adjusted dose of HES was significantly associated with a reduced incidence of AKI [(Odds Ratio (95% CI) = 0.825 (0.727–0.936); P = 0.003]. In the absence of any safety study the cumulative dose of modern HES in cardiac surgery should be kept less than 30 mL/kg. PMID:29045467

Dose-dependent protective effect of BPC 157 on capsaicin-induced rhinitis in rats.

PubMed

Kalogjera, L; Ries, M; Baudoin, T; Ferencic, Z; Trotic, R; Pegan, B

1997-01-01

Protection of BPC 157 on capsaicin-induced rhinitis was studied in Wistar rats for its effect on mastocyte infiltration, degranulation and inflammatory cell infiltration. Animals were pretreated with 10 microg/kg, 10 ng/kg or 2 ml saline i.p. and capsaicin (0.05 ml/nostril of 1750 nmol/l sol.) was applied intranasally. They were then euthanized at 1, 3 and 12 h after capsaicin provocation. Nasal mucosa was analyzed and scored for mastocyte infiltration, degranulation and inflammatory cell infiltration. BPC 157 pretreatment significantly prevented mastocyte infiltration at 1 h. Polymorphonuclear leukocyte infiltration was significantly reduced in rats pretreated with 10 microg/kg BPC 157. A dose-dependent effect of BPC 157 pretreatment was demonstrated only for polymorphonuclear leukocyte infiltration at 12 h.

Dose Comparisons for a Site-specific Representative Person Using the Age-dependent Dose Coefficients in CAP88-PC Version 4.

PubMed

Stagich, Brooke H; Moore, Kelsey R; Newton, Joseph R; Dixon, Kenneth L; Jannik, G Timothy

2017-04-01

Most U.S. Department of Energy (DOE) facilities with radiological airborne releases use the U.S. Environmental Protection Agency's (EPA) environmental dosimetry code CAP88-PC to demonstrate compliance with regulations in 40CFR61, subpart H [National Emission Standards for Hazardous Air Pollutants: Radiological (NESHAP)]. In 2015, EPA released Version 4 of CAP88-PC, which included significant modifications that improved usability and age-dependent dose coefficients and usage factors for six age groups (infant, 1 y, 5 y, 10 y, 15 y, and adult). However, EPA has not yet provided specific guidance on how to use these age-dependent factors. For demonstrating compliance with DOE public dose regulations, the Savannah River Site (SRS) recently changed from using the maximally exposed individual (MEI) concept (adult male) to the representative person concept (age- and gender-averaged reference person). In this study, dose comparisons are provided between the MEI and a SRS-specific representative person using the age-specific dose coefficients and usage factors in CAP88-PC V.4. Dose comparisons also are provided for each of the six age groups using five radionuclides of interest at SRS (tritium oxide, Cs, Sr, Pu, and I). In general, the total effective dose increases about 11% for the representative person as compared to the current NESHAP MEI because of the inclusion of the more radiosensitive age groups.

The dose-effect relationship of baclofen in alcohol dependence: A 1-year cohort study.

PubMed

Pignon, Baptiste; Labreuche, Julien; Auffret, Marine; Gautier, Sophie; Deheul, Sylvie; Simioni, Nicolas; Cottencin, Olivier; Bordet, Régis; Duhamel, Alain; Rolland, Benjamin

2017-07-01

Our aim is to study the relationship between dose of baclofen and effectiveness in alcohol dependence. Two hundred two patients with alcohol dependence, who received baclofen treatment for drinking reduction, were followed up for 1 year. For each patient-month of treatment, the maximum daily dose of baclofen (DDB) and average weekly alcohol consumption (AWAC) were calculated. We defined a favorable drinking outcome as an AWAC under 200 g/w for at least 2 consecutive months. We divided the DDB of each patient-month into 3 categories (low dose: <90 mg/d, medium dose: 90-150 mg/d, and high dose: >150 mg/d) and investigated the relationship between reaching a favorable outcome and the concurrent DDB category in a time-varying Cox regression analysis. Hazard ratios (HRs) were adjusted based on age, sex, and initial AWAC. One hundred forty subjects were followed during at least 1 month. Of these patients, 58 (41%) had a favorable drinking outcome. In comparison to low dose, medium dose was associated with a decreased rate of favorable drinking outcome (HR = 0.42; 95% CI [0.20, 0.88]), whereas no difference was found with high dose (HR = 1.31; 95% CI [0.65, 2.64]). The relationship between dose of baclofen and favorable drinking outcome was U-shaped, that is, was increased at low and high doses compared to medium doses. Copyright © 2017 John Wiley & Sons, Ltd.

Pharmacologic Treatment Reduces Pressure Times Time Dose and Relative Duration of Intracranial Hypertension.

PubMed

Colton, Katharine; Yang, S; Hu, P F; Chen, H H; Bonds, B; Stansbury, L G; Scalea, T M; Stein, D M

2016-05-01

Past work has shown the importance of the "pressure times time dose" (PTD) of intracranial hypertension (intracranial pressure [ICP] > 19 mm Hg) in predicting outcome after severe traumatic brain injury. We used automated data collection to measure the effect of common medications on the duration and dose of intracranial hypertension. Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a single, large urban tertiary care facility, were retrospectively enrolled. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. The ICP data were collected automatically at 6-second intervals and averaged over 5 minutes. The percentage of time of intracranial hypertension (PTI) and PTD (mm Hg h) were calculated. A total of 98 patients with 664 treatment instances were identified. Baseline PTD ranged from 27 (before administration of propofol and fentanyl) to 150 mm Hg h (before mannitol). A "small" dose of hypertonic saline (HTS; ≤250 mL 3%) reduced PTD by 38% in the first hour and 37% in the second hour and reduced the time with ICP >19 by 38% and 39% after 1 and 2 hours, respectively. A "large" dose of HTS reduced PTD by 40% in the first hour and 63% in the second (PTI reduction of 36% and 50%, respectively). An increased dose of propofol or fentanyl infusion failed to decrease PTD but reduced PTI between 14% (propofol alone) and 30% (combined increase in propofol and fentanyl, after 2 hours). Barbiturates failed to decrease PTD but decreased PTI by 30% up to 2 hours after administration. All reductions reported are significantly changed from baseline, P < .05. Baseline PTD values before drug administration reflects varied patient criticality, with much higher values seen before the use of mannitol or barbiturates. Treatment with HTS reduced PTD and PTI burden significantly more than escalation of sedation or pain management, and this effect remained significant at 2 hours after administration. �

Reduced Radiation Dose with Model-based Iterative Reconstruction versus Standard Dose with Adaptive Statistical Iterative Reconstruction in Abdominal CT for Diagnosis of Acute Renal Colic.

PubMed

Fontarensky, Mikael; Alfidja, Agaïcha; Perignon, Renan; Schoenig, Arnaud; Perrier, Christophe; Mulliez, Aurélien; Guy, Laurent; Boyer, Louis

2015-07-01

To evaluate the accuracy of reduced-dose abdominal computed tomographic (CT) imaging by using a new generation model-based iterative reconstruction (MBIR) to diagnose acute renal colic compared with a standard-dose abdominal CT with 50% adaptive statistical iterative reconstruction (ASIR). This institutional review board-approved prospective study included 118 patients with symptoms of acute renal colic who underwent the following two successive CT examinations: standard-dose ASIR 50% and reduced-dose MBIR. Two radiologists independently reviewed both CT examinations for presence or absence of renal calculi, differential diagnoses, and associated abnormalities. The imaging findings, radiation dose estimates, and image quality of the two CT reconstruction methods were compared. Concordance was evaluated by κ coefficient, and descriptive statistics and t test were used for statistical analysis. Intraobserver correlation was 100% for the diagnosis of renal calculi (κ = 1). Renal calculus (τ = 98.7%; κ = 0.97) and obstructive upper urinary tract disease (τ = 98.16%; κ = 0.95) were detected, and differential or alternative diagnosis was performed (τ = 98.87% κ = 0.95). MBIR allowed a dose reduction of 84% versus standard-dose ASIR 50% (mean volume CT dose index, 1.7 mGy ± 0.8 [standard deviation] vs 10.9 mGy ± 4.6; mean size-specific dose estimate, 2.2 mGy ± 0.7 vs 13.7 mGy ± 3.9; P < .001) without a conspicuous deterioration in image quality (reduced-dose MBIR vs ASIR 50% mean scores, 3.83 ± 0.49 vs 3.92 ± 0.27, respectively; P = .32) or increase in noise (reduced-dose MBIR vs ASIR 50% mean, respectively, 18.36 HU ± 2.53 vs 17.40 HU ± 3.42). Its main drawback remains the long time required for reconstruction (mean, 40 minutes). A reduced-dose protocol with MBIR allowed a dose reduction of 84% without increasing noise and without an conspicuous deterioration in image quality in patients suspected of having renal colic.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-01-01

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

PubMed

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

Dose-dependent inhibition of gastric injury by hydrogen in alkaline electrolyzed drinking water.

PubMed

Xue, Jinling; Shang, Guodong; Tanaka, Yoshinori; Saihara, Yasuhiro; Hou, Lingyan; Velasquez, Natalia; Liu, Wenjun; Lu, Yun

2014-03-03

Hydrogen has been reported to relieve damage in many disease models, and is a potential additive in drinking water to provide protective effects for patients as several clinical studies revealed. However, the absence of a dose-response relationship in the application of hydrogen is puzzling. We attempted to identify the dose-response relationship of hydrogen in alkaline electrolyzed drinking water through the aspirin induced gastric injury model. In this study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed water at one atmosphere pressure. After 2 weeks of drinking, we detected the gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced gastric injury model. Hydrogen-dose dependent inhibition was observed in stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high correlation with inhibitory effects showed by erosion area, MPO activity and MDA content in the stomach. Gastric histology also demonstrated the inhibition of damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not significant inhibitory response compared with pH 8.5. Hydrogen is effective in relieving the gastric injury induced by aspirin-HCl, and the inhibitory effect is dose-dependent. The reason behind this may be that hydrogen-rich water directly interacted with the target tissue, while the hydrogen concentration in blood was buffered by liver glycogen, evoking a suppressed dose-response effect. Drinking hydrogen-rich water may protect healthy individuals from gastric damage caused by oxidative stress.

Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.

PubMed

Gong, Enhao; Pauly, John M; Wintermark, Max; Zaharchuk, Greg

2018-02-13

There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P < 0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly

Improved speed and stability of ST-segment recovery with reduced-dose tenecteplase and eptifibatide compared with full-dose tenecteplase for acute ST-segment elevation myocardial infarction.

PubMed

Roe, Matthew T; Green, Cynthia L; Giugliano, Robert P; Gibson, C Michael; Baran, Kenneth; Greenberg, Mark; Palmeri, Sebastian T; Crater, Suzanne; Trollinger, Kathleen; Hannan, Karen; Harrington, Robert A; Krucoff, Mitchell W

2004-02-18

This sub-study of the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial evaluated of the impact of combination reperfusion therapy with reduced-dose tenecteplase plus eptifibatide on continuous ST-segment recovery and angiographic results. Combination therapy with reduced-dose fibrinolytics and glycoprotein IIb/IIIa inhibitors for ST-segment elevation myocardial infarction improves biomarkers of reperfusion success but has not reduced mortality when compared with full-dose fibrinolytics. We evaluated 140 patients enrolled in the INTEGRITI trial with 24-h continuous 12-lead ST-segment monitoring and angiography at 60 min. The dose-combination regimen of 50% of standard-dose tenecteplase (0.27 microg/kg) plus high-dose eptifibatide (2 boluses of 180 microg/kg separated by 10 min, 2.0 microg/kg/min infusion) was compared with full-dose tenecteplase (0.53 microg/kg). The dose-confirmation regimen of reduced-dose tenecteplase plus high-dose eptifibatide was associated with a faster median time to stable ST-segment recovery (55 vs. 98 min, p = 0.06), improved stable ST-segment recovery by 2 h (89.6% vs. 67.7%, p = 0.02), and less recurrent ischemia (34.0% vs. 57.1%, p = 0.05) when compared with full-dose tenecteplase. Continuously updated ST-segment recovery analyses demonstrated a modest trend toward greater ST-segment recovery at 30 min (57.7% vs. 40.6%, p = 0.13) and 60 min (82.7% vs. 65.6%, p = 0.08) with this regimen. These findings correlated with improved angiographic results at 60 min. Combination therapy with reduced-dose tenecteplase and eptifibatide leads to faster, more stable ST-segment recovery and improved angiographic flow patterns, compared with full-dose tenecteplase. These findings question the relationship between biomarkers of reperfusion success and clinical outcomes.

Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis.

PubMed

Osterman, Mark T; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D

2014-11-01

Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized controlled trial to investigate whether increasing doses of mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. We screened 119 patients with UC in remission on the basis of Simple Clinical Colitis Activity Index scores, FC >50 μg/g, and intake of no more than 3 g/day mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n = 26) or a group that increased its dose by 2.4 g/day for 6 weeks (n = 26). The primary outcome was continued remission with FC <50 μg/g. Secondary outcomes were continued remission with FC <100 μg/g or <200 μg/g (among patients with pre-randomization values above these levels). The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P = .0496). More patients in the dose escalation group reduced FC to below 100 μg/g (P = .04) and 200 μg/g (P = .005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 μg/g compared with those with FC <200 μg/g (P = .01). Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov number: NCT00652145. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Mesalamine Dose Escalation Reduces Fecal Calprotectin In Patients With Quiescent Ulcerative Colitis

PubMed Central

Osterman, Mark T.; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D.

2014-01-01

Background & Aims Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized, controlled trial to investigate whether increasing doses mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. Methods We screened 119 patients with UC in remission, based on Simple Clinical Colitis Activity Index scores, FC >50 mcg/g, and intake of no more than 3g/day of mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n=26) or a group that increased its dose by 2.4 g/day for 6 weeks (n=26). The primary outcome was continued remission with FC<50 mcg/g. Secondary outcomes were continued remission with FC<100 mcg/g or <200 mcg/g (among patients with pre-randomization values above these levels). Results The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P=.0496). More patients in the dose escalation group reduced FC to below 100 mcg/g (P=.04) and 200 mcg/g (P=.005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 mcg/g compared to those with FC <200 mcg/g (P=.01). Conclusion Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov: NCT00652145 PMID:24793028

Time-dependent scattering of incident light of various wavelengths in ferrofluids under external magnetic field

NASA Astrophysics Data System (ADS)

Jin, Jingyu; Song, Dongxing; Geng, Jiafeng; Jing, Dengwei

2018-02-01

Ferrofluids can exhibit the anisotropic thermodynamic properties under magnetic fields. The dynamic optical properties of ferrofluids in the presence of magnetic fields are of particular interest due to their potential application as various optical devices. Although time-dependent light scattering by ferrofluids have been extensively studied, the effect of wavelength of incident light have been rarely considered. Here, for the first time, we investigated both the time- and wavelength-dependent light scattering in water based ferrofluids containing Fe3O4 nanoparticles under an external magnetic field. The field-induced response behavior of the prepared ferrofluid samples was determined and verified first by thermal conductivity measurement and numerical simulation. Double-beam UV-Vis spectrophotometer was employed to record the temporal evolution of transmitted intensity of incident light of various wavelengths passing through the ferrofluid sample and propagating parallel to the applied field. As expected, the light intensity decreases to a certain value right after the field is turned on due to the thermal fluctuation induced disorder inside the flexible particle chains. Then the light intensity further decreases with time until the appearance of a minimum at time τ0 followed by an inversed increase before finally reaches equilibrium at a particular time. More importantly, the characteristic inversion time τ0 was found to follow a power law increase with the wavelength of incident light (τ0 ∼ λα, where α = 2.07). A quantitative explanation for the wavelength dependence of characteristic time was proposed based on the finite-difference time-domain (FDTD) method. The simulation results are in good agreement with our experimental observations. The time-dependent light scattering in ferrofluids under different incident wavelengths was rationalized by considering both the coarsening process of the particle chains and the occurrence of resonance within the

Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells

PubMed Central

Ming, Ming; Sinnett-Smith, James; Wang, Jia; Soares, Heloisa P.; Young, Steven H.; Eibl, Guido; Rozengurt, Enrique

2014-01-01

Natural products represent a rich reservoir of potential small chemical molecules exhibiting anti-proliferative and chemopreventive properties. Here, we show that treatment of pancreatic ductal adenocarcinoma (PDAC) cells (PANC-1, MiaPaCa-2) with the isoquinoline alkaloid berberine (0.3–6 µM) inhibited DNA synthesis and proliferation of these cells and delay the progression of their cell cycle in G1. Berberine treatment also reduced (by 70%) the growth of MiaPaCa-2 cell growth when implanted into the flanks of nu/nu mice. Mechanistic studies revealed that berberine decreased mitochondrial membrane potential and intracellular ATP levels and induced potent AMPK activation, as shown by phosphorylation of AMPK α subunit at Thr-172 and acetyl-CoA carboxylase (ACC) at Ser79. Furthermore, berberine dose-dependently inhibited mTORC1 (phosphorylation of S6K at Thr389 and S6 at Ser240/244) and ERK activation in PDAC cells stimulated by insulin and neurotensin or fetal bovine serum. Knockdown of α1 and α2 catalytic subunit expression of AMPK reversed the inhibitory effect produced by treatment with low concentrations of berberine on mTORC1, ERK and DNA synthesis in PDAC cells. However, at higher concentrations, berberine inhibited mitogenic signaling (mTORC1 and ERK) and DNA synthesis through an AMPK-independent mechanism. Similar results were obtained with metformin used at doses that induced either modest or pronounced reductions in intracellular ATP levels, which were virtually identical to the decreases in ATP levels obtained in response to berberine. We propose that berberine and metformin inhibit mitogenic signaling in PDAC cells through dose-dependent AMPK-dependent and independent pathways. PMID:25493642

The modified unified interaction model: incorporation of dose-dependent localised recombination.

PubMed

Lavon, A; Eliyahu, I; Oster, L; Horowitz, Y S

2015-02-01

The unified interaction model (UNIM) was developed to simulate thermoluminescence (TL) linear/supralinear dose-response and the dependence of the supralinearity on ionisation density, i.e. particle type and energy. Before the development of the UNIM, this behaviour had eluded all types of TL modelling including conduction band/valence band (CB/VB) kinetic models. The dependence of the supralinearity on photon energy was explained in the UNIM as due to the increasing role of geminate (localised recombination) with decreasing photon/electron energy. Recently, the Ben Gurion University group has incorporated the concept of trapping centre/luminescent centre (TC/LC) spatially correlated complexes and localised/delocalised recombination into the CB/VB kinetic modelling of the LiF:Mg,Ti system. Track structure considerations are used to describe the relative population of the TC/LC complexes by an electron-hole or by an electron-only as a function of both photon/electron energy and dose. The latter dependence was not included in the original UNIM formulation, a significant over-simplification that is herein corrected. The modified version, the M-UNIM, is then applied to the simulation of the linear/supralinear dose-response characteristics of composite peak 5 in the TL glow curve of LiF:Mg,Ti at two representative average photon/electron energies of 500 and 8 keV. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

PubMed

Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

1999-03-17

Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence.

PubMed

White, Jason; Bell, James; Saunders, John B; Williamson, Paul; Makowska, Maria; Farquharson, Aaron; Beebe, Katherine L

2009-07-01

Buprenorphine, a mu-opioid receptor partial agonist, has been shown to be safe and effective for treatment of opioid dependence. A novel implantable formulation of buprenorphine (Probuphine), using a polymer matrix sustained-release technology, has been developed to offer treatment for opioid dependence while minimizing risks of patient noncompliance and illicit diversion. The goal of the current study was to conduct an initial, open-label, evaluation of the safety, pharmacokinetics, and efficacy of two doses of Probuphine in subjects with opioid dependence maintained on sublingual buprenorphine. Two doses of Probuphine were evaluated in 12 heroin-dependent volunteers switched from daily sublingual buprenorphine dosing to either two or four Probuphine implants based upon their buprenorphine daily maintenance dose of 8 mg or 16 mg respectively, and were monitored for 6 months. Probuphine implants provided continuous steady state delivery of buprenorphine until their removal at 6 months. Withdrawal symptoms and craving remained low throughout the 6 months. For the 12 subjects, an average of 59% of urines were opioid-negative across the 6 month treatment period. Injection site reactions were present in half of patients, but none were serious. No safety concerns were evident. These results suggest that Probuphine implants offer significant promise for enhancing delivery of effective opioid substitution treatment while minimizing risk for abuse of medication.

Fitting the Incidence Data from the City of Campinas, Brazil, Based on Dengue Transmission Modellings Considering Time-Dependent Entomological Parameters

PubMed Central

Yang, Hyun Mo; Boldrini, José Luiz; Fassoni, Artur César; Freitas, Luiz Fernando Souza; Gomez, Miller Ceron; de Lima, Karla Katerine Barboza; Andrade, Valmir Roberto; Freitas, André Ricardo Ribas

2016-01-01

Four time-dependent dengue transmission models are considered in order to fit the incidence data from the City of Campinas, Brazil, recorded from October 1st 1995 to September 30th 2012. The entomological parameters are allowed to depend on temperature and precipitation, while the carrying capacity and the hatching of eggs depend only on precipitation. The whole period of incidence of dengue is split into four periods, due to the fact that the model is formulated considering the circulation of only one serotype. Dengue transmission parameters from human to mosquito and mosquito to human are fitted for each one of the periods. The time varying partial and overall effective reproduction numbers are obtained to explain the incidence of dengue provided by the models. PMID:27010654

Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis.

PubMed

Zhao, R; Wang, H; Wang, X; Feng, F

2017-03-01

This meta-analysis synthesized current evidence from 10 trials to evaluate the association between steroid therapy and osteonecrosis incidence in patients with severe acute respiratory syndrome (SARS). Our results suggest that higher cumulative doses and longer treatment durations of steroids are more likely to lead to the development of osteonecrosis in SARS patients. The link between steroid treatment and the risk of osteonecrosis in SARS patients remains unknown. The present meta-analysis aimed to examine the dose-response association between steroid therapy and osteonecrosis incidence in SARS patients. The sex differences in the development of steroid-induced osteonecrosis were also examined. We searched PubMed, Web of Science, CNKI, and WANFANG for studies that involved steroid therapy and reported osteonecrosis data in SARS patients. Two authors independently extracted the data from the individual studies, and the rate ratio (RR) of osteonecrosis was calculated using random-effect models. Ten studies with 1137 recovered SARS patients met the inclusion criteria. Close relationships between osteonecrosis incidence and both the cumulative dose and treatment duration of steroids were observed. The summary RR of osteonecrosis was 1.57 (95% confidence interval (CI) 1.30-1.89, p < 0.001) per 5.0 g increase in the cumulative dose of steroids and was 1.29 (95% CI 1.09-1.53, p = 0.003) for each 10-day increment of increase in treatment duration. The relationship was non-linear (p non-linear  < 0.001 and p non-linear  = 0.022). There were no significant differences in the risk of developing osteonecrosis between the male and female patients (RR 0.01, 95% CI -0.03 to 0.06, p = 0.582). SARS patients who received higher cumulative doses and longer treatment durations of steroids were more likely to develop osteonecrosis, and there were no sex differences in this dose-dependent side effect. Our findings suggest that it is important to reduce osteonecrosis risk by

Prevalence of bisphosphonate-related osteonecrosis of the jaw-like lesions is increased in a chemotherapeutic dose-dependent manner in mice.

PubMed

Kuroshima, Shinichiro; Sasaki, Muneteru; Nakajima, Kazunori; Tamaki, Saki; Hayano, Hiroki; Sawase, Takashi

2018-07-01

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) worsens oral health-related quality of life. Most BRONJ occurs in multiple myeloma or metastatic breast cancer patients treated with bisphosphonate/chemotherapeutic combination therapies. Cyclophosphamide (CY), an alkylating chemotherapeutic drug, is used to treat multiple myeloma, although its use has been recently reduced. The aim of this study was to clarify the effects of CY dose on tooth extraction socket healing when CY is used with or without bisphosphonate in mice. Low-dose CY (50 mg/kg; CY-L), moderate-dose CY (100 mg/kg; CY-M), high-dose CY (150 mg/kg; CY-H), and bisphosphonate [Zometa (ZA): 0.05 mg/kg] were administered for 7 weeks. Each dose of CY and ZA in combination was also administered for 7 weeks. Both maxillary first molars were extracted at 3 weeks after the initiation of drug administration. Euthanasia was performed at 4 weeks post-extraction. Gross wound healing, microcomputed tomography analysis, histomorphometry, and immunohistochemistry were used to quantitatively evaluate osseous and soft tissue wound healing of tooth extraction sockets. ZA monotherapy induced no BRONJ-like lesions in mice. CY monotherapy rarely induced open wounds, though delayed osseous wound healing occurred in a CY dose-dependent manner. In contrast, CY/ZA combination therapy prevalently induced BRONJ-like lesions with compromised osseous and soft tissue healing in a CY dose-dependent manner. Interestingly, anti-angiogenesis was noted regardless of CY dose and ZA administration, even though only CY-M/ZA and CY-H/ZA combination therapies induced BRONJ-like lesions. Our findings suggest that high-dose CY may be associated with the development of BRONJ following tooth extraction only when CY is used together with ZA. In addition to anti-angiogenesis, other factors may contribute to the pathoetiology of BRONJ. Copyright © 2018 Elsevier Inc. All rights reserved.

Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for Men with Type II Diabetes.

PubMed

Wang, Chen-Pin; Lehman, Donna M; Lam, Yui-Wing F; Kuhn, John G; Mahalingam, Devalingam; Weitman, Steven; Lorenzo, Carlos; Downs, John R; Stuart, Elizabeth A; Hernandez, Javier; Thompson, Ian M; Ramirez, Amelie G

2016-10-01

Racial/ethnic disparity in prostate cancer is under studied in men with diabetes who are at a higher risk of aggressive prostate cancer. This study assessed the race/ethnic disparity in prostate cancer incidence for men with type II diabetes (T2D) and whether the impact of metformin on prostate cancer incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership was utilized to compute the HR of prostate cancer incidence associated with race/ethnicity and compare HR associated with metformin use between race/ethnic groups. Mean follow-up was 6.4 ± 2.8 years; 7% were Hispanics; 17% were African Americans (AA); mean age was 67.8 ± 9.8 years; 5.2% developed prostate cancer; and 38.9% used metformin. Among these diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and AA than in non-Hispanic White (NHW). Use of metformin alone or metformin + statins was associated with a greater prostate cancer incidence reduction in Hispanics compared with NHW, but not between AA and NHW. Use of metformin + finasteride was associated with a greater prostate cancer incidence reduction in Hispanics and AA compared with NHW. Our results suggested that metformin treatment could be a potential strategy to reduce prostate cancer incidence in the minority populations who are at high risk for fatal prostate cancer. It will be important to further examine the pleiotropic effects of metformin in multi-race/ethnic prospective studies to better inform clinical management and potentially reduce racial/ethnic disparity in prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779-87. ©2016 AACR. ©2016 American Association for Cancer Research.

Retention of ion-implanted-xenon in olivine: Dependence on implantation dose

NASA Technical Reports Server (NTRS)

Melcher, C. L.; Tombrello, T. A.; Burnett, D. S.

1982-01-01

The diffusion of Xe in olivine, a major mineral in both meteorites and lunar samples, was studied. Xe ions were implanted at 200 keV into single-crystal synthetic-forsterite targets and the depth profiles were measured by alpha particle backscattering before and after annealing for 1 hour at temperatures up to 1500 C. The fraction of implanted Xe retained following annealing was strongly dependent on the implantation dose. Maximum retention of 100% occurred for an implantion dose of 3 x 10 to the 15th power Xe ions/sq cm. Retention was less at lower doses, with (approximately more than or = 50% loss at one hundred trillion Xe ions/sq cm. Taking the diffusion coefficient at this dose as a lower limit, the minimum activation energy necessary for Xe retention in a 10 micrometer layer for ten million years was calculated as a function of metamorphic temperature.

Dose- and time-dependent activation of rat alveolar macrophages by glucocorticoids

PubMed Central

BROUG-HOLUB, E; KRAAL, G

1996-01-01

Effects of glucocorticoids on immune functions are generally thought to be suppressive and anti-inflammatory. However, most reports dealing with this issue describe effects of long-term treatment with high doses of glucocorticoids on immune functions. In the present study we have investigated both dose and timing effects of exposure of alveolar macrophages with dexamethasone on lipopolysaccharide (LPS)-induced IL-1β and nitric oxide secretion. For this purpose, alveolar macrophages were preincubated with various doses of dexamethasone during varying intervals, followed by stimulation of the cells with endotoxin, either in the absence or presence of dexamethasone. Subsequently, the effects of this treatment on IL-1β and nitric oxide secretion were measured. It was shown that both short-term incubation of alveolar macrophages with high doses of dexamethasone and long-term incubation with low doses of dexamethasone lead to enhanced nitric oxide and enhanced IL-1β secretion upon subsequent stimulation of the cells with LPS. In contrast, long-term incubation of alveolar macrophages with high-dose dexamethasone leads to decreased IL-1β and nitric oxide secretion upon subsequent stimulation. Thus, it is concluded that the effects of dexamethasone on rat alveolar macrophages are both time- and dose-dependent. It is therefore argued that effects of glucocorticoids on immune functions are not a priori suppressive, but that both dose and timing effects should be taken into account. PMID:8625529

Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis.

PubMed

Vasanthamohan, L; Boonyawat, K; Chai-Adisaksopha, C; Crowther, M

2018-05-17

Essentials In venous thromboembolism (VTE), benefits of extended treatment are balanced by bleeding risks. This is a meta-analysis of reduced-dose direct oral anticoagulants (DOACs) in extended treatment. Reduced-dose DOACs are as effective as full anticoagulation with bleeding risks similar to placebo. Reduced-dose DOACs are an attractive option for patients in the extended phase of VTE treatment. Background Extended-duration anticoagulation is beneficial for preventing recurrent venous thromboembolism (VTE). Reduced-dose direct oral anticoagulants (DOACs) may be preferable if they preserve efficacy and cause less bleeding. We conducted a systematic review and meta-analysis of trials comparing reduced-dose DOACs with full-dose DOACs and aspirin or placebo in the extended phase of VTE treatment. Methods A literature search was conducted by use of the MEDLINE, EMBASE and CINAHL databases, supplemented by hand-searching. One thousand three hundred and ninety-nine titles were screened, with data from accepted studies being extracted by two independent reviewers. Major outcomes analyzed included recurrent VTE and major and clinically relevant non-major bleeding events, presented as risk ratios (RRs) and 95% confidence intervals (CI). Results Two trials met the prespecified inclusion criteria. Data from 5847 patients were analyzed for efficacy outcomes, and from 5842 patients for safety outcomes. Reduced-dose DOACs were as effective as full-dose treatment in preventing recurrent VTE at 1 year (RR 1.12 [95% CI 0.67-1.87]), and more effective than aspirin or placebo (RR 0.26 [95% CI 0.14-0.46]). Rates of major or clinically relevant non-major bleeding events were similar between patients receiving reduced-dose DOACs and and those receiving aspirin or placebo (RR 1.19 [95% CI 0.81-1.77]). There was a trend towards less bleeding when reduced-dose and full-dose DOACs were compared (RR 0.74 [95% CI 0.52-1.05]). Conclusions Extended-duration treatment of VTE with

Spectrum of complex DNA damages depends on the incident radiation

NASA Astrophysics Data System (ADS)

Hada, M.; Sutherland, B.

Ionizing radiation induces clustered DNA damages in DNA-two or more abasic sites oxidized bases and strand breaks on opposite DNA strands within a few helical turns Clustered damages are considered to be difficult to repair and therefore potentially lethal and mutagenic damages Although induction of single strand breaks and isolated lesions has been studied extensively little is known of factors affecting induction of clusters other than double strand breaks DSB The aim of the present study was to determine whether the type of incident radiation could affect yield or spectra of specific clusters Genomic T7 DNA a simple 40 kbp linear blunt-ended molecule was irradiated in non-scavenging buffer conditions with Fe 970 MeV n Ti 980 MeV n C 293 MeV n Si 586 MeV n ions or protons 1 GeV n at the NASA Space Radiation Laboratory or with 100 kVp X-rays Irradiated DNA was treated with homogeneous Fpg or Nfo proteins or without enzyme treatment for DSB quantitation then electrophoresed in neutral agarose gels DSB Fpg-OxyPurine clusters and Nfo-Abasic clusters were quantified by number average length analysis The results show that the yields of all these complex damages depend on the incident radiation Although LETs are similar protons induced twice as many DSBs than did X-rays Further the spectrum of damage also depends on the radiation The yield damage Mbp Gy of all damages decreased with increasing linear energy transfer LET of the radiation The relative frequencies of DSBs to Abasic- and OxyBase clusters were higher

Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion.

PubMed

Bray, M J; Vick, T M; Shah, N; Anderson, S M; Rice, L W; Iranmanesh, A; Evans, W S; Veldhuis, J D

2001-07-01

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory

Dosing-time-dependent variation in biliary excretion of flomoxef in rats.

PubMed

Hishikawa, Shuji; Sugimoto, Koh-ichi; Kobayashi, Eiji; Kumagai, Yuji; Fujimura, Akio

2003-05-01

We previously reported that the biliary excretion of flomoxef, an oxacephem antibiotic, was greater after dosing at 21:00 than at 09:00 h in diurnally active human subjects. The present study was undertaken to examine whether the biliary excretion of flomoxef is also dependent on its dosing time in rats. Adult male Wistar rats were housed under light on at 07:00 h and off at 19:00 h. Bile fluid was completely drained through a polyethylene catheter from conscious animals. Flomoxef (20 mg/kg) was injected into the tail vein at 09:00 or 21:00 h by a cross-over design, and drained bile fluid was collected for 8 h after each dosing. The maximum concentration of biliary flomoxef was significantly greater and its total excretion tended to be greater after dosing at 09:00 than 21:00 h. These results suggest the biliary excretion of flomoxef is enhanced after dosing at the beginning of the rest period in rats, as it is in humans.

Interventions to Reduce Myopia Progression in Children.

PubMed

Tay, Su Ann; Farzavandi, Sonal; Tan, Donald

2017-03-01

Efforts to reduce the progression of myopia in childhood are on the rise, due to an increasing incidence of myopia worldwide and its associated sight-threatening complications. Interventions are aimed at reducing myopia in childhood and include environmental considerations, spectacles, contact lenses, and pharmacological agents. We reviewed recent literature with interventions aimed at reducing myopia progression in children and found that a number of interventions were significant in reducing the progression of myopia. Of these interventions, atropine showed the largest dose-related effect on myopia progression control. Although higher doses are associated with side effects of pupil dilatation, loss of accommodation, near vision blur, and rebound phenomenon, low-dose atropine has also been shown to provide effective myopia control with minimal side effects and rebound. To a lesser degree, bifocal soft contact lenses have also been shown to be effective in reducing the progression of myopia, though compliance is an issue. Similarly, orthokeratology lenses have also been shown to be effective in reducing axial length elongation and myopia progression, though long-term data on its rebound effects are unavailable.

Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening

PubMed Central

Walter, Joan E.; Oudkerk, Matthijs

2017-01-01

Currently, lung cancer screening by low-dose computed tomography (LDCT) is widely recommended for high-risk individuals by US guidelines, but there still is an ongoing debate concerning respective recommendations for European countries. Nevertheless, the available data regarding pulmonary nodules released by lung cancer screening studies could improve future screening guidelines, as well as the clinical practice of incidentally detected pulmonary nodules on routine CT scans. Most lung cancer screening trials present results for baseline and incidence screening rounds separately, clustering pulmonary nodules initially found at baseline screening and newly detected pulmonary nodules after baseline screening together. This approach does not appreciate possible differences among pulmonary nodules detected at baseline and firstly detected at incidence screening rounds and is heavily influenced by methodological differences of the respective screening trials. This review intends to create a basis for assessing non-calcified pulmonary nodules detected during LDCT lung cancer screening in a more clinical relevant manner. The aim is to present data of non-calcified pulmonary baseline nodules and new non-calcified pulmonary incident nodules without clustering them together, thereby also simplifying translation to the clinical practice of incidentally detected pulmonary nodules. Small pulmonary nodules newly detected at incidence screening rounds of LDCT lung cancer screening may possess a greater lung cancer probability than pulmonary baseline nodules at a smaller size, which is essential for the development of new guidelines. PMID:28331823

Sex-dependent independent prediction of incident diabetes by depressive symptoms.

PubMed

Akbaş-Şimşek, Tuğba; Onat, Altan; Kaya, Adnan; Tusun, Eyyup; Yüksel, Hüsniye; Can, Günay

2017-12-01

To study the predictive value of depressive symptoms (DeprSs) in a general population of Turkey for type 2 diabetes. Responses to three questions served to assess the sense of depression. Cox regression analyses were used regarding risk estimates for incident diabetes, after exclusion of prevalent cases of diabetes. Mean follow-up consisted of 5.15 (±1.4) years. Depressive symptoms were present at baseline in 16.2% of the whole study sample, threefold in women than men. Reduced physical activity grade was the only significant covariate at baseline in men, while younger age and lower blood pressure were significantly different in women compared with those without DeprS. In men, presence of DeprS predicted incident diabetes at a significant 2.58-fold relative risk (95% confidence interval 1.03; 6.44), after adjustment for age, systolic blood pressure, and antidepressant drug usage. When further covariates were added, waist circumference remained the only significant predictor, while DepS was attenuated to a relative risk of 2.12 (95% confidence interval 0.83; 5.40). DeprS was not associated with diabetes in women, whereas antidepressant drug usage only tended to be positively associated. Gender difference existed in the relationship between DeprS and incident diabetes. DeprS predicted subsequent development of diabetes in men alone, not in women. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Comparing badger (Meles meles) management strategies for reducing tuberculosis incidence in cattle.

PubMed

Smith, Graham C; McDonald, Robbie A; Wilkinson, David

2012-01-01

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, continues to be a serious economic problem for the British cattle industry. The Eurasian badger (Meles meles) is partly responsible for maintenance of the disease and its transmission to cattle. Previous attempts to manage the disease by culling badgers have been hampered by social perturbation, which in some situations is associated with increases in the cattle herd incidence of bTB. Following the licensing of an injectable vaccine, we consider the relative merits of management strategies to reduce bTB in badgers, and thereby reduce cattle herd incidence. We used an established simulation model of the badger-cattle-TB system and investigated four proposed strategies: business as usual with no badger management, large-scale proactive badger culling, badger vaccination, and culling with a ring of vaccination around it. For ease of comparison with empirical data, model treatments were applied over 150 km(2) and were evaluated over the whole of a 300 km(2) area, comprising the core treatment area and a ring of approximately 2 km. The effects of treatment were evaluated over a 10-year period comprising treatment for five years and the subsequent five year period without treatment. Against a background of existing disease control measures, where 144 cattle herd incidents might be expected over 10 years, badger culling prevented 26 cattle herd incidents while vaccination prevented 16. Culling in the core 150 km(2) plus vaccination in a ring around it prevented about 40 cattle herd breakdowns by partly mitigating the negative effects of culling, although this approach clearly required greater effort. While model outcomes were robust to uncertainty in parameter estimates, the outcomes of culling were sensitive to low rates of land access for culling, low culling efficacy, and the early cessation of a culling strategy, all of which were likely to lead to an overall increase in cattle disease.

The selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056) reduces the incidence of reflux episodes in dogs and patients with moderate to severe gastroesophageal reflux disease.

PubMed

Rouzade-Dominguez, M-L; Pezous, N; David, O J; Tutuian, R; Bruley des Varannes, S; Tack, J; Malfertheiner, P; Allescher, H-D; Ufer, M; Rühl, A

2017-08-01

Transient lower esophageal sphincter relaxations (TLESRs) induced by gastric distension are modulated by the metabotropic glutamate receptor 5 (mGluR5) that influences the vagal reflex loop. We therefore aimed to examine the effects of the selective mGluR5 antagonist mavoglurant (AFQ056) on the number of TLESRs in dogs and reflux episodes in patients with gastroesophageal reflux disease (GERD). In a dog model, the number of meal-induced TLESRs was determined after intravenous (0.03, 0.1, 0.3, and 1 mg kg -1 ) and oral (1, 3, and 10 mg kg -1 ) doses of mavoglurant with reference to vehicle. In a multicenter, randomized, double-blind, placebo-controlled, three-period crossover study, the incidence of meal-induced reflux episodes was assessed by esophageal impedance monitoring after single, oral doses of mavoglurant (50 and 400 mg) or baclofen (40 mg) in 30 patients with moderate to severe GERD. In dogs, mavoglurant reduced the number of TLESRs after intravenous and oral administration. In patients with GERD, the incidence of postprandial reflux episodes was significantly lower at a dose of 400 mg mavoglurant (-37.5% ; 90% confidence interval [CI]: -57.8, -17.2), whereas there was no significant difference at 50 mg of mavoglurant compared to placebo. A significantly lower incidence of reflux episodes was also noted with the active comparator baclofen (-50.3%; 90% CI: -66.2, -34.3), thereby validating this study. These data suggest a potential clinical benefit of mGluR5 antagonists such as mavoglurant in patients with GERD, particularly in those with persisting symptoms despite treatment with proton pump inhibitors. © 2017 John Wiley & Sons Ltd.

Hydroxyurea for reducing blood transfusion in non-transfusion dependent beta thalassaemias.

PubMed

Foong, Wai Cheng; Ho, Jacqueline J; Loh, C Khai; Viprakasit, Vip

2016-10-18

Non-transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non-transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non-transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews.Date of last search: 30 April 2016. Randomised or quasi-randomised controlled trials of hydroxyurea in people with non-transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included

High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial.

PubMed

Müller, Christian A; Geisel, Olga; Pelz, Patricia; Higl, Verena; Krüger, Josephine; Stickel, Anna; Beck, Anne; Wernecke, Klaus-Dieter; Hellweg, Rainer; Heinz, Andreas

2015-08-01

Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30-80mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30-270mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Better retention of Malaysian opiate dependents treated with high dose methadone in methadone maintenance therapy

PubMed Central

2010-01-01

Background Methadone is a synthetic opiate mu receptor agonist that is widely used to substitute for illicit opiates in the management of opiate dependence. It helps prevent opiate users from injecting and sharing needles which are vehicles for the spread of HIV and other blood borne viruses. This study has the objective of determining the utility of daily methadone dose to predict retention rates and re-injecting behaviour among opiate dependents. Methods Subjects comprised opiate dependent individuals who met study criteria. They took methadone based on the Malaysian guidelines and were monitored according to the study protocols. At six months, data was collected for analyses. The sensitivity and specificity daily methadone doses to predict retention rates and re-injecting behaviour were evaluated. Results Sixty-four patients volunteered to participate but only 35 (54.69%) remained active and 29 (45.31%) were inactive at 6 months of treatment. Higher doses were significantly correlated with retention rate (p < 0.0001) and re-injecting behaviour (p < 0.001). Of those retained, 80.0% were on 80 mg or more methadone per day doses with 20.0% on receiving 40 mg -79 mg. Conclusions We concluded that a daily dose of at least 40 mg was required to retain patients in treatment and to prevent re-injecting behaviour. A dose of at least 80 mg per day was associated with best results. PMID:21167035

Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner.

PubMed

Landry, David; Paré, Aurélie; Jean, Stéphanie; Martin, Luc J

2015-04-01

Obesity in men is associated with lower testosterone levels, related to reduced sperm concentration and the development of various diseases with aging. Hormones produced by the adipose tissue may have influences on both metabolism and reproductive function. Among them, the production and secretion of adiponectin is inversely correlated to total body fat. Adiponectin receptors (AdipoR1 and AdipoR2) have been found to be expressed in testicular Leydig cells (producing testosterone). Since StAR and Cyp11a1 are essential for testosterone synthesis and adiponectin has been shown to regulate StAR mRNA in swine granulosa cells, we hypothesized that adiponectin might also regulate these genes in Leydig cells. Our objective was to determine whether adiponectin regulates StAR and Cyp11a1 genes in Leydig cells and to better define its mechanisms of action. Methods used in the current study are qPCR for the mRNA levels, transfections for promoter activities, and enzyme-linked immunosorbent assay for the progesterone concentration. We have found that adiponectin cooperates with cAMP-dependent stimulation to activate StAR and Cyp11a1 mRNA expressions in a dose-dependent manner in MA-10 Leydig cells as demonstrated by transfection of a luciferase reporter plasmid. These results led to a significant increase in progesterone production from MA-10 cells. Thus, our data suggest that high doses of adiponectin typical of normal body weight may promote testosterone production from Leydig cells.

Coffee intake and the incident risk of cognitive disorders: A dose-response meta-analysis of nine prospective cohort studies.

PubMed

Wu, Lei; Sun, Dali; He, Yao

2017-06-01

Previous epidemiological studies have provided inconsistent conclusions on the impact of coffee consumption in the developing of cognitive disorders. However, no previous meta-analysis has pooled the evidence from the prospective cohort studies to assess the influence of coffee drinking and its potential dose-response patterns on the risk of developing cognitive disorders specifically. Two databases (PubMed and Embase) were searched for evidence of cohort studies from inception to February 2016. We used a generic inverse-variance method with a random-effects model to pool the fully adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). In the dose-response analyses, a generalized least-squares trend estimation model was applied to computing the study-specific slopes. Nine prospective cohort studies involving 34,282 participants were included in our study. The duration of follow-up years ranged from 1.3 to 28. Compared with <1 cup, daily drinking of 1-2 cups of coffee was inversely linked with the occurrence of cognitive disorders (i.e., Alzheimer's disease, dementia, cognitive decline, and cognitive impairment), and the pooled RR (95% CI) was 0.82 (0.71, 0.94) with evidence of non-significant heterogeneity (I 2  = 25%). Non-significant differences were presented for the association between coffee consumption (>3 vs. <1 cup/d) and incident cognitive disorders. The dose-response analysis showed a "J-shaped" curve relationship of the risk of developing cognitive disorders with coffee consumption. A "J-shaped" association was presented between coffee intake and incident cognitive disorders, with the lowest risk of incident cognitive disorders at a daily consumption level of 1-2 cups of coffee. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Keyboarding Instruction at NABTE Institutions: Are We Teaching Techniques to Reduce CTD Incidence?

ERIC Educational Resources Information Center

Blaszczynski, Carol; Joyce, Marguerite Shane

1996-01-01

Responses from 157 of 193 business teachers who teach keyboarding indicated that 78.7% were aware of cumulative trauma disorder and 22% had experienced it. Only 13% of classrooms were equipped with wrist rests. About 53% teach techniques to reduce incidence, but 20% did not know whether they taught preventive measures. (SK)

Personalized technologist dose audit feedback for reducing patient radiation exposure from CT.

PubMed

Miglioretti, Diana L; Zhang, Yue; Johnson, Eric; Lee, Choonsik; Morin, Richard L; Vanneman, Nicholas; Smith-Bindman, Rebecca

2014-03-01

The aim of this study was to determine whether providing radiologic technologists with audit feedback on doses from CT examinations they conduct and education on dose-reduction strategies reduces patients' radiation exposure. This prospective, controlled pilot study was conducted within an integrated health care system from November 2010 to October 2011. Ten technologists at 2 facilities received personalized dose audit reports and education on dose-reduction strategies; 9 technologists at a control facility received no intervention. Radiation exposure was measured by the dose-length product (DLP) from CT scans performed before (n = 1,630) and after (n = 1,499) the intervention and compared using quantile regression. Technologists were surveyed before and after the intervention. For abdominal CT, DLPs decreased by 3% to 12% at intervention facilities but not at the control facility. For brain CT, DLPs significantly decreased by 7% to 12% at one intervention facility; did not change at the second intervention facility, which had the lowest preintervention DLPs; and increased at the control facility. Technologists were more likely to report always thinking about radiation exposure and associated cancer risk and optimizing settings to reduce exposure after the intervention. Personalized audit feedback and education can change technologists' attitudes about, and awareness of, radiation and can lower patient radiation exposure from CT imaging. Copyright © 2014 American College of Radiology. All rights reserved.

Reducing risk of Anthracycline-related heart failure after childhood cancer | Division of Cancer Prevention

Cancer.gov

Childhood cancer survivors are at a 15-fold risk of developing heart failure (HF) compared to age-matched controls. There is a strong dose-dependent association between anthracyclines and risk of HF; the incidence approaches 20% at cumulative doses between 300-600 mg/m2, and exceeds 30% for doses >600 mg/m2. Outcome following HF is poor; 5-year survival rate is |

Higher CD3(+) and CD34(+) cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia.

PubMed

Gaziev, J; Isgrò, A; Marziali, M; Daniele, N; Gallucci, C; Sodani, P; Simone, M D; Adorno, G; Paciaroni, K; Andreani, M; Lanti, A; Del Proposto, G; Testi, M; De Angelis, G; Roveda, A; Alfieri, C; Saltarelli, F; Lucarelli, G

2012-01-01

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3(+) and CD34(+) cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P=0.005 and 46 vs 23%, P=0.021, respectively). In multivariate analysis, high CD3(+) (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P=0.010) and CD34(+) (HR 4.3; 95% CI 1.4-12.7; P=0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3(+) and CD34(+) cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3(+) (38 × 10(6)/kg) and CD34(+) (4 × 10(6)/kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3(+) and CD34(+) cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.

Ultraviolet radiation cataract: dose dependence

NASA Astrophysics Data System (ADS)

Soderberg, Per G.; Loefgren, Stefan

1994-07-01

Current safety limits for cataract development after acute exposure to ultraviolet radiation (UVR) are based on experiments analyzing experimental data with a quantal, effect-no effect, dose-response model. The present study showed that intensity of forward light scattering is better described with a continuous dose-response model. It was found that 3, 30 and 300 kJ/m2UVR300nm induces increased light scattering within 6 h. For all three doses the intensity of forward light scattering was constant after 6 h. The intensity of forward light scattering was proportional to the log dose of UVR300nm. There was a slight increase of the intensity of forward light scattering on the contralateral side in animals that received 300 kJ/m2. Altogether 72 Sprague-Dawley male rats were included. Half of the rats were exposed in vivo on one side to UVR300nm. The other half was kept as a control group, receiving the same treatment as exposed rats but without delivery of UVR300nm to the eye. Subgroups of the rats received either of the three doses. Rats were sacrificed at varying intervals after the exposure. The lenses were extracted and the forward light scattering was estimated. It is concluded that intensity of forward light scattering in the lens after exposure to UVR300nm should be described with a continuous dose-reponse model.

Incident polarization angle and temperature dependence of polarization and spectral response characteristics in optical fiber couplers.

PubMed

Namihira, Y; Kawazawa, T; Wakabayashi, H

1991-03-20

The incident polarization angle and temperature dependence of the polarization and spectral response characteristics of three different types of fiber coupler are presented. The couplers are (1) the biconicalfused- twisted-taper single-mode fiber (coupler A), (2) the asymmetric-etched-fused-taper wavelength division multiplex (coupler B), and (3) the biconical-polished polarization maintaining fiber (coupler C), respectively. It is confirmed experimentally that the polarization characteristics of couplers A and B vary greatly with temperature, but those of coupler C are independent of temperature. Also, the wavelength dependence characteristics of the power splitting ratio of couplers B and C have almost no change with temperature. However, the wavelength dependence of coupler A is greatly changed with temperature. Comparing couplers A and B, it is postulated that the sinusoidal variations of the polarization state vs the incident polarization angle are due to the stress birefringence caused by the fiber twisting when the fused fiber coupler is fabricated and packaged.

Cutaneous malignant melanoma incidences analyzed worldwide by sex, age, and skin type over personal Ultraviolet-B dose shows no role for sunburn but implies one for Vitamin D3

PubMed Central

Godar, Dianne E.; Subramanian, Madhan; Merrill, Stephen J.

2017-01-01

ABSTRACT Because the incidence of cutaneous malignant melanoma (CMM) was reported to increase with increasing terrestrial UVR (290–400 nm) doses in the US back in 1975 and a recent publication showed no association exists with UVR exposure at all, we set out to fully elucidate the role of UVR in CMM. To achieve this goal, we analyzed the CMM incidences over latitude and estimated the average personal UVR dose in the US and numerous countries (> 50) on 5 continents around the world. Using data from the International Agency for Research on Cancer in 2005, we performed worldwide analysis of CMM over UVR dose by sex, age group (0–14, 15–29, 30–49, 50–69, 70–85+) and Fitzpatrick skin types I-VI. Surprisingly, increasing UVR doses, which represent erythemally-weighted doses comprised primarily of UVB (290–315 nm) radiation, did not significantly correlate with increasing CMM incidence for people with any skin type anywhere in the world. Paradoxically, we found significant correlations between increasing CMM and decreasing UVB dose in Europeans with skin types I-IV. Both Europeans and Americans in some age groups have significant increasing CMM incidences with decreasing UVB dose, which shows UVB is not the main driver in CMM and suggests a possible role for lower cutaneous vitamin D3 levels and UVA (315–400 nm) radiation. CMM may be initiated or promoted by UVA radiation because people are exposed to it indoors through windows and outdoors through some sunscreen formulations. Thus, our findings may explain why some broad-spectrum sunscreen formulations do not protect against getting CMM. PMID:28924456

Dose-dependent effects of an immune challenge at both ultimate and proximate levels in Drosophila melanogaster.

PubMed

Nystrand, M; Dowling, D K

2014-05-01

Immune responses are highly dynamic. The magnitude and efficiency of an immune response to a pathogen can change markedly across individuals, and such changes may be influenced by variance in a range of intrinsic (e.g. age, genotype, sex) and external (e.g. abiotic stress, pathogen identity, strain) factors. Life history theory predicts that up-regulation of the immune system will come at a physiological cost, and studies have confirmed that increased investment in immunity can reduce reproductive output and survival. Furthermore, males and females often have divergent reproductive strategies, and this might drive the evolution of sex-specific life history trade-offs involving immunity, and sexual dimorphism in immune responses per se. Here, we employ an experiment design to elucidate dose-dependent and sex-specific responses to exposure to a nonpathogenic immune elicitor at two scales--the 'ultimate' life history and the underlying 'proximate' immune level in Drosophila melanogaster. We found dose-dependent effects of immune challenges on both male and female components of reproductive success, but not on survival, as well as a response in antimicrobial activity. These results indicate that even in the absence of the direct pathogenic effects that are associated with actual disease, individual life histories respond to a perceived immune challenge--but with the magnitude of this response being contingent on the initial dose of exposure. Furthermore, the results indicate that immune responses at the ultimate life history level may indeed reflect underlying processes that occur at the proximate level. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

The diagnostic performance of reduced-dose CT for suspected appendicitis in paediatric and adult patients: A systematic review and diagnostic meta-analysis.

PubMed

Yoon, Hee Mang; Suh, Chong Hyun; Cho, Young Ah; Kim, Jeong Rye; Lee, Jin Seong; Jung, Ah Young; Kim, Jung Heon; Lee, Jeong-Yong; Kim, So Yeon

2018-06-01

To evaluate the diagnostic performance of reduced-dose CT for suspected appendicitis. A systematic search of the MEDLINE and EMBASE databases was carried out through to 10 January 2017. Studies evaluating the diagnostic performance of reduced-dose CT for suspected appendicitis in paediatric and adult patients were selected. Pooled summary estimates of sensitivity and specificity were calculated using hierarchical logistic regression modelling. Meta-regression was performed. Fourteen original articles with a total of 3,262 patients were included. For all studies using reduced-dose CT, the summary sensitivity was 96 % (95 % CI 93-98) with a summary specificity of 94 % (95 % CI 92-95). For the 11 studies providing a head-to-head comparison between reduced-dose CT and standard-dose CT, reduced-dose CT demonstrated a comparable summary sensitivity of 96 % (95 % CI 91-98) and specificity of 94 % (95 % CI 93-96) without any significant differences (p=.41). In meta-regression, there were no significant factors affecting the heterogeneity. The median effective radiation dose of the reduced-dose CT was 1.8 mSv (1.46-4.16 mSv), which was a 78 % reduction in effective radiation dose compared to the standard-dose CT. Reduced-dose CT shows excellent diagnostic performance for suspected appendicitis. • Reduced-dose CT shows excellent diagnostic performance for evaluating suspected appendicitis. • Reduced-dose CT has a comparable diagnostic performance to standard-dose CT. • Median effective radiation dose of reduced-dose CT was 1.8 mSv (1.46-4.16). • Reduced-dose CT achieved a 78 % dose reduction compared to standard-dose CT.

Treatment outcomes of reduced-dose intravitreal ganciclovir for cytomegalovirus retinitis.

PubMed

Choopong, Pitipol; Vivittaworn, Kamolporn; Konlakij, Duanphen; Thoongsuwan, Somanus; Pituksung, Auengporn; Tesavibul, Nattaporn

2016-04-18

Cytomegalovirus retinitis (CMVR) is one of the most common opportunistic infection in immunocompromised individuals. Intravitreal ganciclovir injection has been used successfully but no standard regimen was established. Risks of drug toxicity, endophthalmitis, and injection-related complications increased with number and frequency of injection. The aim of this study is to evaluate the outcomes of reduced-dose intravitreal ganciclovir (2 mg/0.04 mL) for the treatment of CMVR. A prospective observational cohort study involving 67 eyes of 49 patients with CMVR was performed. Induction therapy involved intravenous ganciclovir (10 mg/kg/day) for 2 weeks unless contraindicated or patients refused. Patients were then treated with reduced-dose intravitreal ganciclovir every week for 4 weeks, and then every other week until the lesion healed. The patients' demographic data were recorded, and vision parameters were examined every visit. Twenty eyes (29.9 %) presented with initial visual acuities less than 6/60. The majority of patients were diagnosed with CMVR in zones 1 or 2 (63 eyes, 94 %), and, at least, one quadrant of the retina was involved (56 eyes, 83.6 %). Forty-one eyes (61.2 %) completely resolved after treatment within the 6-month follow-up. There was no significant difference in healing time, whether or not patients received induction treatment with intravenous ganciclovir (111.00 ± 12.96 vs 105.00 ± 28.32 days, p = 0.8). Five eyes (12.2 %) of patients with healed CMVR had visual acuities less than 6/60. Reduced-dose intravitreal ganciclovir is a safe and effective treatment option. It provides comparable results to other weekly regimens. Induction with intravenous ganciclovir is not crucial in a resolution of retinitis, although it may be necessary to reduce systemic cytomegalovirus loads and mortality rates. The trial was registered with Thai Clinical Trials Registry (TCTR) on 16 March 2016 - TCTR20160316001 .

Dose-dependent biodistribution of prenatal exposure to rutile-type titanium dioxide nanoparticles on mouse testis

NASA Astrophysics Data System (ADS)

Kubo-Irie, Miyoko; Uchida, Hiroki; Mastuzawa, Shotaro; Yoshida, Yasuko; Shinkai, Yusuke; Suzuki, Kenichiro; Yokota, Satoshi; Oshio, Shigeru; Takeda, Ken

2014-02-01

Titanium dioxide nanoparticles (nano-TiO2), believed to be inert and safe, are used in many products especially rutile-type in cosmetics. Detection, localization, and count of nanoparticles in tissue sections are of considerable current interest. Here, we evaluate the dose-dependent biodistribution of rutile-type nano-TiO2 exposure during pregnancy on offspring testes. Pregnant mice were subcutaneously injected five times with 0.1 ml of sequentially diluted of nano-TiO2 powder, 35 nm with primary diameter, suspensions (1, 10, 100, or 1,000 μg/ml), and received total doses of 0.5, 5, 50, and 500 μg, respectively. Prior to injection, the size distribution of nano-TiO2 was analyzed by dynamic light scattering measurement. The average diameter was increased in a dose-dependent manner. The most diluted concentration, 1 μg/ml suspension, contained small agglomerates averaging 193.3 ± 5.4 nm in diameter. The offspring testes were examined at 12 weeks postpartum. Individual particle analysis in testicular sections under scanning and transmission electron microscopy enabled us to understand the biodistribution. The correlation between nano-TiO2 doses injected to pregnant mice, and the number of agglomerates in the offspring testes was demonstrated to be dose-dependent by semiquantitative evaluation. However, the agglomerate size was below 200 nm in the testicular sections of all recipient groups, independent from the injected dose during pregnancy.

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children.

PubMed

Aglipay, Mary; Birken, Catherine S; Parkin, Patricia C; Loeb, Mark B; Thorpe, Kevin; Chen, Yang; Laupacis, Andreas; Mamdani, Muhammad; Macarthur, Colin; Hoch, Jeffrey S; Mazzulli, Tony; Maguire, Jonathon L

2017-07-18

Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown. To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children. A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice-based research network in Toronto, Ontario, Canada. Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May. The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination. Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, -0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was also no significant difference in the median time to the first laboratory-confirmed infection: 3.95 months

Reduced incidence of new-onset diabetes mellitus after renal transplantation with 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors (statins).

PubMed

Prasad, G V Ramesh; Kim, S Joseph; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S; Fenton, Stanley S A; Cattran, Daniel C; Cole, Edward H; Cardella, Carl J

2004-11-01

Statins have anti-inflammatory effects, modify endothelial function and improve peripheral insulin resistance. We hypothesized that statins influence the development of new-onset diabetes mellitus in renal transplant recipients. The records of all previously non-diabetic adults who received an allograft in Toronto between January 1, 1999 and December 31, 2001 were reviewed with follow-up through December 31, 2002. All patients receiving cyclosporine or tacrolimus, mycophenolate mofetil and prednisone were included. New-onset diabetes was diagnosed by the Canadian Diabetic Association criteria: fasting plasma glucose > or =7.0 mmol/L or 2-h postprandial glucose > or =11.1 mmol/L on more than two occasions. Statin use prior to diabetes development was recorded along with other variables. Cox proportional hazards models analyzing statin use as a time-dependent covariate were performed. Three hundred fourteen recipients met study criteria, of whom 129 received statins. New-onset diabetes incidence was 16% (n = 49). Statins (p = 0.0004, HR 0.238[0.109-0.524]) and ACE inhibitors/ARB (p = 0.01, HR 0.309[0.127-0.750]) were associated with decreased risk. Prednisone dose (p = 0.0001, HR 1.007[1.003-1.010] per 1 mg/d at 3 months), weight at transplant (p = 0.02, HR 1.022[1.003-1.042] per 1 kg), black ethnicity (p = 0.02, HR 1.230[1.023-1.480]) and age > or =45 years (p = 0.01, HR 2.226[1.162-4.261]) were associated with increased diabetes. Statin use is associated with reduced new-onset diabetes development after renal transplantation.

Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

PubMed

Anthony, Winston E; Palmer-Young, Evan C; Leonard, Anne S; Irwin, Rebecca E; Adler, Lynn S

2015-01-01

The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees.

Dependence of light transmission through human skin on incident beam diameter at different wavelengths

NASA Astrophysics Data System (ADS)

Zhao, ZhongQuan; Fairchild, Paul W.

1998-05-01

For many skin treatments with light, it is important to have deep photon penetration into the skin. Because of absorption and scattering of photons by skin tissue, both the color and the diameter of the incident beam affect the penetration depth of photons. In this study, the dependence of light transmission through human skin tissues (ear lobs and between the fingers) has been measured in-vivo at six wavelengths (532 nm, 632 nm, 675 nm, 810 nm, 911 nm, and 1064 nm). The same measurement was also made on pig skin in-vitro for comparison. It was observed that (1) the photons at 1064 nm penetrate deeper than the other colors studied for a given incident beam diameter; and (2) the transmittance at a particular wavelength increases asymptotically with incident beam diameter. For some skin tissues, the transmittance flattens at about 8 mm for 532 nm photons and approaches saturation at about 12 mm for all other colors. The results on pig skin is similar.

Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study.

PubMed

Staerk, L; Gerds, T A; Lip, G Y H; Ozenne, B; Bonde, A N; Lamberts, M; Fosbøl, E L; Torp-Pedersen, C; Gislason, G H; Olesen, J B

2018-01-01

Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF). We compared effectiveness and safety of standard and reduced dose NOAC in AF patients. Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula). Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%). Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban. © 2017 The Association for the Publication of

[Occlusion treatment for amblyopia. Age dependence and dose-response relationship].

PubMed

Fronius, M

2016-04-01

Based on clinical experience and studies on animal models the age of 6-7 years was regarded as the limit for treatment of amblyopia, although functional improvement was also occasionally reported in older patients. New technical developments as well as insights from clinical studies and the neurosciences have attracted considerable attention to this topic. Various aspects of the age dependence of amblyopia treatment are discussed in this article, e. g. prescription, electronic monitoring of occlusion dosage, calculation of indicators for age-dependent plasticity of the visual system, and novel, alternative treatment approaches. Besides a discussion of the recent literature, results of studies by our "Child Vision Research Unit" in Frankfurt are presented: results of a questionnaire about prescription habits concerning age limits of patching, electronic recording of occlusion in patients beyond the conventional treatment age, calculation of dose-response function and efficiency of patching and their age dependence. The results of the questionnaire illustrate the uncertainty about age limits of prescription with significant deviations from the guideline of the German Ophthalmological Society (DOG). Electronic recording of occlusion allowed the quantification of declining dose-response function and treatment efficiency between 5 and 16 years of age. Reports about successful treatment with conventional and novel methods in adults are at variance with the notion of a rigid adult visual system lacking plasticity. Electronic recording of patching allowed new insights into the age-dependent susceptibility of the visual system and contributes to a more evidence-based treatment of amblyopia. Alternative approaches for adults challenge established notions about age limits of amblyopia therapy. Further studies comparing different treatment options are urgently needed.

Effectiveness of low-dose naltrexone in the post-detoxification treatment of opioid dependence.

PubMed

Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Murray, Heather W; Wu, Li-Tzy; Hubbard, Robert

2007-10-01

The clinical use of naltrexone (NTX) in the treatment of opioid dependence has been limited because of poor compliance and inconsistent outcomes. In particular, the therapeutic benefit of extended treatment with NTX after opioid detoxification is unclear. The present study evaluated whether the augmentation with low-dose NTX during the post-detoxification treatment of opioid dependence would improve outcomes. In an open-label naturalistic design, 435 opioid-dependent patients who had completed inpatient detoxification were offered the choice of entering 1 of the 2 outpatient treatment arms: clonidine extended treatment (CET) (clonidine + psychosocial treatment), or enhanced extended treatment (EET) (oral NTX [1-10 mg/d] + CET) for 21 days. The primary outcome measure was retention in treatment. Secondary outcomes included abstinence from opioids, dropouts, and adherence to postdischarge care. One hundred sixty-two patients (37.2%) accepted EET. Subjects receiving EET stayed longer in the program (F = 64.4; P = 0.000), were less likely to drop out, used less opioids, and followed through with referral to long-term outpatient treatment in a higher number, compared with patients in the CET arm (P = 0.000 in each case). The NTX + clonidine combination was safe and well tolerated. This preliminary study indicates the potential benefit of augmentation with low-dose NTX to improve outcomes after opioid detoxification for a preferred group of patients. Randomized controlled trials are necessary to further evaluate the role of low-dose NTX in the outpatient treatment of opioid dependence.

Assessment of organ-specific neutron equivalent doses in proton therapy using computational whole-body age-dependent voxel phantoms

NASA Astrophysics Data System (ADS)

Zacharatou Jarlskog, Christina; Lee, Choonik; Bolch, Wesley E.; Xu, X. George; Paganetti, Harald

2008-02-01

Proton beams used for radiotherapy will produce neutrons when interacting with matter. The purpose of this study was to quantify the equivalent dose to tissue due to secondary neutrons in pediatric and adult patients treated by proton therapy for brain lesions. Assessment of the equivalent dose to organs away from the target requires whole-body geometrical information. Furthermore, because the patient geometry depends on age at exposure, age-dependent representations are also needed. We implemented age-dependent phantoms into our proton Monte Carlo dose calculation environment. We considered eight typical radiation fields, two of which had been previously used to treat pediatric patients. The other six fields were additionally considered to allow a systematic study of equivalent doses as a function of field parameters. For all phantoms and all fields, we simulated organ-specific equivalent neutron doses and analyzed for each organ (1) the equivalent dose due to neutrons as a function of distance to the target; (2) the equivalent dose due to neutrons as a function of patient age; (3) the equivalent dose due to neutrons as a function of field parameters; and (4) the ratio of contributions to secondary dose from the treatment head versus the contribution from the patient's body tissues. This work reports organ-specific equivalent neutron doses for up to 48 organs in a patient. We demonstrate quantitatively how organ equivalent doses for adult and pediatric patients vary as a function of patient's age, organ and field parameters. Neutron doses increase with increasing range and modulation width but decrease with field size (as defined by the aperture). We analyzed the ratio of neutron dose contributions from the patient and from the treatment head, and found that neutron-equivalent doses fall off rapidly as a function of distance from the target, in agreement with experimental data. It appears that for the fields used in this study, the neutron dose lateral to the

Vitamin K dependent protein activity and incident ischemic cardiovascular disease: The multi ethnic study of atherosclerosis

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular diseas...

Dose-dependent fate of GFP-E. coli in the alimentary canal of adult house flies

PubMed Central

Naveen, Kumar H.V.; Nayduch, Dana

2015-01-01

Adult house flies (Diptera: Muscidae; Musca domestica L.) can disseminate bacteria from microbe-rich substrates to areas where humans and domesticated animals reside. Because bacterial abundance fluctuates widely across substrates, flies encounter and ingest varying amounts of bacteria. We investigated the dose-dependent survival of bacteria in house flies. Flies were fed four different “doses” of GFP-expressing Escherichia coli (GFP E. coli; very low, low, medium, high, defined in text) and survival was determined at 1, 4, 10 and 22 h post-ingestion via culture and epiflourescent microscopy. Over 22 h, decline of GFP E. coli was significant for all treatments (P<0.04) except the very low dose (P=0.235). Change in survival (Δ S) did not differ between flies fed low and very low doses of bacteria across all time points, although both treatments differed from flies fed high and medium bacterial doses at several time points. At 4, 10 and 22 h, GFP E. coli Δ S significantly differed between medium and high dose-fed flies. A threshold dose, above which bacteria are detected and destroyed by house flies, may exist and likely is immune-mediated. Understanding dose-dependent bacterial survival in flies can help in predicting bacteria transmission potential. PMID:26843509

Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, Darrell R.; Weller, Richard E.

From the early 1970s to the late 1980s, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium (239PuO2, 238PuO2, and 239Pu[NO3]4) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study is to reassess the dose-response relationship for lung cancer induction in the 239PuO2 dogs compared to controls, with particular focus on the dose-response at low lung doses. A 239PuO2 aerosol (2.3 μm AMAD, 1.9 μm GSD) was administered to six groups of 20 young (18-month old) beagle dogs (10 males and 10more » females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 ± 48 Bq (3.5 ± 1.3 nCi), corresponding to 1 Bq g-1 lung tissue (0.029 ± 0.001 nCi g-1. Groups 2 through 6 received initial lung depositions (mean values) of 760, 2724, 10345, 37900, and 200000 Bq (22, 79, 300, 1100, and 5800 nCi) 239PuO2, respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, epidermoid carcinoma) and radiation pneumonitis (highest exposures group) was observed in dogs exposed to 239PuO2. Calculated lung doses ranged from a few cGy in early-sacrificed dogs to 7764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. Lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 �

Delayed adverse effects of neonatal exposure to diethylstilbestrol and their dose dependency in female rats.

PubMed

Yoshida, Midori; Takahashi, Miwa; Inoue, Kaoru; Hayashi, Seigo; Maekawa, Akihiko; Nishikawa, Akiyoshi

2011-08-01

Neonatal exposure to estrogenic chemicals causes irreversible complex damage to the hypothalamus-pituitary-gonadal axis and reproductive system in females. Some lesions are noted after maturation as delayed adverse effects. We investigated the characteristics and dose dependence of delayed effects using female rats neonatally exposed to diethylstilbestrol (DES). Female Donryu rats were subcutaneously injected with a single dose of DES of 0 (control), 0.15, 1.5, 15, 150, or 1,500 µg/kg bw after birth. All except the lowest dose had estrogenic activity in a uterotrophic assay. All rats at 1500 µg/kg and some at 150 µg/kg showed abnormal morphologies in the genital tract, indicating they were androgenized before maturation. Although no morphological abnormalities were noted at 15 µg/kg or lower, onset of persistent estrus was significantly accelerated in the 1.5, 15, and 150 µg/kg groups with dose dependency, and the latest onset was from seventeen to twenty-one weeks of age at 1.5 µg/kg. The neonatal exposure to DES increased uterine adenocarcinoma development only at 150 µg/kg, although uterine anomalies were detected at 1,500 µg/kg. These results indicate that neonatal exposure to DES, which exerts estrogenic activity in vivo, induces delayed adverse effects in female rats in a dose-dependent manner. Early onset of persistent estrus appears to be the most sensitive parameter.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors.

PubMed

Karsch, L; Beyreuther, E; Burris-Mog, T; Kraft, S; Richter, C; Zeil, K; Pawelke, J

2012-05-01

The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10(11) Gy∕s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. The dosimeters are dose rate independent up to 4●10(9) Gy∕s within 2% (OSL and TLD) and up to 15●10(9) Gy∕s within 5% (EBT films). The diamond detectors show strong dose rate dependence. TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karsch, L.; Beyreuther, E.; Burris-Mog, T.

Purpose: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10{sup 11} Gy/s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. Methods: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the numbermore » of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. Results: The dosimeters are dose rate independent up to 410{sup 9} Gy/s within 2% (OSL and TLD) and up to 1510{sup 9} Gy/s within 5% (EBT films). The diamond detectors show strong dose rate dependence. Conclusions: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.« less

Epiphytic lichenosynusia under conditions of chemical pollution: Dose-effect dependencies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mikhailova, I.N.; Vorobeichik, E.L.

1995-11-01

The dose-effect dependencies, which characterize response of the epiphytic lichenosynusia of southern taiga in the Middle Urals to pollution by discharges of a copper-smelting plant, are substantially non-linear and, in most cases, have an S-shaped form. A transition from background to impact state is very sharp and begins when the background level of pollution is exceeded by 1.5 - 2.3 times.

Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory

PubMed Central

Balaguer-Ballester, Emili; Seamans, Jeremy K.; Phillips, Anthony G.; Durstewitz, Daniel

2015-01-01

Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines. PMID:26180194

Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia.

PubMed

Ramachandran, Balaji; Jayavelu, Subramani; Murhekar, Kanchan; Rajkumar, Thangarajan

2016-01-01

EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

A statewide effort to reduce high-dose opioid prescribing through coordinated care organizations.

PubMed

Hartung, Daniel M; Alley, Lindsey; Leichtling, Gillian; Korthuis, P Todd; Hildebran, Christi

2018-05-01

Oregon's Medicaid program is delivered through 16 Coordinated Care Organizations (CCOs) participating in a statewide performance improvement program to reduce high-dose opioid prescribing. CCOs were allowed flexibility to develop their own dose targets and any policies, trainings, guidelines, and/or materials to meet these targets. In this study, we characterize CCO strategies to reduce high-dose opioid prescribing across the 16 CCOs. We reviewed relevant CCO documents and conducted semi-structured interviews with CCO administrators to acquire opioid-related policies, practices, timelines and contextual factors. We applied a systematic coding procedure to develop a comprehensive description of each CCO's strategy. We used administrative data from the state to summarize contextual utilization data for each CCO. Most CCOs selected a target daily morphine milligram equivalent (MME) dose of 90 mg. Sixteen issued quantity limits related to dose, eight restricted specific drug formulations (short-acting or long-acting), and 11 allowed for time-limited taper plan periods for patients over threshold. Many CCOs also employed provider trainings, feedback reports, and/or onsite technical assistance. Other innovations included incentive measures, electronic health record alerts, and toolkits with materials on local alternative therapy resources and strategies for patient communication. CCOs leveraging collaborations with regional partners appeared to mount a greater intensity of interventions than independently operating CCOs. CCOs developed a diversity of interventions to confront high-risk opioid prescribing within their organization. As healthcare systems mount interventions to reduce risky opioid prescribing, it is critical to carefully describe these activities and examine their impact on process and health outcomes. Copyright © 2018 Elsevier Ltd. All rights reserved.

PSA predicts development of incident lower urinary tract symptoms: results from the REDUCE study.

PubMed

Patel, Devin N; Feng, Tom; Simon, Ross M; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Roehrborn, Claus; Andriole, Gerald L; Freedland, Stephen J

2018-05-23

The relationship between baseline prostate-specific antigen (PSA) and development of lower urinary tract symptoms (LUTS) in asymptomatic and mildly symptomatic men is unclear. We sought to determine if PSA predicts incident LUTS in these men. A post-hoc analysis of the 4-year REDUCE study was performed to assess for incident LUTS in 1534 men with mild to no LUTS at baseline. The primary aim was to determine whether PSA independently predicted incident LUTS after adjusting for the key clinical variables of age, prostate size, and baseline International prostate symptom score (IPSS). Incident LUTS was defined as the first report of medical treatment, surgery, or sustained clinically significant symptoms (two IPSS >14). Cox proportional hazards, cumulative incidence curves, and the log-rank test were used to test our hypothesis. A total of 1534 men with baseline IPSS <8 were included in the study cohort. At baseline, there were 335 men with PSA 2.5-4 ng/mL, 589 with PSA 4.1-6 ng/mL, and 610 with PSA 6-10 ng/mL. During the 4-year study, 196 men progressed to incident LUTS (50.5% medical treatment, 9% surgery, and 40.5% new symptoms). As a continuous variable, higher PSA was associated with increased incident LUTS on univariable (HR 1.09, p = 0.019) and multivariable (HR 1.08, p = 0.040) analysis. Likewise, baseline PSA 6-10 ng/mL was associated with increased incident LUTS vs. PSA 2.5-4 ng/mL in adjusted models (HR 1.68, p = 0.016). This association was also observed in men with PSA 4.1-6 ng/mL vs. PSA 2.5-4 ng/mL (HR 1.60, p = 0.032). Men with mild to no LUTS but increased baseline PSA are at increased risk of developing incident LUTS presumed due to benign prostatic hyperplasia.

Prospective Evaluation of Prior Image Constrained Compressed Sensing (PICCS) Algorithm in Abdominal CT: A comparison of reduced dose with standard dose imaging

PubMed Central

Lubner, Meghan G.; Pickhardt, Perry J.; Kim, David H.; Tang, Jie; Munoz del Rio, Alejandro; Chen, Guang-Hong

2014-01-01

Purpose To prospectively study CT dose reduction using the “prior image constrained compressed sensing” (PICCS) reconstruction technique. Methods Immediately following routine standard dose (SD) abdominal MDCT, 50 patients (mean age, 57.7 years; mean BMI, 28.8) underwent a second reduced-dose (RD) scan (targeted dose reduction, 70-90%). DLP, CTDIvol and SSDE were compared. Several reconstruction algorithms (FBP, ASIR, and PICCS) were applied to the RD series. SD images with FBP served as reference standard. Two blinded readers evaluated each series for subjective image quality and focal lesion detection. Results Mean DLP, CTDIvol, and SSDE for RD series was 140.3 mGy*cm (median 79.4), 3.7 mGy (median 1.8), and 4.2 mGy (median 2.3) compared with 493.7 mGy*cm (median 345.8), 12.9 mGy (median 7.9 mGy) and 14.6 mGy (median 10.1) for SD series, respectively. Mean effective patient diameter was 30.1 cm (median 30), which translates to a mean SSDE reduction of 72% (p<0.001). RD-PICCS image quality score was 2.8±0.5, improved over the RD-FBP (1.7±0.7) and RD-ASIR(1.9±0.8)(p<0.001), but lower than SD (3.5±0.5)(p<0.001). Readers detected 81% (184/228) of focal lesions on RD-PICCS series, versus 67% (153/228) and 65% (149/228) for RD-FBP and RD-ASIR, respectively. Mean image noise was significantly reduced on RD-PICCS series (13.9 HU) compared with RD-FBP (57.2) and RD-ASIR (44.1) (p<0.001). Conclusion PICCS allows for marked dose reduction at abdominal CT with improved image quality and diagnostic performance over reduced-dose FBP and ASIR. Further study is needed to determine indication-specific dose reduction levels that preserve acceptable diagnostic accuracy relative to higher-dose protocols. PMID:24943136

Hemodialysis patients receiving a greater Kt dose than recommended have reduced mortality and hospitalization risk.

PubMed

Maduell, Francisco; Ramos, Rosa; Varas, Javier; Martin-Malo, Alejandro; Molina, Manuel; Pérez-Garcia, Rafael; Marcelli, Daniele; Moreso, Francesc; Aljama, Pedro; Merello, Jose Ignacio

2016-12-01

Achieving an adequate dialysis dose is one of the key goals for dialysis treatments. Here we assessed whether patients receiving the current cleared plasma volume (Kt), individualized for body surface area per recommendations, had improved survival and reduced hospitalizations at 2 years of follow-up. Additionally, we assessed whether patients receiving a greater dose gained more benefit. This prospective, observational, multicenter study included 6129 patients in 65 Fresenius Medical Care Spanish facilities. Patients were classified monthly into 1 of 10 risk groups based on the difference between achieved and target Kt. Patient groups with a more negative relationship were significantly older with a higher percentage of diabetes mellitus and catheter access. Treatment dialysis time, effective blood flow, and percentage of on-line hemodiafiltration were significantly higher in groups with a higher dose. The mortality risk profile showed a progressive increase when achieved minus target Kt became more negative but was significantly lower in the group with 1 to 3 L clearance above target Kt and in groups with greater increases above target Kt. Additionally, hospitalization risk appeared significantly reduced in groups receiving 9 L or more above the minimum target. Thus, prescribing an additional 3 L or more above the minimum Kt dose could potentially reduce mortality risk, and 9 L or more reduce hospitalization risk. As such, future prospective studies are required to confirm these dose effect findings. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

Zinc supplementation reduces the incidence of persistent diarrhea and dysentery among low socioeconomic children in India.

PubMed

Sazawal, S; Black, R E; Bhan, M K; Jalla, S; Bhandari, N; Sinha, A; Majumdar, S

1996-02-01

Persistent diarrhea (PD) and dysentery (DD) account for most diarrhea-associated deaths among children in developing countries. Zinc deficiency can cause stunting and impaired immune function, both of which are risk factors for these diarrheal illnesses. We investigated the effect of zinc supplementation on the incidence of PD and DD in a community-based, double-blind randomized trial in children 6-35 mo of age. Increase over baseline in plasma zinc concentrations in the supplemented group compared with a control group (3.61 vs. 0.009 mumol.L-1), indicated successful supplementation. The overall reductions in the zinc supplemented group of 21% in the incidence of PD (95% CI -6 to 42%) and 14% in the incidence of dysentery (95% CI -15 to 36%) were not significant. There was a significant interaction of treatment effect with baseline plasma zinc concentration and age for PD and with gender for DD. In the zinc-supplemented group compared with the control group, the incidence of PD was reduced by 73% (P < 0.05; 95% CI 34 to 91%) in children with a baseline zinc < 7.65 mumol.L-1 and by 49% (P < 0.05; 95%CI 24 to 66%) in children > 11 mo of age. Zinc supplementation resulted in a 38% (P < 0.05 95%CI 8 to 59%) reduction in the incidence of DD in boys. There was no effect on PD among children 6-11 mo old or on DD in girls. In conclusion, zinc supplementation had a significant impact on the incidence of persistent diarrhea in children > 1 y old and in children with low plasma zinc, as well as on dysentery in boys. These findings may have important implications for reducing diarrhea-related morbidity and mortality.

The incidence and experience of rape among chemically dependent women.

PubMed

Teets, J M

1997-01-01

This descriptive study investigated the incidence and experience of rape among chemically dependent women. Sixty women in a residential treatment facility were interviewed about sexual trauma they had experienced in their lives. In this sample 73% had been raped, and 45% had been raped more than once. The stories of rape were classified in five categories: rape while in the context of using, when too high to resist, while prostituting, by a significant other, and by a family member. Some 35% of the rapist described were friends of the women with whom they were using drugs. Only 20% of the rapes were reported to the police. Clinical implications for treatment of addicted women who are also survivors of violence is discussed.

Shock-absorbing insoles reduce the incidence of lower limb overuse injuries sustained during Royal Marine training.

PubMed

House, Carol; Reece, Allyson; Roiz de Sa, Dan

2013-06-01

This study was undertaken to determine whether the incidence of lower limb overuse injuries (LLOIs) sustained during Royal Marine training could be reduced by issuing the recruits with shock-absorbing insoles (SAIs) to wear in their military boots. This was a retrospective longitudinal trial conducted in two phases. Injury data from 1,416 recruits issued with standard Saran insoles and 1,338 recruits issued with SAI were compared. The recruits in the two groups were of similar height, body mass, and aerobic fitness and followed the same training course. The incidence of LLOI sustained by the recruits was lower (p < 0.05) in the SAI Group (19.0%) compared to the Saran Insole Group (31.7%). The incidences of lower limb stress fractures, tibial periostitis, tenosynovitis of foot, achilles tendonopathy, other tendonopathy and anterior knee pain were lower (p < 0.05) in the SAI Group. Tibial stress fracture incidence was lower (p < 0.05) in the SAI Group but metatarsal and femoral stress fracture incidences were the same for the two insole groups. Thus, issuing SAIs to military recruits undertaking a sustained, arduous physical training program with a high incidence of LLOI would provide a beneficial reduction in the incidence of LLOI. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

Dose dependence of true stress parameters in irradiated bcc, fcc, and hcp metals

NASA Astrophysics Data System (ADS)

Byun, T. S.

2007-04-01

The dose dependence of true stress parameters has been investigated for nuclear structural materials: A533B pressure vessel steels, modified 9Cr-1Mo and 9Cr-2WVTa ferritic martensitic steels, 316 and 316LN stainless steels, and Zircaloy-4. After irradiation to significant doses, these alloys show radiation-induced strengthening and often experience prompt necking at yield followed by large necking deformation. In the present work, the critical true stresses for deformation and fracture events, such as yield stress (YS), plastic instability stress (PIS), and true fracture stress (FS), were obtained from uniaxial tensile tests or calculated using a linear strain-hardening model for necking deformation. At low dose levels where no significant embrittlement was detected, the true fracture stress was nearly independent of dose. The plastic instability stress was also independent of dose before the critical dose-to-prompt-necking at yield was reached. A few bcc alloys such as ferritic martensitic steels experienced significant embrittlement at doses above ∼1 dpa; and the true fracture stress decreased with dose. The materials fractured before yield at or above 10 dpa.

Assessment of the risk of solar ultraviolet radiation to amphibians. I. Dose-dependent induction of hindlimb malformations in the northern leopard frog (Rana pipiens).

PubMed

Ankley, Gerald T; Diamond, Stephen A; Tietge, Joseph E; Holcombe, Gary W; Jensen, Kathleen M; Defoe, David L; Peterson, Ryan

2002-07-01

A number of environmental stressors have been hypothesized as responsible for recent increases in limb malformations in several species of North American amphibians. The purpose of this study was to generate dose-response data suitable for assessing the potential role of solar ultraviolet (UV) radiation in causing limb malformations in a species in which this phenomenon seemingly is particularly prevalent, the northern leopard frog (Rana pipiens). Frogs were exposed from early embryonic stages through complete metamorphosis to varying natural sunlight regimes, including unaltered (100%) sunlight, sunlight subjected to neutral density filtration to achieve relative intensities of 85%, 75%, 65%, 50%, and 25% of unaltered sunlight, and sunlight filtered with glass or acrylamide to attenuate, respectively, the UVB (290-320 nm) and UVB plus UVA (290-380 nm) portions of the spectrum. The experiments were conducted in a controlled setting, with continual monitoring of UVB, UVA, and visible light to support a robust exposure assessment. Full sunlight caused approximately 50% mortality of the frogs during early larval development; no significant treatment-related mortality occurred under any of the other exposure regimes, including 100% sunlight with glass or acrylamide filtration. There was a dose-dependent (p < 0.0001) induction of hindlimb malformations in the frogs, with the percentage of affected animals ranging from about 97% under unaltered sunlight to 0% in the 25% neutral density treatment. Malformations were comprised mostly of missing or truncated digits, and generally were bilateral as well as symmetrical. Filtration of sunlight with either glass or acrylamide both significantly reduced the incidence of malformed limbs. The estimated sunlight dose resulting in a 50% limb malformation rate (ED50) was 63.5%. The limb ED50 values based on measured sunlight intensities corresponded to average daily doses of 4.5 and 100 Wh x m(-2) for UVB and UVA, respectively

Tactile massage reduces rescue doses for pain and anxiety: an observational study.

PubMed

Pedersen, Karina; Björkhem-Bergman, Linda

2018-03-01

The aim of this study was to evaluate the effect of tactile massage (TM) on palliative care patients. An observational study at a hospice ward in Sweden was carried out. Forty-one palliative patients were offered TM, at an average of three treatments per patient. Before and after every treatment, self-assessed pain, well-being and anxiety according to the Edmonton Symptom Assessment Scale (0-10) were recorded. In addition, the number of rescue doses for pain and anxiety was monitored 24 hours before and after the treatment and in two consecutive days before the patients were offered TM (control data). TM resulted in improvement of self-assessed pain by 1.7 points (SD 1.6), anxiety by 2.3 points (SD 2.0) and well-being by 2.6 points (SD 1.4). The number of rescue doses for pain was reduced from 1.6 to 0.84 doses/patient (P<0.001) and for anxiety from 0.52 to 0.24 doses/patient (P<0.01). The number of rescue doses was not changed in the same patients in two consecutive days before the patients were offered TM. The effect was evident already after the first treatment and did not increase further with repeated treatments. No patients reported any harmful effects of the treatment. TM reduced the need for administration of rescue doses for pain and anxiety and improved well-being in palliative care patients. Larger randomised studies with parallel control groups are needed to confirm the findings from this observational pilot study. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera).

PubMed

Maze, Ian S; Wright, Geraldine A; Mustard, Julie A

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40-100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 h post-ingestion for low doses and at 24-48 h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.

Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig.

PubMed

Harnett, Erica L; Dickinson, Michelle A; Smith, Graeme N

2007-08-01

This study determined whether a lipopolysaccharide (LPS) dose-dependent increase in fetal brain injury occurs to further characterize the relationship between maternal inflammation and fetal brain injury. Pregnant guinea pigs (n = 59) at 70% gestation were injected intraperitoneally with 1, 5, 25, 50, 100, 200, or 300 microg LPS per kilogram of maternal body weight or an equivalent volume of vehicle. Animals were killed 7 days later. Maternal serum and amniotic fluid samples were assayed for proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 using enzyme-linked immunosorbent assay kits. Fetal brains (n = 72) were stained for evidence of cell death with NeuroTACS stain. Seven days after LPS injections, cytokine concentrations in maternal serum and amniotic fluid were not different (P > .05) from controls. Levels of cell death in all brain regions examined were highest following the maternal administration of 300 mug/kg LPS (P < .05). The dose effect was brain region-dependent (P < .05). A threshold of maternal infection/inflammation exists, beyond which demonstrable fetal brain injury may result.

Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine-dependent volunteers

PubMed Central

Verrico, Christopher D.; Mahoney, James J.; Thompson-Lake, Daisy G. Y.; Bennett, Ryan S.; Newton, Thomas F.; De La Garza, Richard

2015-01-01

Methamphetamine use is increasing in the US. Although there are no Food and Drug Administration (FDA)-approved medications for methamphetamine dependence, preclinical and clinical studies suggest that methamphetamine users may benefit from treatments that enhance cholinergic neurotransmission. Consequently, we determined the safety and the efficacy of varenicline treatment, a partial agonist at α4β2 and a full agonist at α7 nicotinic acetylcholine receptors, to reduce positive subjective effects produced by smoked methamphetamine. Additionally, the effects of treatment with varenicline on the cardiovascular and reinforcing effects of methamphetamine were determined. We conducted a double-blind, placebo-controlled, within-subjects trial of varenicline vs. placebo in methamphetamine-dependent volunteers who were not seeking treatment. Participants were randomly assigned to receive one dose of varenicline (0, 1, or 2 mg) po BID, titrated up to the target dose over days 1–7, during each of three separate inpatient phases. Safety measures included the frequency, duration, severity, and relatedness of adverse events reported. Positive subjective effects included ‘Any drug effect’, ‘High’, ‘Good effects’, ‘Stimulated’, and ‘Drug liking’, which were rated by participants before and for 1 h after smoking methamphetamine (0, 10, and 30 mg). There were no serious adverse events and no differences in adverse events reported during the three phases. Varenicline (2 mg) significantly reduced ratings of ‘Any drug effect’ and ‘Stimulated’, as well as attenuated ratings of ‘High’, ‘Drug liking’, and ‘Good effects’, produced by methamphetamine (30 mg). The ability of varenicline to attenuate the positive subjective effects of methamphetamine in the laboratory suggests that varenicline should continue to be explored as a treatment for methamphetamine dependence. PMID:24393456

Depth Resolution Dependence on Sample Thickness and Incident Energy in On-Axis Transmission Kikuchi Diffraction in Scanning Electron Microscope (SEM).

PubMed

Brodu, Etienne; Bouzy, Emmanuel

2017-12-01

Transmission Kikuchi diffraction is an emerging technique aimed at producing orientation maps of the structure of materials with a nanometric lateral resolution. This study investigates experimentally the depth resolution of the on-axis configuration, via a twinned silicon bi-crystal sample specifically designed and fabricated. The measured depth resolution varies from 30 to 65 nm in the range 10-30 keV, with a close to linear dependence with incident energy and no dependence with the total sample thickness. The depth resolution is explained in terms of two mechanisms acting concomitantly: generation of Kikuchi diffraction all along the thickness of the sample, associated with continuous absorption on the way out. A model based on the electron mean free path is used to account for the dependence with incident energy of the depth resolution. In addition, based on the results in silicon, the use of the mean absorption coefficient is proposed to predict the depth resolution for any atomic number and incident energy.

Reducing statistical uncertainties in simulated organ doses of phantoms immersed in water

DOE PAGES

Hiller, Mauritius M.; Veinot, Kenneth G.; Easterly, Clay E.; ...

2016-08-13

In this study, methods are addressed to reduce the computational time to compute organ-dose rate coefficients using Monte Carlo techniques. Several variance reduction techniques are compared including the reciprocity method, importance sampling, weight windows and the use of the ADVANTG software package. For low-energy photons, the runtime was reduced by a factor of 10 5 when using the reciprocity method for kerma computation for immersion of a phantom in contaminated water. This is particularly significant since impractically long simulation times are required to achieve reasonable statistical uncertainties in organ dose for low-energy photons in this source medium and geometry. Althoughmore » the MCNP Monte Carlo code is used in this paper, the reciprocity technique can be used equally well with other Monte Carlo codes.« less

Asleep Deep Brain Stimulation Reduces Incidence of Intracranial Air during Electrode Implantation.

PubMed

Ko, Andrew L; Magown, Philippe; Ozpinar, Alp; Hamzaoglu, Vural; Burchiel, Kim J

2018-05-30

Asleep deep brain stimulation (aDBS) implantation replaces microelectrode recording for image-guided implantation, shortening the operative time and reducing cerebrospinal fluid egress. This may decrease pneumocephalus, thus decreasing brain shift during implantation. To compare the incidence and volume of pneumocephalus during awake (wkDBS) and aDBS procedures. A retrospective review of bilateral DBS cases performed at Oregon Health & Science University from 2009 to 2017 was undertaken. Postimplantation imaging was reviewed to determine the presence and volume of intracranial air and measure cortical brain shift. Among 371 patients, pneumocephalus was noted in 66% of wkDBS and 15.6% of aDBS. The average volume of air was significantly higher in wkDBS than aDBS (8.0 vs. 1.8 mL). Volumes of air greater than 7 mL, which have previously been linked to brain shift, occurred significantly more frequently in wkDBS than aDBS (34 vs 5.6%). wkDBS resulted in significantly larger cortical brain shifts (5.8 vs. 1.2 mm). We show that aDBS reduces the incidence of intracranial air, larger air volumes, and cortical brain shift. Large volumes of intracranial air have been correlated to shifting of brain structures during DBS procedures, a variable that could impact accuracy of electrode placement. © 2018 S. Karger AG, Basel.

Thyroid function, reduced kidney function and incident chronic kidney disease in a community-based population: the Atherosclerosis Risk in Communities study.

PubMed

Schultheiss, Ulla T; Daya, Natalie; Grams, Morgan E; Seufert, Jochen; Steffes, Michael; Coresh, Josef; Selvin, Elizabeth; Köttgen, Anna

2017-11-01

Reduced kidney function is a common public health problem that increases risk for a wide variety of adverse outcomes, making the identification of potentially modifiable factors associated with the development of incident chronic kidney disease (CKD) important. Alterations in the hypothalamic-pituitary-thyroid axis have been linked to reduced kidney function, but the association of thyroid function with the development of incident CKD is largely uncharacterized. Concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3) and thyroid peroxidase antibody (TPOAb) were quantified in 12 785 black and white participants of the ongoing community-based prospective Atherosclerosis Risk in Communities study. Thyroid markers and clinical categories of thyroid dysfunction (euthyroidism, combined subclinical and overt hypothyroidism, combined subclinical and overt hyperthyroidism) were also evaluated for their association with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2) at study baseline and with incident CKD over a median follow-up time of 19.6 years. Higher TSH and FT4 as well as lower T3 concentrations were strongly and independently associated with reduced kidney function at study baseline. The clinical entities hypothyroidism and hyperthyroidism were also associated with higher odds of baseline reduced kidney function, but this was not significant. However, none of the markers of thyroid function nor different clinical categories of thyroid dysfunction (hypothyroidism, hyperthyroidism or TPOAb positivity) were associated with incident CKD in adjusted analyses. Elevated TSH, FT4 and reduced T3 concentrations were associated with reduced kidney function cross-sectionally. The lack of association with the development of incident CKD suggests that altered thyroid function in the general population is not causally related to CKD development, but screening for thyroidal status may be especially relevant

Oscillating cascade aerodynamics at large mean incidence

NASA Technical Reports Server (NTRS)

Buffum, Daniel H.; King, Aaron J.; El-Aini, Yehia M.; Capece, Vincent R.

1996-01-01

The aerodynamics of a cascade of airfoils oscillating in torsion about the midchord is investigated experimentally at a large mean incidence angle and, for reference, at a low mean incidence angle. The airfoil section is representative of a modern, low aspect ratio, fan blade tip section. Time-dependent airfoil surface pressure measurements were made for reduced frequencies of up to 1.2 for out-of-phase oscillations at a Mach number of 0.5 and chordal incidence angles of 0 deg and 10 deg; the Reynolds number was 0.9 x l0(exp 6). For the 10 deg chordal incidence angle, a separation bubble formed at the leading edge of the suction surface. The separated flow field was found to have a dramatic effect on the chordwise distribution of the unsteady pressure. In this region, substantial deviations from the attached flow data were found with the deviations becoming less apparent in the aft region of the airfoil for all reduced frequencies. In particular, near the leading edge the separated flow had a strong destabilizing influence while the attached flow had a strong stabilizing influence.

Low-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

PubMed

Cheng, Ji-Wei; Zhang, Xiao-Jing; Cheng, Li-Shan; Li, Guo-Yi; Zhang, Li-Jun; Ji, Kang-Xiang; Zhao, Qing; Bai, Yu

2018-02-01

Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However, it brings financial burden to patients and is associated with symptomatic intracranial hemorrhage (SICH). Whether low-dose tPA can effectively reduce SICH and has the same efficacy as standard-dose tPA is still controversial. We searched for English clinical trials published before March, 2017on the comparison of the efficacy and safety between low and standard dose of tPA in the treatment of AIS using MEDLINE, Embase, and Cochrane Library. The modified Rankin scale (mRS) score was used as the primary efficacy outcome. The mRS1 corresponded to 0-1, whereas mRS2 corresponded to 0-2. The SICH and mortality were adopted as primary safety outcomes. Twelve high-quality studies were selected, including 7686 patients (low-dose: 2888, standard-dose: 4798). With no statistical heterogeneity, the fixed effects model was adopted in the analysis. Similarly to standard doses, low-dose tPA improved the mRS scores (mRS1: odds ratio [OR] = .92, 95% confidence interval [CI] .84-1.02; P = .12; mRS2: OR = .97, 95% CI .88-1.08; P = .57). Compared with standard-dose tPA, low-dose tPA reduced the incidence of SICH (by National Institute of Neurological Disorders and Stroke [NINDS] definition: OR = .71, 95% CI .57-0.89; P = .003; by Safe Implementation of Thrombolysis in Stroke Monitoring Study [SITS-MOST] definition: OR = .64, 95% CI .42-0.99; P = .04), while both reduced mortality (OR = .87, 95% CI .74-1.02; P = .08). Low-dose tPA is comparable to standard-dose tPA in improving the neurologic function and reducing mortality in AIS patients. Moreover, low-dose tPA can reduce the incidence of SICH compared with standard-dose tPA. Therefore, low-dose tPA is highly recommended in AIS patients. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Glucose and insulin do not decrease in a dose-dependent manner after increasing doses of mixed fibers that are consumed in muffins for breakfast.

PubMed

Willis, Holly J; Thomas, William; Eldridge, Alison L; Harkness, Laura; Green, Hilary; Slavin, Joanne L

2011-01-01

Conventional wisdom suggests that fiber consumption leads to lower postprandial glucose and insulin response. We hypothesized that increasing doses of mixed, viscous fiber would lower glucose and insulin levels in a dose-dependent manner. Healthy men (n = 10) and women (n = 10) with a body mass index of 24 ± 2 (mean ± SEM) participated in this double-blind, crossover study. On 4 separate visits, fasting subjects consumed an approximately 2093 kJ (500 calorie) muffin with 0, 4, 8, or 12 g of mixed fibers. Blood was drawn to measure glucose and insulin at regular intervals throughout a 3-hour test period. Area under the curve (AUC) glucose was significantly lower after 0 g of fiber than after 4, 8, or 12 g of fiber (arbitrary AUC units ± SEM: 25.3 ± 5.2 vs 44.6 ± 7.7, 49.7 ± 7.9, 51.5 ± 6.6, respectively; P < .006). Area under the curve glucose increased with increasing fiber doses (P for trend = .0003). Area under the curve insulin was higher after the 4-g dose than after the 0-, 8-, and 12-g doses (arbitrary AUC units ± SEM: 84.4 ± 8.0 vs 60.1 ± 6.5, 69.4 ± 8.7, 69.7 ± 8.5, respectively; P < .05); it did not change in a dose-dependent manner. Area under the curve glucose and AUC insulin did not correlate with each other. Glucose and insulin did not decrease in a dose-dependent manner after 0, 4, 8, and 12 g of mixed fibers were consumed in muffins for breakfast. The lack of differences was largely based on the individual variation in glucose response. Caution should be used when making general claims about the expected impact of fiber on glucose and insulin levels. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose-dependent effects of isoflurane and dobutamine on cardiovascular function in dogs with experimental mitral regurgitation.

PubMed

Goya, Seijirow; Wada, Tomoki; Shimada, Kazumi; Hirao, Daiki; Tanaka, Ryou

2018-04-18

To investigate the dose-dependent effects of isoflurane and dobutamine on haemodynamics in dogs with experimentally induced mitral valve insufficiency (MI). Experimental, dose-response study. Six healthy Beagle dogs. Dogs with surgically induced MI were anaesthetized once. First, anaesthesia was maintained at an end-tidal isoflurane concentration (Fe'Iso) 1.0% (ISO1.0) for 20 minutes. Then, dobutamine was infused successively at 2, 4, 8 and 12 μg kg -1 minute -1 (DOB2-12) for 10 minutes at each dose rate. Measurements were recorded at each stage. Dobutamine was discontinued and Fe'Iso was increased to 1.5% (ISO1.5) for 20 minutes. Dobutamine was administered similarly to ISO1.0, and cardiovascular variables were recorded. The same sequence was repeated for Fe'Iso 2.0% (ISO2.0). Aortic pressure (AoP) and left atrial pressure (LAP) were recorded by radiotelemetry. The combination method of the pressure-volume loop analysis and transoesophageal echocardiography was used to measure cardiovascular variables: end-systolic elastance (Ees), effective arterial elastance (Ea), Ea/Ees, forward stroke volume (FSV), heart rate (HR), and cardiac output (CO). High isoflurane concentration resulted in reduced Ees and increased Ea/Ees, which indicated low arterial pressure. High-dose dobutamine administration resulted in increased Ees and FSV at all isoflurane concentrations. In ISO1.5 and ISO2.0, HR was lower at DOB4 than baseline (BL) but increased at DOB12 compared with DOB4. CO increased at ≥ DOB8 compared with BL. In ISO1.5 and ISO2.0, systolic and mean AoP increased at ≥ DOB4 and ≥ DOB8, respectively. LAP did not change under all conditions. The dose-dependent hypotensive effect of isoflurane in MI dogs was mainly derived from the decrease in contractility. Dobutamine increased AoP without increasing LAP by increasing the contractility attenuated by isoflurane. Our findings may improve the cardiovascular management of dogs with MI undergoing general anaesthesia with

Local factors modify the dose dependence of 56Fe-induced atherosclerosis.

NASA Astrophysics Data System (ADS)

Kucik, Dennis; Gupta, Kiran; Wu, Xing; Yu, Tao; Chang, Polly; Kabarowski, Janusz; Yu, Shaohua

2012-07-01

Radiation exposure from a number of terrestrial sources is associated with an increased risk of cardiovascular disease, but evidence establishing whether high-LET radiation has similar effects has been lacking. We recently demonstrated that 600 MeV/n 56Fe induces atherosclerosis as well. Ten-week old male apolipoprotein-E deficient mice, a well-characterized atherosclerosis animal model, were exposed to 0 (control) 2, or 5Gy 56Fe targeted to the chest and neck. In these mice, 56Fe-induced atherosclerosis was similar in character to that induced by X-rays in the same mouse model and to that resulting from therapeutic radiation in cancer patients. Atherosclerosis was exacerbated by 56Fe only in targeted areas, however, suggesting a direct effect of the radiation on the arteries themselves. This is in contrast to some other risk factors, such as high cholesterol or tobacco use, which have systemic effects. The radiation dose required to accelerate development of atherosclerotic plaques, however, differed depending on the vessel that was irradiated and even the location within the vessel. For example, atherosclerosis in the aortic arch was accelerated only by the highest dose (5 Gy), while the carotid arteries and the aortic root showed effects at 2 Gy (a dose four- to eight-fold lower than the dose of X-rays that produces similar effects in this model). Since shear stress is disrupted in the area of the aortic root, it is likely that at least part of the site-specificity is due to additive or synergistic effects of radiation and local hydrodynamics. Other factors, such as local oxidative stress or gene expression may also have been involved. Since the pro-atherogenic effects of 56Fe depend on additional local factors, this suggests that radiation exposure, when unavoidable, might be mitigated by modification of factors unrelated to the radiation itself.

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children

PubMed Central

Aglipay, Mary; Birken, Catherine S.; Parkin, Patricia C.; Loeb, Mark B.; Thorpe, Kevin; Chen, Yang; Laupacis, Andreas; Mamdani, Muhammad; Macarthur, Colin; Hoch, Jeffrey S.; Mazzulli, Tony

2017-01-01

Importance Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown. Objective To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children. Design, Setting, and Participants A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice–based research network in Toronto, Ontario, Canada. Interventions Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May. Main Outcome Measures The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination. Results Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, −0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was

Ovarian and endocrine responses in tropical sheep treated with reduced doses of cloprostenol.

PubMed

Contreras-Solis, Ignacio; Vasquez, B; Diaz, T; Letelier, C; Lopez-Sebastian, A; Gonzalez-Bulnes, A

2009-09-01

The present study aimed to assess the efficacy of reduced doses of cloprostenol for synchronizing estrus and ovulation in hair sheep. With the aim to evaluate the luteolytic activity of reduced cloprostenol doses, a first experiment was performed using a relatively large (group H: 126 microg; n=8), medium (group M: 68.25 microg; n=6) and small (group L: 38.5 microg; n=6) cloprostenol dose. Luteolysis was assessed at Days 3 and 6 after injection (Day 0) by progesterone concentrations (P(4)) and transrectal ultrasonography (US). In Experiment 2, sheep were randomly assigned to the same three doses to evaluate a protocol for estrous synchronization using two injections administered 9 days apart. A third trial was performed with ewes treated (9 days apart) with the large dose (H=126 microg; n=12) and with a small dose adjusted for facilitating volume management (LA=43.75 microg; n=12). Presence of estrous cycling was determined in all the ewes by US and P(4) assay, at Days -9, -6, -2, 0 (Day of second cloprostenol injection), 8 and 11. Bleeding and US were done every 4h from 16 h of the beginning of the estrus during the third trial to assess the preovulatory LH surge and timing of ovulation. Additionally, blood samples were drawn at Days 0, 1, 2 and 3 to assess estradiol (Experiments 2 and 3) and P(4) (Experiment 2) concentrations during the ovarian follicular phase. In all experiments, percentage of animals showing luteolysis, preovulatory follicular dynamics and function and percentage of ewes showing behavioral estrus in response to treatment was similar among groups. Timing of estrus for group H was earlier than group L (28.6+/-1.8h compared with 37.1+/-2.4h; P<0.05). In the third trial, the preovulatory LH peak was higher in the LA group than group H, in terms of maximum mean concentration during the surge (27.7+/-1.8 ng/mL compared with 21.3+/-2.2 ng/mL; P<0.05) and area under the curve (AUC; 183.4+/-12.7 ng/mL compared with 127.7+/-10.9 ng/mL; P<0.01). However

Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reduced-intensity conditioning: The incidence is not reduced.

PubMed

Shimoni, Avichai; Yeshurun, Moshe; Hardan, Izhar; Avigdor, Abraham; Ben-Bassat, Isaac; Nagler, Arnon

2004-07-01

Thrombotic microangiopathy (TMA) is one of the most severe complications of stem cell transplantation (SCT). Endothelial cell injury caused by the toxic effects of high-dose chemoradiotherapy is likely the primary event in pathogenesis. The incidence, clinical settings, and risk factors for TMA in the era of nonmyeloablative conditioning have not been well defined. The data on 147 consecutive SCTs in a single center were collected, and patients with TMA were identified. Patient characteristics, response to therapy, and outcome were recorded, and risk factors were determined. TMA occurred in 22 of 147 transplantations, with a projected incidence of 20% +/- 4%. TMA occurred in 3 clinical settings: classic multifactorial TMA, TMA associated with severe hepatic graft-versus-host disease (GVHD), and TMA associated with second SCT, with a projected incidence of 8% +/- 3%, 73% +/- 14%, and 70% +/- 16% of patients at risk, respectively. TMA occurred after 23% +/- 6% of nonmyeloablative and 16% +/- 5% of myeloablative conditioning regimens (not significant). Univariate analysis determined SCT from unrelated donors, SCT during advanced or active disease, second SCT within 6 months of a prior SCT, and acute GVHD as risk factors for TMA. The last 2 factors remained significant in a multivariate model. Thirty-two percent of patients responded to therapy. The peri-TMA mortality rate was 68% +/- 10%. Six patients had diffuse alveolar hemorrhage complicating TMA. SCT-associated TMA is a relatively common complication with unsatisfactory therapy and grim prognosis. Fludarabine-based nonmyeloablative conditioning does not confer a lesser risk for TMA. This observation may relate to the selective use of these regimens in elderly and heavily pretreated patients or to the lack of reduction of GVHD with these regimens, and fludarabine itself may be involved in causing endothelial damage. Further exploration of novel preventive and therapeutic measurements is required in high

A one-year proprioceptive exercise programme reduces the incidence of falls in community-dwelling elderly people: A before-after non-randomised intervention study.

PubMed

Pérez-Ros, Pilar; Martinez-Arnau, Francisco M; Malafarina, Vincenzo; Tarazona-Santabalbina, Francisco J

2016-12-01

The risk of falls increases with age. Balance alteration and polypharmacy are independent contributors to an increased risk of falls. The primary aim was to assess whether a proprioceptive exercise programme reduces the incidence of falls. A secondary aim was to assess the association between drugs and falls. This was a before-after non-randomised intervention study. The study recruited independent and cognitively intact community-dwelling people aged over 69 years, from December 2012 to May 2014. The intervention was done by a nurse and consisted of a monthly supervised group session of proprioceptive training for 1 year, supplemented by a home diary exercise. Daily medication was reviewed. We included 572 subjects (63.3% women), mean age 76.1±3.9 years. The mean number of drugs prescribed at the start of the study was 4.7±3.0and 353 of the participants (61.7%) were taking four or more drugs a day. The elderly who fell were more dependent in their activities of daily living (Barthel index), and their balance was worse (determined using the Tinetti scale), as were their results on a cognitive scale (the MEC). After the intervention, an increase in self-perceived quality of life (EQ5D) was reported. The incidence of falls was reduced from 37.5% in the 12 months prior to the intervention to 25.7% in the 12 months after the intervention. During the follow-up, beta-blocker use was associated with an increased incidence of falls (OR=2.05; 95%IC: 1.24-3.39; p=0.005). In contrast, antiplatelet/anticoagulation drugs were associated with a lower risk of falls (OR=0.7; 95%IC: 0.55-0.88; p=0.003). The proprioceptive exercise programme reduced the incidence of falls in community-dwelling older people. Multiple drug use was an independent predictor of an increased risk of falls, and specific drug groups were associated with falls. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Proton depth dose distribution: 3-D calculation of dose distributions from solar flare irradiation

NASA Astrophysics Data System (ADS)

Leavitt, Dennis D.

1990-11-01

Relative depth dose distribution to the head from 3 typical solar flare proton events were calculated for 3 different exposure geometries: (1) single directional radiation incident upon a fixed head; (2) single directional radiation incident upon head rotating axially (2-D rotation); and (3) omnidirectional radiation incident upon head (3-D rotation). Isodose distributions in the transverse plane intersecting isocenter are presented for each of the 3 solar flare events in all 3 exposure geometries. In all 3 calculation configurations the maximum predicted dose occurred on the surface of the head. The dose at the isocenter of the head relative to the surface dose for the 2-D and 3-D rotation geometries ranged from 2 to 19 percent, increasing with increasing energy of the event. The calculations suggest the superficially located organs (lens of the eye and skin) are at greatest risk for the proton events studied here.

Magnetic properties of square Py nanowires: Irradiation dose and geometry dependence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ehrmann, A., E-mail: andrea.ehrmann@fh-bielefeld.de; Blachowicz, T.; Komraus, S.

Arrays of ferromagnetic patterned nanostructures with single particle lateral dimensions between 160 nm and 400 nm were created by electron-beam lithography. The fourfold particles with rectangular-shaped walls around a square open area were produced from permalloy. Their magnetic properties were measured using the longitudinal magneto-optical Kerr effect. The article reports about the angle-dependent coercive fields and the influence of the e-beam radiation dose on sample shapes. It is shown that a broad range of radiation dose intensities enables reliable creation of nanostructures with parameters relevant for the desired magnetization reversal scenario. The experimental results are finally compared with micromagnetic simulations to explainmore » the findings.« less

Dose-dependent effects of β-phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) on animal behavior.

PubMed

Tyurenkov, I N; Bagmetova, V V; Chernyshova, Yu V; Merkushenkova, O V

2014-12-01

β-Phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) in doses of 13-650 mg/kg suppressed depressive behavior of animals in the Porsolt test (i.e. produced antidepressant properties), reduced anxiety in the open-field, elevated plus maze, and Vogel conflict tests (i.e. produced anxiolytic effects). RGPU-135 in doses of 26-130 mg/kg exhibited more pronounced antidepressant action and in doses of 26 and 52 mg/kg had more pronounced anxiolytic effects. RGPU-135 in doses of 13-78 mg/kg increased locomotor and exploratory activity of animals in the open-field test. Activating effects of this agent decreased with increasing the dose. RGPU-135 in the subtoxic dose (650 mg/kg) suppressed locomotor activity of animals (produced sedative effect).

Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate.

PubMed

Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J; Ravelli, Raimond B G

2011-05-01

Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50-250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e(-)Å(-2) s(-1) or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection combined with

Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate

PubMed Central

Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J.; Ravelli, Raimond B. G.

2011-01-01

Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50–250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e−Å−2 s−1 or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection

Febuxostat exerts dose-dependent renoprotection in rats with cisplatin-induced acute renal injury.

PubMed

Fahmi, Alaa N A; Shehatou, George S G; Shebl, Abdelhadi M; Salem, Hatem A

2016-08-01

The aim of the present study was to investigate possible renoprotective effects of febuxostat, a highly potent xanthine oxidase inhibitor, against cisplatin (CIS)-induced acute kidney injury in rats. Male Sprague Dawley rats were randomly assigned into four groups of six rats each, as follows: normal control; CIS, received a single intraperitoneal injection of CIS (7.5 mg/kg); [febuxostat 10 + CIS] and [febuxostat 15 + CIS], received febuxostat (10 and 15 mg/kg/day, respectively, orally) for 14 days, starting 7 days before CIS injection. At the end of experiment, 24-h urine output was collected and serum was separated for biochemical assessments. Kidney tissue homogenate was prepared for determination of oxidative stress-related parameters, nitric oxide (NO), and tumor necrosis factor-α (TNF-α). Moreover, histological alterations of kidney tissues were evaluated. Serum creatinine, blood urea, and urinary total protein were significantly elevated, while serum albumin and creatinine clearance were significantly reduced, in CIS-intoxicated rats, indicating depressed renal function. CIS administration also elicited renal oxidative stress, evidenced by increased malondialdehyde content and depleted levels of reduced glutathione and superoxide dismutase activity. Moreover, enhancement of renal levels of the pro-inflammatory TNF-α indicated renal inflammation. CIS-administered rats also showed increased serum lactate dehydrogenase activity and reduced renal NO bioavailability. Febuxostat dose-dependently improved or restored these changes to near-normal (e.g., mean ± SD of serum creatinine levels in control, CIS, [febuxostat 10 + CIS] and [febuxostat 15 + CIS] groups were 0.78 ± 0.19, 3.28 ± 2.0 (P < 0.01 versus control group), 1.03 ± 0.36 (P < 0.01 versus CIS group), and 0.93 ± 0.21 (P < 0.01 versus CIS group) mg/dl, respectively, and blood urea levels for the different groups were 36.80 ± 4.36, 236.10 ± 89.19 (P < 0

Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huddart, Robert A., E-mail: robert.huddart@icr.ac.uk; Hall, Emma; Hussain, Syed A.

2013-10-01

Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. Themore » primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.« less

Dose-Dependent Pheromone Responses of Ips pini, Orthotomicus latiden (Coleoptera: Scolytidae), and associates in stands of lodgepole pine

Treesearch

Daniel R. Miller; John H. Borden; B. Staffan Lidgren

2005-01-01

We conducted four behavioral choice tests in stands of mature lodgepole pine in British Columbia, from 1988 to 1991, to determine the dose-dependent responses of Orthotomicus latidens (LeConte) and Ips pini (Say) to their respective pheromones. Dose-dependent responses were exhibited by I. pini to (±)-ipsdienol and lanierone, with...

Dose/Exposure‐Response Modeling to Support Dosing Recommendation for Phase III Development of Baricitinib in Patients with Rheumatoid Arthritis

PubMed Central

Chua, Laiyi; Ernest, Charles; Macias, William; Rooney, Terence; Tham, Lai San

2017-01-01

Baricitinib is an oral inhibitor of Janus kinases (JAKs), selective for JAK1 and 2. It demonstrated dose‐dependent efficacy in patients with moderate‐to‐severe rheumatoid arthritis (RA) in a phase IIb study up to 24 weeks. Population pharmacokinetic/pharmacodynamic (PopPK/PD) models were developed to characterize concentration‐time profiles and dose/exposure‐response (D/E‐R) relationships for the key efficacy (proportion of patients achieving American College of Rheumatology 20%, 50%, or 70% response rate) and safety endpoints (incidence of anemia) for the phase IIb study. The modeling suggested that 4 mg q.d. was likely to offer the optimum risk/benefit balance, whereas 2 mg q.d. had the potential for adequate efficacy. In addition, at the same total daily dose, a twice‐daily regimen is not expected to provide an advantage over q.d. dosing for the efficacy or safety endpoints. The model‐based simulations formed the rationale for key aspects of dosing, such as dose levels and dosing frequency for phase III development. PMID:28891251

Dose-dependent effects of homologous seminal plasma on motility and kinematic characteristics of post-thaw stallion epididymal spermatozoa.

PubMed

Neuhauser, S; Dörfel, S; Handler, J

2015-05-01

Preservation of epididymal spermatozoa is important to save genetic material of endangered species and breeds, or in case of unexpected injury, which will end the breeding career of valuable sires. Seminal plasma (SP) influences sperm quality in a dose-dependent manner and its addition to preserved semen immediately before insemination may be beneficial for sperm fertility. Increased plasma membrane stability of epididymal spermatozoa reduces freezing injury of cells, and the addition of SP after freezing and thawing might have activating and protecting effects on spermatozoa within the female genital tract. In this study, epididymal spermatozoa were harvested by retrograde flush of the epididymal cauda immediately after routine castration and frozen. Seminal plasma was collected from other six stallions. Homologous SP (SP from the same species, but from a different animal) was added to frozen-thawed epididymal spermatozoa at concentrations of 0, 5, 20, 50 and 80% SP. Addition of SP increased sperm motility and influenced kinematic values in a dose-dependent manner (p < 0.05). Motility improved at concentrations of 20 and 50% SP, but did not further increase at 80% SP. There was no difference in sperm motility among SP from six different donor stallions regardless of the concentrations of SP (p > 0.05). Total and progressive motility of ten frozen-thawed epididymal spermatozoa samples collected from different stallions after dilution with extender and 5, 20, 50 or 80% SP differed significantly (p < 0.05). In conclusion, addition of homologous SP to frozen-thawed stallion epididymal spermatozoa immediately improved motility in a dose-dependent manner regardless of semen quality of SP donor stallions. This might positively influence fertility when SP is added before insemination. Moreover, there seems to be a threshold level of SP concentration for optimal improvement of sperm motility. © 2015 American Society of Andrology and European Academy of Andrology.

Dose-dependent establishment of Trichuris suis larvae in Göttingen minipigs.

PubMed

Vejzagić, Nermina; Roepstorff, Allan; Kringel, Helene; Thamsborg, Stig Milan; Nielsen, Mads Pårup; Kapel, Christian M O

2015-03-15

Embryonated eggs of the pig whipworm Trichuris suis (TSOee) constitute the active pharmaceutical ingredient (API) in a medicinal product explored in human clinical trials against several immune-mediated diseases. The measurement of TSO biological potency (hatchability and infectivity) is a requirement for the assessment of TSO's pharmacological potency in human clinical trials. The present study aims to validate the dose-dependent establishment of T. suis larvae in Göttingen minipigs and eventual clinical implication of a dose range (1000-10,000 TSO). Four groups of 5 minipigs were inoculated with doses of 1000, 2500, 7500, and 10,000 TSOee, respectively, to evaluate a range of concentrations of TSOee in a minipig infectivity model. Unembryonated eggs (TSOue) were added to keep the total egg number in the inoculum constant at 10,000 eggs. Two groups received 2500 and 7500 TSOee per pig without the addition of TSOue as controls. The intestinal larval establishment at 21 days post inoculation (dpi) demonstrated a clear positive linear dose-response relationship between numbers of inoculated TSOee and recovered larvae. There was a low level of variation in larval counts in all study groups. Thus, the infectivity model in minipigs within the tested dose range offers a reliable, sensitive and accurate assay for testing biological potency of TSO. Copyright © 2015 Elsevier B.V. All rights reserved.

Investigation of the dependence of BLS frequencies on angle of incidence for thin iron films

NASA Astrophysics Data System (ADS)

From, M.; Cochran, J. F.; Heinrich, B.; Celinski, Z.

1993-05-01

Brillouin light-scattering experiments have been done at various angles of incidence, θ, for four specimens prepared by molecular-beam epitaxy. The specimens were single ultrathin films of Fe deposited on single-crystal Ag substrates. Dependence of magnon frequency on θ is easily resolvable in all specimens. We find that the magnitude of this dependence is in good agreement with a theoretical calculation that takes into account magnetic anisotropies, dipole-dipole, and exchange interactions. Our results imply that magnetic excitations in these specimens are correlated over distances of at least 5000 Å.

Combined evaluation of grazing incidence X-ray fluorescence and X-ray reflectivity data for improved profiling of ultra-shallow depth distributions☆

PubMed Central

Ingerle, D.; Meirer, F.; Pepponi, G.; Demenev, E.; Giubertoni, D.; Wobrauschek, P.; Streli, C.

2014-01-01

The continuous downscaling of the process size for semiconductor devices pushes the junction depths and consequentially the implantation depths to the top few nanometers of the Si substrate. This motivates the need for sensitive methods capable of analyzing dopant distribution, total dose and possible impurities. X-ray techniques utilizing the external reflection of X-rays are very surface sensitive, hence providing a non-destructive tool for process analysis and control. X-ray reflectometry (XRR) is an established technique for the characterization of single- and multi-layered thin film structures with layer thicknesses in the nanometer range. XRR spectra are acquired by varying the incident angle in the grazing incidence regime while measuring the specular reflected X-ray beam. The shape of the resulting angle-dependent curve is correlated to changes of the electron density in the sample, but does not provide direct information on the presence or distribution of chemical elements in the sample. Grazing Incidence XRF (GIXRF) measures the X-ray fluorescence induced by an X-ray beam incident under grazing angles. The resulting angle dependent intensity curves are correlated to the depth distribution and mass density of the elements in the sample. GIXRF provides information on contaminations, total implanted dose and to some extent on the depth of the dopant distribution, but is ambiguous with regard to the exact distribution function. Both techniques use similar measurement procedures and data evaluation strategies, i.e. optimization of a sample model by fitting measured and calculated angle curves. Moreover, the applied sample models can be derived from the same physical properties, like atomic scattering/form factors and elemental concentrations; a simultaneous analysis is therefore a straightforward approach. This combined analysis in turn reduces the uncertainties of the individual techniques, allowing a determination of dose and depth profile of the implanted

Reduced extinction of hippocampal-dependent memories in CPEB knockout mice.

PubMed

Berger-Sweeney, Joanne; Zearfoss, N Ruth; Richter, Joel D

2006-01-01

CPEB is a sequence-specific RNA binding protein that regulates translation at synapses. In neurons of CPEB knockout mice, synaptic efficacy is reduced. Here, we have performed a battery of behavioral tests and find that relative to wild-type animals, CPEB knockout mice, although similar on many baseline behaviors, have reduced extinction of memories on two hippocampal-dependent tasks. A corresponding microarray analysis reveals that about 0.14% of hippocampal genes have an altered expression in the CPEB knockout mouse. These data suggest that CPEB-dependent local protein synthesis may be an important cellular mechanism underlying extinction of hippocampal-dependent memories.

Prolonged hydrocephalus induced by intraventricular hemorrhage in rats is reduced by curcumin therapy.

PubMed

Qi, Zhihua; Zhang, Huiqin; Fu, Chuhua; Liu, Xiao; Chen, Bo; Dang, Yanwei; Chen, Huayun; Liu, Lijun

2017-01-10

Prolonged hydrocephalus is a major cause of severe disability and death of intraventricular hemorrhage (IVH) patients. However, the therapeutic options to minimize the detrimental effects of post-hemorrhagic hydrocephalus are limited. Curcumin has been reported to confer neuroprotective effects in numerous neurological diseases and injuries, but its role in IVH-induced hydrocephalus has not been determined. The aim of present study was to determine whether curcumin treatment ameliorates blood brain barrier (BBB) damage and reduces the incidence of post-hemorrhagic hydrocephalus in IVH rat model. Autologous blood intraventricular injection was used to establish the IVH model. Our results revealed that repeated intraperitoneal injection of curcumin ameliorated IVH-induced learning and memory deficits as determined by Morris water maze and reduced the incidence of post-hemorrhagic hydrocephalus in a dose-dependent manner at 28 d post-IVH induction. Further, the increased BBB permeability and brain edema induced by IVH were significantly reduced by curcumin administration. In summary, these findings highlighted the important role of curcumin in improving neurological function deficits and protecting against BBB disruption via promoting the neurovascular unit restoration, and thus it reduced the severity of post-hemorrhagic hydrocephalus in the long term. It is believed that curcumin might prove to be an effective therapeutic component in prevent the post-IVH hydrocephalus in the near future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deeg, H.J.; Storb, R.; Weiden, P.L.

1981-11-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs diedmore » from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.« less

RhBMP-2-induced radiculitis in patients undergoing transforaminal lumbar interbody fusion: relationship to dose.

PubMed

Villavicencio, Alan T; Burneikiene, Sigita

2016-10-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) remains the primary synthetic osteoinductive material used in spinal fusion surgery today. The early inflammation reaction to rhBMP-2 manifesting with radicular symptoms has been previously reported in patients undergoing transforaminal lumbar interbody fusion (TLIF). There is a disagreement with regard to the factors affecting its occurrence and whether such symptoms are dose dependent. The purpose of this analysis was to determine the incidence of rhBMP-2-induced radiculitis and its relationship to dose. A retrospective cohort analysis was performed of the prospectively collected data. All consecutive patients (n=204) who underwent one- or two-level TLIF and instrumented posterolateral fusion with an off-label rhBMP-2 use were included in this analysis. The patients who developed new radicular symptoms after initial improvement postoperatively and had sterile fluid collections indicative of inflammatory process, or in the absence of any structural abnormalities that would explain these symptoms on imaging studies, were deemed to have rhBMP-2-induced radiculitis. Magnetic resonance imaging (MRI) scans were obtained for all patients who developed postoperative radicular symptoms. Correlations between the total rhBMP-2 dose, dose per spinal level, and incidence of radiculitis were evaluated while controlling for age, sex, number of TLIF levels, and surgeon. The incidence of postoperative radiculitis was 11.3% (23 out of 204). The average total rhBMP-2 dose was 4.9 mg (range=2.1-12) and the average dose per spinal level was 3.8 mg (range=1.05-12). Logistic regression analysis did not identify any significant correlations between the rhBMP-2 doses and the incidence of radiculitis (p=.6). The incidence of rhBMP-2-induced radiculitis in patients undergoing TLIF is quite high, but there were no dose-related correlations found. The study, however, cannot rule out a possibility that a larger variation in bone

Angular dependence of the nanoDot OSL dosimeter.

PubMed

Kerns, James R; Kry, Stephen F; Sahoo, Narayan; Followill, David S; Ibbott, Geoffrey S

2011-07-01

Optically stimulated luminescent detectors (OSLDs) are quickly gaining popularity as passive dosimeters, with applications in medicine for linac output calibration verification, brachytherapy source verification, treatment plan quality assurance, and clinical dose measurements. With such wide applications, these dosimeters must be characterized for numerous factors affecting their response. The most abundant commercial OSLD is the InLight/OSL system from Landauer, Inc. The purpose of this study was to examine the angular dependence of the nanoDot dosimeter, which is part of the InLight system. Relative dosimeter response data were taken at several angles in 6 and 18 MV photon beams, as well as a clinical proton beam. These measurements were done within a phantom at a depth beyond the build-up region. To verify the observed angular dependence, additional measurements were conducted as well as Monte Carlo simulations in MCNPX. When irradiated with the incident photon beams parallel to the plane of the dosimeter, the nanoDot response was 4% lower at 6 MV and 3% lower at 18 MV than the response when irradiated with the incident beam normal to the plane of the dosimeter. Monte Carlo simulations at 6 MV showed similar results to the experimental values. Examination of the results in Monte Carlo suggests the cause as partial volume irradiation. In a clinical proton beam, no angular dependence was found. A nontrivial angular response of this OSLD was observed in photon beams. This factor may need to be accounted for when evaluating doses from photon beams incident from a variety of directions.

Angular dependence of the nanoDot OSL dosimeter

PubMed Central

Kerns, James R.; Kry, Stephen F.; Sahoo, Narayan; Followill, David S.; Ibbott, Geoffrey S.

2011-01-01

Purpose: Optically stimulated luminescent detectors (OSLDs) are quickly gaining popularity as passive dosimeters, with applications in medicine for linac output calibration verification, brachytherapy source verification, treatment plan quality assurance, and clinical dose measurements. With such wide applications, these dosimeters must be characterized for numerous factors affecting their response. The most abundant commercial OSLD is the InLight∕OSL system from Landauer, Inc. The purpose of this study was to examine the angular dependence of the nanoDot dosimeter, which is part of the InLight system.Methods: Relative dosimeter response data were taken at several angles in 6 and 18 MV photon beams, as well as a clinical proton beam. These measurements were done within a phantom at a depth beyond the build-up region. To verify the observed angular dependence, additional measurements were conducted as well as Monte Carlo simulations in MCNPX.Results: When irradiated with the incident photon beams parallel to the plane of the dosimeter, the nanoDot response was 4% lower at 6 MV and 3% lower at 18 MV than the response when irradiated with the incident beam normal to the plane of the dosimeter. Monte Carlo simulations at 6 MV showed similar results to the experimental values. Examination of the results in Monte Carlo suggests the cause as partial volume irradiation. In a clinical proton beam, no angular dependence was found.Conclusions: A nontrivial angular response of this OSLD was observed in photon beams. This factor may need to be accounted for when evaluating doses from photon beams incident from a variety of directions. PMID:21858992

Dose-Dependent Effects of Sirolimus on mTOR Signaling and Polycystic Kidney Disease

PubMed Central

Novalic, Zlata; van der Wal, Annemieke M.; Leonhard, Wouter N.; Koehl, Gudrun; Breuning, Martijn H.; Geissler, Edward K.; de Heer, Emile

2012-01-01

Inhibition of the mammalian target of rapamycin (mTOR) shows beneficial effects in animal models of polycystic kidney disease (PKD); however, two clinical trials in patients with autosomal dominant PKD failed to demonstrate a short-term benefit in either the early or progressive stages of disease. The stage of disease during treatment and the dose of mTOR inhibitors may account for these differing results. Here, we studied the effects of a conventional low dose and a higher dose of sirolimus (blood levels of 3 ng/ml and 30–60 ng/ml, respectively) on mTOR activity and renal cystic disease in two Pkd1-mutant mouse models at different stages of the disease. When initiated at early but not late stages of disease, high-dose treatment strongly reduced mTOR signaling in renal tissues, inhibited cystogenesis, accelerated cyst regression, and abrogated fibrosis and the infiltration of immune cells. In contrast, low-dose treatment did not significantly reduce renal cystic disease. Levels of p-S6RpSer240/244, which marks mTOR activity, varied between kidneys; severity of the renal cystic phenotype correlated with the level of mTOR activity. Taken together, these data suggest that long-term treatment with conventional doses of sirolimus is insufficient to inhibit mTOR activity in renal cystic tissue. Mechanisms to increase bioavailability or to target mTOR inhibitors more specifically to kidneys, alone or in combination with other compounds, may improve the potential for these therapies in PKD. PMID:22343118

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera)

PubMed Central

Maze, Ian S.; Wright, Geraldine A.; Mustard, Julie A.

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses lead to hemolymph ethanol levels of approximately 40 to 100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 hr post-ingestion for low doses and at 24 to 48 hours for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior. PMID:17070538

Co-Administration of Low-Dose Naltrexone and Bupropion Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats.

PubMed

Nicholson, Emily R; Dilley, Julian E; Froehlich, Janice C

2018-03-01

This study examined whether combining naltrexone (NTX) with bupropion (BUP) is more effective in reducing alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake than either drug alone. Alcohol-experienced, adult, male, P rats were fed NTX alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 20.0 mg/kg BW, NTX (10.0 mg/kg BW) + BUP (10.0 mg/kg BW), or vehicle (VEH) at 1 hour prior to onset of a daily 2-hour alcohol access period for 5 consecutive days. When administered alone, neither NTX (10.0 mg/kg BW) nor BUP, in either of 2 doses (10.0 mg/kg BW or 20.0 mg/kg BW), reduced voluntary alcohol intake in P rats. However, NTX combined with BUP (10.0 mg/kg NTX + 10.0 mg/kg BUP) and given as a single medication significantly reduced alcohol consumption throughout prolonged treatment. Combining low doses of NTX and BUP, each of which is ineffective when given alone, increases the efficacy of the medication. Low drug doses circumvent the problem of negative side effects that can occur with higher doses of either drug. A reduction in side effects can facilitate patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake. The results, together with those from our prior studies, demonstrate the strength of a combinatorial pharmacotherapeutic approach to the treatment of alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

Preemptive antibiotic treatment based on gram staining reduced the incidence of ARDS in mechanically ventilated patients.

PubMed

Matsushima, Asako; Tasaki, Osamu; Shimizu, Kentaro; Tomono, Kazunori; Ogura, Hiroshi; Shimazu, Takeshi; Sugimoto, Hisashi

2008-08-01

Ventilator-associated pneumonia (VAP) is one of the major complications in the intensive care unit. VAP sometimes results in acute respiratory distress syndrome (ARDS), and the associated mortality is high. We hypothesized that preemptive antibiotic therapy based on results of bedside gram staining would reduce the incidence of VAP. Patients who were endotracheally intubated in our intensive care unit for more than 72 hours were included. Patients younger than 16 years of age or patients died because of brain death were excluded. The study was divided into two periods. During the first period, we used antibiotics according to the American Thoracic Society guidelines. During the second period, antibiotics were given according to the results of bedside gram staining even before radiographic infiltrate appeared. One hundred twenty-eight patients and 133 patients were included in the first and second periods, respectively. The incidence of VAP was significantly decreased in the second period (first period, 22%; second period, 9%, p < 0.01). The incidence of ARDS was also decreased significantly in the second period (first period, 11%; second period, 3%, p < 0.01). The duration and total amount of antibiotics administered did not increase in the second period. VAP associated mortality was significantly lower in the second period (first period, 5%; second period, 0.8%, p < 0.05). Early diagnosis and treatment of respiratory infection based on results of gram staining significantly reduced the incidences of VAP and ARDS without an increase in the use of antibiotics.

DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate.

PubMed

Li, Wen; Yu, Min; Luo, Suhui; Liu, Huan; Gao, Yuxia; Wilson, John X; Huang, Guowei

2013-07-01

The proliferative response of neural stem cells (NSCs) to folate may play a critical role in the development, function and repair of the central nervous system. It is important to determine the dose-dependent effects of folate in NSC cultures that are potential sources of transplantable cells for therapies for neurodegenerative diseases. To determine the optimal concentration and mechanism of action of folate for stimulation of NSC proliferation in vitro, NSCs were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 μmol/L) for 24, 48 or 72 h. Immunocytochemistry and methyl thiazolyl tetrazolium assay showed that the optimal concentration of folic acid for NSC proliferation was 20-40 μmol/L. Stimulation of NSC proliferation by folic acid was associated with DNA methyltransferase (DNMT) activation and was attenuated by the DNMT inhibitor zebularine, which implies that folate dose-dependently stimulates NSC proliferation through a DNMT-dependent mechanism. Based on these new findings and previously published evidence, we have identified a mechanism by which folate stimulates NSC growth. Copyright © 2013 Elsevier Inc. All rights reserved.

Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys.

PubMed

Grégoire, Laurent; Samadi, Pershia; Graham, Julie; Bédard, Paul J; Bartoszyk, Gerd D; Di Paolo, Thérèse

2009-07-01

Dyskinesia is an important complication of treatment in Parkinson's disease (PD). Sarizotan, a 5-HT(1A) agonist with high affinity for D3 and D4 receptors was investigated on L-Dopa-induced dyskinesia (LID) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. Five MPTP female cynomolgus monkeys (Macaca fascicularis) with a moderate to severe parkinsonian syndrome and LID were used. Sarizotan 0.2, 1, and 2 mg/kg administered alone did not worsen parkinsonian symptoms; there were no effect on locomotor counts or on normal behavior of the monkeys. Sarizotan 0.2, 1, and 2 mg/kg administered 30 min before a fixed dose of L-Dopa (25-30 mg/kg s.c.) + benserazide (50 mg) did not affect the antiparkinsonian response to L-Dopa. However, mean dyskinetic scores were significantly reduced with sarizotan 1 and 2 mg/kg but not at 0.2 mg/kg. Higher doses of sarizotan (4 and 8 mg/kg, administered immediately before L-Dopa) reduced L-Dopa-induced locomotor response in all monkeys. A pharmacokinetic investigation in these monkeys showed a dose-dependent increase in mean plasma sarizotan concentrations with similar mean plasma concentrations for sarizotan 1 mg/kg alone or with L-Dopa, indicating a lack of sarizotan/L-Dopa interaction. The time course of plasma sarizotan concentrations was associated with time of maximal reduction of dyskinesias. When administered daily for two weeks in combination with L-Dopa in the same MPTP monkeys, sarizotan 1 mg/kg had a sustained antidyskinetic effect while maintaining the antiparkinsonian and locomotor effect of L-Dopa. This detailed sarizotan investigation in MPTP monkeys supports the antidyskinetic activity of this drug and for 5-HT(1A) agonists.

Dose-Dependent and Lasting Influences of Intranasal Vasopressin on Face Processing in Men

PubMed Central

Price, Daniel; Burris, Debra; Cloutier, Anna; Thompson, Carol B.; Rilling, James K.; Thompson, Richmond R.

2017-01-01

Arginine vasopressin (AVP) and related peptides have diverse effects on social behaviors in vertebrates, sometimes promoting affiliative interactions and sometimes aggressive or antisocial responses. The type of influence, in at least some species, depends on social contexts, including the sex of the individuals in the interaction and/or on the levels of peptide within brain circuits that control the behaviors. To determine if AVP promotes different responses to same- and other-sex faces in men, and if those effects are dose dependent, we measured the effects of two doses of AVP on subjective ratings of male and female faces. We also tested if any influences persist beyond the time of drug delivery. When AVP was administered intranasally on an initial test day, 20 IU was associated with decreased social assessments relative to placebo and 40 IU, and some of the effects persisted beyond the initial drug delivery and appeared to generalize to novel faces on subsequent test days. In single men, those influences were most pronounced, but not exclusive, for male faces, whereas in coupled men they were primarily associated with responses to female faces. Similar influences were not observed if AVP was delivered after placebo on a second test day. In a preliminary analysis, the differences in social assessments observed between men who received 20 and 40 IU, which we suggest primarily reflect lowered social assessments induced by the lower dose, appeared most pronounced in subjects who carry what has been identified as a risk allele for the V1a receptor gene. Together, these results suggest that AVP’s effects on face processing, and possibly other social responses, differ according to dose, depend on relationship status, and may be more prolonged than previously recognized. PMID:29018407

Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

PubMed

Crist, Richard C; Li, James; Doyle, Glenn A; Gilbert, Alex; Dechairo, Bryan M; Berrettini, Wade H

2018-01-01

Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose. Genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study was associated with mean dose of methadone or buprenorphine/naloxone. This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence.

PubMed

Ezard, Nadine; Dunlop, Adrian; Clifford, Brendan; Bruno, Raimondo; Carr, Andrew; Bissaker, Alexandra; Lintzeris, Nicholas

2016-12-01

The treatment of methamphetamine dependence is a continuing global health problem. Agonist type pharmacotherapies have been used successfully to treat opioid and nicotine dependence and are being studied for the treatment of methamphetamine dependence. One potential candidate is lisdexamfetamine, a pro-drug for dexamphetamine, which has a longer lasting therapeutic action with a lowered abuse potential. The purpose of this study is to determine the safety of lisdexamfetamine in this population at doses higher than those currently approved for attention deficit hyperactivity disorder or binge eating disorder. This is a phase 2 dose escalation study of lisdexamfetamine for the treatment of methamphetamine dependence. Twenty individuals seeking treatment for methamphetamine dependence will be recruited at two Australian drug and alcohol services. All participants will undergo a single-blinded ascending-descending dose regime of 100 to 250 mg lisdexamfetamine, dispensed daily on site, over an 8-week period. Participants will be offered counselling as standard care. For the primary objectives the outcome variables will be adverse events monitoring, drug tolerability and regimen completion. Secondary outcomes will be changes in methamphetamine use, craving, withdrawal, severity of dependence, risk behaviour and other substance use. Medication acceptability, potential for non-prescription use, adherence and changes in neurocognition will also be measured. Determining the safety of lisdexamfetamine will enable further research to develop pharmacotherapies for the treatment of methamphetamine dependence. Australian and New Zealand Clinical Trials Registry ACTRN12615000391572 Registered 28 th April 2015.

Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.

These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, andmore » percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats.« less

Study protocol for a randomised controlled double-blinded trial of the dose-dependent efficacy and safety of primaquine for clearance of gametocytes in children with uncomplicated falciparum malaria in Uganda.

PubMed

Eziefula, Alice Chijioke; Staedke, Sarah G; Yeung, Shunmay; Webb, Emily; Kamya, Moses; White, Nicholas J; Bousema, Teun; Drakeley, Chris

2013-03-26

For the purpose of blocking transmission of Plasmodium falciparum malaria from humans to mosquitoes, a single dose of primaquine is recommended by the WHO as an addition to artemisinin combination therapy. Primaquine clears gametocytes but causes dose-dependent haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the optimal dosing of primaquine for malaria elimination programmes and for the purpose of interrupting the spread of artemisinin-resistant malaria. This study investigates the efficacy and safety of reducing doses of primaquine for clearance of gametocytes in participants with normal G6PD status. In this prospective, four-armed randomised placebo-controlled double-blinded trial, children aged 1-10 years, weighing over 10 kg, with haemoglobin ≥8 g/dl and uncomplicated P falciparum malaria are treated with artemether lumefantrine and randomised to receive a dose of primaquine (0.1, 0.4 or 0.75 mg base/kg) or placebo on the third day of treatment. Participants are followed up for 28 days. Gametocytaemia is measured by quantitative nucleic acid sequence-based analysis on days 0, 2, 3, 7, 10 and 14 with a primary endpoint of the number of days to gametocyte clearance in each treatment arm and secondarily the area under the curve of gametocyte density over time. Analysis is for non-inferiority of efficacy compared to the reference dose, 0.75 mg base/kg. Safety is assessed by pair-wise comparisons of the arithmetic mean (±SD) change in haemoglobin concentration per treatment arm and analysed for superiority to placebo and incidence of adverse events. Ethics and dissemination Approval was obtained from the ethical committees of Makerere University School of Medicine, the Ugandan National Council of Science and Technology and the London School of Hygiene and Tropical Medicine. These will be disseminated to inform malaria elimination policy, through peer-reviewed publication and academic presentations.

Renewable Energy Can Help Reduce Oil Dependency

ScienceCinema

Arvizu, Dan

2017-12-21

In a speech to the Economic Club of Kansas City on June 23, 2010, NREL Director Dan Arvizu takes a realistic look at how renewable energy can help reduce America's dependence on oil, pointing out that the country gets as much energy from renewable sources now as it does from offshore oil production.

Dose-dependent EEG effects of zolpidem provide evidence for GABA(A) receptor subtype selectivity in vivo.

PubMed

Visser, S A G; Wolters, F L C; van der Graaf, P H; Peletier, L A; Danhof, M

2003-03-01

Zolpidem is a nonbenzodiazepine GABA(A) receptor modulator that binds in vitro with high affinity to GABA(A) receptors expressing alpha(1) subunits but with relatively low affinity to receptors expressing alpha(2), alpha(3), and alpha(5) subunits. In the present study, it was investigated whether this subtype selectivity could be detected and quantified in vivo. Three doses (1.25, 5, and 25 mg) of zolpidem were administered to rats in an intravenous infusion over 5 min. The time course of the plasma concentrations was determined in conjunction with the change in the beta-frequency range of the EEG as pharmacodynamic endpoint. The concentration-effect relationship of the three doses showed a dose-dependent maximum effect and a dose-dependent potency. The data were analyzed for one- or two-site binding using two pharmacodynamic models based on 1) the descriptive model and 2) a novel mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for GABA(A) receptor modulators that aims to separates drug- and system-specific properties, thereby allowing the estimation of in vivo affinity and efficacy. The application of two-site models significantly improved the fits compared with one-site models. Furthermore, in contrast to the descriptive model, the mechanism-based PK/PD model yielded dose-independent estimates for affinity (97 +/- 40 and 33,100 +/- 14,800 ng x ml(-1)). In conclusion, the mechanism-based PK/PD model is able to describe and explain the observed dose-dependent EEG effects of zolpidem and suggests the subtype selectivity of zolpidem in vivo.

Tailor-made Surgical Guide Reduces Incidence of Outliers of Cup Placement.

PubMed

Hananouchi, Takehito; Saito, Masanobu; Koyama, Tsuyoshi; Sugano, Nobuhiko; Yoshikawa, Hideki

2010-04-01

Malalignment of the cup in total hip arthroplasty (THA) increases the risks of postoperative complications such as neck cup impingement, dislocation, and wear. We asked whether a tailor-made surgical guide based on CT images would reduce the incidence of outliers beyond 10 degrees from preoperatively planned alignment of the cup compared with those without the surgical guide. We prospectively followed 38 patients (38 hips, Group 1) having primary THA with the conventional technique and 31 patients (31 hips, Group 2) using the surgical guide. We designed the guide for Group 2 based on CT images and fixed it to the acetabular edge with a Kirschner wire to indicate the planned cup direction. Postoperative CT images showed the guide reduced the number of outliers compared with the conventional method (Group 1, 23.7%; Group 2, 0%). The surgical guide provided more reliable cup insertion compared with conventional techniques. Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Modelling the effects of booster dose vaccination schedules and recommendations for public health immunization programs: the case of Haemophilus influenzae serotype b.

PubMed

Charania, Nadia A; Moghadas, Seyed M

2017-09-13

Haemophilus influenzae serotype b (Hib) has yet to be eliminated despite the implementation of routine infant immunization programs. There is no consensus regarding the number of primary vaccine doses and an optimal schedule for the booster dose. We sought to evaluate the effect of a booster dose after receiving the primary series on the long-term disease incidence. A stochastic model of Hib transmission dynamics was constructed to compare the long-term impact of a booster vaccination and different booster schedules after receiving the primary series on the incidence of carriage and symptomatic disease. We parameterized the model with available estimates for the efficacy of Hib conjugate vaccine and durations of both vaccine-induced and naturally acquired immunity. We found that administering a booster dose substantially reduced the population burden of Hib disease compared to the scenario of only receiving the primary series. Comparing the schedules, the incidence of carriage for a 2-year delay (on average) in booster vaccination was comparable or lower than that observed for the scenario of booster dose within 1 year after primary series. The temporal reduction of symptomatic disease was similar in the two booster schedules, suggesting no superiority of one schedule over the other in terms of reducing the incidence of symptomatic disease. The findings underscore the importance of a booster vaccination for continued decline of Hib incidence. When the primary series provides a high level of protection temporarily, delaying the booster dose (still within the average duration of protection conferred by the primary series) may be beneficial to maintain longer-term protection levels and decelerate the decline of herd immunity in the population.

Radiation brain dose to vascular surgeons during fluoroscopically guided interventions is not effectively reduced by wearing lead equivalent surgical caps.

PubMed

Kirkwood, Melissa L; Arbique, Gary M; Guild, Jeffrey B; Zeng, Katie; Xi, Yin; Rectenwald, John; Anderson, Jon A; Timaran, Carlos

2018-03-12

Radiation to the interventionalist's brain during fluoroscopically guided interventions (FGIs) may increase the incidence of cerebral neoplasms. Lead equivalent surgical caps claim to reduce radiation brain doses by 50% to 95%. We sought to determine the efficacy of the RADPAD (Worldwide Innovations & Technologies, Lenexa, Kan) No Brainer surgical cap (0.06 mm lead equivalent at 90 kVp) in reducing radiation dose to the surgeon's and trainee's head during FGIs and to a phantom to determine relative brain dose reductions. Optically stimulated, luminescent nanoDot detectors (Landauer, Glenwood, Ill) inside and outside of the cap at the left temporal position were used to measure cap attenuation during FGIs. To check relative brain doses, nanoDot detectors were placed in 15 positions within an anthropomorphic head phantom (ATOM model 701; CIRS, Norfolk, Va). The phantom was positioned to represent a primary operator performing femoral access. Fluorography was performed on a plastic scatter phantom at 80 kVp for an exposure of 5 Gy reference air kerma with or without the hat. For each brain location, the percentage dose reduction with the hat was calculated. Means and standard errors were calculated using a pooled linear mixed model with repeated measurements. Anatomically similar locations were combined into five groups: upper brain, upper skull, midbrain, eyes, and left temporal position. This was a prospective, single-center study that included 29 endovascular aortic aneurysm procedures. The average procedure reference air kerma was 2.6 Gy. The hat attenuation at the temporal position for the attending physician and fellow was 60% ± 20% and 33% ± 36%, respectively. The equivalent phantom measurements demonstrated an attenuation of 71% ± 2.0% (P < .0001). In the interior phantom locations, attenuation was statistically significant for the skull (6% ± 1.4%) and upper brain (7.2% ± 1.0%; P < .0001) but not for the middle brain (1.4% ± 1.0%; P = .15

Brassinolide Increases Potato Root Growth In Vitro in a Dose-Dependent Way and Alleviates Salinity Stress

PubMed Central

Xia, Shitou; Su, Yi; Wang, Huiqun; Luo, Weigui; Su, Shengying

2016-01-01

Brassinosteroids (BRs) are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL) affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01 μg/L) promoted root elongation and lateral root development, whereas high BL concentrations (1–100 μg/L) inhibited root elongation. There was a significant (P < 0.05) positive correlation between root activity and BL concentrations within a range from 0.01 to 100 μg/L, with the peak activity of 8.238 mg TTC·g−1 FW·h−1 at a BL concentration of 100 μg/L. Furthermore, plants treated with 50 μg/L BL showed enhanced salt stress tolerance through in vitro growth. Under this scenario, BL treatment enhanced the proline content and antioxidant enzymes' (superoxide dismutase, peroxidase, and catalase) activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K+ and Na+ homeostasis by improving tissue K+/Na+ ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K+/Na+ homeostasis in potato shoots and roots. PMID:27803931

Historical Study of Radiation Exposures and the Incidence of Cataracts in Astronauts

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Manuel, F. K.; Iszard, G.; Feiveson, A.; Peterson, L. E.; Hardy, D.; Marak, L.; Tung, W.; Wear, M.; Chylack, L. T., Jr.

2004-01-01

For over 35 years, astronauts in low Earth orbit or on missions to the moon have been exposed to space radiation comprised of high-energy protons, heavy ions, and secondary neutrons. We reviewed the radiation exposures received by astronauts in space and on Earth, and presented results from the first epidemiological study of cataract incidence in the astronauts. Our data suggested an increased risk for cataracts from space radiation exposures. Using parametric survival analysis and the maximum likelihood method, we estimated the dose-response and age distribution for cataract incidence in astronauts by space radiation. Considering the high-LET dose contributions on specific space missions as well as data from animal studies with neutrons and heavy ions, suggested a linear response with no dose-threshold for cataracts. However, there are unanswered questions related to the importance and the definition of clinically significant cataracts commonly used in radiation protection, especially in light of epidemiological data suggesting that the probability that sub-clinical cataracts will progress is highly dependent on the age at which cataracts appear. We briefly describe a new study that will address the measurement of cataract progression-rates in astronauts and a ground-based comparison group.

Historical Study of Radiation Exposures and the Incidence of Cataracts in Astronauts

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Manuel, F. K.; Iszard, G.; Feiveson, A.; Peterson, L. E.; Hardy, D.; Marak, L.; Tung, W.; Wear, M.; Chylack, L. T., Jr.

2004-01-01

For over 35 years, astronauts in low Earth orbit or on missions to the moon have been exposed to space radiation comprised of high-energy protons, heavy ions, and secondary neutrons. We reviewed the radiation exposures received by astronauts in space and on Earth, and presented results from the first epidemiological study of cataract incidence in the astronauts. Our data suggested an increased risk for cataracts from space radiation exposures*. Using parametric survival analysis and the maximum likelihood method, we estimated the dose-response and age distribution for cataract incidence in astronauts by space radiation. Considering the high-LET dose contributions on specific space missions as well as data from animal studies with neutrons and heavy ions, suggested a linear response with no dose-threshold for cataracts. However, there are unanswered questions related to the importance and the definition of "clinically significant" cataracts commonly used in radiation protection, especially in light of epidemiological data suggesting that the probability that "sub-clinical" cataracts will progress is highly dependent on the age at which cataracts appear. We briefly describe a new study that will address the measurement of cataract progression-rates in astronauts and a ground-based comparison group.

Lateral topography for reducing effective dose in low-dose chest CT.

PubMed

Bang, Dong-Ho; Lim, Daekeon; Hwang, Wi-Sub; Park, Seong-Hoon; Jeong, Ok-man; Kang, Kyung Wook; Kang, Hohyung

2013-06-01

The purposes of this study were to assess radiation exposure during low-dose chest CT by using lateral topography and to compare the lateral topographic findings with findings obtained with anteroposterior topography alone and anteroposterior and lateral topography combined. From November 2011 to February 2012, 210 male subjects were enrolled in the study. Age, weight, and height of the men were recorded. All subjects were placed into one of three subgroups based on the type of topographic image obtained: anteroposterior topography, lateral topography, and both anteroposterior and lateral topography. Imaging was performed with a 128-MDCT scanner. CT, except for topography, was the same for all subjects. A radiologist analyzed each image, recorded scan length, checked for any insufficiencies in the FOV, and calculated the effective radiation dose. One-way analysis of variance and multiple comparisons were used to compare the effective radiation exposure and scan length between groups. The mean scan length in the anteroposterior topography group was significantly greater than that of the lateral topography group and the combined anteroposterior and lateral topography group (p < 0.001). The mean effective radiation dose for the lateral topography group (0.735 ± 0.033 mSv) was significantly lower than that for the anteroposterior topography group (0.763 ± 0.038 mSv) and the combined anteroposterior and lateral topography group (0.773 ± 0.038) (p < 0.001). Lateral topographic low-dose CT was associated with a lower effective radiation dose and scan length than either anteroposterior topographic low-dose chest CT or low-dose chest CT with both anteroposterior and lateral topograms.

Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process.

PubMed

Lee, Hyun Soo; Schlereth, Simona; Khandelwal, Payal; Saban, Daniel R

2013-01-01

A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 µg) versus hi-dose (1000 µg) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.

AN EXTRACT OF PENICILLIUM CHRYSOGENUM INDUCES DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES IN MICE

EPA Science Inventory

Rationale: Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typ...

THE CHALLENGES IN THE ESTIMATION OF THE EFFECTIVE DOSE WHEN WEARING RADIOPROTECTIVE GARMENTS.

PubMed

Saldarriaga Vargas, C; Struelens, L; Vanhavere, F

2018-01-01

The performance of a single or double dosimetry (SD or DD) algorithm on estimating effective dose wearing radioprotective garments (ERPG) depends on the specific irradiation conditions. This study investigates the photon energies and angles of incidence for which the estimation of ERPG with the personal dose equivalents measured over and under the RPG (Ho and Hu) becomes more challenging. The energy and angular dependences of ERPG, Ho and Hu were Monte Carlo calculated for photon exposures. The personal dosimeter of SCK · CEN was modeled and used to determine Ho and Hu. Different SD and DD algorithms were tested and critical exposure conditions were identified. Moreover, the influence of calibration methods was investigated for the SCK · CEN dosimeter when worn over RPG. We found that the accuracy with which ERPG is calculated using SD and DD is strongly dependent on the energy and angle of incidence of photons. Also, the energy of the photon beam used to calibrate the Ho dosimeter can bias the estimation of ERPG. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SU-E-T-96: Energy Dependence of the New GafChromic- EBT3 Film's Dose Response-Curve.

PubMed

Chiu-Tsao, S; Massillon-Jl, G; Domingo-Muñoz, I; Chan, M

2012-06-01

To study and compare the dose response curves of the new GafChromic EBT3 film for megavoltage and kilovoltage x-ray beams, with different spatial resolution. Two sets of EBT3 films (lot#A101711-02) were exposed to each x-ray beam (6MV, 15MV and 50kV) at 8 dose values (50-3200cGy). The megavoltage beams were calibrated per AAPM TG-51 protocol while the kilovoltage beam was calibrated following the TG-61 using an ionization chamber calibrated at NIST. Each film piece was scanned three consecutive times in the center of Epson 10000XL flatbed scanner in transmission mode, landscape orientation, 48-bit color at two separate spatial resolutions of 75 and 300 dpi. The data were analyzed using ImageJ and, for each scanned image, a region of interest (ROI) of 2×2cm 2 at the field center was selected to obtain the mean pixel value with its standard deviation in the ROI. For each energy, dose value and spatial resolution, the average netOD and its associated uncertainty were determined. The Student's t-test was performed to evaluate the statistical differences between the netOD/dose values of the three energy modalities, with different color channels and spatial resolutions. The dose response curves for the three energy modalities were compared in three color channels with 75 and 300dpi. Weak energy dependence was found. For doses above 100cGy, no statistical differences were observed between 6 and 15MV beams, regardless of spatial resolution. However, statistical differences were observed between 50kV and the megavoltage beams. The degree of energy dependence (from MV to 50kV) was found to be function of color channel, dose level and spatial resolution. The dose response curves for GafChromic EBT3 films were found to be weakly dependent on the energy of the photon beams from 6MV to 50kV. The degree of energy dependence varies with color channel, dose and spatial resolution. GafChromic EBT3 films were supplied by Ashland Corp. This work was partially supported by DGAPA

Dose Response of Endotoxin on Hepatocyte and Muscle Mitochondrial Respiration In Vitro

PubMed Central

Brandt, Sebastian; Porta, Francesca; Jakob, Stephan M.; Takala, Jukka; Djafarzadeh, Siamak

2015-01-01

Introduction. Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria. Methods. Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1–100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry. Results. In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS). Conclusion. LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner. PMID:25649304

Ground effects on aircraft noise. [near grazing incidence

NASA Technical Reports Server (NTRS)

Willshire, W. L., Jr.; Hilton, D. A.

1979-01-01

A flight experiment was conducted to investigate air-to-ground propagation of sound near grazing incidence. A turbojet-powered aircraft was flown at low altitudes over the ends of two microphone arrays. An eight-microphone array was positioned along a 1850 m concrete runway. The second array consisted of 12 microphones positioned parallel to the runway over grass. Twenty-eight flights were flown at altitudes ranging from 10 m to 160 m. The acoustic data recorded in the field reduced to one-third-octave band spectra and time correlated with the flight and weather information. A small portion of the data was further reduced to values of ground attenuation as a function of frequency and incidence angle by two different methods. In both methods, the acoustic signals compared originated from identical sources. Attenuation results obtained by using the two methods were in general agreement. The measured ground attenuation was largest in the frequency range of 200 to 400 Hz. A strong dependence was found between ground attenuation and incidence angle with little attenuation measured for angles of incidence greater than 10 to 15 degrees.

Online 3D EPID-based dose verification: Proof of concept

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spreeuw, Hanno; Rozendaal, Roel, E-mail: r.rozenda

Purpose: Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID-based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of thismore » study to show that our EPID-based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification. Methods: The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near-maximum dose (D2) is compared as well. The real-time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head-and-neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested. Results: The precomputation time per treatment was ∼180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame

Online 3D EPID-based dose verification: Proof of concept.

PubMed

Spreeuw, Hanno; Rozendaal, Roel; Olaciregui-Ruiz, Igor; González, Patrick; Mans, Anton; Mijnheer, Ben; van Herk, Marcel

2016-07-01

Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID-based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of this study to show that our EPID-based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification. The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near-maximum dose (D2) is compared as well. The real-time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head-and-neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested. The precomputation time per treatment was ∼180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame, including dose verification, took

Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.

PubMed

Walker, L A; Watson, E S; elSohly, M A

1995-08-01

Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly

Cost savings of human milk as a strategy to reduce the incidence of necrotizing enterocolitis in very low birth weight infants.

PubMed

Johnson, Tricia J; Patel, Aloka L; Bigger, Harold R; Engstrom, Janet L; Meier, Paula P

2015-01-01

Necrotizing enterocolitis (NEC) is a costly morbidity in very low birth weight (VLBW; <1,500 g birth weight) infants that increases hospital length of stay and requires expensive treatments. To evaluate the cost of NEC as a function of dose and exposure period of human milk (HM) feedings received by VLBW infants during the neonatal intensive care unit (NICU) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC. This study included 291 VLBW infants enrolled in an NIH-funded prospective observational cohort study between February 2008 and July 2012. We examined the incidence of NEC, NICU hospitalization cost, and cost of individual resources used during the NICU hospitalization. Twenty-nine (10.0%) infants developed NEC. The average total NICU hospitalization cost (in 2012 USD) was USD 180,163 for infants with NEC and USD 134,494 for infants without NEC (p = 0.024). NEC was associated with a marginal increase in costs of USD 43,818, after controlling for demographic characteristics, risk of NEC, and average daily dose of HM during days 1-14 (p < 0.001). Each additional ml/kg/day of HM during days 1-14 decreased non-NEC-related NICU costs by USD 534 (p < 0.001). Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants. Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs. © 2015 S. Karger AG, Basel.

Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants

PubMed Central

Johnson, Tricia J.; Patel, Aloka L.; Bigger, Harold R.; Engstrom, Janet L.; Meier, Paula P.

2015-01-01

Background Necrotizing enterocolitis (NEC) is a costly morbidity in very low birth weight (VLBW; <1500g birth weight) infants that increases hospital length of stay and requires expensive treatments. Objectives To evaluate the cost of NEC as a function of dose and exposure period of human milk (HM) feedings received by VLBW infants during the neonatal intensive care unit (NICU) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC. Methods This study included 291 VLBW infants enrolled in an NIH-funded prospective observational cohort study between February 2008 and July 2012. We examined the incidence of NEC, NICU hospitalization cost, and cost of individual resources used during the NICU hospitalization. Results Twenty-nine (10.0%) infants developed NEC. The average total NICU hospitalization cost (in 2012 dollars) was $180,163 for infants with NEC and $134,494 for infants without NEC (p=0.024). NEC was associated with a marginal increase in costs of $43,818, after controlling for demographic characteristics, risk of NEC and average daily dose of HM during Days 1–14 (p<0.001). Each additional mL/kg/day of HM during Days 1–14 decreased non-NEC-related NICU costs by $534 (p<0.001). Conclusions Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants. Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs. PMID:25765818

The leaded apron revisited: does it reduce gonadal radiation dose in dental radiology?

PubMed

Wood, R E; Harris, A M; van der Merwe, E J; Nortjé, C J

1991-05-01

A tissue-equivalent anthropomorphic human phantom was used with a lithium fluoride thermoluminescent dosimetry system to evaluate the radiation absorbed dose to the ovarian and testicular region during dental radiologic procedures. Measurements were made with and without personal lead shielding devices consisting of thyroid collar and apron of 0.25 mm lead thickness equivalence. The radiation absorbed dose with or without lead shielding did not differ significantly from control dosimeters in vertex occlusal and periapical views (p greater than 0.05). Personal lead shielding devices did reduce gonadal dose in the case of accidental exposure (p less than 0.05). A leaded apron of 0.25 mm lead thickness equivalent was permeable to radiation in direct exposure testing.

Radiotherapy Dose Fractionation under Parameter Uncertainty

NASA Astrophysics Data System (ADS)

Davison, Matt; Kim, Daero; Keller, Harald

2011-11-01

In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.

Reducing signs of aging and increasing lifespan by drug synergy.

PubMed

Huang, Xinhe; Liu, Jun; Withers, Bradley R; Samide, Aaron J; Leggas, Markos; Dickson, Robert C

2013-08-01

Disease incidence rises rapidly with age and increases both human suffering and economic hardship while shortening life. Advances in understanding the signaling pathways and cellular processes that influence aging support the possibility of reducing the incidence of age-related diseases and increasing lifespan by pharmacological intervention. Here, we demonstrate a novel pharmacological strategy that both reduces signs of aging in the budding yeast Saccharomyces cerevisiae and generates a synergistic increase in lifespan. By combining a low dose of rapamycin, to reduce activity of the target of rapamycin complex 1 (TORC1) protein kinase, and myriocin, to reduce sphingolipid synthesis, we show enhancement of autophagy, genomic stability, mitochondrial function, and AMP kinase pathway activity. These processes are controlled by evolutionarily conserved signal transduction pathways that are vital for maintaining a healthy state and promoting a long life. Thus, our data show that it ought to be possible to find pharmacological approaches to generate a synergistic reduction in the incidence of human age-related diseases to improve health quality in the elderly and enhance lifespan. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

[Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

PubMed

Koterov, A N; Ushenkova, L N; Biryukov, A P

2016-01-01

reduce the strength of associations for RET/PTC in total. On the basis of ordinal scale doses (background, "low" (0.1 Gy), "middle" (0.1-1 Gy) and "large" (1-10 Gy) dose) also found was a significant correlation (Spearman) with the dose for the frequency RET/PTC in total (r = 0.736; p = 0.0098), but for certain types of rearrangements the results were reverse to the previous analysis (the effect was significant only for the RET/PTC3: r = 0.731; p = 0.024). The linear dose-response trends of the Cochrane-Armitage-test for the frequency of RET/PTC in total, RET/PTC1 and RET/PTC3 depending on the dose to the thyroid in the ordinal scale were registered (p, respectively: < 0.0001 < 0.0001 and 0.007). Thus; after more than 20 years of the molecular and epidemiological research of RET/PTC in thyroid radiogenic carcinomas the comprehensive evidence of the dose-effect dependence existence indicating a real relationship between the studied parameters and a radiation factor was obtained for the first time.

SU-F-18C-11: Diameter Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakalyar, D; McKenney, S; Feng, W

Purpose: The radial dose distribution in the central plane of a long cylinder following a long CT scan depends upon the diameter and composition of the cylinder. An understanding of this behavior is required for determining the spatial average of the dose in the central plane. Polyethylene, the material for construction of the TG200/ICRU phantom (30 cm in diameter) was used for this study. Size effects are germane to the principles incorporated in size specific dose estimates (SSDE); thus diameter dependency was explored as well. Method: ssuming a uniform cylinder and cylindrically symmetric conditions of irradiation, the dose distribution canmore » be described using a radial function. This function must be an even function of the radial distance due to the conditions of symmetry. Two effects are accounted for: The direct beam makes its weakest contribution at the center while the contribution due to scatter is strongest at the center and drops off abruptly at the outer radius. An analytic function incorporating these features was fit to Monte Carlo results determined for infinite polyethylene cylinders of various diameters. A further feature of this function is that it is integrable. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. The competing effects described above can Resultin an absolute maximum occurring between the center and outer edge of the cylinders. For the smallest cylinders, the maximum dose may occur at the center. Conclusion: An integrable, analytic function can be used to characterize the radial dependency of dose for cylindrical CT phantoms of various sizes. One use for this is to help determine average dose distribution over the central cylinder plane when equilibrium dose has been reached.« less

Reducing US Oil Dependence Using Simulation

NASA Technical Reports Server (NTRS)

Ayoub, Fadi; Arnaout, Georges M.

2011-01-01

People across the world are addicted to oil; as a result, the instability of oil prices and the shortage of oil reserves have influenced human behaviors and global businesses. Today, the United States makes up only 5% of the global population but consumes 25% of the. world total energy. Most of this energy is generated from fossil fuels in the form of electricity. The contribution of this paper is to examine the possibilities of replacing fossil fuel with renewable energies to generate electricity as well as to examine other methods to reduce oil and gas consumption. We propose a system dynamics model in an attempt to predict the future US dependence on fossil fuels by using renewable energy resources such as, nuclear, wind, solar, and hydro powers. Based on the findings of our model, the study expects to provide insights towards promising solutions of the oil dependency problem.

Dose-dependent interaction between gemfibrozil and repaglinide in humans: strong inhibition of CYP2C8 with subtherapeutic gemfibrozil doses.

PubMed

Honkalammi, Johanna; Niemi, Mikko; Neuvonen, Pertti J; Backman, Janne T

2011-10-01

Gemfibrozil 1-O-β-glucuronide inactivates CYP2C8 irreversibly. We investigated the effect of gemfibrozil dose on CYP2C8 activity in humans using repaglinide as a probe drug. In a randomized, five-phase crossover study, 10 healthy volunteers ingested 0.25 mg of repaglinide 1 h after different doses of gemfibrozil or placebo. Concentrations of plasma repaglinide, gemfibrozil, their metabolites, and blood glucose were measured. A single gemfibrozil dose of 30, 100, 300, and 900 mg increased the area under the concentration-time curve of repaglinide 1.8-, 4.5-, 6.7-, and 8.3-fold (P < 0.001), and its peak concentration 1.4-, 1.7-, 2.1-, and 2.4-fold (P < 0.05), compared with placebo, respectively. Gemfibrozil pharmacokinetics was characterized by a slightly more than dose-proportional increase in the area under the curve of gemfibrozil and its glucuronide. The gemfibrozil-repaglinide interaction could be mainly explained by gemfibrozil 1-O-β-glucuronide concentration-dependent, mechanism-based inhibition of CYP2C8, with a minor contribution by competitive inhibition of organic anion-transporting polypeptide 1B1 at the highest gemfibrozil dose. The findings are consistent with ∼50% inhibition of CYP2C8 already with a single 30-mg dose of gemfibrozil and >95% inhibition with 900 mg. In clinical drug-drug interaction studies, a single 900-mg dose of gemfibrozil can be used to achieve nearly complete inactivation of CYP2C8.

Systemic SMAD7 Gene Therapy Increases Striated Muscle Mass and Enhances Exercise Capacity in a Dose-Dependent Manner.

PubMed

Maricelli, Joseph W; Bishaw, Yemeserach M; Wang, Bo; Du, Min; Rodgers, Buel D

2018-03-01

Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated virus (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and, as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to improve systemic muscle function similarly, especially exercise capacity. A 2-month-long dose-escalation study was therefore conducted using 5 × 10 11 , 1 × 10 12 , and 5 × 10 12 vg/mouse and different tests of systemic muscle function. Body mass, skeletal muscle mass, heart mass, and forelimb grip strength were all increased in a dose-dependent manner, as was the fiber cross-sectional area of tibialis anterior muscles. Maximal oxygen consumption (VO 2 max), a measure of metabolic rate, was similarly enhanced during forced treadmill running, and although the total distance traveled was only elevated by the highest dose, all doses reduced the energy expenditure rate compared to control mice injected with an empty vector. Such improvements in VO 2 max are consistent with physiological cardiac hypertrophy, which is highly beneficial and a normal adaptive response to exercise. This was particularly evident at the lowest dose tested, which had minimal significant effects on skeletal muscle mass and/or function, but increased heart weight and exercise capacity. These results together suggest that AVGN7 enhances striated muscle mass and systemic muscle function. They also define minimally effective and optimal doses for future preclinical trials and toxicology studies and in turn will aid in establishing dose ranges for clinical trials.

Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.

PubMed

Younger, Jarred; Mackey, Sean

2009-01-01

Fibromyalgia is a chronic pain disorder that is characterized by diffuse musculoskeletal pain and sensitivity to mechanical stimulation. In this pilot clinical trial, we tested the effectiveness of low-dose naltrexone in treating the symptoms of fibromyalgia. Participants completed a single-blind, crossover trial with the following time line: baseline (2 weeks), placebo (2 weeks), drug (8 weeks), and washout (2 weeks). Ten women meeting criteria for fibromyalgia and not taking an opioid medication. Naltrexone, in addition to antagonizing opioid receptors on neurons, also inhibits microglia activity in the central nervous system. At low doses (4.5 mg), naltrexone may inhibit the activity of microglia and reverse central and peripheral inflammation. Participants completed reports of symptom severity everyday, using a handheld computer. In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity. Low-dose naltrexone reduced fibromyalgia symptoms in the entire cohort, with a greater than 30% reduction of symptoms over placebo. In addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug. Side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Baseline erythrocyte sedimentation rate predicted over 80% of the variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone. We conclude that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.

Incident angle dependence of proton response of CR-39 (TS-16) track detector

NASA Technical Reports Server (NTRS)

Oda, K.; Csige, I.; Yamauchi, T.; Miyake, H.; Benton, E. V.

1993-01-01

The proton response of the TS-16 type of CR-39 plastic nuclear track detector has been studied with accelerated and fast neutron induced protons in vacuum and in air. The diameters of etched tracks were measured as a function of etching time and the etch rate ratio and the etch induction layer were determined from the growth curve of the diameter using a variable etch rate ratio model. In the case of the accelerated protons in vacuum an anomalous incident angle dependence of the response is observed.

A dose ranging study of ibuprofen suspension as an antipyretic.

PubMed Central

Marriott, S C; Stephenson, T J; Hull, D; Pownall, R; Smith, C M; Butler, A

1991-01-01

A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic. PMID:1929509

Dose-dependent high-resolution electron ptychography

NASA Astrophysics Data System (ADS)

D'Alfonso, A. J.; Allen, L. J.; Sawada, H.; Kirkland, A. I.

2016-02-01

Recent reports of electron ptychography at atomic resolution have ushered in a new era of coherent diffractive imaging in the context of electron microscopy. We report and discuss electron ptychography under variable electron dose conditions, exploring the prospects of an approach which has considerable potential for imaging where low dose is needed.

Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

NASA Astrophysics Data System (ADS)

Fontenot, Jonas; Taddei, Phillip; Zheng, Yuanshui; Mirkovic, Dragan; Jordan, Thomas; Newhauser, Wayne

2008-03-01

Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy-1. Sensitivity analysis revealed that E/D varied by ±30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy-1 in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy-1 in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.

WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, D; Debeb, B; Larson, R

Purpose: Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with acute lymphoblastic leukemia and small-cell lung cancer. We examined whether PCI could benefit breast cancer patients at high risk of developing brain metastases. Methods: We utilized our mouse model in which 500k green fluorescent protein (GFP)-labeled breast cancer cells injected into the tail vein of SCID/Beige mice resulted in brain metastases in approximately two-thirds of untreated mice. To test the efficacy of PCI, one set of mice was irradiated five days after cell injection withmore » a single fraction of 4-Gy (two 2-Gy opposing fields) whole-brain irradiation on the XRAD 225Cx small-animal irradiator. Four controls were included: a non-irradiated group, a group irradiated two days prior to cell injection, and two groups irradiated 3 or 6 weeks after cell injection. Mice were sacrificed four and eight weeks post-injection and were evaluated for the presence of brain metastases on a fluorescent stereomicroscope. Results: The incidence of brain metastasis in the non-irradiated group was 77% and 90% at four and eight weeks, respectively. The PCI group had a significantly lower incidence, 20% and 30%, whereas the other three control groups had incidence rates similar to the non-treated control (70% to 100%). Further, the number of metastases and the metastatic burden were also significantly lower in the PCI group compared to all other groups. Conclusion: The timing of irradiation to treat subclinical disease is critical, as a small dose of whole-brain irradiation given five days after cell injection abrogated tumor burden by greater than 90%, but had no effect when administered twenty-one days after cell injection. PCI is likely to benefit breast cancer patients at high risk of developing brain metastases and should be strongly considered in the clinic.« less

Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial.

PubMed

Denham, James W; Steigler, Allison; Joseph, David; Lamb, David S; Spry, Nigel A; Duchesne, Gillian; Atkinson, Chris; Matthews, John; Turner, Sandra; Kenny, Lizbeth; Tai, Keen-Hun; Gogna, Nirdosh Kumar; Gill, Suki; Tan, Hendrick; Kearvell, Rachel; Murray, Judy; Ebert, Martin; Haworth, Annette; Kennedy, Angel; Delahunt, Brett; Oldmeadow, Christopher; Holliday, Elizabeth G; Attia, John

2015-06-01

The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS±18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (p<0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively. RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Angular dependence of the nanoDot OSL dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerns, James R.; Kry, Stephen F.; Sahoo, Narayan

Purpose: Optically stimulated luminescent detectors (OSLDs) are quickly gaining popularity as passive dosimeters, with applications in medicine for linac output calibration verification, brachytherapy source verification, treatment plan quality assurance, and clinical dose measurements. With such wide applications, these dosimeters must be characterized for numerous factors affecting their response. The most abundant commercial OSLD is the InLight/OSL system from Landauer, Inc. The purpose of this study was to examine the angular dependence of the nanoDot dosimeter, which is part of the InLight system. Methods: Relative dosimeter response data were taken at several angles in 6 and 18 MV photon beams, asmore » well as a clinical proton beam. These measurements were done within a phantom at a depth beyond the build-up region. To verify the observed angular dependence, additional measurements were conducted as well as Monte Carlo simulations in MCNPX. Results: When irradiated with the incident photon beams parallel to the plane of the dosimeter, the nanoDot response was 4% lower at 6 MV and 3% lower at 18 MV than the response when irradiated with the incident beam normal to the plane of the dosimeter. Monte Carlo simulations at 6 MV showed similar results to the experimental values. Examination of the results in Monte Carlo suggests the cause as partial volume irradiation. In a clinical proton beam, no angular dependence was found. Conclusions: A nontrivial angular response of this OSLD was observed in photon beams. This factor may need to be accounted for when evaluating doses from photon beams incident from a variety of directions.« less

Health Benefits from Nature Experiences Depend on Dose

NASA Astrophysics Data System (ADS)

Shanahan, Danielle F.; Bush, Robert; Gaston, Kevin J.; Lin, Brenda B.; Dean, Julie; Barber, Elizabeth; Fuller, Richard A.

2016-06-01

Nature within cities will have a central role in helping address key global public health challenges associated with urbanization. However, there is almost no guidance on how much or how frequently people need to engage with nature, and what types or characteristics of nature need to be incorporated in cities for the best health outcomes. Here we use a nature dose framework to examine the associations between the duration, frequency and intensity of exposure to nature and health in an urban population. We show that people who made long visits to green spaces had lower rates of depression and high blood pressure, and those who visited more frequently had greater social cohesion. Higher levels of physical activity were linked to both duration and frequency of green space visits. A dose-response analysis for depression and high blood pressure suggest that visits to outdoor green spaces of 30 minutes or more during the course of a week could reduce the population prevalence of these illnesses by up to 7% and 9% respectively. Given that the societal costs of depression alone in Australia are estimated at AUD$12.6 billion per annum, savings to public health budgets across all health outcomes could be immense.

Schistosoma mansoni: is acquired immunity induced by highly x-irradiated cercariae dependent on the size of the challenging dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsue, S.Y.; Hsue, H.F.; Osborne, J.W.

1982-04-01

A high degree of immunity, as shown by a 91% reduction of the number of worms recovered was found in five groups of mice that were immunized five times with highly X-irradiated cercariae and then challenged with 10, 20, 50, 100, or 500 normal Schistosoma mansoni cercariae. The results indicated that there were no significant differences in worm reduction in immunized mice challenged with different numbers of cercariae; consequently the immunity induced by this immunization method did not appear to be challenge-dose-dependent. However, the results also showed that when immunized mice were challenged with 500, 100, 50, 20, and 10more » cercariae, 0, 13, 26, 56, and 68%, respectively, of the experimental animals were free of worms. Thus, the percentage of worm-negative cases increased as the number of challenge cercariae decreased. When viewed in this manner, the acquired immunity may be considered challenge-dose-dependent as well. If this method of vaccination is used for schistosomiasis control, we may anticipate that in both hypo- and hyperendemic areas, the intensity of infection and the severity of the disease will be reduced owing to a reduction in worms burdens, and in hypoendemic areas, there will be a number of worm-free cases.« less

A feasibility study on the use of phantoms with statistical lung masses for determining the uncertainty in the dose absorbed by the lung from broad beams of incident photons and neutrons

PubMed Central

Khankook, Atiyeh Ebrahimi; Hakimabad, Hashem Miri

2017-01-01

Abstract Computational models of the human body have gradually become crucial in the evaluation of doses absorbed by organs. However, individuals may differ considerably in terms of organ size and shape. In this study, the authors sought to determine the energy-dependent standard deviations due to lung size of the dose absorbed by the lung during external photon and neutron beam exposures. One hundred lungs with different masses were prepared and located in an adult male International Commission on Radiological Protection (ICRP) reference phantom. Calculations were performed using the Monte Carlo N-particle code version 5 (MCNP5). Variation in the lung mass caused great uncertainty: ~90% for low-energy broad parallel photon beams. However, for high-energy photons, the lung-absorbed dose dependency on the anatomical variation was reduced to <1%. In addition, the results obtained indicated that the discrepancy in the lung-absorbed dose varied from 0.6% to 8% for neutron beam exposure. Consequently, the relationship between absorbed dose and organ volume was found to be significant for low-energy photon sources, whereas for higher energy photon sources the organ-absorbed dose was independent of the organ volume. In the case of neutron beam exposure, the maximum discrepancy (of 8%) occurred in the energy range between 0.1 and 5 MeV. PMID:28077627

An organ-based approach to dose calculation in the assessment of dose-dependent biological effects of ionising radiation in Arabidopsis thaliana.

PubMed

Biermans, Geert; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Saenen, Eline; Van Hees, May; Wannijn, Jean; Vives i Batlle, Jordi; Cuypers, Ann

2014-07-01

There is a need for a better understanding of biological effects of radiation exposure in non-human biota. Correct description of these effects requires a more detailed model of dosimetry than that available in current risk assessment tools, particularly for plants. In this paper, we propose a simple model for dose calculations in roots and shoots of Arabidopsis thaliana seedlings exposed to radionuclides in a hydroponic exposure setup. This model is used to compare absorbed doses for three radionuclides, (241)Am (α-radiation), (90)Sr (β-radiation) and (133)Ba (γ radiation). Using established dosimetric calculation methods, dose conversion coefficient values were determined for each organ separately based on uptake data from the different plant organs. These calculations were then compared to the DCC values obtained with the ERICA tool under equivalent geometry assumptions. When comparing with our new method, the ERICA tool appears to overestimate internal doses and underestimate external doses in the roots for all three radionuclides, though each to a different extent. These observations might help to refine dose-response relationships. The DCC values for (90)Sr in roots are shown to deviate the most. A dose-effect curve for (90)Sr β-radiation has been established on biomass and photosynthesis endpoints, but no significant dose-dependent effects are observed. This indicates the need for use of endpoints at the molecular and physiological scale. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cystathionine beta synthase gene dose dependent vascular remodeling in murine model of hyperhomocysteinemia.

PubMed

Tyagi, Neetu; Qipshidze, Natia; Sen, Utpal; Rodriguez, Walter; Ovechkin, Alexander; Tyagi, Suresh C

2011-09-30

Although children born with severe homocystinurea (i.e. cystathionine beta synthase homozygote knockout, CBS-/-) develop deleterious vascular complications with structural malformation and do not live past teenage, the heterozygote (CBS-/+) lives with apparently normal phenotype. Interestingly, this differential role of CBS expression in vascular remodeling is unclear. Peroxisome proliferator activated receptor gamma (PPARγ) is nuclear transcription factor that mitigates vascular complications. The hypothesis was that homocysteine (Hcy) decreased thioredoxin (Trx), peroxiredoxin (Prx), increased NADPH oxidase (NOX1), mitochondrial nitric oxide synthase (mtNOS) activity and reactive oxygen species (ROS) in mitochondria in a CBS gene dose-dependent manner. ROS transduced matrix metalloproteinase (MMP) activation causing thickening (fibrosis) of the basement membrane, rendering ineffective endothelial nitric oxide synthase (eNOS) and promoted endothelial-smooth muscle disconnection/uncoupling by antagonizing PPARγ. Wild type (WT-CBS+/+), CBS-/+ and CBS -/- mice were treated with or without ciglitazone (CZ, a PPARγ agonist) in food at birth. Aortic nuclear PPARγ expression was measured by EMSA. Aortic mtNOS activity and ROS production was measured using NO- and H(2)O(2)-electrodes, respectively. Aorta was analyzed for Trx, Prx, by Western blot, and PCR. MMP activity was by in situ zymography. Aortic function was measured in tissue myobath. The results suggested 90% morbidity in CBS-/- allele at 12 wks. However, treatment with the PPARγ agonist, CZ significantly reduced the morbidity to 20%. In addition, CZ restored the PPARγ activity in CBS-/+ and -/- mice to normal levels. The oxidative stress was alleviated by CZ treatment. In situ labeling with mito-tracker suggests co-localization of ROS with mitochondrial mitophagy. The mtNOS activity was increased in HHcy compared to WT. The data support the notion that Hcy decreases redoxins, increases mtNOS activity and

Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells

PubMed Central

Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

2015-01-01

Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body γ-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to γ-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

Adherence to Mediterranean Diet Reduces Incident Frailty Risk: Systematic Review and Meta-Analysis.

PubMed

Kojima, Gotaro; Avgerinou, Christina; Iliffe, Steve; Walters, Kate

2018-04-01

To conduct a systematic review of the literature on prospective cohort studies examining associations between adherence to a Mediterranean diet and incident frailty and to perform a meta-analysis to synthesize the pooled risk estimates. Systematic review and meta-analysis. Embase, MEDLINE, CINAHL, PsycINFO, and Cochrane Library were systematically searched on September 14, 2017. We reviewed references of included studies and relevant review papers and performed forward citation tracking for additional studies. Corresponding authors were contacted for additional data necessary for a meta-analysis. Community-dwelling older adults (mean age ≥60). Incident frailty risk according to adherence to a Mediterranean diet. Two reviewers independently screened the title, abstract, and full text to ascertain the eligibility of 125 studies that the systematic search of the literature identified, and four studies were included (5,789 older people with mean follow-up of 3.9 years). Two reviewers extracted data from the studies independently. All four studies provided adjusted odds ratios (ORs) of incident frailty risk according to three Mediterranean diet score (MDS) groups (0-3, 4-5, and 6-9). Greater adherence to a Mediterranean diet was associated with significantly lower incident frailty risk (pooled OR = 0.62, 95% CI = 0.47-0.82, P = .001 for MDS 4-5; pooled OR = 0.44, 95% CI = 0.31-0.64, P < .001 for MDS 6-9) than poorer adherence (MDS 0-3). Neither significant heterogeneity (I 2  = 0-16%, P = .30) nor evidence of publication bias was observed. Greater adherence to a Mediterranean diet is associated with significantly lower risk of incident frailty in community-dwelling older people. Future studies should confirm these findings and evaluate whether adherence to a Mediterranean diet can reduce the risk of frailty, including in non-Mediterranean populations. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Impact of FIB-4 index on hepatocellular carcinoma incidence during nucleos(t)ide analogue therapy in patients with chronic hepatitis B: An analysis using time-dependent receiver operating characteristic.

PubMed

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Tsuji, Kunihiko; Hiraoka, Atsushi; Tanaka, Junko

2017-02-01

Nucleos(t)ide analogue (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). However, even during NA therapy, development of HCC has been observed in patients with CHB. Therefore, we clarified the predictive power of clinical factors for HCC incidence using receiver operating characteristic (ROC) analysis that takes time dependence into account. A total of 539 patients with CHB treated with NAs were enrolled. Univariate, multivariate, and time-dependent ROC curves for clinical factors associated with the development of HCC were analyzed. Eighty-one patients developed HCC during the follow-up period (median duration, 5.9 years). α-fetoprotein (AFP) and FIB-4 index at 24 weeks from the initiation of treatment and sex were significantly associated with HCC incidence according to the log-rank test. Cox proportional hazards models including the covariates of sex, hepatitis B genotype, basal core promoter mutations, AFP at 24 weeks, and FIB-4 index at 24 weeks showed that FIB-4 index >2.65 (HR, 5.03; 95% CI, 3.06-8.26; P < 0.001) and male sex were independently associated with HCC incidence. In addition, time-dependent ROC analysis showed that compared with AFP at 24 weeks, FIB-4 index at 24 weeks had higher predictive power for HCC incidence throughout the follow-up period. Elevated FIB-4 index at 24 weeks in patients with CHB receiving NA therapy is a risk factor for developing HCC. The FIB-4 index is an excellent predictor of HCC development. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karunamuni, Roshan; Bartsch, Hauke; White, Nathan S.

Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thicknessmore » between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.« less

The incidence of blood contamination of lead unit dose containers with and without single-use protective inserts used with commercially prepared radiopharmaceutical unit doses.

PubMed

Pickett, M W; Kosegi, J E; Thomas, K S; Waterstram-Rich, K M

1998-09-01

This investigation evaluated the effectiveness of disposable plastic inserts in radiopharmaceutical unit dose lead containers (pigs) in preventing the distribution of doses in blood-contaminated containers. Technologists commonly dispose of the syringes by placing them into the lead pigs, leaving the needles uncapped. This process raises the question of unsuspected blood contamination of these pigs. Consequently, the distribution of commercially prepared radiopharmaceutical doses in reusable lead pigs may result in radiopharmaceutical doses being distributed in containers that are contaminated with blood. Using a simple chemical wipe test designed to determine the presence or absence of blood contamination, 618 pigs from commercial radiopharmacies throughout the U.S. were tested for contamination. The inside of the pigs and inserts, if present, were wiped before and after dose administration. Of the pigs tested, 292 came from radiopharmacies that used a protective, disposable plastic insert inside the pig, and 326 came from radiopharmacies that did not use an insert. Of those pigs without the protective disposable inserts, 39.3% arrived in the nuclear medicine department in pigs contaminated with blood. Of those pigs with inserts, 1% arrived with blood-contaminated inserts. After dose administration, 46.3% of the pigs without inserts were contaminated with blood and 3% of the protective inserts were contaminated. The proper use of disposable plastic inserts reduces the possibility of distributing radiopharmaceutical unit doses in containers contaminated with blood.

Reirradiation of Large-Volume Recurrent Glioma With Pulsed Reduced-Dose-Rate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adkison, Jarrod B.; Tome, Wolfgang; Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI

2011-03-01

Purpose: Pulsed reduced-dose-rate radiotherapy (PRDR) is a reirradiation technique that reduces the effective dose rate and increases the treatment time, allowing sublethal damage repair during irradiation. Patients and Methods: A total of 103 patients with recurrent glioma underwent reirradiation using PRDR (86 considered to have Grade 4 at PRDR). PRDR was delivered using a series of 0.2-Gy pulses at 3-min intervals, creating an apparent dose rate of 0.0667 Gy/min to a median dose of 50 Gy (range, 20-60) delivered in 1.8-2.0-Gy fractions. The mean treatment volume was 403.5 {+-} 189.4 cm{sup 3} according to T{sub 2}-weighted magnetic resonance imaging andmore » a 2-cm margin. Results: For the initial or upgraded Grade 4 cohort (n = 86), the median interval from the first irradiation to PRDR was 14 months. Patients undergoing PRDR within 14 months of the first irradiation (n = 43) had a median survival of 21 weeks. Those treated {>=}14 months after radiotherapy had a median survival of 28 weeks (n = 43; p = 0.004 and HR = 1.82 with a 95% CI ranging from 1.25 to 3.10). These data compared favorably to historical data sets, because only 16% of the patients were treated at first relapse (with 46% treated at the second relapse, 32% at the third or fourth relapse, and 4% at the fourth or fifth relapse). The median survival since diagnosis and retreatment was 6.3 years and 11.4 months for low-grade, 4.1 years and 5.6 months for Grade 3, and 1.6 years and 5.1 months for Grade 4 tumors, respectively, according to the initial histologic findings. Multivariate analysis revealed age at the initial diagnosis, initial low-grade disease, and Karnofsky performance score of {>=}80 to be significant predictors of survival after initiation of PRDR. Conclusion: PRDR allowed for safe retreatment of larger volumes to high doses with palliative benefit.« less

Dose-dependent pheromone responses of mountain pine beetle in stands of lodgepole pine

Treesearch

Daniel R. Miller; B. Staffan Lindgren; John H. Borden

2005-01-01

We conducted seven behavioral choice tests with Lindgren multiple-funnel traps in stands of mature lodgepole pine in British Columbia, from 1988 to 1994, to determine the dosedependent responses of the mountain pine beetle, Dendroctonus ponderosae Hopkins, to its pheromones. Amultifunctional dose-dependent response was exhibited by D. ...

Effectiveness of Exergaming Training in Reducing Risk and Incidence of Falls in Frail Older Adults With a History of Falls.

PubMed

Fu, Amy S; Gao, Kelly L; Tung, Arthur K; Tsang, William W; Kwan, Marcella M

2015-12-01

To use Nintendo's Wii Fit balance board to determine the effectiveness of exergaming training in reducing risk and incidence of falls in older adults with a history of falls. Randomized controlled trial. Nursing home for older adults. Adults aged 65 years and older (N=60). Participants who lived in a nursing home had 6 weeks of balance training with either Wii Fit equipment or conventional exercise. Physiological Profile Assessment scores and incidence of falls were observed with subsequent intention-to-treat statistical analyses. Physiological Profile Assessment scores and incidence of falls improved significantly in both groups after the intervention (all P<.01), but participants in the Wii Fit training group showed a significantly greater improvement in both outcome measures (P=.004 and P<.001, respectively). In institutionalized older adults with a history of falls, Wii Fit balance training was more effective than conventional balance training in reducing the risk and incidence of falls. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Dose-dependent inhibition of gastric injury by hydrogen in alkaline electrolyzed drinking water

PubMed Central

2014-01-01

Background Hydrogen has been reported to relieve damage in many disease models, and is a potential additive in drinking water to provide protective effects for patients as several clinical studies revealed. However, the absence of a dose–response relationship in the application of hydrogen is puzzling. We attempted to identify the dose–response relationship of hydrogen in alkaline electrolyzed drinking water through the aspirin induced gastric injury model. Methods In this study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed water at one atmosphere pressure. After 2 weeks of drinking, we detected the gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced gastric injury model. Results Hydrogen-dose dependent inhibition was observed in stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high correlation with inhibitory effects showed by erosion area, MPO activity and MDA content in the stomach. Gastric histology also demonstrated the inhibition of damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not significant inhibitory response compared with pH 8.5. Conclusions Hydrogen is effective in relieving the gastric injury induced by aspirin-HCl, and the inhibitory effect is dose-dependent. The reason behind this may be that hydrogen-rich water directly interacted with the target tissue, while the hydrogen concentration in blood was buffered by liver glycogen, evoking a suppressed dose–response effect. Drinking hydrogen-rich water may protect healthy individuals from gastric damage caused by oxidative stress. PMID:24589018

Quantitative effect of combined chemotherapy and fractionated radiotherapy on the incidence of radiation-induced lung damage: A prospective clinical study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mah, K.; Van Dyk, J.; Braban, L.E.

1994-02-01

The objective of this work was to assess the incidence of radiological changes compatible with radiation-induced lung damage as determined by computed tomography (CT), and subsequently calculate the dose effect factors (DEF) for specified chemotherapeutic regimens. Radiation treatments were administered once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, adriamycin, and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent with either 50-52more » Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations were taken before and at predetermined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung density within the irradiated volume. The radiation dose to lung was calculated using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect models, the estimated single dose (ED) and the normalized total dose (NTD). The actuarial incidence of radiological pneumonitis was 71% for the ABVD, 49% for MOPP, 52% for MOPP/ABVD, 67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols. Depending on the isoeffect model selected and the method of analysis, the DEF was 1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1.03-1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU palliative protocols. DEF were measured by comparing the incidence of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those receiving radiotherapy alone. The addition of ABVD or CAV appeared to reduce the tolerance of lung to radiation. 40 refs., 3 figs., 3 tabs.« less

p-MOSFET total dose dosimeter