[Dose-response of aspirin on platelet function in very elderly patients].

PubMed

Feng, X R; Liu, M L; Liu, F; Fan, Y; Tian, Q P

2016-10-18

To assess the consequences of switching aspirin dosage from 100 mg/d to 40 mg/d on cardiovascular benefit, bleeding risk and platelet aggregation in very elderly patients. Arachidonic acid induced platelet aggregation(AA-Ag) was measured in 537 patients aged 80 or older treated with aspirin (100 mg/d). In the study, 100 patients with low on-treatment platelet aggregation and at high risk of bleeding and low risk of cardiovascular events, were switched to aspirin (40 mg/d) and their platelet aggregation was measured again 7 days later.Their bleeding and upper gastrointestinal symptoms were also recorded in following 3 months. The study observed a heterogeneous distributed aspirin 100 mg/d AA-Ag (range: 0.42% to 28.78%)in the 537 very elderly patients.Aspirin 100 mg/d AA-Ag before the switch in aspirin 40 mg/d group was 5.00%±2.32% and the rate of the patients with low on-treatment platelet aggregation was 71.00%. The rates of melena or occult blood positive, other minimal bleeding,upper gastrointestinal symptoms and a history of gastrointestinal bleeding in 40 mg/d group were higher than those in 100 mg/d group. On a regimen of aspirin 40 mg/d, AA-Ag increased to 11.21%±4.95%(range: 2.12% to 28.84%) with 95.00%of the patients with AA-Ag<20% and the rate of the patients with low on-treatment platelet aggregation was 15.00%. Multiple variable analysis revealed that aspirin 40 mg/d AA-Ag was significantly influenced by aspirin 100 mg/d AA-Ag, BMI and platelet counts. The rate of gastrointestinal bleeding decreased from 12.00% to 5.00%,and upper gastrointestinal symptoms decreased from 59.00% to 21.00% after the switch in 40 mg/d group. Switching aspirin dosage from 100 mg/d to 40 mg/d reduces the bleeding events and improves upper gastrointestinal symptoms, thus inhibiting platelet aggregation effectively in very elderly patients.

Efficacy and Safety of S-Amlodipine 2.5 and 5 mg/d in Hypertensive Patients Who Were Treatment-Naive or Previously Received Antihypertensive Monotherapy.

PubMed

Şen, Selçuk; Demir, Meral; Yiğit, Zerrin; Üresin, Ali Yağız

2018-07-01

The aim of the present study was to evaluate the efficacy and safety of S-amlodipine 2.5 and 5 mg/d in patients with hypertension who were treatment-naive or previously received antihypertensive monotherapy. During the 8-week treatment period, all patients received S-amlodipine 2.5 mg/d for the first 4 weeks, followed by S-amlodipine 5 mg/d for the second 4 weeks. For efficacy assessments, ambulatory and office blood pressure (BP) measurements were performed during the baseline, fourth-week, and eighth-week visits. For safety assessments, all adverse events and abnormal laboratory findings were recorded. This study is registered with ClinicalTrials.gov (NCT03038451). Of 43 patients evaluated at the screening visit, 33 were enrolled. In the treatment-naive arm, significant reductions in both office and ambulatory systolic BP (SBP) and diastolic BP (DBP) were observed with S-amlodipine 2.5 mg/d and additional significant reductions were achieved with dose titration (S-amlodipine 5 mg/d). At the end of the study, the rate of the treatment-naive patients with BP under control (SBP/DBP <140/90 mm Hg) was 53% with S-amlodipine 2.5 mg and increased to 78% with S-amlodipine 5 mg. For the noninferiority evaluation, S-amlodipine 2.5 and 5 mg/d treatments were generally noninferior to both office and ambulatory BP levels achieved with the medications that the patients received before participating in the study. Five nonserious adverse events likely to be associated with the study drug were observed. No serious adverse event was encountered. Consequently, S-amlodipine can be suggested as an effective and safe treatment option for patients with hypertension.

[Serum and total body potassium during treatment with chlortalidone and hydrochlorothiazide. Influence of triamterene (author's transl)].

PubMed

Schäfer, G E; Werner, E; Kober, G; Kaltenbach, M

1977-12-16

The serum and total body potassium was investigated in 25 patients with non-congestive cardaic failure before and during saluretic treatment. Treatment with triamterene (100 mg/d; n = 10) over a period of 3 weeks led to an increase of serum potassium (from 4.1 +/- 0.65 to 4.7 +/- 0.51 mmol/l) and of total body potassium (by 110 mmol). After treatment with chlortalidon for 7 days (100 mg/d; n = 6) serum potassium concentration decreased from 4.38 "/- 0.37 to 3.30 +/- 0.46 mmol/l (approximately 25%). The total body potassium decreased by 240 mmol (approximately 10%). Continuation of the treatment with a combination of chlortalidon (50 mg/d) and triamterene (150 mg/d) led to correction of the extra- and intracellular potassium loss after 1 to 2 weeks. No significant change of serum and total body potassium was found during and after 6 months of treatment with hydrochlorothiazide (50 mg/d) and triamterene (100 mg/d; n = 9). The results demonstrate the potassium loss which occurs in the early stage of saluretic treatment and show the antikaluretic potency of triamterene.

Dissipative effects in multi-component systems

NASA Astrophysics Data System (ADS)

El, Andrej; Bouras, Ioannis; Xu, Zhe; Greiner, Carsten

2013-05-01

Using a smooth initial condition of Glauber type in the kinetic transport algorithm BAMPS we investigate differences in behavior of a multi-component system and its one-component equivalent with the same η/s value. Flow harmonic coefficients v2 and v4 are shown to have very low sensitivity to the details of microscopic interactions in the system.

Citalopram and escitalopram in the treatment of major depressive disorder: a pooled analysis of 3 clinical trials.

PubMed

Li, Huafang; Li, Ting; Li, Guanjun; Luo, Jianfeng

2014-11-01

Pooled analysis is a powerful technique that is increasingly used to detect differences in efficacy between pharmacologic agents. Some studies have compared the efficacy and tolerability of citalopram and escitalopram, with contradictory results. The aim of this study was to compare the efficacy and tolerability of citalopram and escitalopram in the treatment of major depressive disorder (MDD) using pooled analyses. Data from 3 randomized, double-blind studies that compared citalopram (20 to 40 mg/d) and escitalopram (10 to 20 mg/d) were pooled and analyzed. The primary efficacy parameter was change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. Efficacy assessments were made at weeks 0 (baseline), 1, 2, 4, and 6. Based on the mean change from baseline in the HAM-D-17 at weeks 1, 2, 4, and 6, the efficacy of citalopram, 20 to 40 mg/d, was equivalent to escitalopram, 10 to 20 mg/d (P > .05). Similar results were seen for severely depressed patients, with a mean treatment difference of 13.9 (SE = 7.6) vs 15.9 (SE = 7.5). Response and remission rates at week 6 were similar (response, 72.4% for citalopram, compared with 73.5% for escitalopram; remission, 52.6% vs 54.5%, respectively). The pooled analysis showed that over a 6-week treatment period, citalopram, 20 to 40 mg/d, is equivalent to escitalopram, 10 to 20 mg/d, in both efficacy and tolerability.

Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study

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

Bradley, Kristin A., E-mail: bradley@humonc.wisc.edu; Zhou Tianni; McNall-Knapp, Rene Y.

2013-01-01

Purpose: To evaluate the effects on 1-year event-free survival (EFS) and overall survival (OS) of combining motexafin and gadolinium (MGd), a potent radiosensitizer, with daily fractionated radiation therapy in children with newly diagnosed intrinsic pontine gliomas. Methods and Materials: Patients with newly diagnosed intrinsic pontine glioma were treated with MGd daily for 5 consecutive days each week, for a total of 30 doses. Patients received a 5- to 10-min intravenous bolus of MGd, 4.4 mg/kg/day, given 2 to 5 h prior to standard dose irradiation. Radiation therapy was administered at a daily dose of 1.8 Gy for 30 treatments overmore » 6 weeks. The total dose was 54 Gy. Results: Sixty eligible children received MGd daily, concurrent with 6 weeks of radiation therapy. The estimated 1-year EFS was 18% {+-} 5%, and the estimated 1-year OS was 53% {+-} 6.5%. The most common grade 3 to 4 toxicities were lymphopenia, transient elevation of liver transaminases, and hypertension. Conclusions: Compared to historical controls, the addition of MGd to a standard 6-week course of radiation did not improve the survival of pediatric patients with newly diagnosed intrinsic pontine gliomas.« less

Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Jin, Sang-Man; Han, Kyung Ah; Yu, Jae Myung; Sohn, Tae Seo; Choi, Sung Hee; Chung, Choon Hee; Park, Ie Byung; Rhee, Eun Jung; Baik, Sei Hyun; Park, Tae Sun; Lee, In-Kyu; Ko, Seung-Hyun; Hwang, You-Cheol; Cha, Bong Soo; Lee, Hyoung Woo; Nam, Moon-Suk; Lee, Moon-Kyu

2016-10-01

To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was -7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively. Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion. © 2016 American Heart Association, Inc.

Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non-Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial

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

Mehta, Minesh P.; Shapiro, William R.; Phan, See C.

2009-03-15

Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% ofmore » the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable.« less

Longitudinal effects of dietary sodium and potassium on blood pressure in adolescent girls.

PubMed

Buendia, Justin R; Bradlee, M Loring; Daniels, Stephen R; Singer, Martha R; Moore, Lynn L

2015-06-01

Identification of risk factors early in life for the development of high blood pressure is critical to the prevention of cardiovascular disease. To study prospectively the effect of dietary sodium, potassium, and the potassium to sodium ratio on adolescent blood pressure. The National Heart, Lung, and Blood Institute's Growth and Health Study is a prospective cohort study with sites in Richmond, California; Cincinnati, Ohio; and Washington, DC. Participants included 2185 black and white girls initially aged 9 to 10 years with complete data for early-adolescent to midadolescent diet and blood pressure who were followed up for 10 years. The first examination visits were from March 1987 through February 1988 and follow-up continued until February 1999. Longitudinal mixed models and analysis of covariance models were used to assess the effect of dietary sodium, potassium, and the potassium to sodium ratio on systolic and diastolic blood pressures throughout adolescence and after 10 years of follow-up, adjusting for race, height, activity, television/video time, energy intake, and other dietary factors. Mean dietary sodium and potassium intakes and the mean potassium to sodium ratio in individuals aged 9 to 17 years. To eliminate potential confounding by energy intake, energy-adjusted sodium and potassium residuals were estimated. Mean systolic and diastolic blood pressures throughout adolescence and at the end of follow-up (individuals aged 17-21 years). Sodium intakes were classified as less than 2500 mg/d (19.4% of participants), 2500 mg/d to less than 3000 mg/d (29.5%), 3000 mg/d to less than 4000 mg/d (41.4%), and 4000 mg/d or more (9.7%). Potassium intakes ranged from less than 1800 mg/d (36.0% of participants) to 1800 mg/d to less than 2100 mg/d (26.2%), 2100 mg/d to less than 2400 mg/d (18.8%), and 2400 mg/d or more (19.0%). There was no evidence that higher sodium intakes (3000 to <4000 mg/d and ≥4000 mg/d vs <2500 mg/d) had an adverse effect on adolescent blood pressure and longitudinal mixed models showed that those consuming 3500 mg/d or more had generally lower diastolic blood pressures compared with individuals consuming less than 2500 mg/d (P = .18). However, higher potassium intakes were inversely associated with blood pressure change throughout adolescence (P < .001 for systolic and diastolic) and at the end of follow-up (P = .02 and P = .05 for systolic and diastolic, respectively). While the potassium to sodium ratio was also inversely associated with systolic blood pressure (P = .04), these effects were generally weaker compared with effects for potassium alone. In this study of adolescent girls, consumption of 3500 mg/d of sodium or more had no adverse effect on blood pressure. The beneficial effects of dietary potassium on both systolic and diastolic blood pressures suggest that consuming more potassium-rich foods during childhood may help suppress the adolescent increase in blood pressure.

Uneven Meibomian Gland Dropout Over the Tarsal Plate and its Correlation With Meibomian Gland Dysfunction.

PubMed

Yin, Yue; Gong, Lan

2015-10-01

To evaluate the distribution of meibomian gland dropout and analyze the correlation between dropout and meibomian gland dysfunction (MGD). A total of 161 eyes of 85 patients with MGD were recruited as the MGD group; 88 eyes of 46 health volunteers were enrolled as the control group (2:1 matched for age and sex). Examinations included the Schirmer I test, breakup time, symptom questionnaire, corneal fluorescein staining, meibum quality, meibomian gland expressibility, and meibomian gland dropout. (1) The incidences of chalazion and eyelid surgery were significantly higher in patients with MGD. (2) All clinical indexes were better in healthy volunteers (all P < 0.05). (3) The dropout in the upper eyelid was statistically lower (P < 0.01) in both groups. The nasal and/or temporal part had higher dropout than did the middle part, except in the lower eyelid of the control group. (4) The entire or partial dropout was positively related to MGD occurrence. Both additive dropout of the entire 2 eyelids and that of the 2 nasal parts had the strongest correlation (r = 0.792, P < 0.01). (5) In the MGD group, breakup time was most negatively related to upper nasal dropout (r = -0.229, P < 0.05). The corneal staining score was positively related only to the dropout of additive (r = 0.185, P < 0.05) and lower (r = 0.258, P < 0.05) middle parts. (1) Uneven dropouts exist in different or single eyelids. (2) Dropout evaluation is better when covering the entire area of both upper and lower meibomians. (3) Nasal part dropout plays a more essential role than the other dropouts in MGD occurrence.

Towards Standardization of X-ray Beam Filters in Digital Mammography and Digital Breast Tomosynthesis: Monte Carlo simulations and analytical modelling

PubMed Central

Shrestha, Suman; Vedantham, Srinivasan; Karellas, Andrew

2017-01-01

In digital breast tomosynthesis and digital mammography, the x-ray beam filter material and thickness vary between systems. Replacing K-edge filters with Al was investigated with the intent to reduce exposure duration and to simplify system design. Tungsten target x-ray spectra were simulated with K-edge filters (50μm Rh; 50μm Ag) and Al filters of varying thickness. Monte Carlo simulations were conducted to quantify the x-ray scatter from various filters alone, scatter-to-primary ratio (SPR) with compressed breasts, and to determine the radiation dose to the breast. These data were used to analytically compute the signal-difference-to-noise ratio (SDNR) at unit (1 mGy) mean glandular dose (MGD) for W/Rh and W/Ag spectra. At SDNR matched between K-edge and Al filtered spectra, the reductions in exposure duration and MGD were quantified for three strategies: (i) fixed Al thickness and matched tube potential in kilovolts (kV); (ii) fixed Al thickness and varying the kV to match the half-value layer (HVL) between Al and K-edge filtered spectra; and, (iii) matched kV and varying the Al thickness to match the HVL between Al and K-edge filtered spectra. Monte Carlo simulations indicate that the SPR with and without the breast were not different between Al and K-edge filters. Modelling for fixed Al thickness (700μm) and kV matched to K-edge filtered spectra, identical SDNR was achieved with 37–57% reduction in exposure duration and with 2–20% reduction in MGD, depending on breast thickness. Modelling for fixed Al thickness (700μm) and HVL matched by increasing the kV over [0,4] range, identical SDNR was achieved with 62–65% decrease in exposure duration and with 2–24% reduction in MGD, depending on breast thickness. For kV and HVL matched to K-edge filtered spectra by varying Al filter thickness over [700,880]μm range, identical SDNR was achieved with 23–56% reduction in exposure duration and 2–20% reduction in MGD, depending on breast thickness. These simulations indicate that increased fluence with Al filter of fixed or variable thickness substantially decreases exposure duration while providing for similar image quality with moderate reduction in MGD. PMID:28075335

Infrared thermography in the evaluation of meibomian gland dysfunction.

PubMed

Su, Tai-Yuan; Ho, Wei-Ting; Chiang, Shu-Chiung; Lu, Chien-Yi; Chiang, Huihua Kenny; Chang, Shu-Wen

2017-07-01

To evaluate meibomian gland dysfunction (MGD) by infrared thermography. An observational study was conducted at the Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei City, Taiwan. Participants included 89 MGD patients (30 in Grade 1, 49 in Grade 2, and 10 in Grade 3) and 65 controls. The close-eye thermographic images of the eyelid were obtained noninvasively by infrared thermography. Temperatures at 8 regions of interest (ROIs) of the eyelid margin and a reference temperature at the center of the upper eyelid were measured. The temperature ratio was defined as the temperature of ROI divided by the reference temperature. Eyelid margin temperature measured by infrared thermography increased from temporal side (ROI 1) to the nasal side (ROI 8) of the eye in both MGD patients and control groups. The temperature ratios were significantly higher in MGD participants than in controls, especially at ROI 8. The eyelid margin temperature measured by infrared thermography was higher in MGD participants. Further development of this infrared thermography system may become a rapid and non-invasive tool for MGD screening. Copyright © 2016. Published by Elsevier B.V.

The Deposition of Multicomponent Films for Electrooptic Applications via a Computer Controlled Dual Ion Beam Sputtering System

DTIC Science & Technology

1991-12-31

AD-A252 218 The Deposition of Multicomponent Films for Electrooptic Applications via a Computer Controlled Dual Ion Beam Sputtering System ONR...6 3 2. Deposition of Electrooptic Thin Films ................................... 11 3. High Resolution Imaging of Twin and Antiphase...Domain Boundaries in Perovskite KNbO3 Thin Films .......... 30 4. Microstructural Characterization of the Epitaxial3 (111) KNbO3 on (0001) Sapphire

Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial

PubMed Central

Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim

2017-01-01

The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial Registration: ClinicalTrials.gov #06010453 PMID:28056021

Experimental evidence for excess entropy discontinuities in glass-forming solutions.

PubMed

Lienhard, Daniel M; Zobrist, Bernhard; Zuend, Andreas; Krieger, Ulrich K; Peter, Thomas

2012-02-21

Glass transition temperatures T(g) are investigated in aqueous binary and multi-component solutions consisting of citric acid, calcium nitrate (Ca(NO(3))(2)), malonic acid, raffinose, and ammonium bisulfate (NH(4)HSO(4)) using a differential scanning calorimeter. Based on measured glass transition temperatures of binary aqueous mixtures and fitted binary coefficients, the T(g) of multi-component systems can be predicted using mixing rules. However, the experimentally observed T(g) in multi-component solutions show considerable deviations from two theoretical approaches considered. The deviations from these predictions are explained in terms of the molar excess mixing entropy difference between the supercooled liquid and glassy state at T(g). The multi-component mixtures involve contributions to these excess mixing entropies that the mixing rules do not take into account. © 2012 American Institute of Physics

Microbial ingrowth around single- and multi-component adhesives studied in vitro.

PubMed

Preussker, S; Klimm, W; Pöschmann, M; Koch, R

2003-01-01

The aim of this study was to compare the in vitro microbial leakage in 4 micro-hybrid composites in combination with 4 single-component dental adhesives (Scotchbond 1/Z100 MP = group 1; Syntac Single-Component/Tetric Flow = group 3; OptiBond Solo/XRV Herculite = group 5; Solobond M/Arabesk Top = group 7) and 4 multi-component dental adhesives (Scotchbond Multi-Purpose/Z100 MP = group 2; Syntac/Tetric Flow = group 4; OptiBond FL/XRV Herculite = group 6; Solobond Plus/Arabesk Top = group 8). Ninety-four mixed standardized Class V cavities of human caries-free extracted premolars were filled with eight different composite adhesive systems using a one-layer (groups 1-4) or a two-layer technique (groups 5-8). After thermocycling and incubation in a broth culture of Streptococcus mutans and Lactobacillus acidophilus, followed by decalcification and staining, the extent and the type of microbial leakage were measured histologically. The extent of microbial leakage in the composite restorations was very low in all groups and there were no significant differences between adhesives. Z100 MP in combination with single- and multi-component adhesives showed a significantly higher microbial leakage than Tetric Flow systems (U test: p=0.037). XRV Herculite adhesive systems showed significantly less extensive microbial leakage than Arabesk Top adhesive systems (U test: p<0.001). The single-component dental adhesives achieved a marginal adaptation of composites comparable to that of multi-component adhesives in vitro. Copyright 2003 S. Karger AG, Basel

Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial.

PubMed

Bakris, George L; Agarwal, Rajiv; Chan, Juliana C; Cooper, Mark E; Gansevoort, Ron T; Haller, Hermann; Remuzzi, Giuseppe; Rossing, Peter; Schmieder, Roland E; Nowack, Christina; Kolkhof, Peter; Joseph, Amer; Pieper, Alexander; Kimmeskamp-Kirschbaum, Nina; Ruilope, Luis M

2015-09-01

Steroidal mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events. To evaluate the safety and efficacy of different oral doses of the nonsteroidal mineralocorticoid receptor antagonist finerenone, given for 90 days to patients with diabetes and high or very high albuminuria who are receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Randomized, double-blind, placebo-controlled, parallel-group study conducted at 148 sites in 23 countries. Patients were recruited from June 2013 to February 2014 and the study was completed in August 2014. Of 1501 screened patients, 823 were randomized and 821 received study drug. Participants were randomly assigned to receive oral, once-daily finerenone (1.25 mg/d, n = 96; 2.5 mg/d, n = 92; 5 mg/d, n = 100; 7.5 mg/d, n = 97; 10 mg/d, n = 98; 15 mg/d, n = 125; and 25 mg/d, n = 119) or matching placebo (n = 94) for 90 days. The primary outcome was the ratio of the urinary albumin-creatinine ratio (UACR) at day 90 vs at baseline. Safety end points were changes from baseline in serum potassium and estimated glomerular filtration rate. The mean age of the participants was 64.2 years; 78% were male. At baseline, 36.7% of patients treated had very high albuminuria (UACR ≥300 mg/g) and 40.0% had an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower. Finerenone demonstrated a dose-dependent reduction in UACR. The primary outcome, the placebo-corrected mean ratio of the UACR at day 90 relative to baseline, was reduced in the finerenone 7.5-, 10-, 15-, and 20-mg/d groups (for 7.5 mg/d, 0.79 [90% CI, 0.68-0.91; P = .004]; for 10 mg/d, 0.76 [90% CI, 0.65-0.88; P = .001]; for 15 mg/d, 0.67 [90% CI, 0.58-0.77; P<.001]; for 20 mg/d, 0.62 [90% CI, 0.54-0.72; P < .001]). The prespecified secondary outcome of hyperkalemia leading to discontinuation was not observed in the placebo and finerenone 10-mg/d groups; incidences in the finerenone 7.5-, 15-, and 20-mg/d groups were 2.1%, 3.2%, and 1.7%, respectively. There were no differences in the incidence of the prespecified secondary outcome of an estimated glomerular filtration rate decrease of 30% or more or in incidences of adverse events and serious adverse events between the placebo and finerenone groups. Among patients with diabetic nephropathy, most receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, the addition of finerenone compared with placebo resulted in improvement in the urinary albumin-creatinine ratio. Further trials are needed to compare finerenone with other active medications. clinicaltrials.gov Identifier: NCT1874431.

Pregabalin monotherapy in patients with partial-onset seizures

PubMed Central

Kwan, Patrick; Fakhoury, Toufic; Pitman, Verne; DuBrava, Sarah; Knapp, Lloyd; Yurkewicz, Lorraine

2014-01-01

Objective: To assess pregabalin monotherapy for partial-onset seizures using a historical-controlled conversion-to-monotherapy design. Methods: Adults with inadequately controlled partial-onset seizures while receiving 1 or 2 antiepileptic drugs during an 8-week prospective baseline were randomized to double-blind monotherapy with pregabalin 600 or 150 mg/d (4:1) for 20 weeks (8-week conversion and 12-week monotherapy period). The primary endpoint was the seizure-related exit rate for pregabalin 600 mg/d, based on discontinuations due to predefined criteria. Efficacy was declared if the upper limit of the 95% confidence interval for the exit rate was below a historical-control threshold of 74%, with stepwise evaluation using a threshold of 68%. Results: The trial was stopped early for positive efficacy after an interim analysis in 125 patients. The full study population included 161 patients, with 148 evaluable for efficacy. The mean time since epilepsy diagnosis was 14 years. Overall, 54.3% (600 mg/d) and 46.9% (150 mg/d) of patients completed 20 weeks of double-blind treatment. Seizure-related exit rate in the 600 mg/d group (27.5%; 95% confidence interval, 17.8%–37.2%) was significantly below the 74% and 68% thresholds (p < 0.001 for both). Eight patients on 600 mg/d and 2 on 150 mg/d were seizure-free throughout pregabalin monotherapy. Pregabalin's overall safety profile was consistent with prior trials. Conclusions: Pregabalin monotherapy was safe and efficacious for patients with inadequately controlled partial-onset seizures. Classification of evidence: This study provides Class III evidence that patients with inadequately controlled partial-onset seizures switched to pregabalin monotherapy have fewer seizure-related exit events compared with historical controls switched to pseudo-placebo monotherapy. PMID:24415567

Slot scanning versus antiscatter grid in digital mammography: comparison of low-contrast performance using contrast-detail measurement

NASA Astrophysics Data System (ADS)

Lai, Chao-Jen; Shaw, Chris C.; Geiser, William; Kappadath, Srinivas C.; Liu, Xinming; Wang, TianPeng; Tu, Shu-Ju; Altunbas, Mustafa C.

2004-05-01

Slot scanning imaging techniques allow for effective scatter rejection without attenuating primary x-rays. The use of these techniques should generate better image quality for the same mean glandular dose (MGD) or a similar image quality for a lower MGD as compared to imaging techniques using an anti-scatter grid. In this study, we compared a slot scanning digital mammography system (SenoScan, Fisher Imaging Systems, Denver, CO) to a full-field digital mammography (FFDM) system used in conjunction with a 5:1 anti-scatter grid (SenoGraphe 2000D, General Electric Medical Systems, Milwaukee, WI). Images of a contrast-detail phantom (University Hospital Nijmegen, The Netherlands) were reviewed to measure the contrast-detail curves for both systems. These curves were measured at 100%, 71%, 49% and 33% of the reference mean glandular dose (MGD), as determined by photo-timing, for the Fisher system and 100% for the GE system. Soft-copy reading was performed on review workstations provided by the manufacturers. The correct observation ratios (CORs) were also computed and used to compare the performance of the two systems. The results showed that, based on the contrast-detail curves, the performance of the Fisher images, acquired at 100% and 71% of the reference MGD, was comparable to the GE images at 100% of the reference MGD. The CORs for Fisher images were 0.463 and 0.444 at 100% and 71% of the reference MGD, respectively, compared to 0.453 for the GE images at 100% of the reference MGD.

75 FR 52049 - Notice of Projects Approved for Consumptive Uses of Water

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-24

....; Consumptive Use of up to 4.990 mgd; Approval Date: July 6, 2010. 3. Talisman Energy USA, Inc.; Pad ID: Shedden... County, Pa.; Consumptive Use of up to 4.000 mgd; Approval Date: July 7, 2010. 10. Talisman Energy USA....; Consumptive Use of up to 7.500 mgd; Approval Date: July 9, 2010. 20. Talisman Energy USA, Inc.; Pad ID: Nolt...

Estimation of mean glandular dose for patients who undergo mammography and studying the factors affecting it

NASA Astrophysics Data System (ADS)

Barzanje, Sana L. N. H.; Harki, Edrees M. Tahir Nury

2017-09-01

The objective of this study was to determine mean glandular dose (MGD) during diagnostic mammography. This study was done in two hospitals in Hawler city in Kurdistan -region /Iraq, the exposure parameters kVp and mAs was recorded for 40 patients under go mammography. The MGD estimated by multiplied ESD with normalized glandular dose (Dn). The ESD measured indirectly by measuring output radiation mGy/mAs by using PalmRAD 907 as a suitable detector (Gigger detector).the results; shown that the mean and its standard deviation of MGD for Screen Film Mammography and Digital Mammography are (0.95±0.18)mGy and (0.99±0.26)mGy, respectively. And there is a significant difference between MGD for Screen Film Mammography and Digital Mammography views (p≤0. 05). Also the mean value and its standard deviation of MGD for screen film mammography is (0.96±0.21) for CC projection and (1.03±0.3) mGy for MLO projection, but mean value and its standard deviation evaluated of MGD for digital mammography is (0.92±0.17) mGy for CC projection and (0.98±0.2) mGy for MLO projection. As well as, the effect of kVp and mAs in MGD were studied, shows that in general as kVp and mAs increased the MGD increased accordingly in both of mammography systems.

Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of Tocotrienols in Healthy Fed Humans.

PubMed

Qureshi, Asaf A; Khan, Dilshad A; Silswal, Neerupma; Saleem, Shahid; Qureshi, Nilofer

2016-04-01

Tocotrienols has been known to lower serum lipid parameters below 500 mg/d, while increase lipid parameters at higher dose of 750 mg/d. δ-Tocotrienol has a novel inflammatory property of concentration-dependent inhibition and activation. Therefore, inhibition (anti-inflammatory) property of tocotrienols at low doses is useful for cardiovascular disease, whereas, activation (pro-inflammatory) property using high dose is found effective for treatments of various types of cancer. We have recently described plasma bioavailability of 125 mg/d, 250 mg/d and 500 mg/d doses of δ-tocotrienol in healthy fed subjects, which showed dose-dependent increases in area under the curve (AUC) and maximum concentration (C max ). Hence, in the current study, higher doses of tocotrienols have used to analyze its effect on plasma pharmacokinetic parameters. To evaluate the safety and bioavailability of higher doses (750 mg and 1000 mg) of annatto-based tocotrienols in healthy fed subjects. All four isomers (α-, β-, γ-, δ-) of tocols (tocotrienols and tocopherols) present in the plasmas of subjects were quantified and analyzed for various pharmacokinetic parameters. An open-label, randomized study was performed to analyze pharmacokinetics and bioavailability of δ-tocotrienol in 6 healthy fed subjects. All subjects (3/dose) were randomly assigned to one of each dose of 750 mg or 1000 mg. Blood samples were collected at 0, 1, 2, 4, 6, 8 h intervals and all isomers of α-,β-,γ-,δ-tocotrienols, and tocopherols in plasmas were quantified by HPLC. Oral administration of 750 and 1000 mg/d of tocotrienols resulted in dose-dependent increases in plasmas (ng/ml) AUCt 0- t 8 6621, 7450; AUCt 0-∞ 8688, 9633; AUMC t 0-∞ 52497, 57199; MRT 6.04, 5.93; C max 1444, 1592 (P<0.05), respectively, of δ-tocotrienol isomer. Moreover, both doses also resulted in plasmas T max 3.33-4 h; elimination half-life (t 1/2 h) 2.74, 2.68; time of clearance (Cl-T, l/h) 0.086, 0.078; volume of distribution (Vd/f, mg/h) 0.34, 0.30; and elimination rate constant (ke; h -1 ) 0.25, 0.17, respectively of δ- tocotrienol isomer. Similar results of these parameters were reported for γ-tocotrienol, β- tocotrienol, α-tocotrienol, δ-tocopherol, γ-tocopherol, and β-tocopherol, except for α- tocopherol. This study has described pharmacokinetics using higher doses of 750 mg/d and 1000 mg/d of δ-tocotrienol. These results confirmed earlier findings that T max was 3-4 h for all isomers of tocotrienols and tocopherols except for α-tocopherol (6 h). These higher doses of tocotrienols were found safe in humans and may be useful for treatments of various types of cancer, diabetes, and Alzheimer's disease.

Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's disease. The Huntington Study Group.

PubMed

1998-05-01

Oxidative damage due to free-radical generation in the setting of underlying defects of neuronal energy metabolism has been implicated as a pathogenetic mechanism for Huntington's disease (HD). The authors conducted a randomized, double-blind, placebo-controlled, multicenter trial of the tolerability of OPC-14117, a lipophilic free-radical scavenger that concentrates in the brain. Ambulatory patients with HD received OPC-14117 60 mg/d, 120 mg/d, 240 mg/d, or placebo and were assessed by the Unified Huntington's Disease Rating Scale (UHDRS) for 20 weeks, including 12 or 16 weeks of assigned treatment and 8 or 4 weeks of blinded withdrawal of the study drug. Tolerability was measured by the proportion of patients completing the initial 12-week course of treatment on their originally assigned regimen. Sixty-four patients were enrolled in the study, 56 of whom completed the 12 weeks of treatment. Treatment was discontinued in four patients (1 placebo, 1 60 mg/d, 2 240 mg/d) due to asymptomatic but persistent serum elevations of liver transaminase. Two patients (1 60 mg/d and 1 120 mg/d) withdrew because of increased involuntary movements, one patient (60 mg/d) withdrew due to persistent dry eyes, and one patient (120 mg/d) withdrew because of persistent vomiting. There were no significant differences between treatment arms in the primary measures of tolerability, the frequency and types of clinical adverse events, or the clinical/functional features of HD. OPC-14117 was safe and generally well tolerated; however, elevations of liver transaminase suggested that continued surveillance monitoring is warranted in conducting more long-term studies of this antioxidant therapy.

Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women.

PubMed

Smith, Gordon I; Reeds, Dominic N; Okunade, Adewole L; Patterson, Bruce W; Mittendorfer, Bettina

2014-07-01

Sexual dimorphism in plasma triglyceride (TG) metabolism is well established but it is unclear to what extent it is driven by differences in the sex hormone milieu. RESULTS from previous studies evaluating the effects of sex steroids on plasma TG homeostasis are inconclusive because they relied on orally administered synthetic hormone preparations or evaluated only plasma lipid concentrations but not kinetics. The purpose of this study was to evaluate the effects of systemically delivered 17β-estradiol, progesterone, and T on very low density lipoprotein-triglyceride (VLDL-TG) concentration and kinetics in postmenopausal women. VLDL-TG concentration and kinetics were evaluated by using stable isotope-labeled tracer techniques in four groups of postmenopausal women (n = 27 total) who were studied before and after treatment with either 17β-estradiol (0.1 mg/d via continuous delivery skin patch), progesterone (100 mg/d via vaginal insert) and T (12.5 mg/d via skin gel), or no intervention (control group). VLDL-TG concentration and kinetics were unchanged in the control group and not altered by T and progesterone administration. Estradiol treatment, in contrast, reduced VLDL-TG concentration by approximately 30% due to accelerated VLDL-TG plasma clearance (25.1 ± 2.5 vs. 17.4 ± 2.7 mL/min; P < .01). Estradiol, but not progesterone or T, is a major regulator of VLDL-TG metabolism.

Reversibility of Gland Dropout and Significance of Eyelid Hygiene Treatment in Meibomian Gland Dysfunction.

PubMed

Yin, Yue; Gong, Lan

2017-03-01

To observe reversibility of meibomian gland (MG) dropout and analyze correlated factors and to compare the treatment efficiency with and without eyelid hygiene in patients with meibomian gland dysfunction (MGD). Consecutive 78 eyes of 78 MGD (stage 2-3) patients who finished follow-up examination after 1-month of treatment were recruited in this retrospective study. All patients were treated with artificial lubricant and eyelid hygiene. Related ocular surface evaluation and meibomian gland assessment were examined. There were 26 (33%) patients (included in group 1) who ignored doctors' order for eyelid hygiene, and 52 (67%) patients (included in group 2) were compliant. There was no statistical difference between group 1 (age, 44.4 ± 12.2) and group 2 (age, 38.9 ± 16.6) in characteristics and pretreatment clinical indexes. However, after 1-month of treatment, only the ocular surface disease index of group 1 improved (P = 0.048), whereas all clinical indexes of group 2, except the Schirmer test result, improved (including expressibility, all P < 0.05). A 5% decrease in MG dropout of both upper (5.4%) and lower (4.6%) eyelids in group 2 was observed. Improvement in upper-eyelid dropout and expressibility were the predictors of lower-eyelid dropout improvement. The reversibility had no correlation with age, sex, pretreatment MGD stage, disease duration, and use of topical antiinflammation medication. With expressibility-improving treatment, MG dropout was reversible to some extent. Eyelid hygiene is an efficient treatment of MGD; however, there is a need for ophthalmologists to instruct patients on conduct and supervise patients' compliance.

Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies

PubMed Central

Mameniškienė, Rūta; Quarato, Pier Paolo; Klein, Pavel; Gamage, Jessica; Schiemann, Jimmy; Johnson, Martin E.; Whitesides, John; McDonough, Belinda; Eckhardt, Klaus

2016-01-01

Objective: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. Methods: Data were pooled from patients (aged 16–80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. Results: In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%–29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%–31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%–31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). Conclusions: Adjunctive BRV was effective and generally well tolerated in adults with POS. Classification of evidence: This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures. PMID:27335114

A cross-sectional study of equol producer status and self-reported vasomotor symptoms.

PubMed

Newton, Katherine M; Reed, Susan D; Uchiyama, Shigeto; Qu, Conghui; Ueno, Tomomi; Iwashita, Soh; Gunderson, Gabrielle; Fuller, Sharon; Lampe, Johanna W

2015-05-01

This study aims to evaluate the associations of vasomotor symptom (VMS) frequency, bother, and severity with equol producer status and dietary daidzein intake. This is an observational study. This study included women aged 45 to 55 years, in postmenopause or in the menopausal transition, who had soy food intake of three or more servings per week. Exclusion criteria included severe concurrent disease, pregnancy or planned pregnancy, and current use of oral or transdermal hormones or selective estrogen receptor modulators. After screening, 375 participants completed a 3-day VMS diary and a 24-hour urine collection. Women with a urine daidzein or genistein concentration of 100 ng/mL or higher were included. We evaluated the association of VMS--dichotomized as lower than or equal to versus higher than the mean number of VMS per day (<2.33, ≥ 2.33)--with quartiles of daidzein intake. Overall, 129 (35%) of 365 women were equol producers. The mean (SD) urinary equol excretion was 0.67 (1.57) mg/day (50th percentile, 0 mg/d; 95th percentile, 4.12 mg/d). Among equol producers, the mean (SD) urinary equol excretion was 1.91 (2.15) mg/day (50th percentile, 1.09 mg/d; 95th percentile, 6.27 mg/d). Among equol producers, compared with those in the lowest quartile of dietary daidzein intake (mean, 4.9 mg/d), those in the highest quartile (mean, 28.5 mg/d) were 76% less likely to have VMS higher than the mean number of VMS (odds ratio, 0.24; 95% CI, 0.07-0.83; trend test across all daidzein levels, P = 0.06). Among equol nonproducers, there were no associations between daidzein intake and VMS frequency. There were no differences in VMS bother or severity among equol producers or nonproducers by dietary daidzein level. Among equol producers, higher equol availability attributable to higher soy consumption contributes to decreased VMS.

Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

PubMed

Sargento, Luis; Simões, Andre Vicente; Longo, Susana; Lousada, Nuno; Reis, Roberto Palma Dos

2017-05-01

Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

Assessment of Mean Glandular Dose in Mammography System with Different Anode-Filter Combinations Using MCNP Code.

PubMed

Gholamkar, Lida; Mowlavi, Ali Asghar; Sadeghi, Mahdi; Athari, Mitra

2016-10-01

X-ray mammography is one of the general methods for early detection of breast cancer. Since glandular tissue in the breast is sensitive to radiation and it increases the risk of cancer, the given dose to the patient is very important in mammography. The aim of this study was to determine the average absorbed dose of X-ray radiation in the glandular tissue of the breast during mammography examinations as well as investigating factors that influence the mean glandular dose (MGD). One of the precise methods for determination of MGD absorbed by the breast is Monte Carlo simulation method which is widely used to assess the dose. We studied some different X-ray sources and exposure factors that affect the MGD. "Midi-future" digital mammography system with amorphous-selenium detector was simulated using the Monte Carlo N-particle extended (MCNPX) code. Different anode/filter combinations such as tungsten/silver (W/Ag), tungsten/rhodium (W/Rh), and rhodium/aluminium (Rh/Al) were simulated in this study. The voltage of X-ray tube ranged from 24 kV to 32 kV with 2 kV intervals and the breast phantom thickness ranged from 3 to 8 cm, and glandular fraction g varied from 10% to 100%. MGD was measured for different anode/filter combinations and the effects of changing tube voltage, phantom thickness, combination and glandular breast tissue on MGD were studied. As glandular g and X-ray tube voltage increased, the breast dose increased too, and the increase of breast phantom thickness led to the decrease of MGD. The obtained results for MGD were consistent with the result of Boone et al. that was previously reported. By comparing the results, we saw that W/Rh anode/filter combination is the best choice in breast mammography imaging because of the lowest delivered dose in comparison with W/Ag and Rh/Al. Moreover, breast thickness and g value have significant effects on MGD.

Defined single-gene and multi-gene deletion mutant collections in Salmonella enterica sv Typhimurium.

PubMed

Porwollik, Steffen; Santiviago, Carlos A; Cheng, Pui; Long, Fred; Desai, Prerak; Fredlund, Jennifer; Srikumar, Shabarinath; Silva, Cecilia A; Chu, Weiping; Chen, Xin; Canals, Rocío; Reynolds, M Megan; Bogomolnaya, Lydia; Shields, Christine; Cui, Ping; Guo, Jinbai; Zheng, Yi; Endicott-Yazdani, Tiana; Yang, Hee-Jeong; Maple, Aimee; Ragoza, Yury; Blondel, Carlos J; Valenzuela, Camila; Andrews-Polymenis, Helene; McClelland, Michael

2014-01-01

We constructed two collections of targeted single gene deletion (SGD) mutants and two collections of targeted multi-gene deletion (MGD) mutants in Salmonella enterica sv Typhimurium 14028s. The SGD mutant collections contain (1), 3517 mutants in which a single gene is replaced by a cassette containing a kanamycin resistance (KanR) gene oriented in the sense direction (SGD-K), and (2), 3376 mutants with a chloramphenicol resistance gene (CamR) oriented in the antisense direction (SGD-C). A combined total of 3773 individual genes were deleted across these SGD collections. The MGD collections contain mutants bearing deletions of contiguous regions of three or more genes and include (3), 198 mutants spanning 2543 genes replaced by a KanR cassette (MGD-K), and (4), 251 mutants spanning 2799 genes replaced by a CamR cassette (MGD-C). Overall, 3476 genes were deleted in at least one MGD collection. The collections with different antibiotic markers permit construction of all viable combinations of mutants in the same background. Together, the libraries allow hierarchical screening of MGDs for different phenotypic followed by screening of SGDs within the target MGD regions. The mutants of these collections are stored at BEI Resources (www.beiresources.org) and publicly available.

Can gradual dose titration of ketamine for management of neuropathic pain prevent psychotomimetic effects in patients with advanced cancer?

PubMed

Okamoto, Yoshiaki; Tsuneto, Satoru; Tanimukai, Hitoshi; Matsuda, Yoichi; Ohno, Yumiko; Tsugane, Mamiko; Uejima, Etsuko

2013-08-01

Ketamine is often used to manage neuropathic pain in patients with cancer. However, it occasionally causes psychotomimetic effects such as vivid dreams, nightmares, illusions, hallucinations, and altered body image. To examine whether gradual dose titration of ketamine for management of neuropathic pain prevents psychotomimetic effects in patients with advanced cancer. This was a retrospective chart review. We administered ketamine when neuropathic pain in patients with advanced cancer became refractory to opioids and oral adjuvant analgesics. The starting dose of ketamine was 10 mg/d by continuous intravenous infusion. The dose was gradually increased by 10 mg/d every 4 to 6 hours to 50 mg/d or until the pain was relieved. It was subsequently increased by 25 mg/d every 12 to 24 hours until the pain was relieved. For this study, we enrolled 46 patients with advanced cancer. The mean age was 52.2 ± 16.9 years. The mean dose at onset of action and maximum dose of ketamine were 56 ± 58 and 272 ± 214 mg/d, respectively. The mean pain intensity (numerical rating scale) decreased significantly from 7.3 ± 2.0 to 3.5 ± 2.2 after the administration of ketamine (P < .01). The effectiveness was 69.5%. No psychotomimetic effect of less than 300 mg/d was observed during the introduction phase even though psychotropic drugs were not prescribed. Mild sedation was observed in 3 patients (7%) as the only adverse effect during the introduction phase. Gradual dose titration of ketamine for management of neuropathic pain can prevent psychotomimetic effects in patients with advanced cancer.

Association of Celecoxib Use With Decreased Opioid Requirements After Head and Neck Cancer Surgery With Free Tissue Reconstruction.

PubMed

Carpenter, Patrick S; Shepherd, Hailey M; McCrary, Hilary; Torrecillas, Vanessa; Kull, Amanda; Hunt, Jason P; Monroe, Marcus M; Buchmann, Luke O; Cannon, Richard B

2018-04-18

Head and neck cancer (HNC) surgery with free tissue reconstruction is associated with considerable postoperative pain. Opioids are typically used but can have adverse effects, including respiratory depression and high rates of dependence and addiction. Safe alternative analgesics that minimize opioid requirements are beneficial in HNC surgery. To investigate the association of celecoxib use with opioid requirements in the postoperative setting after HNC surgery with free tissue reconstruction. A retrospective, matched-cohort study of 147 patients who had undergone HNC surgery with free tissue reconstruction between June 2015 and Sept 2017 in an academic cancer hospital. Patients were separated into groups based on whether celecoxib had been used perioperatively or not. These groups were then matched by stage and site resulting in 102 included participants (51 celecoxib, 51 control). Oral, intravenous (IV), and total morphine equivalents used in the postoperative setting per patient per day. There were 51 patients in the celecoxib cohort (19 women and 32 men) and 51 patients in the control cohort (20 women and 31 men) who met inclusion criteria after clinicopathologic data were matched. The mean age of the celecoxib and control cohorts was 61.6 years and 66.1 years, respectively. Treatment with celecoxib in the postoperative setting was associated with decreased mean use of opioids in oral (mean difference, 9.9 mg/d; 95% CI, -1.2 to 21.1), IV (mean difference, 3.9 mg/d; 95% CI, 1.0-6.8), and total (mean difference, 14 mg/d; 95% CI, 2.6-25.4) amount of morphine equivalents per day. When patients were matched to surgical procedure, the effect was more significant. Patients who underwent composite oral resection and received celecoxib had decreased opioid use in oral (mean difference, 25 mg/d; 95% CI, 12.5-25.4), IV (mean difference, 3.4 mg/d; 95% CI, 1.5-5.5), and total (mean difference, 28.4 mg/d; 95% CI, 15.7-41.5) amounts compared with those in the control group. There was no significant difference in complication rates between the 2 cohorts. Use of celecoxib after head and neck cancer surgery and reconstruction with free tissue transfer was associated with a decrease in oral, IV, and total opioid requirements without increasing surgical or flap-related complications.

Dyslipidemia and its association with meibomian gland dysfunction.

PubMed

Braich, Puneet S; Howard, Mary K; Singh, Jorawer S

2016-08-01

Abnormal serum lipid levels significantly increase the risk for cardiovascular disease. Furthermore, abnormal compositions of cholesterol in glandular secretions have been hypothesized as an etiology for meibomian gland dysfunction, yet this relationship has not been well studied in clinical settings. The primary purpose of this study was to determine if there is an association between dyslipidemia and meibomian gland dysfunction (MGD). The secondary purpose was to identify the factors, if any, that play a role in this association. A case-control study was performed between October 2013 and February 2015 which recruited 109 patients with MGD and 115 control patients without MGD. All participants were of Indian descent and had no history of dyslipidemia. Basic demographic information was collected as well as fasting levels of serum glucose, creatinine, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). To calculate differences between groups, Z test or Student t test were used. A stepwise logistic regression model was used to calculate the estimates of odds ratios (ORs), where MGD was the dependent variable, making the independent variables consist of sex, age, body mass index (BMI), triglycerides ≥150 mg/dL, total cholesterol ≥200 mg/dL, LDL ≥130 mg/dL, or HDL ≤40 mg/dL, serum glucose, and serum creatinine. Dyslipidemia, defined by either a fasting total cholesterol level of ≥ 200 mg/dL, triglycerides ≥150 mg/dL, LDL ≥130 mg/dL, or HDL ≤40 mg/dL, was detected in 70 cases (64 %) and 21 controls (18 %), P < 0.001. Mean levels of triglycerides, total cholesterol, LDL, and HDL were 98.5 ± 42.1, 203.1 ± 13.2, 126.1 ± 10.2, and 53.3 ± 4.2 mg/dL, respectively, in cases and 82.3 ± 36.5, 156.6 ± 14.5, 92.2 ± 12.4, 45.8 ± 2.6 mg/dL, respectively, in controls. All differences were statistically significant (P < 0.05). MGD was significantly associated with age >65 years (OR 2.1; 95 % CI 1.2-3.2, P = 0.04), serum triglyceride concentration ≥150 mg/dL (OR 3.2; 95 % CI 1.9-4.4; P = 0.03), total cholesterol ≥200 mg/dL (OR 14.3; 95 % CI 8.2-20.7, P < 0.01), and LDL ≥130 mg/dL (OR 9.1; 95 % CI 6.6-13.2, P < 0.01). Adults from northern rural India with MGD are more likely to have abnormal serum lipid levels compared to age- and sex-matched adults without MGD. Eye care providers may have a role in discovering undiagnosed dyslipidemia, an important risk factor for cardiovascular illness.

Speed of Improvement in Symptoms of Depression With Desvenlafaxine 50 mg and 100 mg Compared With Placebo in Patients With Major Depressive Disorder.

PubMed

Katzman, Martin A; Nierenberg, Andrew A; Wajsbrot, Dalia B; Meier, Ellen; Prieto, Rita; Pappadopulos, Elizabeth; Mackell, Joan; Boucher, Matthieu

2017-10-01

This post hoc analysis examined the time point at which clinically significant improvement in major depressive disorder (MDD) symptoms occurs with desvenlafaxine versus placebo. Data were pooled from 9 short-term, double-blind, placebo-controlled studies in adults with MDD randomly assigned to desvenlafaxine 50 mg/d, 100 mg/d, or placebo. A mixed-effects model for repeated-measures analysis of change from baseline score was used to determine the time point at which desvenlafaxine treatment groups separated from placebo on the 17-item Hamilton Rating Scale for Depression and psychosocial outcomes. The association between early improvement and week 8 outcomes was examined using logistic regression analyses. Time to remission for patients with early improvement versus without early improvement was assessed using Kaplan-Meier techniques. Comparisons between groups were performed with log-rank tests. In the intent-to-treat population (N = 4279 patients: desvenlafaxine 50 mg/d, n = 1714; desvenlafaxine 100 mg/d, n = 870; placebo, n = 1695), a statistically significant improvement on the 17-item Hamilton Rating Scale for Depression was observed with desvenlafaxine 50 mg/d at week 1 (P = 0.0129) and with desvenlafaxine 100 mg/d at week 2 (P = 0.0002) versus placebo. Early improvement was a significant predictor of later remission. Treatment assignment, baseline depression scale scores, and race were significantly associated with probability of early improvement. On several measures of depressive symptoms and function, desvenlafaxine 50 mg/d and 100 mg/d separated from placebo as early as week 1 and no later than week 4 in patients with MDD. These findings suggest that clinicians may be able to use depression rating scale scores early in treatment as a guide to inform treatment optimization.

Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of Tocotrienols in Healthy Fed Humans

PubMed Central

Qureshi, Asaf A; Khan, Dilshad A; Silswal, Neerupma; Saleem, Shahid; Qureshi, Nilofer

2016-01-01

Background Tocotrienols has been known to lower serum lipid parameters below 500 mg/d, while increase lipid parameters at higher dose of 750 mg/d. δ-Tocotrienol has a novel inflammatory property of concentration-dependent inhibition and activation. Therefore, inhibition (anti-inflammatory) property of tocotrienols at low doses is useful for cardiovascular disease, whereas, activation (pro-inflammatory) property using high dose is found effective for treatments of various types of cancer. We have recently described plasma bioavailability of 125 mg/d, 250 mg/d and 500 mg/d doses of δ-tocotrienol in healthy fed subjects, which showed dose-dependent increases in area under the curve (AUC) and maximum concentration (Cmax). Hence, in the current study, higher doses of tocotrienols have used to analyze its effect on plasma pharmacokinetic parameters. Aims To evaluate the safety and bioavailability of higher doses (750 mg and 1000 mg) of annatto-based tocotrienols in healthy fed subjects. All four isomers (α-, β-, γ-, δ-) of tocols (tocotrienols and tocopherols) present in the plasmas of subjects were quantified and analyzed for various pharmacokinetic parameters. Study design An open-label, randomized study was performed to analyze pharmacokinetics and bioavailability of δ-tocotrienol in 6 healthy fed subjects. All subjects (3/dose) were randomly assigned to one of each dose of 750 mg or 1000 mg. Blood samples were collected at 0, 1, 2, 4, 6, 8 h intervals and all isomers of α-,β-,γ-,δ-tocotrienols, and tocopherols in plasmas were quantified by HPLC. Results Oral administration of 750 and 1000 mg/d of tocotrienols resulted in dose-dependent increases in plasmas (ng/ml) AUCt0-t8 6621, 7450; AUCt0-∞ 8688, 9633; AUMC t0-∞ 52497, 57199; MRT 6.04, 5.93; Cmax 1444, 1592 (P<0.05), respectively, of δ-tocotrienol isomer. Moreover, both doses also resulted in plasmas Tmax 3.33–4 h; elimination half-life (t1/2 h) 2.74, 2.68; time of clearance (Cl-T, l/h) 0.086, 0.078; volume of distribution (Vd/f, mg/h) 0.34, 0.30; and elimination rate constant (ke; h-1) 0.25, 0.17, respectively of δ- tocotrienol isomer. Similar results of these parameters were reported for γ-tocotrienol, β- tocotrienol, α-tocotrienol, δ-tocopherol, γ-tocopherol, and β-tocopherol, except for α- tocopherol. Conclusions This study has described pharmacokinetics using higher doses of 750 mg/d and 1000 mg/d of δ-tocotrienol. These results confirmed earlier findings that Tmax was 3-4 h for all isomers of tocotrienols and tocopherols except for α-tocopherol (6 h). These higher doses of tocotrienols were found safe in humans and may be useful for treatments of various types of cancer, diabetes, and Alzheimer's disease. PMID:27493840

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

PubMed

Azizi, Michel; Pereira, Helena; Hamdidouche, Idir; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Girerd, Xavier; Michel Halimi, Jean; Zannad, Faiez; Ormezzano, Olivier; Vaïsse, Bernard; Herpin, Daniel; Ribstein, Jean; Chamontin, Bernard; Mourad, Jean-Jacques; Ferrari, Emile; Plouin, Pierre-François; Jullien, Vincent; Sapoval, Marc; Chatellier, Gilles

2016-09-20

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777. © 2016 American Heart Association, Inc.

Inducible NAD(H)-linked methylglyoxal oxidoreductase regulates cellular methylglyoxal and pyruvate through enhanced activities of alcohol dehydrogenase and methylglyoxal-oxidizing enzymes in glutathione-depleted Candida albicans.

PubMed

Kwak, Min-Kyu; Ku, MyungHee; Kang, Sa-Ouk

2018-01-01

High methylglyoxal content disrupts cell physiology, but mammals have scavengers to prevent glycolytic and mitochondrial dysfunctions. In yeast, methylglyoxal accumulation triggers methylglyoxal-oxidizing alcohol dehydrogenase (Adh1) activity. While methylglyoxal reductases and glyoxalases have been well studied in prokaryotes and eukaryotes, experimental evidence for methylglyoxal dehydrogenase (Mgd) and other catalytic activities of this enzyme affecting glycolysis and the tricarboxylic acid cycle is lacking. A glycine-rich cytoplasmic Mgd protein, designated as Mgd1/Grp2, was isolated from glutathione-depleted Candida albicans. The effects of Mgd1/Grp2 activities on metabolic pathophysiology were investigated using knockout and overexpression mutants. We measured glutathione-(in)dependent metabolite contents and metabolic effects, including viability, oxygen consumption, ADH1 transcripts, and glutathione reductase and α-ketoglutarate dehydrogenase activities in the mutants. Based on the findings, methylglyoxal-oxidizing proteins were monitored to determine effects of MGD1/GRP2 disruption on methylglyoxal-scavenging traits during glutathione deprivation. Methylglyoxal-oxidizing NAD(H)-linked Mgd1/Grp2 was found solely in glutathione auxotrophs, and it catalyzed the reduction of both methylglyoxal and pyruvate. MGD1/GRP2 disruptants showed growth defects, cell-cycle arrest, and methylglyoxal and pyruvate accumulation with mitochondrial impairment, regardless of ADH1 compensation. Other methylglyoxal-oxidizing enzymes were identified as key glycolytic enzymes with enhanced activity and transcription in MGD1/GRP2 disruptants, irrespective of glutathione content. Failure of methylglyoxal and pyruvate dissimilation by Mgd1/Grp2 deficiency leads to poor glutathione-dependent redox regulation despite compensation by Adh1. This is the first report that multifunctional Mgd activities contribute to scavenging methylglyoxal and pyruvate to maintain metabolic homeostasis and the redox pool via glycolytic enzymes and Adh1 expression. Copyright © 2017 Elsevier B.V. All rights reserved.

Availability of ground water in the area surrounding the Trident submarine construction facility, Kitsap County, Washington

USGS Publications Warehouse

Hansen, Arnold J.; Molenaar, Dee

1976-01-01

General information is presented on water resources--with emphasis on ground-water occurrence and availability--in that part of Kitsap County (referred to as Trident Impact Area) that would be most affected by the development of the Trident submarine construction facility at Bangor, Washington. The estimated 1970 water use in the study area averaged about 13 million gallons per day (mgd); of this amount about 9 mgd came from surface-water sources--from a large reservoir outside the study area--and about 4 mgd came from ground water pumped from two aquifers in the area. Anticipated water use soon will be about 18 to 21 mgd; virtually all the additional quantity required (about 5 to 8 mgd) above present use must come from ground-water sources. Preliminary evaluation of the aquifers suggests that an additional 1.5 mgd can be developed from the upper aquifer and 7 mgd from the lower aquifer. Existing wells tapping the lower aquifer might yield additional water and increase the total yield in the area by 3.5 mgd, and new wells drilled in selected areas could produce an additional 3.5 mgd from this aquifer. However, additional, large-scale ground-water withdrawal from the lower aquifer could induce saltwater intrusion into wells situated in coastal areas. (Woodard-USGS)

Surface-water availability, Tuscaloosa County, Alabama

USGS Publications Warehouse

Knight, Alfred L.; Davis, Marvin E.

1975-01-01

The average annual runoff, about 1,270 mgd (million gallons per day), originating in Tuscaloosa County is equivalent to 20 inches or 0.95 mgd per square mile. The Black Warrior and Sipsey Rivers, the largest streams in the county, have average flows of 5,230 mgd and 580 mgd, respectively, where they leave the county, and median annual 7-day low flows in excess of 150 mgd and 35 mgd, respectively. North River, Big Sandy Creek, and Hurricane Creek have average flows in excess of 100 mgd and median annual 7-day low flows in excess of 2 mgd. Surface water generally contains less than 100 mg/l (milligrams per liter) dissolved solids, less than 10 mg/l chloride, and is soft to moderately hard. Streams having the higher hardness and the higher dissolved-solids content are in eastern Tuscaloosa County.

The latest results on colloid associated radionuclide migration from the CFM Project, Grimsel Test Site (GTS, Switzerland)

NASA Astrophysics Data System (ADS)

Schaefer, T.; Blechschmidt, I.; Bouby, M.; Buechner, S.; Brendlé, J.; Geckeis, H.; Kupcik, T.; Goetz, R.; Hauser, W.; Heck, S.; Huber, F. M.; Lagos, M.; Martin, A. J.

2013-12-01

The influence of colloidal/nano-scale phases on the radionuclide (RNs) solubility and migration behavior is still one of the uncertainties in repository safety assessment [1]. Within the Colloid Formation and Migration (CFM) project at the Grimsel Test Site (GTS Switzerland) a huge geo-technical effort was taken to isolate hydraulically a shear-zone from the artificially introduced hydraulic gradient due to the tunnel construction. The construction is a combination of polymer resin impregnation of the tunnel surface and a steel torus to seal the tunnel surface. Natural outflow points of the MI shear zone were localized prior to the construction and sealed by surface packers. This design gives the opportunity to adjust the flow velocity in the fracture. After optimization of the experimental setup and injection procedure through a number of conservative tracer tests a license was granted in January 2012 by the Swiss regulator (BAG) to perform the first radionuclide tracer test under these low-flow conditions. The injection cocktail of 2.25L volume consisted of 101.4 × 2.5 mg/L montmorillonite clay colloids, whereas 8.9 × 0.4mg/L were present as synthetic montmorillonite with structural incorporated Ni. For details on the structural characterization of the Ni-montmorillonite phyllosilicate, see [2]. Beside the colloids and the conservative tracer Amino-G (1646 × 8ppb) the radioisotopes Na-22, Ba-133, Cs-137, Th-232, Np-237, Pu-242 and Am-243 were injected. The trivalent and tetravalent actinides were quantitatively associated with the colloids present as well as a part of the Cs, whereas Np(V) and Na are not bentonite colloid bond. For on-site colloid analysis a mobile Laser- Induced Breakdown Detection (LIBD) system similar to the one used in the CRR experiments [3] was transferred to Grimsel and installed in-line at the 'Pinkel' outlet to directly monitor the mobile colloid fraction throughout the experiment. The conservative tracer Amino-G was recovered quantitatively and for the weakly sorbing tracers analyzed by γ-spectrometry recoveries for Na-22, Cs-137 and Ba-133 of 64%, 10% and 1%, respectively, were found. The clay colloid recovery determined by LIBD and HR-ICP-MS analyzing Al and Ni as structural components of the clay particles provided 48-52%. For the initial quantitatively colloid associated actinides Am(III) and Pu(IV) a recovery of 21-22% and 30-35%, respectively, could be determined. Np recovery is significantly reduced to ~4 %, which hints to a kinetic controlled Np(V) reduction. The data obtained so far clearly show the mobility of bentonite derived montmorillonite colloids under near-natural flow conditions in the MI shear zone of the Grimsel Test Site [4]. The experimental data will be discussed in detail in the presentation. [1] T. Schäfer, et al. Appl. Geochem., 27 (2012) 390-403. [2] Reinholdt, et al., Nanomaterials, 3 (2013) 48-69. [3] H. Geckeis, et al., Radiochim. Acta, 92 (2004) 765-774. [4] www.grimsel.com

Assessment of Mean Glandular Dose in Mammography System with Different Anode-Filter Combinations Using MCNP Code

PubMed Central

Gholamkar, Lida; Mowlavi, Ali Asghar; Sadeghi, Mahdi; Athari, Mitra

2016-01-01

Background X-ray mammography is one of the general methods for early detection of breast cancer. Since glandular tissue in the breast is sensitive to radiation and it increases the risk of cancer, the given dose to the patient is very important in mammography. Objectives The aim of this study was to determine the average absorbed dose of X-ray radiation in the glandular tissue of the breast during mammography examinations as well as investigating factors that influence the mean glandular dose (MGD). One of the precise methods for determination of MGD absorbed by the breast is Monte Carlo simulation method which is widely used to assess the dose. Materials and Methods We studied some different X-ray sources and exposure factors that affect the MGD. “Midi-future” digital mammography system with amorphous-selenium detector was simulated using the Monte Carlo N-particle extended (MCNPX) code. Different anode/filter combinations such as tungsten/silver (W/Ag), tungsten/rhodium (W/Rh), and rhodium/aluminium (Rh/Al) were simulated in this study. The voltage of X-ray tube ranged from 24 kV to 32 kV with 2 kV intervals and the breast phantom thickness ranged from 3 to 8 cm, and glandular fraction g varied from 10% to 100%. Results MGD was measured for different anode/filter combinations and the effects of changing tube voltage, phantom thickness, combination and glandular breast tissue on MGD were studied. As glandular g and X-ray tube voltage increased, the breast dose increased too, and the increase of breast phantom thickness led to the decrease of MGD. The obtained results for MGD were consistent with the result of Boone et al. that was previously reported. Conclusion By comparing the results, we saw that W/Rh anode/filter combination is the best choice in breast mammography imaging because of the lowest delivered dose in comparison with W/Ag and Rh/Al. Moreover, breast thickness and g value have significant effects on MGD. PMID:27895876

Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults.

PubMed

Li, Danni; Radulescu, Angela; Shrestha, Rupendra T; Root, Matthew; Karger, Amy B; Killeen, Anthony A; Hodges, James S; Fan, Shu-Ling; Ferguson, Angela; Garg, Uttam; Sokoll, Lori J; Burmeister, Lynn A

2017-09-26

Biotinylated antibodies and analogues, with their strong binding to streptavidin, are used in many clinical laboratory tests. Excess biotin in blood due to supplemental biotin ingestion may affect biotin-streptavidin binding, leading to potential clinical misinterpretation. However, the degree of interference remains undefined in healthy adults. To assess performance of specific biotinylated immunoassays after 7 days of ingesting 10 mg/d of biotin, a dose common in over-the-counter supplements for healthy adults. Nonrandomized crossover trial involving 6 healthy adults who were treated at an academic medical center research laboratory. Administration of 10 mg/d of biotin supplementation for 7 days. Analyte concentrations were compared with baseline (day 0) measures on the seventh day of biotin treatment and 7 days after treatment had stopped (day 14). The 11 analytes included 9 hormones (ie, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, 25-hydroxyvitamin D) and 2 nonhormones (prostate-specific antigen and ferritin). A total of 37 immunoassays for the 11 analytes were evaluated on 4 diagnostic systems, including 23 assays that incorporated biotin and streptavidin components and 14 assays that did not include biotin and streptavidin components and served as negative controls. Among the 2 women and 4 men (mean age, 38 years [range, 31-45 years]) who took 10 mg/d of biotin for 7 days, biotin ingestion-associated interference was found in 9 of the 23 (39%) biotinylated assays compared with none of the 14 nonbiotinylated assays (P = .007). Results from 5 of 8 biotinylated (63%) competitive immunoassays tested falsely high and results from 4 out of 15 (27%) biotinylated sandwich immunoassays tested falsely low. In this preliminary study of 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassays, ingesting 10 mg/d of biotin for 1 week was associated with potentially clinically important assay interference in some but not all biotinylated assays studied. These findings should be considered for patients taking biotin supplements before ordering blood tests or when interpreting results. clinicaltrials.gov Identifier: NCT03034707.

Reduction of resting heart rate with antianginal drugs: review and meta-analysis.

PubMed

Cucherat, Michel; Borer, Jeffrey S

2012-07-01

The benefit of heart rate (HR) reduction in patients with stable coronary artery disease is well demonstrated for symptom prevention and relief, and benefits on outcomes are being actively investigated. We aimed to quantify the reduction in resting HR induced by 5 antianginal drugs frequently used for symptom prevention (diltiazem, verapamil, atenolol, metoprolol, and ivabradine) in stable angina pectoris. We identified studies published between 1966 and 2007 in PubMed, Embase, and the Cochrane database and reviewed the bibliographies to locate additional studies. Eligible studies were double-blind, randomized, placebo-controlled trials in patients with stable angina. Trials were combined using weighted mean difference and fixed-effect model meta-analysis. The main outcome measure was resting HR at the study end. For diltiazem, resting HR reduction versus placebo ranged from -0.08 beats per minute (bpm) [95% confidence interval (CI) -1.5 to +1.4] for 120 mg/d to -8.0 bpm (95% CI, -11.1 to -5.0) with 360 mg/d. For sustained-release diltiazem, there was a reduction in resting HR of -4.5 bpm (95% CI, -6.4 to -2.5), with no dose-response relationship (heterogeneity P = 0.62). Resting HR reductions for the other agents were -3.2 bpm (95% CI, -5.1 to -1.3) for verapamil (with no dose-response relationship, heterogeneity P = 0.87); -19.0 bpm (95% CI, -20.4 to -17.6) for atenolol; -13.2 bpm (95% CI, -14.7 to -11.7) for metoprolol (with greater reductions for 150 mg/d and long-acting 190 mg/d); and between -9.3 bpm (95% CI, -13.8 to -4.8) and -19.6 bpm (95% CI, -23.8 to -15.4) for ivabradine. Ivabradine, atenolol, and metoprolol give similar reductions in resting HR (-10 to -20 bpm), whereas verapamil and diltiazem produce only marginal reductions (<10 bpm).

Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson's disease.

PubMed

Hauser, Robert A; Silver, Dee; Choudhry, Azhar; Eyal, Eli; Isaacson, Stuart

2014-07-01

Dopamine agonists (DA) are often used as first-line monotherapy for the symptomatic control of Parkinson's disease (PD). However, DA monotherapy typically becomes inadequate within a few years, at which time the DA dosage must be increased or other antiparkinsonian medications added. Adding a monoamine oxidase-B (MAO-B) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability. We conducted an 18-week, randomized, double-blind, placebo-controlled trial of rasagiline 1 mg/d as an add-on to DA therapy (ropinirole ≥ 6 mg/d or pramipexole ≥ 1.0 mg/d) in early PD patients whose conditions were not adequately controlled on their current treatment regimen. The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from baseline to week 18, comparing rasagiline and placebo groups. The modified intent-to-treat (ITT) population included 321 subjects whose mean ± SD age was 62.6 ± 9.7, and duration of PD was 2.1 ± 2.1 years. Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group (least squares [LS] mean difference ± SE, -2.4 ± 0.95; 95% confidence interval [CI], -4.3, -0.5; P = 0.012). Mean improvement (LS mean ± SE) was -3.6 ± 0.68 in the rasagiline group and -1.2 ± 0.68 in the placebo group. Rasagiline was well tolerated, and the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4% vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated. © 2014 International Parkinson and Movement Disorder Society.

Upregulation of Zinc Absorption Matches Increases in Physiologic Requirements for Zinc in Women Consuming High- or Moderate-Phytate Diets during Late Pregnancy and Early Lactation.

PubMed

Hambidge, K Michael; Miller, Leland V; Mazariegos, Manolo; Westcott, Jamie; Solomons, Noel W; Raboy, Victor; Kemp, Jennifer F; Das, Abhik; Goco, Norman; Hartwell, Ty; Wright, Linda; Krebs, Nancy F

2017-06-01

Background: Estimated physiologic requirements (PRs) for zinc increase in late pregnancy and early lactation, but the effect on dietary zinc requirements is uncertain. Objective: The aim of this study was to determine changes in daily fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of differing phytate contents in relation to physiologic zinc requirements during pregnancy and lactation. Methods: This was a prospective observational study of zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3) and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of childbearing age whose major food staple was maize and who had been randomly assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined from duplicate diets and fractional absorption (FAZ) by dual isotope ratio technique (TAZ = TDZ × FAZ). All variables were examined longitudinally and by group and compared with PRs. TAZ values at later phases were compared with phase 1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating (NPNL) women. Results: TAZ was greater in the LP group than in the C group at all phases. All variables increased from phase 1 to phases 2 and 3 and declined at phase 4. TAZ increased by 1.25 mg/d ( P = 0.045) in the C group and by 0.81 mg/d ( P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d ( P = 0.002) in the C group and 2.28 mg/d ( P = 0.0004) in the LP group, compared with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values in phases 2-4. Conclusions: Upregulation of zinc absorption in late pregnancy and early lactation matches increases in PRs of pregnant and lactating women, regardless of dietary phytate, which has implications for dietary zinc requirements of pregnant and lactating women. © 2017 American Society for Nutrition.

An open-label tolerability study of BL-1020 antipsychotic: a novel gamma aminobutyric acid ester of perphenazine.

PubMed

Anand, Ravi; Geffen, Yona; Vasile, Daniel; Dan, Irina

2010-01-01

BL-1020, a novel gamma aminobutyric acid (GABA) ester of perphenazine, is a new oral antipsychotic with a strong affinity for dopamine and serotonin receptors. Unlike first- and second-generation antipsychotics, it has agonist activity at GABA(A). This is the first study to examine tolerability and safety of BL-1020 in schizophrenia. This was a phase-II, open-label, multicenter, 6-week study treating patients (n = 36) with chronic schizophrenia. Dosing started at 20 mg/d and increased over 7 days to 40 mg/d. Weekly assessments were conducted. All but 1 patient was titrated to 30 mg/d at day 4; on day 7, 30 were titrated to 40 mg/d. Four patients discontinued the study prematurely. There was no clinically relevant increase in vital signs, sedation, dizziness, or other central nervous system effects or electrocardiogram or laboratory abnormalities and a small increase in weight. Ten patients experienced extrapyramidal symptoms (EPS) requiring treatment with an anticholinergic; 4 patients were unable to reach maximum dose because of EPS. Extrapyramidal Symptom Rating Scale did not indicate clinically significant changes in EPS. The most common adverse event was insomnia (6 patients); other frequent adverse effects (all n = 3) were extrapyramidal disorder, headache, parkinsonism, tremor, and hyperprolactinemia. There was improvement on Positive and Negative Syndrome Scale and Clinical Global Impression of Change with 22 patients showing at least 20% decrease by end point on Positive and Negative Syndrome Scale and 31 patients showing at least minimal improvement on Clinical Global Impression of Change. These data suggest that 20 to 40 mg/d of BL-1020 is associated with clinically relevant improvement of psychosis with no worsening of EPS and support further testing in randomized controlled trials.

A new method for multicomponent activity coefficients of electrolytes in aqueous atmospheric aerosols

NASA Astrophysics Data System (ADS)

Zaveri, Rahul A.; Easter, Richard C.; Wexler, Anthony S.

2005-01-01

Three-dimensional models of atmospheric inorganic aerosols need accurate and computationally efficient parameterizations of activity coefficients of various electrolytes in multicomponent aqueous solutions. In this paper, we extend the Taylor's series expansion mixing rule used by C. Wagner in 1952 for estimating activity coefficients in dilute alloy solutions to aqueous electrolyte solutions at any concentration. The resulting method, called the multicomponent Taylor expansion method (MTEM), estimates the mean activity coefficient of an electrolyte in a multicomponent solution on the basis of its values in binary solutions of all the electrolytes present in the mixture at the solution water activity aw, assuming aw is equal to the ambient relative humidity. MTEM is applied here for atmospheric aerosol systems containing H+, NH4+, Na+, Ca2+, SO42-, HSO4-, NO3-, and Cl- ions. The aerosol water content is calculated using the Zdanovskii-Stokes-Robinson (ZSR) method. For self-consistency, most of the MTEM and ZSR parameters are derived using the comprehensive Pitzer-Simonson-Clegg model at 298.15 K and are valid for an aw range of 0.2-0.97. Because CaSO4 is sparingly soluble, it is treated as a solid in the model over the entire aw range. MTEM is evaluated for several multicomponent systems representing various continental and marine aerosols and is contrasted against the mixing rule of C. L. Kusik and H. P. Meissner and of L. A. Bromley and the newer approach of S. Metzger and colleagues. Predictions of MTEM are found to be generally within a factor of 0.8-1.25 of the comprehensive Pitzer-Simonson-Clegg model and are shown to be significantly more accurate than predictions of the other three methods. MTEM also yields a noniterative solution of the bisulfate ion dissociation in sulfate-rich systems: a major computational advantage over other ionic-strength-based methods that require an iterative solution. CPU time requirements of MTEM relative to other methods for sulfate-poor and sulfate-rich systems are also discussed.

Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed?

PubMed

Citrome, Leslie

2012-07-01

To describe the efficacy, safety and tolerability of lurasidone for the acute treatment of schizophrenia using the metrics number needed to treat (NNT) and number needed to harm (NNH). Study data were pooled from six Phase II and III, 6-week, randomized, placebo-controlled trials that were conducted to test the efficacy and safety of lurasidone for the acute treatment of schizophrenia. Included were the following interventions: fixed doses of lurasidone 20, 40, 80, 120 and 160 mg/d; haloperidol 10 mg/d; olanzapine 15 mg/d; quetiapine extended-release 600 mg/d; placebo. The following outcomes were assessed: responder rates as defined by a reduction of ≥20, 30, 40 or 50% from baseline on the Positive and Negative Syndrome Scale (PANSS) total score; study completion; discontinuation due to an adverse event (AE); weight gain ≥7% from baseline; incidence of spontaneously reported AEs; incidence of total cholesterol ≥240 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, fasting triglycerides ≥200 mg/dL and glucose ≥126 mg/dL at endpoint. NNT for the efficacy outcomes were calculated after excluding one failed study. NNH for the safety/tolerability outcomes were calculated using all six studies. Likelihood of being helped or harmed (LHH) was also calculated to illustrate trade-offs between outcomes of improvement ≥30% on the PANSS vs. incidence of akathisia, nausea, sedation, somnolence and parkinsonism. NNT vs. placebo for PANSS reductions ≥30% were 6, 6, 7 and 4 for lurasidone doses of 40, 80, 120 and 160 mg/d, respectively, and 4 and 3 for olanzapine 15 mg/d and quetiapine extended-release 600 mg/d, respectively. Lurasidone was not associated with any statistically significant disadvantages over placebo for weight gain or metabolic abnormalities; NNH vs. placebo for weight gain ≥7% from baseline was 4 for olanzapine and 9 for quetiapine extended-release in contrast to a NNH for this outcome ranging from 43 to 150 for lurasidone 40-160 mg/d. The 5 most consistently encountered adverse events attributable to lurasidone were akathisia, nausea, sedation, somnolence and parkinsonism, with NNH vs. placebo for lurasidone 40-120 mg/d ranging from 6 (akathisia with 120 mg/d) to 30 (parkinsonism with 80 mg/d). Lurasidone 160 mg/d appeared better tolerated than doses of 40, 80 or 120 mg/d for akathisia, nausea, sedation or somnolence, with no NNH values for these adverse events for 160 mg/d vs. placebo being statistically significant. LHH was favorable for lurasidone when contrasting PANSS reductions vs. adverse events. NNT and NNH can help quantify efficacy, safety and tolerability outcomes and place lurasidone into clinical perspective. Advantages for lurasidone include a low propensity for weight gain and metabolic abnormalities. More commonly encountered adverse events include akathisia, nausea, sedation, somnolence and parkinsonism, but NNH values are generally in the double digits, reflecting an overall tolerable profile. Individual patient characteristics, values and preferences will need to be considered when selecting lurasidone over other antipsychotics.

Mammographic compression in Asian women.

PubMed

Lau, Susie; Abdul Aziz, Yang Faridah; Ng, Kwan Hoong

2017-01-01

To investigate: (1) the variability of mammographic compression parameters amongst Asian women; and (2) the effects of reducing compression force on image quality and mean glandular dose (MGD) in Asian women based on phantom study. We retrospectively collected 15818 raw digital mammograms from 3772 Asian women aged 35-80 years who underwent screening or diagnostic mammography between Jan 2012 and Dec 2014 at our center. The mammograms were processed using a volumetric breast density (VBD) measurement software (Volpara) to assess compression force, compression pressure, compressed breast thickness (CBT), breast volume, VBD and MGD against breast contact area. The effects of reducing compression force on image quality and MGD were also evaluated based on measurement obtained from 105 Asian women, as well as using the RMI156 Mammographic Accreditation Phantom and polymethyl methacrylate (PMMA) slabs. Compression force, compression pressure, CBT, breast volume, VBD and MGD correlated significantly with breast contact area (p<0.0001). Compression parameters including compression force, compression pressure, CBT and breast contact area were widely variable between [relative standard deviation (RSD)≥21.0%] and within (p<0.0001) Asian women. The median compression force should be about 8.1 daN compared to the current 12.0 daN. Decreasing compression force from 12.0 daN to 9.0 daN increased CBT by 3.3±1.4 mm, MGD by 6.2-11.0%, and caused no significant effects on image quality (p>0.05). Force-standardized protocol led to widely variable compression parameters in Asian women. Based on phantom study, it is feasible to reduce compression force up to 32.5% with minimal effects on image quality and MGD.

Multicomponent Implant Releasing Dexamethasone

NASA Astrophysics Data System (ADS)

Nikkola, L.; Vapalahti, K.; Ashammakhi, N.

2008-02-01

Several inflammatory conditions are usually treated with corticosteroids. There are various problems like side effects with traditional applications of steroids, e.g. topical, or systemic routes. Local drug delivery systems have been studied and developed to gain more efficient administration with fewer side effects. Earlier, we reported on developing Dexamethasone (DX) releasing biodegradable fibers. However, their drug release properties were not satisfactory in terms of onset of drug release. Thus, we assessed the development of multicomponent (MC) implant to enhance earlier drug release from such biodegradable fibers. Poly (lactide-co-glycolide) (PLGA) and 2 wt-% and 8 wt-% DX were compounded and extruded with twin-screw extruder to form of fibers. Some of the fibers were sterilized to obtain a change in drug release properties. Four different fiber classes were studied: 2 wt-%, 8 wt-%, sterilized 2 wt-%, and sterilized 8 wt-%. 3×4 different DX-releasing fibers were then heat-pressed to form one multicomponent rod. Half of the rods where sterilized. Drug release was measured from initial fibers and multicomponent rods using a UV/VIS spectrometer. Shear strength and changes in viscosity were also measured. Drug release studies showed that drug release commenced earlier from multicomponent rods than from component fibers. Drug release from multicomponent rods lasted from day 30 to day 70. The release period of sterilized rods extended from day 23 to day 57. When compared to the original component fibers, the drug release from MC rods commenced earlier. The initial shear strength of MC rods was 135 MPa and decreased to 105 MPa during four weeks of immersion in phosphate buffer solution. Accordingly, heat pressing has a positive effect on drug release. After four weeks in hydrolysis, no disintegration was observed.

Performance evaluation of a digital mammography unit using a contrast-detail phantom

NASA Astrophysics Data System (ADS)

Elizalde-Cabrera, J.; Brandan, M.-E.

2015-01-01

The relation between image quality and mean glandular dose (MGD) has been studied for a Senographe 2000D mammographic unit used for research in our laboratory. The magnitudes were evaluated for a clinically relevant range of acrylic thicknesses and radiological techniques. The CDMAM phantom was used to determine the contrast-detail curve. Also, an alternative method based on the analysis of signal-to-noise (SNR) and contrast-to-noise (CNR) ratios from the CDMAM image was proposed and applied. A simple numerical model was utilized to successfully interpret the results. Optimum radiological techniques were determined using the figures-of-merit FOMSNR=SNR2/MGD and FOMCNR=CNR2/MGD. Main results were: the evaluation of the detector response flattening process (it reduces by about one half the spatial non-homogeneities due to the X- ray field), MGD measurements (the values comply with standards), and verification of the automatic exposure control performance (it is sensitive to fluence attenuation, not to contrast). For 4-5 cm phantom thicknesses, the optimum radiological techniques were Rh/Rh 34 kV to optimize SNR, and Rh/Rh 28 kV to optimize CNR.

Inhibition of neutral endopeptidase potentiates neutrophil activation during Mg-deficiency in the rat

PubMed Central

Mak, I. T.; Kramer, J. H.; Chmielinska, J. J.; Khalid, M. H.; Landgraf, K. M.; Weglicki, W. B.

2013-01-01

Neutral endopeptidase (NEP), which degrades substance P (SP), may regulate neutrophil activation during Mg-deficiency (MgD). Male Sprague-Dawley rats (180g) were fed MgD (~50 mg Mg/kg) or Mg-sufficient (MgS, 608 mg Mg/kg) diets for 7 days ± NEP inhibitor phosphoramidon (PR, 5 mg/kg/day, s. c.). MgD alone induced a 9-fold (vs. MgS, p <0.01) elevation in plasma SP; MgD+PR enhanced it further to 18-fold (p <0.001). Neutrophils from MgD+PR rats displayed a 3.9-fold higher (p <0.01) basal ·O2- generation, but those from MgD or PR alone were not activated. Plasma PGE2-metabolite levels rose 2.67- (p <0.01) and 1.56- (p <0.05) fold, respectively, in MgD+PR and MgD groups; the corresponding red blood cell glutathione levels were decreased 21 % (p <0.025) and 7 % (NS). MgD+PR significantly reduced neutrophil NEP activity by 48 % (p <0.02); PR or MgD alone only reduced this activity 26 % and 15 %, respectively. We conclude that NEP inhibition potentiates SP-mediated neutrophil ·O2- production and may promote other inflammatory activities during MgD. PMID:18607539

Inhibition of neutral endopeptidase potentiates neutrophil activation during Mg-deficiency in the rat.

PubMed

Mak, I T; Kramer, J H; Chmielinska, J J; Khalid, M H; Landgraf, K M; Weglicki, W B

2008-07-01

Neutral endopeptidase (NEP), which degrades substance P (SP), may regulate neutrophil activation during Mg-deficiency (MgD). Male Sprague-Dawley rats (180g) were fed MgD (approximately 50 mg Mg/kg) or Mg-sufficient (MgS, 608 mg Mg/kg) diets for 7 days +/- NEP inhibitor phosphoramidon (PR, 5 mg/kg/day, s.c.). MgD alone induced a 9-fold (vs. MgS, p <0.01) elevation in plasma SP; MgD+PR enhanced it further to 18-fold (p <0.001). Neutrophils from MgD+PR rats displayed a 3.9-fold higher (p <0.01) basal .O(2-) generation, but those from MgD or PR alone were not activated. Plasma PGE2-metabolite levels rose 2.67- (p <0.01) and 1.56- (p <0.05) fold, respectively, in MgD+PR and MgD groups; the corresponding red blood cell glutathione levels were decreased 21% (p <0.025) and 7% (NS). MgD+PR significantly reduced neutrophil NEP activity by 48% (p <0.02); PR or MgD alone only reduced this activity 26% and 15%, respectively. We conclude that NEP inhibition potentiates SP-mediated neutrophil .O(2-) production and may promote other inflammatory activities during MgD.

Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures.

PubMed

Faught, E; Ayala, R; Montouris, G G; Leppik, I E

2001-11-27

Zonisamide is a sulfonamide antiepilepsy drug with sodium and calcium channel-blocking actions. Experience in Japan and a previous European double-blind study have demonstrated its efficacy against partial-onset seizures. A randomized, double-blind, placebo-controlled trial enrolling 203 patients was conducted at 20 United States sites to assess zonisamide efficacy and dose response as adjunctive therapy for refractory partial-onset seizures. Zonisamide dosages were elevated by 100 mg/d each week. The study design allowed parallel comparisons with placebo for three dosages and a final crossover to 400 mg/d of zonisamide for all patients. The primary efficacy comparison was change in seizure frequency from a 4-week placebo baseline to weeks 8 through 12 on blinded therapy. At 400 mg/d, zonisamide reduced the median frequency of all seizures by 40.5% from baseline, compared with a 9% reduction (p = 0.0009) with placebo treatment, and produced a > or =50% seizure reduction (responder rate) in 42% of patients. A dosage of 100 mg/d produced a 20.5% reduction in median seizure frequency (p = 0.038 compared with placebo) and a dosage of 200 mg/d produced a 24.7% reduction in median seizure frequency (p = 0.004 compared with placebo). Dropouts from adverse events (10%) did not differ from placebo (8.2%, NS). The only adverse event differing significantly from placebo was weight loss, though somnolence, anorexia, and ataxia were slightly more common with zonisamide treatment. Serum zonisamide concentrations rose with increasing dose. Zonisamide is effective and well tolerated as an adjunctive agent for refractory partial-onset seizures. The minimal effective dosage was 100 mg/d, but 400 mg/d was the most effective dosage.

A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.

PubMed

2004-04-01

Treatment with rasagiline mesylate, an irreversible monoamine oxidase type B inhibitor, improves symptoms of early Parkinson disease (PD). Preclinical studies suggest that this compound may also modify the progression of PD. To compare the effects of early and later initiation of rasagiline on progression of disability in patients with PD. Double-blind, parallel-group, randomized, delayed-start clinical trial. Four hundred four subjects with early PD, not requiring dopaminergic therapy, enrolled at 32 sites in the United States and Canada. Subjects were randomized to receive rasagiline, 1 or 2 mg/d, for 1 year or placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months. Change in total Unified Parkinson's Disease Rating Scale score from baseline to 12 months. Three hundred seventy-one subjects were included in the 1-year efficacy analysis. Subjects treated with rasagiline, 2 mg/d, for 1 year had a 2.29-unit smaller increase in mean adjusted total Unified Parkinson's Disease Rating Scale score compared with subjects treated with placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months (P =.01). The mean adjusted difference between the placebo/rasagiline, 2 mg/d, group and those receiving rasagiline, 1 mg/d, for 1 year was -1.82 unit on the Unified Parkinson's Disease Rating Scale score (P =.05). Subjects treated with rasagiline, 2 and 1 mg/d, for 12 months showed less functional decline than subjects whose treatment was delayed for 6 months.

Comparative study of quality characteristics of meju, a Korean soybean fermentation starter, made by soybeans germinated under dark and light conditions.

PubMed

Choi, Ung Kyu; Bajpai, Vivek K

2010-01-01

This study was conducted to evaluate the effect of dark and light conditions on the quality characteristics of whole soybean meju, a Koran soybean fermentation starter, made by germinated soybeans. The sprouting rates of soybeans under dark and light conditions after 24h were 25.6+/-1.2% and 20.5+/-1.5%, respectively and reaching to a level of 99.4+/-0.4% and 98.9+/-0.5%, respectively at 60h. The pH, moisture contents and amino-type nitrogen contents had no significant differences under dark and light conditions, however, the contents were significantly different as compared to control. Also there was a significant difference in the color change values of whole soybean meju under dark and light conditions. The compositions of total organic acids in MNG, MGD and MGL were noted to be 942.2+/-111.0, 1075+/-120.2 and 1019+/-108.1mg%, respectively. However, no significant differences were observed in free amino acid contents of MNG, MGD and MGL. It was observed that isoflavone contents were significantly differed in MGD and MGL as compared to MNG. Copyright 2009 Elsevier Ltd. All rights reserved.

Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis.

PubMed

Lindgren, Cecilia; Tyagi, Mohit; Viljanen, Johan; Toms, Johannes; Ge, Changrong; Zhang, Naru; Holmdahl, Rikard; Kihlberg, Jan; Linusson, Anna

2018-05-24

Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259-273, together with the positioning of the galactose moiety of CII259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.

Supplementation with lutein or lutein plus green tea extracts does not change oxidative stress in adequately nourished older adults1

PubMed Central

Li, Lei; Chen, C-Y. Oliver; Aldini, Giancarlo; Johnson, Elizabeth J; Rasmussen, Helen; Yoshida, Yasukazu; Niki, Etsuo; Blumberg, Jeffrey B; Russell, Robert M.; Yeum, Kyung-Jin

2009-01-01

Epigallocatechin gallate, a major component of green tea polyphenols, protects against the oxidation of fat-soluble antioxidants including lutein. The current study determined the effect of relatively high but a dietary achievable dose of lutein or lutein plus green tea extract on antioxidant status. Healthy subjects (50–70 yrs) were randomly assigned to one of 2 groups, (n=20 in each group) 1) a lutein (12mg/d) supplemented group, or 2) a lutein (12 mg/d) plus green tea extract (200 mg/d) supplemented group. After 2 wks of run-in period consumed less than two servings of lightly-colored fruit & vegetables in their diet, each group was treated for 112 days while on their customary regular diets. Plasma carotenoids including lutein, tocopherols, flavanols and ascorbic acid were analyzed by HPLC-UVD and -ECD systems; total antioxidant capacity by fluorometry; lipid peroxidation by malondialdehyde using a HPLC system with a fluorescent detector and by total hydroxyoctadecadienoic acids using a GC/MS. Plasma lutein, total carotenoids and ascorbic acid concentrations of subjects in either lutein group or lutein plus green tea extract group were significantly increased (p<0.05) at 4 wks and throughout the 16 wks study period. However, no significant changes from baseline in any biomarker of overall antioxidant activity or lipid peroxidation of the subjects were seen in either group. Our results indicate that an increase of antioxidant concentrations within a range that could readily be achieved in a healthful diet does not affect in vivo antioxidant status in normal healthy subjects when sufficient amounts of antioxidants already exist. PMID:19447020

Orthology for comparative genomics in the mouse genome database.

PubMed

Dolan, Mary E; Baldarelli, Richard M; Bello, Susan M; Ni, Li; McAndrews, Monica S; Bult, Carol J; Kadin, James A; Richardson, Joel E; Ringwald, Martin; Eppig, Janan T; Blake, Judith A

2015-08-01

The mouse genome database (MGD) is the model organism database component of the mouse genome informatics system at The Jackson Laboratory. MGD is the international data resource for the laboratory mouse and facilitates the use of mice in the study of human health and disease. Since its beginnings, MGD has included comparative genomics data with a particular focus on human-mouse orthology, an essential component of the use of mouse as a model organism. Over the past 25 years, novel algorithms and addition of orthologs from other model organisms have enriched comparative genomics in MGD data, extending the use of orthology data to support the laboratory mouse as a model of human biology. Here, we describe current comparative data in MGD and review the history and refinement of orthology representation in this resource.

Plasma carotenoid concentrations before and after supplementation with astaxanthin in middle-aged and senior subjects.

PubMed

Miyazawa, Taiki; Nakagawa, Kiyotaka; Kimura, Fumiko; Satoh, Akira; Miyazawa, Teruo

2011-01-01

A randomized, double-blind human trial was conducted to assess the effect on the plasma carotenoid concentration of 4- or 12-week astaxanthin supplementation (1 or 3 mg/d) of 20 Japanese middle-aged and senior subjects. The plasma carotenoid concentration was significantly higher after the astaxanthin supplementation than that before in both the 1 mg/d (10 subjects) and 3 mg/d (10 subjects) groups.

Multicomponent order parameter superconductivity of Sr2RuO4 revealed by topological junctions

NASA Astrophysics Data System (ADS)

Anwar, M. S.; Ishiguro, R.; Nakamura, T.; Yakabe, M.; Yonezawa, S.; Takayanagi, H.; Maeno, Y.

2017-06-01

Single crystals of the Sr2RuO4 -Ru eutectic system are known to exhibit enhanced superconductivity at 3 K in addition to the bulk superconductivity of Sr2RuO4 at 1.5 K. The 1.5 K phase is believed to be a spin-triplet, chiral p -wave state with a multicomponent order parameter, giving rise to chiral domain structure. In contrast, the 3 K phase is attributable to enhanced superconductivity of Sr2RuO4 in the strained interface region between Ru inclusion of a few to tens of micrometers in size and the surrounding Sr2RuO4 . We investigate the dynamic behavior of a topological junction, where a superconductor is surrounded by another superconductor. Specifically, we fabricated Nb/Ru/Sr2RuO4 topological superconducting junctions, in which the difference in phase winding between the s -wave superconductivity in Ru microislands induced from Nb and the superconductivity of Sr2RuO4 mainly governs the junction behavior. Comparative results of the asymmetry, hysteresis, and noise in junctions with different sizes, shapes, and configurations of Ru inclusions are explained by the chiral domain-wall motion in these topological junctions. Furthermore, a striking difference between the 1.5 and 3 K phases is clearly revealed: the large noise in the 1.5 K phase sharply disappears in the 3 K phase. These results confirm the multicomponent order-parameter superconductivity of the bulk Sr2RuO4 , consistent with the chiral p -wave state, and the proposed nonchiral single-component superconductivity of the 3 K phase.

Refeeding syndrome in Southeastern Taiwan: Our experience with 11 cases

PubMed Central

Chen, Li-Ju; Chen, Huan-Lin; Bair, Ming-Jong; Wu, Chia-Hsien; Lin, I-Tsung; Lee, Yuan-Kai; Chu, Cheng-Hsin

2014-01-01

AIM: To present our experience with refeeding syndrome in southeastern Taiwan. METHODS: We conducted a retrospective study during a 2-year period at the Mackay Memorial Hospital, Taitung Branch. We enrolled patients with very little or no nutrition intake for more than 10 d, a high risk group of refeeding syndrome, including those suffering from alcohol abuse, cancerous cachexia, chronic malnutrition, and prolonged starvation. RESULTS: A total of 11 patients (7 males, 4 females) with nasogastric feeding were included as having refeeding syndrome. Most of them had the symptoms of diarrhea, lethargy, and leg edema. The initial nutritional supplement was found to be relatively high in calories (1355.1 ± 296.2 kcal/d), high in protein (47.3 ± 10.4 gm/d), low in vitamin B1 (2.0 ± 0.5 mg/d), low in potassium (1260.4 ± 297.7 mg/d), and low in phosphorus (660.1 ± 151.8 mg/d). Furthermore, hypophosphatemia (2.4 ± 0.9 mg/dL) was noted during follow-up. Based on the suggestions of a dietician and a gastroenterologist, the clinical disorders of diarrhea, malaise and leg edema were significantly improved. The level of phosphate was also increased (3.3 ± 0.6 mg/dL). CONCLUSION: Refeeding syndrome is an overlooked and risky disorder that has some potentially fatal complications. Nasogastric feeding in nursing homes is an important risk factor for patients and deserves greater attention based on the initial results of this study. PMID:25132771

Refeeding syndrome in Southeastern Taiwan: our experience with 11 cases.

PubMed

Chen, Li-Ju; Chen, Huan-Lin; Bair, Ming-Jong; Wu, Chia-Hsien; Lin, I-Tsung; Lee, Yuan-Kai; Chu, Cheng-Hsin

2014-08-14

To present our experience with refeeding syndrome in southeastern Taiwan. We conducted a retrospective study during a 2-year period at the Mackay Memorial Hospital, Taitung Branch. We enrolled patients with very little or no nutrition intake for more than 10 d, a high risk group of refeeding syndrome, including those suffering from alcohol abuse, cancerous cachexia, chronic malnutrition, and prolonged starvation. A total of 11 patients (7 males, 4 females) with nasogastric feeding were included as having refeeding syndrome. Most of them had the symptoms of diarrhea, lethargy, and leg edema. The initial nutritional supplement was found to be relatively high in calories (1355.1 ± 296.2 kcal/d), high in protein (47.3 ± 10.4 gm/d), low in vitamin B1 (2.0 ± 0.5 mg/d), low in potassium (1260.4 ± 297.7 mg/d), and low in phosphorus (660.1 ± 151.8 mg/d). Furthermore, hypophosphatemia (2.4 ± 0.9 mg/dL) was noted during follow-up. Based on the suggestions of a dietician and a gastroenterologist, the clinical disorders of diarrhea, malaise and leg edema were significantly improved. The level of phosphate was also increased (3.3 ± 0.6 mg/dL). Refeeding syndrome is an overlooked and risky disorder that has some potentially fatal complications. Nasogastric feeding in nursing homes is an important risk factor for patients and deserves greater attention based on the initial results of this study.

Assessment of Dietary Sodium and Potassium in Canadians Using 24-Hour Urinary Collection.

PubMed

Mente, Andrew; Dagenais, Gilles; Wielgosz, Andreas; Lear, Scott A; McQueen, Matthew J; Zeidler, Johannes; Fu, Lily; DeJesus, Jane; Rangarajan, Sumathy; Bourlaud, Anne-Sophie; De Bluts, Anne Leblanc; Corber, Erica; de Jong, Veronica; Boomgaardt, Jacob; Shane, Alexandra; Jiang, Ying; de Groh, Margaret; O'Donnell, Martin J; Yusuf, Salim; Teo, Koon

2016-03-01

Although salt intake derived from data on urinary sodium excretion in free-living populations has been used in public policy, a population study on urinary sodium excretion has not been done in Canada. We assessed dietary sodium and potassium intake using a 24-hour urine collection in a large survey of urban and rural communities from 4 Canadian cities and determined the association of these electrolytes with blood pressure (BP). One thousand seven hundred consecutive individuals, aged 37-72 years, attending their annual follow-up visits of the ongoing Prospective and Urban Rural Epidemiology (PURE) study in Vancouver, Hamilton, Ottawa, and Quebec City, Canada, collected a 24-hour urine sample using standardized procedures. Mean sodium excretion was 3325 mg/d and mean potassium excretion was 2935 mg/d. Sodium excretion ranged from 3093 mg/d in Vancouver to 3642 mg/d in Quebec City, after adjusting for covariates. Potassium excretion ranged from 2844 mg/d in Ottawa to 3082 mg/d in Quebec City. Both electrolytes were higher in men than in women and in rural populations than in urban settings (P < 0.001 for all). Sodium excretion was between 3000 and 6000 mg/d in 48.3% of the participants, < 3000 mg/d in 46.7%, and > 6000 mg/d in only 5%. No significant association between sodium or potassium excretion and BP was found. Sodium consumption in these Canadians is within a range comparable to other Western countries, and intake in most individuals is < 6000 mg/d, with only 5% at higher levels. Within this range, sodium or potassium levels were not associated with BP. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Galantamine for Alzheimer's disease.

PubMed

Olin, J; Schneider, L

2002-01-01

Galantamine (also called galanthamine, marketed by Janssen as Reminyl) was originally isolated from several plants, including daffodil bulbs, but is now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer's disease (AD), and recently several multicentre clinical trials have been published with positive findings. Galantamine has received regulatory approval in 29 counties: Argentina, Australia, Canada, Czechia, the European Union (except for The Netherlands), Iceland, Korea, Mexico, Norway, Poland, Singapore, South Africa, Switzerland, Thailand, and the United States. The objective of this overview is to assess the clinical effects of galantamine in patients with probable AD, and to investigate potential moderators of an effect. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 15 May 2002 using the terms galantamine and Reminyl. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. Trials selected were randomized, double-blind, parallel-group, unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks for people with AD. Data were extracted independently by the reviewers and pooled where appropriate and possible. The pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Intention-to-treat and observed cases data were both reported, if the data were available. Outcomes of interest include the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), clinical global impression of change (CIBIC-plus or CGIC), Alzheimer's Disease Cooperative Study Activities of Daily Living Scale (ADCS-ADL), Disability Assessment for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI). Potential moderating variables of a treatment effect included trial duration and dose. Seven trials were identified that met criteria for entry, with six being Phase II or III industry-sponsored multicentre trials. Two were of 12 weeks duration; one of 13 weeks, one of 5 months; one of 29 weeks; and two of 6 months duration. Trials of 5 months or more were aggregated together in the analyses as '6 months.' Overall, galantamine showed significant treatment effects at daily doses of 16-32 mg for trials of 3- to 6-months duration. For global ratings, trials of 3 months duration with doses of 24-32mg/d (Odds Ratio (OR) 2.3; 95%CI 1.3 - 3.9) and 36mg/d (OR 3.4; 95%CI 1.2 - 9.5) were statistically significant in favour of treatment. For trials of 6 months duration (5-months to 29 weeks), only doses of 8mg/d failed to be associated with statistically significant benefit (16mg: OR 2.25; 95% CI 1.6 - 3.3; 24mg: OR 2.0; 95%CI 1.5 -2.5; 32mg: OR 1.9; 95%CI 1.4 - 2.5). For cognitive function over 6 months duration: at 16mg/d, improvements measured -3.3 points (k=1; 95%CI -4.4 - -2.1) on weighted mean difference on the ADAS-Cog scale; -3.5 points at 24mg/d (k=3; 95%CI -4.3 - -2.8), and -4.0 points at 32mg/d (k=2; 95%CI -5.0 - -3.0). The two 3-month trials with ADAS-Cog data also showed statistically significant improvement. Both observed cases (WMD 3.8; 95%CI 0.3 - 7.3) and intention-to-treat analyses using the Disability Assessment of Dementia scale gave statistically significant results in favour of treatment for daily doses of 32mg for 6 months duration (as did the single 3-month trial of 24-32mg/d treatment that used this scale). The small number of trials available for analysis, however, limited the power of subgroup analyses to detect differences. Galantamine consistently failed to show statistically significant treatment effects at doses of 8mg/day. Galantamine's adverse effects appear similar to those of other cholinesterase inhibitors, in that it tends to produce gastrointestinal symptoms acutely and with dosage increases. Overall, participants treated with galantamine at all doses for 3 months were more likely to discontinue that were those given placebo. Participants treated with galantamine at doses of 24-32 mg/d for 6 months were more likely to discontinue in most trials than were those treated with lower doses or placebo, with 32mg/d being associated with significantly higher withdrawal rates than was 24mg/d. However, in the one trial with a slower rate of titration the discontinuation rate was not significantly greater than placebo for the 16 mg/day dose. Patients in these trials were similar to those seen in earlier anti dementia AD trials, and consisted predominantly of mildly to moderately impaired outpatients. Galantamine's effects on more severely impaired people has not yet been assessed. Never the less, this review shows consistent positive effects for galantamine for trials of 3 months, 5 months and 6 months duration. In addition, although there was not a statistically significant dose-response effect, benefits associated with doses above 8mg/d were, for the most part, consistently statistically significant. There is therefore evidence for efficacy of galantamine on global ratings, cognitive tests, assessments of ADLs and behaviour. This magnitude for the cognitive effect is similar to that associated with other cholinesterase inhibitors including donepezil, rivastigmine, and tacrine. Galantamine's safety profile is similar to that of other cholinesterase inhibitors with regard to cholinergically mediated gastrointestinal symptoms. No information is available on adverse events that occurred less than 5% of the time. It appears that doses of 16 mg/d were best tolerated in the single trial where medication was titrated over 4-week periods, and because this dose showed statistically indistinguishable efficacy with higher doses, it is probably preferable initially. Longer-term use of galantamine has not been assessed in a controlled fashion.

[Study on high accuracy detection of multi-component gas in oil-immerse power transformer].

PubMed

Fan, Jie; Chen, Xiao; Huang, Qi-Feng; Zhou, Yu; Chen, Gang

2013-12-01

In order to solve the problem of low accuracy and mutual interference in multi-component gas detection, a kind of multi-component gas detection network with high accuracy was designed. A semiconductor laser with narrow bandwidth was utilized as light source and a novel long-path gas cell was also used in this system. By taking the single sine signal to modulate the spectrum of laser and using space division multiplexing (SDM) and time division multiplexing (TDM) technique, the detection of multi-component gas was achieved. The experiments indicate that the linearity relevance coefficient is 0. 99 and the measurement relative error is less than 4%. The system dynamic response time is less than 15 s, by filling a volume of multi-component gas into the gas cell gradually. The system has advantages of high accuracy and quick response, which can be used in the fault gas on-line monitoring for power transformers in real time.

Mucosal healing effect of mesalazine granules in naproxen-induced small bowel enteropathy

PubMed Central

Rácz, István; Szalai, Milán; Kovács, Valéria; Regőczi, Henriett; Kiss, Gyöngyi; Horváth, Zoltán

2013-01-01

AIM: To investigate the effect of mesalazine granules on small intestinal injury induced by naproxen using capsule endoscopy (CE). METHODS: This was a single center, non-randomized, open-label, uncontrolled pilot study, using the PillCam SB CE system with RAPID 5 software. The Lewis Index Score (LIS) for small bowel injury was investigated to evaluate the severity of mucosal injury. Arthropathy patients with at least one month history of daily naproxen use of 1000 mg and proton pump inhibitor co-therapy were screened. Patients with a minimum LIS of 135 were eligible to enter the 4-wk treatment phase of the study. During this treatment period, 3 × 1000 mg/d mesalazine granules were added to ongoing therapies of 1000 mg/d naproxen and 20 mg/d omeprazole. At the end of the 4-wk combined treatment period, a second small bowel CE was performed to re-evaluate the enteropathy according to the LIS results. The primary objective of this study was to assess the mucosal changes after 4 wk of mesalazine treatment. RESULTS: A total of 18 patients (16 females), ranging in age from 46 to 78 years (mean age 60.3 years) were screened, all had been taking 1000 mg/d naproxen for at least one month. Eight patients were excluded from the mesalazine therapeutic phase of the study for the following reasons: the screening CE showed normal small bowel mucosa or only insignificant damages (LIS < 135) in five patients, the screening esophagogastroduodenoscopy revealed gastric ulcer in one patient, capsule technical failure and incomplete CE due to poor small bowel cleanliness in two patients. Ten patients (9 female, mean age 56.2 years) whose initial LIS reached mild and moderate-to-severe enteropathy grades (between 135 and 790 and ≥ 790) entered the 4-wk therapeutic phase and a repeat CE was performed. When comparing the change in LIS from baseline to end of treatment in all patients, a marked decrease was seen (mean LIS: 1236.4 ± 821.9 vs 925.2 ± 543.4, P = 0.271). Moreover, a significant difference between pre- and post-treatment mean total LIS was detected in 7 patients who had moderate-to-severe enteropathy gradings at the inclusion CE (mean LIS: 1615 ± 672 vs 1064 ± 424, P = 0.033). CONCLUSION: According to the small bowel CE evaluation mesalazine granules significantly attenuated mucosal injuries in patients with moderate-to-severe enteropathies induced by naproxen. PMID:23431027

Impact of multilayered compression bandages on sub-bandage interface pressure: a model.

PubMed

Al Khaburi, J; Nelson, E A; Hutchinson, J; Dehghani-Sanij, A A

2011-03-01

Multi-component medical compression bandages are widely used to treat venous leg ulcers. The sub-bandage interface pressures induced by individual components of the multi-component compression bandage systems are not always simply additive. Current models to explain compression bandage performance do not take account of the increase in leg circumference when each bandage is applied, and this may account for the difference between predicted and actual pressures. To calculate the interface pressure when a multi-component compression bandage system is applied to a leg. Use thick wall cylinder theory to estimate the sub-bandage pressure over the leg when a multi-component compression bandage is applied to a leg. A mathematical model was developed based on thick cylinder theory to include bandage thickness in the calculation of the interface pressure in multi-component compression systems. In multi-component compression systems, the interface pressure corresponds to the sum of the pressures applied by individual bandage layers. However, the change in the limb diameter caused by additional bandage layers should be considered in the calculation. Adding the interface pressure produced by single components without considering the bandage thickness will result in an overestimate of the overall interface pressure produced by the multi-component compression systems. At the ankle (circumference 25 cm) this error can be 19.2% or even more in the case of four components bandaging systems. Bandage thickness should be considered when calculating the pressure applied using multi-component compression systems.

A self-calibrating multicomponent force/torque measuring system

NASA Astrophysics Data System (ADS)

Marangoni, Rafael R.; Schleichert, Jan; Rahneberg, Ilko; Hilbrunner, Falko; Fröhlich, Thomas

2018-07-01

A multicomponent self-calibrating force and torque sensor is presented. In this system, the principle of a Kibble balance is adapted for the traceable force and torque measurement in three orthogonal directions. The system has two operating modes: the velocity mode and the force/torque sensing mode. In the velocity mode, the calibration of the sensor is performed, while in the force/torque sensing mode, forces and torques are measured by using the principle of the electromagnetic force compensation. Details about the system are provided, with the main components of the sensor and a description of the operational procedure. A prototype of the system is currently being implemented for measuring forces and torques in a range of  ±2 N and  ±0.1 N · m respectively. A maximal relative expanded measurement uncertainty (k  =  2) of 1 · 10‑4 is expected for the force and torque measurements.

Randomized controlled trial of the effects of vitamin D–fortified milk and bread on serum 25-hydroxyvitamin D concentrations in families in Denmark during winter: the VitmaD study.

PubMed

Madsen, Katja H; Rasmussen, Lone B; Andersen, Rikke; Mølgaard, Christian; Jakobsen, Jette; Bjerrum, Poul J; Andersen, Elisabeth W; Mejborn, Heddie; Tetens, Inge

2013-08-01

Vitamin D intakes are lower than dietary recommendations in most populations, and thus, a low vitamin D status is widespread, especially during winter. We investigated the effects of increasing vitamin D intake to the recommended amount by fortification of milk and bread on serum 25-hydroxyvitamin D [25(OH)D] concentrations in families during winter in Denmark. The study was a randomized controlled trial in 782 children and adults (4-60 y old) recruited as 201 families. Families were randomly assigned to vitamin D-fortified or nonfortified milk and bread for 6 mo starting in September. The milk and bread replaced the participants' usual consumptions of products. Median (IQR) vitamin D intakes (habitual diet plus fortified products) were 9.4 mg/d (6.5, 12.3 mg/d) and 2.2 mg/d (1.5, 3.0 mg/d) in fortification and control groups, respectively. Geometric mean (IQR) serum 25(OH)D concentrations decreased from 73.1 nmol/L (61.9, 88.5 nmol/L) to 67.6 nmol/L (56.2, 79.4 nmol/L) in the fortification group and from 71.1 nmol/L (61.2, 85.9 nmol/L) to 41.7 nmol/L (29.5, 58.9 nmol/L) in the control group (both P , 0.001). The final 25(OH)D concentration was significantly higher in the fortification group than in the control group (P , 0.001). By the end of the study, ,1% of subjects in the fortification group and 25% of subjects in the control group had 25(OH)D concentrations ,30 nmol/L and 16% and 65% of subjects, respectively, had 25(OH)D concentrations ,50 nmol/L. Vitamin D fortification of milk and bread reduces the decrease in serum 25(OH)D concentrations during winter and ensures 25(OH)D concentrations .50 nmol/L in children and adults in Denmark.

A Multicomponent Behavioral Intervention to Reduce Stroke Risk Factor Behaviors: The Stroke Health and Risk Education Cluster-Randomized Controlled Trial.

PubMed

Brown, Devin L; Conley, Kathleen M; Sánchez, Brisa N; Resnicow, Kenneth; Cowdery, Joan E; Sais, Emma; Murphy, Jillian; Skolarus, Lesli E; Lisabeth, Lynda D; Morgenstern, Lewis B

2015-10-01

The Stroke Health and Risk Education Project was a cluster-randomized, faith-based, culturally sensitive, theory-based multicomponent behavioral intervention trial to reduce key stroke risk factor behaviors in Hispanics/Latinos and European Americans. Ten Catholic churches were randomized to intervention or control group. The intervention group received a 1-year multicomponent intervention (with poor adherence) that included self-help materials, tailored newsletters, and motivational interviewing counseling calls. Multilevel modeling, accounting for clustering within subject pairs and parishes, was used to test treatment differences in the average change since baseline (ascertained at 6 and 12 months) in dietary sodium, fruit and vegetable intake, and physical activity, measured using standardized questionnaires. A priori, the trial was considered successful if any one of the 3 outcomes was significant at the 0.05/3 level. Of 801 subjects who consented, 760 completed baseline data assessments, and of these, 86% completed at least one outcome assessment. The median age was 53 years; 84% subjects were Hispanic/Latino; and 64% subjects were women. The intervention group had a greater increase in fruit and vegetable intake than the control group (0.25 cups per day [95% confidence interval: 0.08, 0.42], P=0.002), a greater decrease in sodium intake (-123.17 mg/d [-194.76, -51.59], P=0.04), but no difference in change in moderate- or greater-intensity physical activity (-27 metabolic equivalent-minutes per week [-526, 471], P=0.56). This multicomponent behavioral intervention targeting stroke risk factors in predominantly Hispanics/Latinos was effective in increasing fruit and vegetable intake, reaching its primary end point. The intervention also seemed to lower sodium intake. Church-based health promotions can be successful in primary stroke prevention efforts. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01378780. © 2015 American Heart Association, Inc.

Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults

PubMed Central

Radulescu, Angela; Shrestha, Rupendra T.; Root, Matthew; Karger, Amy B.; Killeen, Anthony A.; Hodges, James S.; Fan, Shu-Ling; Ferguson, Angela; Garg, Uttam; Sokoll, Lori J.; Burmeister, Lynn A.

2017-01-01

Importance Biotinylated antibodies and analogues, with their strong binding to streptavidin, are used in many clinical laboratory tests. Excess biotin in blood due to supplemental biotin ingestion may affect biotin-streptavidin binding, leading to potential clinical misinterpretation. However, the degree of interference remains undefined in healthy adults. Objective To assess performance of specific biotinylated immunoassays after 7 days of ingesting 10 mg/d of biotin, a dose common in over-the-counter supplements for healthy adults. Design, Setting, and Participants Nonrandomized crossover trial involving 6 healthy adults who were treated at an academic medical center research laboratory Exposure Administration of 10 mg/d of biotin supplementation for 7 days. Main Outcomes and Measures Analyte concentrations were compared with baseline (day 0) measures on the seventh day of biotin treatment and 7 days after treatment had stopped (day 14). The 11 analytes included 9 hormones (ie, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, 25-hydroxyvitamin D) and 2 nonhormones (prostate-specific antigen and ferritin). A total of 37 immunoassays for the 11 analytes were evaluated on 4 diagnostic systems, including 23 assays that incorporated biotin and streptavidin components and 14 assays that did not include biotin and streptavidin components and served as negative controls. Results Among the 2 women and 4 men (mean age, 38 years [range, 31-45 years]) who took 10 mg/d of biotin for 7 days, biotin ingestion–associated interference was found in 9 of the 23 (39%) biotinylated assays compared with none of the 14 nonbiotinylated assays (P = .007). Results from 5 of 8 biotinylated (63%) competitive immunoassays tested falsely high and results from 4 out of 15 (27%) biotinylated sandwich immunoassays tested falsely low. Conclusions and Relevance In this preliminary study of 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassays, ingesting 10 mg/d of biotin for 1 week was associated with potentially clinically important assay interference in some but not all biotinylated assays studied. These findings should be considered for patients taking biotin supplements before ordering blood tests or when interpreting results. Trial Registration clinicaltrials.gov Identifier: NCT03034707 PMID:28973622

Comparison of four proton pump inhibitors for the short-term treatment of esophagitis in elderly patients.

PubMed

Pilotto, Alberto; Franceschi, Marilisa; Leandro, Gioacchino; Scarcelli, Carlo; D'Ambrosio, Luigi Piero; Paris, Francesco; Annese, Vito; Seripa, Davide; Andriulli, Angelo; Di Mario, Francesco

2007-09-07

To compare efficacy and tolerability of four proton pump inhibitors (PPIs) commonly used in the short-term therapy of esophagitis in elderly patients. A total of 320 patients over 65 years with endoscopically diagnosed esophagitis were randomly assigned to one of the following treatments for 8 wk: (1) omeprazole 20 mg/d; (2) lansoprazole 30 mg/d; (3) pantoprazole 40 mg/d, or (4) rabeprazole 20 mg/d. Major symptoms, compliance, and adverse events were recorded. After 8 wk, endoscopy and clinical evaluation were repeated. Per protocol and intention to treat healing rates of esophagitis were: omeprazole = 81.0% and 75.0%, lansoprazole = 90.7% (P = 0.143 vs omeprazole) and 85.0%, pantoprazole = 93.5% (P = 0.04 vs omeprazole) and 90.0% (P = 0.02 vs omeprazole), rabeprazole = 94.6% (P = 0.02 vs omeprazole) and 88.8% (P = 0.04 vs omeprazole). Dividing patients according to the grades of esophagitis, omeprazole was significantly less effective than the three other PPIs in healing grade 1 esophagitis (healing rates: 81.8% vs 100%, 100% and 100%, respectively, P = 0.012). Pantoprazole and rabeprazole (100%) were more effective vs omeprazole (89.6%, P = 0.0001) and lansoprazole (82.4%, P = 0.0001) in decreasing heartburn. Pantoprazole and rabeprazole (92.2% and 90.1%, respectively) were also more effective vs lansoprazole (75.0%, P < 0.05) in decreasing acid regurgitation. Finally, pantoprazole and rabeprazole (95.2% and 100%) were also more effective vs lansoprazole (82.6%, P < 0.05) in decreasing epigastric pain. In elderly patients, pantoprazole and rabeprazole were significantly more effective than omeprazole in healing esophagitis and than omeprazole or lansoprazole in improving symptoms. H pylori infection did not influence the healing rates of esophagitis after a short-term treatment with PPI.

Reversible Pisa Syndrome Induced by Rivastigmine in a Patient With Early-Onset Alzheimer Disease.

PubMed

Hsu, Chih-Wei; Lee, Yu; Lee, Chun-Yi; Lin, Pao-Yen

Pisa syndrome (PS) is a state of dystonic muscle contraction with a marked truncal deviation to one side. It is an uncommon adverse effect of antipsychotic drugs, but is rarely reported in patients receiving acetylcholinesterase inhibitors, especially rivastigmine. We present a 57-year-old female patient with Alzheimer disease who began to develop symptoms of dementia at the age of 51 years. She was observed to have symptoms of PS after continuous use of rivastigmine (9 mg/d) for nearly 2 years. The PS symptoms improved after the dose of rivastigmine was reduced but recurred when the dose was added back to 9 mg/d. Finally, after we decreased the dose to 4.5 mg/d, her PS symptoms were remitted. This report reminds us that clinicians need to be cautious about the risk of PS when prescribing rivastigmine in a patient with early-onset Alzheimer disease.

Mean glandular dose to patients from stereotactic breast biopsy procedures.

PubMed

Paixão, Lucas; Chevalier, Margarita; Hurtado-Romero, Antonio E; Garayoa, Julia

2018-06-07

The aim of this work is to study the radiation doses delivered to a group of patients that underwent a stereotactic breast biopsy (SBB) procedure. Mean glandular doses (MGD) were estimated from the air-kerma measured at the breast surface entrance multiplying by specific conversion coefficients (DgN) that were estimated using Monte Carlo simulations. DgN were calculated for the 0º and ±15º projections used in SBB and for the particular beam quality. Data on 61 patients were collected showing that a typical SBB procedure is composed by 10 images. MGD was on average (4 ± 2) mGy with (0.38 ± 0.06) mGy per image. The use of specific conversion coefficients instead of typical DgN for mammography/tomosynthesis yields to obtain MGD values for SBB that are around a 65% lower on average. © 2018 Institute of Physics and Engineering in Medicine.

Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial.

PubMed

Lees, Andrew J; Ferreira, Joaquim; Rascol, Olivier; Poewe, Werner; Rocha, José-Francisco; McCrory, Michelle; Soares-da-Silva, Patricio

2017-02-01

Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Current COMT inhibitors carry a high risk for toxic effects to hepatic cells or show moderate improvement. Opicapone was designed to be effective without the adverse effects. To evaluate the efficacy and safety of 25- and 50-mg/d dosages of opicapone compared with placebo as adjunct to levodopa therapy in patients with PD experiencing end-of-dose motor fluctuations. This phase 3 international, multicenter outpatient study evaluated a 25- and a 50-mg/d dosage of opicapone in a randomized, double-blind, 14- to 15-week, placebo-controlled clinical trial, followed by a 1-year open-label phase during which all patients received active treatment with opicapone. Patients with PD who experienced signs of end-of-dose deterioration and had a mean total awake off-time (state of akinesia or decreased mobility) of at least 1.5 hours, not including morning akinesia, were enrolled. Data were collected from March 18, 2011, through June 25, 2013. Data from the evaluable population were analyzed from July 31, 2013, to July 31, 2014. The primary efficacy outcome of the double-blind phase was the change from baseline in absolute off-time vs placebo based on patient diaries. The open-label phase focused on maintenance of treatment effect in off-time. A total of 427 patients (258 men [60.4%] and 169 women [39.6%]; mean [SD] age, 63.1 [8.8] years) were randomized to a 25-mg/d (n = 129) or a 50-mg/d (n = 154) dosage of opicapone or to placebo (n = 144). Of these, 376 patients completed the double-blind phase and entered the open-label phase, of whom 286 completed 1 year of open-label treatment. At the end of the double-blind phase, the least squares mean change (SE) in off-time was -64.5 (14.4) minutes for the placebo group, -101.7 (14.9) minutes for the 25-mg/d opicapone group, and -118.8 (13.8) minutes for the 50-mg/d opicapone group. The adjusted treatment difference vs placebo was significant for the 50-mg/d opicapone group (treatment effect, -54.3 [95% CI, -96.2 to -12.4] minutes; P = .008), but not for the 25-mg/d opicapone group (treatment effect, -37.2 [95% CI, -80.8 to 6.4] minutes; P = .11). The off-time reduction was sustained throughout the open-label phase (-126.3 minutes at 1-year open-label end point). The most common adverse events in the opicapone vs placebo groups were dyskinesia, constipation, and dry mouth. Fifty-one patients (11.9%) discontinued from the study during the double-blind phase. Treatment with a 50-mg once-daily dose of opicapone was associated with a significant reduction in mean daily off-time in levodopa-treated patients with PD and motor fluctuations, and this effect is maintained for at least 1 year. Opicapone was safe and well tolerated. clinicaltrials.gov Identifier: NCT01227655.

75 FR 71094 - Notice of Commission Meeting and Public Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-22

...-093 CP-4. An application for renewal of the Tamiment Wastewater Treatment Plant (WWTP). The existing 0...-1990-078 CP-3. An application to renew the approval of the existing 4.0 mgd Amity WWTP. Effluent limits.... Shoemakersville Borough Authority, D-1993-074 CP-3. An application to renew the discharge of up to 0.75 mgd of...

Higher Strength Lanthanum Carbonate Provides Serum Phosphorus Control With a Low Tablet Burden and Is Preferred by Patients and Physicians: A Multicenter Study

PubMed Central

Mehrotra, Rajnish; Martin, Kevin J.; Fishbane, Steven; Sprague, Stuart M.; Zeig, Steven; Anger, Michael

2008-01-01

Background and objectives: Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d. Design, setting, participants, & measurements: This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with ≤3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B. Results: At the end of week 4, 54% of patients achieved serum phosphorus control at dosages ≤3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication. Conclusions: Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden. PMID:18579668

Liquid-Vapor Equilibrium of Multicomponent Cryogenic Systems

NASA Technical Reports Server (NTRS)

Thompson, W. Reid; Calado, Jorge C. G.; Zollweg, John A.

1990-01-01

Liquid-vapor and solid-vapor equilibria at low to moderate pressures and low temperatures are important in many solar system environments, including the surface and clouds of Titan, the clouds of Uranus and Neptune, and the surfaces of Mars and Triton. The familiar cases of ideal behavior are limiting cases of a general thermodynamic representation for the vapor pressure of each component in a homogeneous multicomponent system. The fundamental connections of laboratory measurements to thermodynamic models are through the Gibbs-Duhem relation and the Gibbs-Helmholtz relation. Using laboratory measurements of the total pressure, temperature, and compositions of the liquid and vapor phases at equilibrium, the values of these parameters can be determined. The resulting model for vapor-liquid equilibrium can then conveniently and accurately be used to calculate pressures, compositions, condensation altitudes, and their dependencies on changing climatic conditions. A specific system being investigated is CH4-C2H6-N2, at conditions relevant to Titan's surface and atmosphere. Discussed are: the modeling of existing data on CH4-N2, with applications to the composition of Titan's condensate clouds; some new measurements on the CH4-C2H6 binary, using a high-precision static/volumetric system, and on the C2H6-N2 binary, using the volumetric system and a sensitive cryogenic flow calorimeter; and describe a new cryogenic phase-equilibrium vessel with which we are beginning a detailed, systematic study of the three constituent binaries and the ternary CH4-C2H6-N2 system at temperatures ranging from 80 to 105 K and pressures from 0.1 to 7 bar.

Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence

PubMed Central

Liu, Chun-Jen; Chang, Juliana; Lee, Po-Huang; Lin, Deng-Yn; Wu, Cheng-Chung; Jeng, Long-Bin; Lin, Yih-Jyh; Mok, King-Tong; Lee, Wei-Chen; Yeh, Hong-Zen; Ho, Ming-Chih; Yang, Sheng-Shun; Yang, Mei-Due; Yu, Ming-Chin; Hu, Rey-Heng; Peng, Cheng-Yuan; Lai, Kuan-Lang; Chang, Stanley Shi-Chung; Chen, Pei-Jer

2014-01-01

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection. METHODS: A total of 143 patients (83.1% of the 172 participants in the phase II study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase II trial. Safety parameters and the following efficacy endpoints were investigated: (1) time to recurrence; (2) disease-free survival; and (3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group: (1) the recurrence-free rate increased from 50% to 63%, and (2) time to recurrence at the 36th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate (11 out of 54 patients). Additionally, subgroup analyses of patients with (1) multiple tumors or a single tumor ≥ 2 cm; and (2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage (56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC. PMID:25170226

Analysis of opioid-mediated analgesia in Phase III studies of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain

PubMed Central

Webster, Lynn R; Brenner, Darren M; Barrett, Andrew C; Paterson, Craig; Bortey, Enoch; Forbes, William P

2015-01-01

Background Subcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC) but may theoretically disrupt opioid-mediated analgesia. Methods Opioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores) were reported in a randomized, double-blind trial with an open-label extension (RCT) and an open-label trial (OLT) evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methyl naltrexone 12 mg once daily (n=150), every other day (n=148), or placebo (n=162) for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364) for 8 weeks. In the OLT, patients (n=1,034) on stable opioid doses with OIC received methylnaltrexone 12 mg prn for up to 48 weeks. Results Minimal fluctuations of median morphine equivalent dose from baseline (BL) were observed in the RCT double-blind period (BL, 154.8–161.0 mg/d; range, 137.1–168.0 mg/d), RCT open-label period (BL, 156.3–174.6; range, 144.0–180.0) and OLT (BL, 120 mg/d; range, 117.3–121.1 mg/d). No significant change from BL in pain intensity score occurred in any group at weeks 2 or 4 (both P≥0.1) of the RCT double-blind period, and scores remained stable during the open-label period and in the OLT (mean change, −0.2 to 0.1). Changes from BL in OOWS and SOWS scores during the double-blind period were not significantly impacted by methylnaltrexone exposure at weeks 2 or 4 (P>0.05 for all). Conclusion Methylnaltrexone did not affect opioid-mediated analgesia in patients with chronic noncancer pain and OIC. PMID:26586963

76 FR 9630 - Notice of Public Hearing and Commission Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-18

... Township, Perry County, Pa. Application for groundwater withdrawal of up to 0.465 mgd from Well PW-5. 2... County, Pa. Application for groundwater withdrawal of up to 1.210 mgd from Well 1. 12. Project Sponsor..., Pa. Application for groundwater withdrawal of up to 0.055 mgd from Well MP- 1. 13. Project Sponsor...

A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.

PubMed

Shifren, Jan L; Desindes, Sophie; McIlwain, Marilyn; Doros, Gheorghe; Mazer, Norman A

2007-01-01

To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women. Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens. Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C. Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.

Automated Breast Density Computation in Digital Mammography and Digital Breast Tomosynthesis: Influence on Mean Glandular Dose and BIRADS Density Categorization.

PubMed

Castillo-García, Maria; Chevalier, Margarita; Garayoa, Julia; Rodriguez-Ruiz, Alejandro; García-Pinto, Diego; Valverde, Julio

2017-07-01

The study aimed to compare the breast density estimates from two algorithms on full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) and to analyze the clinical implications. We selected 561 FFDM and DBT examinations from patients without breast pathologies. Two versions of a commercial software (Quantra 2D and Quantra 3D) calculated the volumetric breast density automatically in FFDM and DBT, respectively. Other parameters such as area breast density and total breast volume were evaluated. We compared the results from both algorithms using the Mann-Whitney U non-parametric test and the Spearman's rank coefficient for data correlation analysis. Mean glandular dose (MGD) was calculated following the methodology proposed by Dance et al. Measurements with both algorithms are well correlated (r ≥ 0.77). However, there are statistically significant differences between the medians (P < 0.05) of most parameters. The volumetric and area breast density median values from FFDM are, respectively, 8% and 77% higher than DBT estimations. Both algorithms classify 35% and 55% of breasts into BIRADS (Breast Imaging-Reporting and Data System) b and c categories, respectively. There are no significant differences between the MGD calculated using the breast density from each algorithm. DBT delivers higher MGD than FFDM, with a lower difference (5%) for breasts in the BIRADS d category. MGD is, on average, 6% higher than values obtained with the breast glandularity proposed by Dance et al. Breast density measurements from both algorithms lead to equivalent BIRADS classification and MGD values, hence showing no difference in clinical outcomes. The median MGD values of FFDM and DBT examinations are similar for dense breasts (BIRADS d category). Published by Elsevier Inc.

Long Term Outcome after Application of the Angio-Seal Vascular Closure Device in Minipigs

PubMed Central

Kabelitz, Lisa; Nonn, Andrea; Nolte, Kay W.; Nikoubashman, Omid; Othman, Ahmed; Heringer, Sarah; Kramer, Martin; Wiesmann, Martin; Brockmann, Marc A.

2016-01-01

Minipigs are frequently used in (neuro-)interventional research. Longitudinal experiments may require repeated vessel access via the femoral artery. Anticoagulation and incompliance of the animals necessitates the use of a vascular closure device (VCD). The effects of the Angio-Seal VCD in minipigs were longitudinally assessed. Minipig (42±8.4 kg body weight) femoral arteries were sealed using the 8F (n = 6) or 6F (n = 7) Angio-Seal VCD. The pre-interventional femoral artery diameter was 5.1±0.4 mm (4.3–5.8 mm). Sealed puncture sites were analysed angiographically as well as by computed tomography angiography (CTA) for a mean period of 14.1±8.0 weeks (1–22 weeks). All animals were constantly treated with acetylsalicylic acid (ASS) (450 mg/d (n = 7) or 100 mg/d (n = 1)) and clopidogrel (75 mg/d (n = 8)). Non-instrumented (n = 2) and arteries sealed using the VCD (n = 2) were examined histologically. No postoperative hemorrhagic complications were observed. Three arteries were occluded after VCD placement (1 animal diagnosed after 4 weeks (8F), 2 animals after 1 week (6F)) and remained so until the end of the experiments after 22, 12 and 4 weeks, respectively. In one artery a 50% stenosis 8 weeks after application of a 6F Angio-Seal was detected. In 69.2% (n = 9) the VCD was applied without complications. Histopathological analysis of the sealed arterial segments showed subtotal obliteration of the vessel lumen, formation of collagenous tissue and partial damage of the internal elastic lamina. The Angio-Seal VCD prevents relevant hemorrhagic complications in minipigs treated with dual platelet inhibition, but is associated with increased vessel occlusion rates. PMID:27682594

Meibomian Gland Dysfunction Model in Hairless Mice Fed a Special Diet With Limited Lipid Content.

PubMed

Miyake, Hideki; Oda, Tomoko; Katsuta, Osamu; Seno, Masaharu; Nakamura, Masatsugu

2016-06-01

A novel meibomian gland dysfunction (MGD) model was developed to facilitate understanding of the pathophysiology of MGD and to evaluate treatment with azithromycin ophthalmic solution (azithromycin). MGD was induced in HR-1 hairless mice by feeding them a special diet with limited lipid content (HR-AD). Male HR-1 hairless mice were fed an HR-AD diet for 16 weeks. Development of MGD was assessed by histopathology at 4-week intervals. The lid margin was observed by slit-lamp examination. After cessation of the HR-AD diet, the mice were fed a normal diet to restore normal eye conditions. Expression of cytokeratin 6 was determined by immunostaining. We evaluated the effects of topically applied azithromycin on the plugged orifice in this model. After mice were fed the HR-AD diet, histopathology analysis showed hyperkeratinization of the ductal epithelium in the meibomian gland. Ductal hyperkeratinization resulted in the loss of acini, followed by atrophy of the gland. Slit-lamp examination revealed a markedly plugged orifice, telangiectasia, and a toothpaste-like meibum compared with that of a normal eyelid. Cessation of feeding with HR-AD ameliorated both the MGD signs and the expression of cytokeratin 6, restoring the tissue to a histologically normal state. Azithromycin treatment significantly decreased the number of plugged orifices and ameliorated atrophy, as revealed by histopathologic analysis. We developed a novel model that mimics human MGD signs in HR-1 hairless mice fed an HR-AD diet. Azithromycin treatment led to therapeutic improvement in this model. This MGD model could be useful for the evaluation of drug candidates for MGD.

On the prescribing of oral doxycycline or minocycline by UK optometrists as part of management of chronic Meibomian Gland Dysfunction (MGD).

PubMed

Doughty, Michael J

2016-02-01

To review the special pharmacology of tetracycline antibiotics as anti-inflammatory drugs for treatment of obstructive Meibomian gland disease (MGD) METHODS: PubMed was used as principal resource for articles, regardless of language, on doxycycline and minocycline with key interests being on their serum and tissue pharmacokinetics and their use in clinical studies as part of management of MGD. With oral dosing of between 50 and 200mg, peak blood levels of these antibiotics have been reported to be predictably dose-dependent at between 1 and 5 microgram/mL, with human tear film levels not being detectable with 100mg dosing of doxycycline but levels of 0.2 microgram/mL with 200mg minocycline. That these two tetracycline antibiotics reach the conjunctiva is indicated by conjunctival pigmentary changes due to photosensitization after very long term use. Based the reported use in a range of clinical studies on MGD, dosing with these two antibiotics for MGD is likely to be useful at relatively low doses (e.g. 100mg for doxycycline or 50mg for minocycline, either at once or twice daily depending on severity at presentation and previous history) continued for 2 to 3 months, with the expected outcome being small-to-substantial decreases in abnormal appearance of the glands (from -4 to -89%) and increases in tear film stability (from 21 to 273%). Oral doxycycline and minocycline have predictable pharmacokinetics and have been reported to improve Meibomian gland dysfunction over a few months of use. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

In-situ characterization of nanoparticle beams focused with an aerodynamic lens by Laser-Induced Breakdown Detection

PubMed Central

Barreda, F.-A.; Nicolas, C.; Sirven, J.-B.; Ouf, F.-X.; Lacour, J.-L.; Robert, E.; Benkoula, S.; Yon, J.; Miron, C.; Sublemontier, O.

2015-01-01

The Laser-Induced Breakdown Detection technique (LIBD) was adapted to achieve fast in-situ characterization of nanoparticle beams focused under vacuum by an aerodynamic lens. The method employs a tightly focused, 21 μm, scanning laser microprobe which generates a local plasma induced by the laser interaction with a single particle. A counting mode optical detection allows the achievement of 2D mappings of the nanoparticle beams with a reduced analysis time thanks to the use of a high repetition rate infrared pulsed laser. As an example, the results obtained with Tryptophan nanoparticles are presented and the advantages of this method over existing ones are discussed. PMID:26498694

The effects of a 2-year individualized and family-based lifestyle intervention on physical activity, sedentary behavior and diet in children.

PubMed

Viitasalo, Anna; Eloranta, Aino-Maija; Lintu, Niina; Väistö, Juuso; Venäläinen, Taisa; Kiiskinen, Sanna; Karjalainen, Panu; Peltola, Jaana; Lampinen, Eeva-Kaarina; Haapala, Eero A; Paananen, Jussi; Schwab, Ursula; Lindi, Virpi; Lakka, Timo A

2016-06-01

To investigate the effects of a long-term, individualized and family-based lifestyle intervention on physical activity, sedentary behavior and diet quality in children. We carried out a 2-year intervention study in a population sample of 506 children aged 6-8years in Finland in 2007-2012. We allocated the participants at baseline in the intervention and control group. We assessed physical activity and sedentary behavior by questionnaires and diet by food records. Total physical activity (+9min/d in intervention group vs. -5min/d in control group, p=0.001 for time*group interaction), unsupervised physical activity (+7min/d vs. -9min/d, p<0.001) and organized sports (+8min/d vs. +3min/d, p=0.001) increased in the intervention group but not in the control group. Using computer and playing video games increased less in the intervention group than in the control group (+9min/d vs. +19min/d, p=0.003). Consumption of vegetables (+12g/d vs. -12g/d, p=0.001), high-fat vegetable-oil based margarine (+10g/d vs. +3g/d, p<0.001) and low-fat milk (+69g/d vs. +11g/d, p=0.042) and intake of dietary fiber (+1.3g/d vs. +0.2g/d, p=0.023), vitamin C (+4.5mg/d vs. -7.2mg/d, p=0.042) and vitamin E (+1.4mg/d vs. +0.5mg/d, p=0.002) increased in the intervention group but not in the control group. Consumption of butter-based spreads increased in the control group but not in the intervention group (+2g/d vs. -1g/d, p=0.002). Individualized and family-based lifestyle intervention increased physical activity, attenuated increase in sedentary behavior and enhanced diet quality in children. ClinicalTrials.gov: NCT01803776. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Antiproteinuric Intervention on Elevated Connective Tissue Growth Factor (CTGF/CCN-2) Plasma and Urine Levels in Nondiabetic Nephropathy

PubMed Central

Slagman, Maartje C.J.; Nguyen, Tri Q.; Waanders, Femke; Vogt, Liffert; Hemmelder, Marc H.; Goldschmeding, Roel; Navis, Gerjan

2011-01-01

Summary Background and objectives Connective Tissue Growth Factor (CTGF/CCN-2) is a key player in fibrosis. Plasma CTGF levels predict end-stage renal disease and mortality in diabetic chronic kidney disease (CKD), supporting roles in intra- and extrarenal fibrosis. Few data are available on CTGF in nondiabetic CKD. We investigated CTGF levels and effects of antiproteinuric interventions in nondiabetic proteinuric CKD. Design, setting, participants, & measurements In a crossover randomized controlled trial, 33 nondiabetic CKD patients (3.2 [2.5 to 4.0] g/24 h proteinuria) were treated during 6-week periods with placebo, ARB (100 mg/d losartan), and ARB plus diuretics (100 mg/d losartan plus 25 mg/d hydrochlorothiazide) combined with consecutively regular and low sodium diets (193 ± 62 versus 93 ± 52 mmol Na+/d). Results CTGF was elevated in plasma (464 [387 to 556] pmol/L) and urine (205 [135 to 311] pmol/24 h) of patients compared with healthy controls (n = 21; 96 [86 to 108] pmol/L and 73 [55 to 98] pmol/24 h). Urinary CTGF was lowered by antiproteinuric intervention, in proportion to the reduction of proteinuria, with normalization during triple therapy (CTGF 99 [67 to 146] in CKD versus 73 [55 to 98] pmol/24 h in controls). In contrast, plasma CTGF was not affected. Conclusions Urinary and plasma CTGF are elevated in nondiabetic CKD. Only urinary CTGF is normalized by antiproteinuric intervention, consistent with amelioration of tubular dysfunction. The lack of effect on plasma CTGF suggests that its driving force might be independent of proteinuria and that short-term antiproteinuric interventions are not sufficient to correct the systemic profibrotic state in CKD. PMID:21784839

Surface Degassing Rates of Carbon Dioxide, Helium and Hydrogen at Tenerife, Canary Islands

NASA Astrophysics Data System (ADS)

Salazar, P.; Morales, A.; Lima, R.; Castro, L.; Galindo, I.; Salazar, J.; Hernandez, P.; Perez, N.

2001-12-01

Tenerife is the largest island of the Canarian archipelago (2,034 Km2), and its most recent eruption took place along the NW rift-zone in 1909, Chinyero volcano. Water supply is mainly obtained from its ground water reservoir which is reached by thousands of well and galleries. Some galleries showed an enriched-CO2 inner atmosphere because of a continuous magmatic degassing process, which is also affecting the ground water chemistry. Gas emission studies through galleries could provide a 3-D picture of the degassing model for Tenerife. An in situ method was applied for measuring CO2, He and H2 fluxes from a horizontal drilling "gallery" by means of a tracer gas method. Methane (99.995%) was applied as a tracer and injected into the gallery "Fuente del Valle" at known flow, 38 mL/min. Well mixed gas and tracer were regularly analyzed, every 5 minutes, by means of a VARIAN 2002P microGC from April 27 to May 2, 2000. CO2 and CH4 measurements were performed by means of a 10 m Poraplot Q column at 40° C, a TCD, and He as gas carrier. He, Ne and H2 measurements were analyzed by means of a 20 m high resolution Molecular Sieve 5Å column at 60° C, a TCD, and Ar as gas carrier. (CH4)gas/(CH4)air ratio was >1000 during this experiment. CO2 concentrations seem to be affected by short-term meteorological fluctuations and showed a range from 23 to 30%. An strong correlation is observed between CO2 content and He/Ne ratios, which ranged from 0.320 to 0.390. CO2 flux ranged from 1.5 to 5.5 Kg/d showing an average of 2.9 +/- 0.7 Kg/d. Secular variations of CO2 flux showed regularly peak levels almost every 12 hours. Assuming that a number of 100 galleries at Tenerife might release this level of CO2, the island subsurface degassing rate of CO2 could account for 300 Kg/d. Observed He flux ranged 2.8 to 9.0 mg/d showing an average of 5.0 +/- 1.2 mg/d. In the case of H2, flux levels ranged from 2.5 to 7.0 mg/d showing an average of 4.5 +/- 0.9 mg/d. Subsurface degassing rate monitoring could be a potential geochemical tool for seismic-volcanic surveillance at Tenerife.

A New Bioinspired Perchlorate Reduction Catalyst with Significantly Enhanced Stability via Rational Tuning of Rhenium Coordination Chemistry and Heterogeneous Reaction Pathway.

PubMed

Liu, Jinyong; Han, Mengwei; Wu, Dimao; Chen, Xi; Choe, Jong Kwon; Werth, Charles J; Strathmann, Timothy J

2016-06-07

Rapid reduction of aqueous ClO4(-) to Cl(-) by H2 has been realized by a heterogeneous Re(hoz)2-Pd/C catalyst integrating Re(O)(hoz)2Cl complex (hoz = oxazolinyl-phenolato bidentate ligand) and Pd nanoparticles on carbon support, but ClOx(-) intermediates formed during reactions with concentrated ClO4(-) promote irreversible Re complex decomposition and catalyst deactivation. The original catalyst design mimics the microbial ClO4(-) reductase, which integrates Mo(MGD)2 complex (MGD = molybdopterin guanine dinucleotide) for oxygen atom transfer (OAT). Perchlorate-reducing microorganisms employ a separate enzyme, chlorite dismutase, to prevent accumulation of the destructive ClO2(-) intermediate. The structural intricacy of MGD ligand and the two-enzyme mechanism for microbial ClO4(-) reduction inspired us to improve catalyst stability by rationally tuning Re ligand structure and adding a ClOx(-) scavenger. Two new Re complexes, Re(O)(htz)2Cl and Re(O)(hoz)(htz)Cl (htz = thiazolinyl-phenolato bidentate ligand), significantly mitigate Re complex decomposition by slightly lowering the OAT activity when immobilized in Pd/C. Further stability enhancement is then obtained by switching the nanoparticles from Pd to Rh, which exhibits high reactivity with ClOx(-) intermediates and thus prevents their deactivating reaction with the Re complex. Compared to Re(hoz)2-Pd/C, the new Re(hoz)(htz)-Rh/C catalyst exhibits similar ClO4(-) reduction activity but superior stability, evidenced by a decrease of Re leaching from 37% to 0.25% and stability of surface Re speciation following the treatment of a concentrated "challenge" solution containing 1000 ppm of ClO4(-). This work demonstrates the pivotal roles of coordination chemistry control and tuning of individual catalyst components for achieving both high activity and stability in environmental catalyst applications.

Multi-component hydrogen storage material

DOEpatents

Faheem, Syed A.; Lewis, Gregory J.; Sachtler, J.W. Adriaan; Low, John J.; Lesch, David A.; Dosek, Paul M.; Wolverton, Christopher M.; Siegel, Donald J.; Sudik, Andrea C.; Yang, Jun

2010-09-07

A reversible hydrogen storage composition having an empirical formula of: Li.sub.(x+z)N.sub.xMg.sub.yB.sub.zH.sub.w where 0.4.ltoreq.x.ltoreq.0.8; 0.2.ltoreq.y.ltoreq.0.6; 0

A Research-Based Undergraduate Organic Laboratory Project: Investigation of a One-Pot, Multicomponent, Environmentally Friendly Prins-Friedel-Crafts-Type Reaction

ERIC Educational Resources Information Center

Dintzner, Matthew R.; Maresh, Justin J.; Kinzie, Charles R.; Arena, Anthony F.; Speltz, Thomas

2012-01-01

Students in the undergraduate organic laboratory synthesize tetrahydro-2-(4-nitrophenyl)-4-phenyl-2"H"-pyran via the Montmorillonite K10 clay-catalyzed reaction of p-nitrobenzaldehye with methanol, 3-buten-1-ol, and benzene. The synthesis comprises an environmentally friendly tandem Prins-Friedel-Crafts-type multicomponent reaction (MCR) and sets…

Image quality, threshold contrast and mean glandular dose in CR mammography

NASA Astrophysics Data System (ADS)

Jakubiak, R. R.; Gamba, H. R.; Neves, E. B.; Peixoto, J. E.

2013-09-01

In many countries, computed radiography (CR) systems represent the majority of equipment used in digital mammography. This study presents a method for optimizing image quality and dose in CR mammography of patients with breast thicknesses between 45 and 75 mm. Initially, clinical images of 67 patients (group 1) were analyzed by three experienced radiologists, reporting about anatomical structures, noise and contrast in low and high pixel value areas, and image sharpness and contrast. Exposure parameters (kV, mAs and target/filter combination) used in the examinations of these patients were reproduced to determine the contrast-to-noise ratio (CNR) and mean glandular dose (MGD). The parameters were also used to radiograph a CDMAM (version 3.4) phantom (Artinis Medical Systems, The Netherlands) for image threshold contrast evaluation. After that, different breast thicknesses were simulated with polymethylmethacrylate layers and various sets of exposure parameters were used in order to determine optimal radiographic parameters. For each simulated breast thickness, optimal beam quality was defined as giving a target CNR to reach the threshold contrast of CDMAM images for acceptable MGD. These results were used for adjustments in the automatic exposure control (AEC) by the maintenance team. Using optimized exposure parameters, clinical images of 63 patients (group 2) were evaluated as described above. Threshold contrast, CNR and MGD for such exposure parameters were also determined. Results showed that the proposed optimization method was effective for all breast thicknesses studied in phantoms. The best result was found for breasts of 75 mm. While in group 1 there was no detection of the 0.1 mm critical diameter detail with threshold contrast below 23%, after the optimization, detection occurred in 47.6% of the images. There was also an average MGD reduction of 7.5%. The clinical image quality criteria were attended in 91.7% for all breast thicknesses evaluated in both patient groups. Finally, this study also concluded that the use of the AEC of the x-ray unit based on the constant dose to the detector may bring some difficulties to CR systems to operate under optimal conditions. More studies must be performed, so that the compatibility between systems and optimization methodologies can be evaluated, as well as this optimization method. Most methods are developed for phantoms, so comparative studies including clinical images must be developed.

A multicenter, randomized, double-blind, retrospective comparison of 5- and 10-day regimens of levofloxacin in a subgroup of patients aged > or =65 years with community-acquired pneumonia.

PubMed

Shorr, Andrew F; Zadeikis, Neringa; Xiang, Jim X; Tennenberg, Alan M; Wes Ely, E

2005-08-01

This subgroup analysis sought to determine the efficacy and tolerability of a 5-day regimen of levofloxacin 750 mg/d compared with a 10-day regimen of levofloxacin 500 mg/d in the treatment of community-acquired pneumonia (CAP) in elderly patients (aged > or =65 years). This subgroup analysis was based on the outcomes in patients aged > or =65 years from a randomized, double-blind, controlled trial conducted at 70 US centers. Patients in Pneumonia Severity Index (PSI) class I/II and III/IV were randomized to receive levofloxacin 750 mg/d for 5 days or levofloxacin 500 mg/d for 10 days. Study investigators assessed clinical and microbiologic outcomes 7 to 14 days after administration of the last dose of medication and collected adverse events for 30 days after the last dose. This analysis included 177 elderly patients, 80 receiving levofloxacin 750 mg/d for 5 days and 97 receiving levofloxacin 500 mg/d for 10 days. Although most demographic and baseline clinical characteristics were comparable between the 2 groups, the group that received levofloxacin 500 mg/d was older than the group that received levofloxacin 750 mg/d (median age, 76.0 vs 72.5 years, respectively; P = 0.029) and had a higher mean PSI score (90.7 vs 83.1; P = 0.017). Despite the halved duration of therapy, unadjusted clinical success rates were comparable between the 2 groups (89.0% and 91.9% in the 750- and 500-mg arms, respectively; 95% CI, -7.1 to 12.7). Microbiologic eradication rates were 90.3% (28/31) in the 750-mg arm and 87.5% (14/16) in the 500-mg arm (P = NS). Multivariate analysis adjusting for baseline PSI score indicated that treatment assignment was not statistically associated with clinical success (adjusted odds ratio for clinical success with 500-mg dose, 1.92; 95% CI, 0.62 to 5.99). The incidence of treatment-emergent adverse events did not differ between the 2 study treatments. The most common adverse events in both groups were insomnia, constipation, and headache. This subgroup analysis found that levofloxacin 750 mg/d for 5 days was well tolerated in the treatment of CAP in elderly patients. Undajusted and adjusted rates of clinical success were statistically similar between levofloxacin 750 mg/d for 5 days and levofloxacin 500 mg/d for 10 days.

Availability of water in Kalamazoo County, southwestern Michigan

USGS Publications Warehouse

Allen, William Burrows; Miller, John B.; Wood, Warren W.

1972-01-01

Kalamazoo County comprises an area of 572 square miles in the southwestern part of Michigan. It includes parts of the Kalamazoo, St. Joseph, and Paw Paw River basins, which drain into Lake Michigan. The northern two-thirds of the county is drained by the Kalamazoo River and its tributaries. A small area in the western piart of the county is drained by the Paw Paw River, and the rest, by tributaries of the St. Joseph River. Glacial deposits, containing sand and gravel, form an upper aquifer and a lower aquifer underlying large parts of the county. Areas of high transmissibility and thick saturated deposits are sufficiently localized to be considered as separate ground-water reservoirs having limited areal extent and definite hydrologic boundaries. Ground-water runoff from the basins constitutes a large part of the streamflow. Hydrograph separation shows that ground-water runoff composed 65 and 73 percent of the discharge of Kalamazoo River at Comstock and 75 and 79 percent of the discharge of Portage River near Vicksburg in 1965 and 1966, respectively. Based on the hydrologic budgets for the same years, ground-water recharge was 9.1 and 9.0 inches in the Kalamazoo River basin and 12.2 and 11.6 inches in the St. Joseph River basin. Ground-water recharge in the Kalamazoo River basin extrapolated for the 34-year period 1933-66 ranged from 4 to 13 inches and averaged 9 inches. In the St. Joseph River basin average recharge was about 9 inches for the same period. There is a wide range in runoff in the county. Augusta Creek, Portage Creek near Kalamazoo, and Gourdneck Creek have the highest annual runoff and maintain high yields even during periods of deficient precipitation. Spring Brook also reflects large ground-water contributions to streamflow. Storage in these basins could provide additional water during low flows for municipal and industrial needs. The primary use of lakes in the county is for recreational and esthetic purposes. Maintaining lake levels is therefore of the utmost importance. Levels at Crooked and Eagle Lakes have been maintained by pumping from lower aquifers. Diversion of water from Gourdneck Creek to West and Austin Lakes has helped in maintaining levels. Several relatively undeveloped lakes could be utilized as reservoirs whose storage could be used to augment streamflow or for water supply.Water in streams is generally of good chemical quality; however, several streams, including the Kalamazoo River downstream from Kalamazoo, have been degraded by municipal and industrial waste disposal. Water in the lakes is generally of good chemical quality with the exception of Barton Lake, which has been degraded by waste disposal. There is sufficient surface water available in Kalamazoo County to meet requirements for development of large quantities of water. The total available supply (average discharge of a stream) is about 680 mgd (million gallons per day). The dependable supply (7-day Q2, or average 7-day low flow having a recurrence interval of 2 years) is about 303 mgd. By developing artificial recharge facilities, surface runoff during winter and spring could be utilized to recharge ground-water reservoirs. Surface-water withdrawal in 1966 was about 58 mgd, of which 33 mgd was withdrawn from the Kalamazoo River. The quantity of water now being withdrawn from the ground and surface sources is small compared to the total that may be obtained in the area through full utilization of these resources. Mathematical models were used to simulate hydrologic conditions in the ground-water reservoirs and to evaluate maximum drawdowns for periods of little or no recharge. The practical limits of development as determined for the ground-water reservoirs are estimated to be at the following average withdrawal rates: Kalamazoo, 39 .mgd; Schoolcraft, 17 mgd; Kalamazoo-Portage, 24 mgd; and several small reservoirs, 67 mgd. These total 147 mgd. Further development would require additional artificial recharge facilities. Average ground-water withdrawal in 1966 was about 54 mgd. The Kalamazoo River ground-water reservoir furnished about 28 mgd, the Kalamazoo-Portage ground-water reservoir, about 21 mgd, and the other reservoirs, about 5 mgd. Thus, further development without artificial recharge is estimated to be about 11 mgd in the Kalamazoo River reservoir, 17 mgd in the Schoolcraft reservoir, 62 mgd in the several small reservoirs, and only 3 mgd in the Kalamazoo-Portage reservoir.The ground water is generally of good chemical quality and is suitable for most uses; however, it is Usually very hard and may contain objectionable amounts of iron. Some deterioration of water quality- has .been observed in several areas because of seepage from stockpiles of industrial minerals. The presence of many inland lakes, streams having high ground-water runoff, and, in places, relatively undeveloped ground-water reservoirs provides -flexibility in water management.

Glutamate supply positively affects serum cholesterol concentrations without increases in total protein and urea around the onset of puberty in goats.

PubMed

Meza-Herrera, C A; Calderón-Leyva, G; Soto-Sanchez, M J; Serradilla, J M; García-Martinez, A; Mellado, M; Veliz-Deras, F G

2014-06-30

Different neurotransmitter and neuromodulatory systems regulate synthesis and secretion of GnRH. Whereas the endocrine and neural systems are activated in response to the metabolic status and the circulating levels of specific blood metabolites, glutamate receptors have been reported at hepatic level. This study evaluated the possible effect of glutamate supplementation upon changes in serum concentrations across time for total protein (TP), urea (UR) and cholesterol (CL) around the onset of puberty in goats. Prepuberal female goats (n=18) were randomly assigned to: (1) excitatory amino acids group, GLUT, n=10; 16.52±1.04kg live weight (LW), 3.4±0.12 body condition score (BCS) receiving an i.v. infusion of 7mgkg(-1) LW of l-glutamate, and (2) Control group, CONT, n=8; 16.1±1.04kg LW, 3.1±0.12 BCS. General averages for LW (23.2±0.72kg), BCS (3.37±0.10 units), serum TP (65.28±2.46mgdL(-1)), UR (23.42±0.95mgdL(-1)), CL (77.89±1.10mgdL(-1)) as well as the serum levels for TP and UR across time did not differ (P>0.05) between treatments. However, while GLUT positively affected (P<0.05) both the onset (207±9 vs. 225±12 d) and the percentage (70 vs. 25%) of females showing puberty, a treatment×time interaction effect (P<0.05) was observed in the GLUT group, with increases in serum cholesterol, coincident with the onset of puberty. Therefore, in peripuberal glutamate supplemented goats, serum cholesterol profile could act as a metabolic modulator for the establishment of puberty, denoting also a potential role of glutamate as modulator of lipid metabolism. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of Mean Glandular Dose and Modulation Transfer Function for Different Tube Potentials and Target-Filter Combinations in Computed Radiography Mammography

PubMed Central

Abdul Aziz,, Siti Aishah; Mohd Saparudin, Abdul Khaliq; Harun, Ahmad Zaky

2013-01-01

Background: Different target-filter combinations in computed radiography have different impacts on the dose and image quality in digital radiography. This study aims to evaluate the mean glandular dose (MGD) and modulation transfer function (MTF) of various target-filter combinations by investigating the signal intensities of X-ray beams. Methods: General Electric (GE) Senographe DMR Plus mammography unit was used for MGD and MTF evaluation. The measured MGD was compared with the dose reference level (DRL), whereas the MTF was evaluated using ImageJ 1.46o software. A modified Mammography Accreditation Phantom RMI 156 was exposed using different target-filter combinations of molybdenum-molybdenum (Mo-Mo), molybdenum-rhodium (Mo-Rh) and rhodium-rhodium (Rh-Rh) at two different tube voltages, 26 kV and 32 kV with 50 mAs. Results: In the MGD evaluations, all target-filters gave an MGD value of < 1.5 mGy. The one-way ANOVA test showed a highly significant interaction between the MGD and the kilovoltage and target-filter material used (26 kV: F (2,12) = 49,234, P = 0.001;32 kV: F (2,12) = 89,972, P = 0.001). A Tukey post-hoc test revealed that the MGD for 26 kV and 32 kV was highly affected by the target-filter combinations. The test of homogeneity of variances indicates that the MGD varies significantly for 26 kV and 32 kV images (0.045 and 0.030 (P < 0.05), respectively). However, the one-way ANOVA for the MTF shows that no significant difference exists between the target-filter combinations used with 26 kV and 32 kV images either in parallel or perpendicular to the chest wall side F (2,189) = 0.26, P > 0.05). Conclusion: Higher tube voltage and atomic number target-filter yield higher MGD values. However, the MTF is independent of the X-ray energy and the type of target-filter combinations used. PMID:23966821

Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study.

PubMed

Foulks, Gary N; Borchman, Douglas; Yappert, Marta; Kakar, Shelley

2013-01-01

Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease as well as spectroscopic characteristics of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution and oral doxycycline treatment. Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid-lipid interaction strength, conformation, and phase transition parameters, and meibum protein content were measured using Fourier transform infrared spectroscopy and principal component analysis. Terpenoids, short-chain CH3 moieties, lipid oxidation, wax, cholesterylesters and glycerides were measured with a proton nuclear magnetic resonance (H-NMR) spectrometer. Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal. Compared with 4 weeks of azithromycin treatment reported in our previous study, oral doxycycline treatment was slightly less effective in improving foreign body sensation and the signs of plugging and secretion. In subjects with clinical evidence of MGD, changes in ordering of the lipids and phase transition temperature were brought closer to normal with azithromycin treatment than doxycycline treatment. Treatment with doxycycline but not azithromycin restored the Fourier transform infrared spectroscopy-principal component analysis scores and relative area of the H-NMR resonance at 1.26 ppm. Both doxycycline and azithromycin treatment restored the levels of the relative areas of the H-NMR resonance at 5.2 and 7.9 ppm to normal levels. The levels of meibum protein and meibum lipid oxidation were not influenced by azithromycin or doxycycline treatment. The mechanism of action of doxycycline may be different from that of azithromycin in therapy of MGD. It is notable that when carotenoids in meibum are low, as in MGD, the tear film is unstable and patients have the signs and symptoms of dry eyes. When carotenoids are restored with azithromycin and doxycycline treatment, tear film stability is restored and patients no longer have the signs and symptoms of dry eyes.

The US Food and Drug Administration's perspective on the new antidepressant vortioxetine.

PubMed

Zhang, Jing; Mathis, Mitchell V; Sellers, Jenn W; Kordzakhia, George; Jackson, Andre J; Dow, Antonia; Yang, Peiling; Fossom, Linda; Zhu, Hao; Patel, Hiren; Unger, Ellis F; Temple, Robert J

2015-01-01

This article summarizes the US Food and Drug Administration's (FDA's) review of the New Drug Application for vortioxetine, especially the clinical efficacy and safety data. It emphasizes the issues that were important to the FDA's approval decision, particularly the difference in the effective dose in domestic and foreign studies, and notes several new labeling features, specifically, description of time course of treatment response and detailed sexual dysfunction evaluation. The data sources were the original raw data sets for all clinical trials included in the development program for vortioxetine, as well as the sponsor's original analyses of these data. Data were available from 51 human trials involving vortioxetine, and included a total of 7,666 healthy volunteers and patients with a diagnosis of major depressive disorder (MDD) or generalized anxiety disorder who were exposed to at least 1 dose of vortioxetine for a total of 2,743 patient-years. Vortioxetine was effective in treating MDD in the United States at a dose of 20 mg/d. The recommended starting dose is 10 mg once daily without regard to food, with increase to 20 mg/d if the 10 mg/d dose is tolerated. For patients who do not tolerate 20 mg/d, 10 mg/d can be used and 5-mg/d dose can be considered. Vortioxetine can be discontinued abruptly, but it is recommended that doses of 15 mg/d or 20 mg/d be reduced to 10 mg/d for 1 week prior to full discontinuation to avoid potential withdrawal symptoms. Although the non-US maintenance study showed that maintenance doses of 5 to 10 mg/d were effective, a clinical judgment needs to be made to decide the maintenance dose in the United States. The applicant has agreed to conduct a US maintenance dose-response study covering the US-approved dose range. Vortioxetine's adverse event profile is similar to that of other selective serotonin reuptake inhibitors (SSRIs). Nausea is the most common adverse event and is dose dependent. No dose adjustment is needed based on age, gender, or the presence of renal or mild to moderate hepatic impairment. The maximum recommended dose is 10 mg/d in known cytochrome P450 2D6 poor metabolizers. Vortioxetine is a new treatment for MDD, and its adverse event profile is similar to that of other SSRIs. © Copyright 2015 Physicians Postgraduate Press, Inc.

Galantamine for Alzheimer's disease.

PubMed

Olin, J; Schneider, L

2001-01-01

Galantamine (also called galanthamine, marketed as Reminyl (Janssen)) was isolated from several plants, including daffodil bulbs, but is now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer's disease (AD), and recently several multicenter clinical trials have been published with positive findings. Galantamine has received regulatory approval in 29 counties: Argentina, Australia, Canada, Czechia, the European Union (except for The Netherlands), Iceland, Korea, Mexico, Norway, Poland, Singapore, South Africa, Switzerland, Thailand, and the United States. The objective of this overview is to assess the clinical effects of galantamine in patients with probable AD, and to investigate potential moderators of an effect. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 4 July 2001 using the terms galantamine and Reminyl. The Specialized Register at that time contained records from the following databases: CCTR/Central:April 2001 (issue 2); Medline: 1966 to June 2001; Embase: 1980 to April 2001; PsycLit: 1887 to April 2001; Cinahl: 1982 to March 2001; SIGLE (Grey Literature in Europe): 1980 to December 2000; ISTP (Index to Scientific and Technical Proceedings): to May 2000; INSIDE (BL database of Conference Proceedings and Journals): to June 2000; Aslib Index to Theses (UK and Ireland theses): 1970 to June 2001; Dissertation Abstract (USA): 1861 to June 2001; ADEAR (Alzheimer's Disease Clinical Trials Database): to June 2001; National Research Register (including the MRC Clinical Trials Directory): April 2001 (issue 2) Alzheimers Society Trials Database: to June 2001; Glaxo-Wellcome Trials Database: to June 2001; Centerwatch Trials Database: to December 2000. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. Trials selected were randomized, double-blind, parallel-group, and unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in subjects with AD. Data were extracted independently by the reviewers and pooled where appropriate and possible. The pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Intention-to-treat and observed cases data were both reported, if the data were available to be reported. Outcomes of interest include the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), clinical global impression of change (CIBIC-plus or CGIC), Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL), Disability Assessment for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI). Potential moderating variables of a treatment effect included trial duration and dose. Seven trials were identified that met criteria for entry, with six being Phase II or III industry-sponsored multicenter trials. Two were of 12 weeks duration; one of 13 weeks, one of 5 months; one of 29 weeks; and two of 6 months duration. Trials of 5 months or more were aggregated together in the analyses as '6 months.' Overall, galantamine showed significant treatment effects at daily doses of 16-32 mg/d for trials of 3- to 6-months duration. For global ratings, trials of 3 months duration with doses of 24-32mg/d (Odds Ratio (OR) 2.3; 95%CI 1.3 - 3.9) and 36mg/d (OR 3.3; 95%CI 1.2 - 9.3) were statistically significant in favor of treatment. For trials of 6 months duration (5-months to 29 weeks), only doses of 8mg/d failed to be statistically significant (16mg: OR 2.25; 95% CI 1.6 - 3.3; 24mg: OR 2.0; 95%CI 1.5 -2.5; 32mg: OR 1.9; 95%CI 1.4 - 2.5). For cognitive function over 6 months duration: at 16mg/d, improvements measured -3.3 points (k=1; 95%CI -4.4 - -2.1) on weighted mean difference on the ADAS-Cog scale; -3.5 points at 24mg/d (k=3; 95%CI -4.3 - -2.8), and -4.0 points at 32mg/d (k=2; 95%CI -5.0 - -3.0). The single 3 month trial with ADAS-Cog data also showed statistically significant improvement. Both observed cases (WMD 3.8; 95%CI 0.3 - 7.3) and intent to treat analyses using the Disability Assessment of Dementia scale gave statistically significant results in favor of treatment for daily doses of 32mg for 6 months duration (as did the single 3 month trial of 24-32mg/d treatment that used this scale) The small number of trials available for analysis, however, limited the power of subgroup analyses to detect differences. Galantamine consistently failed to show statistically significant treatment effects at doses of 8mg/day. Galantamine's adverse effects appear similar to those of other cholinesterase inhibitors, in that it tends to produce gastrointestinal effects acutely and with dosage increases. Overall, subjects treated with galantamine at doses of 24-32 mg/d were more likely to discontinue participation in most trials compared to subjects treated with lower doses or placebo, but in the one trial with a slower rate of titration the discontinuation rate was not significantly greater than placebo for the 16 mg/day dose. Patients in these trials were similar to those seen in earlier antidementia AD trials, and consisted primarily of mildly to moderately impaired outpatients. Galantamine's effects on more severely impaired subjects has not yet been assessed. Nevertheless, this review shows consistent positive effects for galantamine for trials of 3 months, 5 months and 6 months duration. In addition, although there was not a statistically significant dose-response effect, doses above 8mg/d were, for the most part, consistently statistically significant. Thus, there is evidence demonstrating efficacy for galantamine on global ratings, cognitive tests, assessments of ADLs and behavior. This magnitude for the cognitive effect is similar to other cholinesterase inhibitors including donepezil, rivastigmine, and tacrine. Galantamine's safety profile is similar to other cholinesterase inhibitors with respect to cholinergically mediated gastrointestinal symptoms. No information is available on adverse events that occurred less than 5% of the time. It appears that doses of 16 mg/d were best tolerated in the single trial where medication was titrated over 4 week periods, and because this dose showed statistically indistinguishable efficacy with higher doses, it is probably most preferable initially.

Effect of low-dose calcium supplements on bone loss in perimenopausal and postmenopausal Asian women: a randomized controlled trial.

PubMed

Nakamura, Kazutoshi; Saito, Toshiko; Kobayashi, Ryosaku; Oshiki, Rieko; Kitamura, Kaori; Oyama, Mari; Narisawa, Sachiko; Nashimoto, Mitsue; Takahashi, Shunsuke; Takachi, Ribeka

2012-11-01

Current standard-dose calcium supplements (eg, 1000 mg/d) may increase the risk for cardiovascular events. Effectiveness of lower-dose supplements in preventing bone loss should thus be considered. This study aimed to assess whether calcium supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal and postmenopausal Japanese women. We recruited 450 Japanese women between 50 and 75 years of age. They were randomly assigned to receive 500 mg of calcium (as calcium carbonate), 250 mg of calcium, or placebo daily. Medical examinations conducted three times over a 2-year follow-up period assessed bone mineral density (BMD) of the lumbar spine and femoral neck. One-factor repeated measures ANOVA was used for statistical tests. Subgroup analyses were also conducted. Average total daily calcium intake at baseline for the 418 subjects who underwent follow-up examinations was 493 mg/d. Intention-to-treat analysis showed less dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group compared to the placebo group (1.2% difference over 2 years, p = 0.027). Per-protocol analysis (≥80% compliance) revealed that spinal BMD for the 500-mg/d and 250-mg/d calcium supplement groups decreased less than the placebo group (1.6%, p = 0.010 and 1.0%, p = 0.078, respectively), and that femoral neck BMD for the 500-mg/d calcium supplement group decreased less relative to the placebo group (1.0%, p = 0.077). A low-dose calcium supplement of 500 mg/d can effectively slow lumbar spine bone loss in perimenopausal and postmenopausal women with habitually low calcium intake, but its effect on the femoral neck is less certain. Calcium supplementation dosage should thus be reassessed. (Clinical Trials Registry number: UMIN000001176). Copyright © 2012 American Society for Bone and Mineral Research.

Impact of solifenacin on quality of life, medical care use, work productivity, and health utility in the elderly: an exploratory subgroup analysis.

PubMed

Zinner, Norman; Noe, Les; Rasouliyan, Lawrence; Marshall, Thomas; Runken, M Christopher; Seifeldin, Raafat

2009-12-01

Overactive bladder (OAB) is a common problem among the elderly and a financial burden to society. The prevalence of OAB increases with age and affects > or = 25% of people aged > or = 65 years. The goal of this exploratory subgroup analysis of the VESIcare Efficacy and Research Study US (VERSUS) was to assess changes in health-related quality of life (HRQoL), medical care resource utilization, work and activity impairment, and health utility among elderly patients with OAB who continued to have urgency symptoms with tolterodine and were willing to try solifenacin. This was a 12-week, multicenter, prospective, open-label, noncomparative, flexible-dosing study designed to assess the efficacy and tolerability of solifenacin. Patients who received tolterodine 4 mg/d for > or = 4 weeks but continued to experience urgency symptoms (> or = 3 urgency episodes/24 hours) were enrolled. This exploratory analysis describes results from 2 elderly cohorts (patients 65 to 74 years and > or = 75 years of age). After a washout period of > or = 14 days, patients began treatment with solifenacin 5 mg/d with dosing adjustments allowed at week 4 (to 10 mg/d) and at week 8 (back to 5 mg/d for patients whose dose was increased to 10 mg/d at week 4). Outcomes were assessed using the OAB-q (a questionnaire specific to OAB and HRQoL), the Work Productivity and Activity Impairment-Specific Health Problem index, the Medical Care Use Index, and the Health Utilities Index Mark 2 and Mark 3 (HUI2/3), administered at the prewashout and week-12 visits. The subgroup analysis included 108 patients 65 to 74 years of age and 86 patients > or = 75 years of age. Patients in both age groups experienced significant improvement in HRQoL (P < 0.001), as well as significant reductions in nonprotocol-related office visits (P < 0.001) and activity impairment (P < 0.025). A significant reduction in the use of pads/diapers was reported for patients 65 to 74 years of age (P < 0.018), and patients in this age group who were working reported significantly less impairment related to OAB while working during solifenacin treatment than during tolterodine treatment (P < 0.042). No significant differences in HUI2/3 scores were observed in either of the elderly subgroups. Overall, solifenacin was found to improve symptom bother, HRQoL, work productivity, activity participation, and reduced medical care resource utilization in these elderly subjects with OAB who continued to have urgency symptoms with tolterodine and were willing to try solifenacin. This was an exploratory subgroup analysis of an open-label, noncomparative study; further research is needed to confirm these results. Copyright 2009 Excerpta Medica Inc. All rights reserved.

Development of MGD007, a gpA33 x CD3 bispecific DART® protein for T-cell immunotherapy of metastatic colorectal cancer.

PubMed

Moore, Paul A; Shah, Kalpana; Yang, Yinhua; Alderson, Ralph; Roberts, Penny; Long, Vatana; Liu, Daorong; Li, Jonathan C; Burke, Steve; Ciccarone, Valentina; Li, Hua; Fieger, Claudia B; Hooley, Jeff; Easton, Ann; Licea, Monica; Gorlatov, Sergey; King, Kathleen L; Young, Peter; Adami, Arash; Loo, Deryk; Chichili, Gurunadh R; Liu, Liqin; Smith, Douglas H; Brown, Jennifer G; Chen, Francine Z; Koenig, Scott; Mather, Jennie; Bonvini, Ezio; Johnson, Syd

2018-06-04

We have developed MGD007 (anti-glycoprotein A33 x anti-CD3), a DART® protein designed to redirect T-cells to target gpA33 expressing colon cancer. The gpA33 target was selected based on an antibody-based screen to identify cancer antigens universally expressed in both primary and metastatic CRC specimens, including putative cancer stem cell populations. MGD007 displays the anticipated bispecific binding properties and mediates potent lysis of gpA33-positive cancer cell lines, including models of colorectal cancer stem cells, through recruitment of T-cells. Xenograft studies showed tumor growth inhibition at doses as low as 4 µg/kg. Both CD8 and CD4 T cells mediated lysis of gpA33-expressing tumor cells, with activity accompanied by increases in granzyme and perforin. Notably, suppressive T-cell populations could also be leveraged to mediate lysis of gpA33 expressing tumor cells. Concomitant with CTL activity, both T-cell activation and expansion are observed in a gpA33-dependent manner. No cytokine activation was observed with human PBMC alone, consistent with the absence of gpA33 expression on peripheral blood cell populations. Following prolonged exposure to MGD007 and gpA33 positive tumor cells, T cells express PD 1 and LAG-3 and acquire a memory phenotype but retain ability to support potent cell killing. In cynomolgus monkeys, 4 weekly doses of 100 µg/kg were well tolerated, with prolonged PK consistent with that of an Fc-containing molecule. Taken together MGD007 displays potent activity against colorectal cancer cells consistent with a mechanism of action endowed in its design and support further investigation of MGD007 as a potential novel therapeutic treatment for colorectal cancer. Copyright ©2018, American Association for Cancer Research.

Effects of a behavioral intervention that emphasizes spices and herbs on adherence to recommended sodium intake: results of the SPICE randomized clinical trial.

PubMed

Anderson, Cheryl A M; Cobb, Laura K; Miller, Edgar R; Woodward, Mark; Hottenstein, Annette; Chang, Alex R; Mongraw-Chaffin, Morgana; White, Karen; Charleston, Jeanne; Tanaka, Toshiko; Thomas, Letitia; Appel, Lawrence J

2015-09-01

For decades, dietary sodium intake in the United States has remained high, and few studies have examined strategies for maintaining recommended intakes. We examined the effects of a behavioral intervention, which emphasized spices and herbs, on the maintenance of sodium intake at the recommended intake of 1500 mg/d in individuals to whom the US Dietary Guidelines for Americans apply. We conducted a 2-phase study that included adults ≥18 y of age for whom Dietary Guidelines for Americans recommends 1500 mg Na/d. The study was conducted in Baltimore, Maryland, from 2012 to 2014. In phase 1, 55 individuals consumed a low-sodium diet for 4 wk. Participants were provided all foods, snacks, and calorie-containing drinks. In phase 2, 40 participants from phase 1 were randomly assigned to either a behavioral intervention to reduce sodium intake (n = 20) or a self-directed control group (n = 20) for 20 wk. The primary study outcome was the change in mean 24-h urinary sodium excretion during phase 2. Linear regression analyses were used to determine intervention effects on urinary sodium excretion. Participant characteristics were as follows: women: 65%; African American: 88%; hypertension: 63%; diabetes: 18%; mean age: 61 y; and mean body mass index (in kg/m(2)): 30. At the end of phase 2, mean 24-h sodium excretion was lower in the behavioral intervention than in the self-directed group (mean difference: -956.8 mg/d; 95% CI: -1538.7, -374.9 mg/d) after sodium intake at screening was controlled for (P = 0.002). These findings persisted in sensitivity analyses that excluded potentially incomplete urine collections [Mage's equation mean difference: -1090 mg/d (P = 0.001); Joosens' equation mean difference: -796 mg/d (P = 0.04)]. A multifactorial behavioral intervention emphasizing spices and herbs significantly reduced sodium intake. Because of the ubiquity of sodium in the US food supply, multilevel strategies addressing individual behaviors and the food supply are needed to improve adherence to recommendations. This trial was registered at clinicaltrials.gov as NCT01615159. © 2015 American Society for Nutrition.

Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study.

PubMed

Gulløv, A L; Koefoed, B G; Petersen, P; Pedersen, T S; Andersen, E D; Godtfredsen, J; Boysen, G

1998-07-27

Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients. The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996. We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P = .67). After 3 years, no difference among the groups was seen. Major bleeding events were rare. Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.

Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma

PubMed Central

Wu, Shaowei; Han, Jiali; Song, Fengju; Cho, Eunyoung; Gao, Xiang; Hunter, David J.; Qureshi, Abrar A.

2015-01-01

Background Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. Objectives We evaluated the association between caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. Methods The analysis used data from 163,886 women in the Nurses’ Health Study II (NHS II, 1991–2009) and Nurses’ Health Study (NHS, 1980–2008) and 39,424 men in the Health Professionals Follow-up Study (HPFS, 1986–2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CI) of melanoma associated with dietary intakes. Results We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/d vs. <60 mg/d: HR=0.78, 95% CI=0.64–0.96, Ptrend=0.048). The association was more apparent in women (≥393 mg/d vs. <60 mg/d: HR=0.70, 95% CI=0.58–0.85, Ptrend=0.001) than in men (HR=0.94, 95% CI=0.75–1.18, Ptrend=0.81), and more apparent for melanomas occurred on the body sites with higher continuous sun exposure (head, neck and extremities) (≥393 mg/d vs. <60 mg/d: HR=0.71, 95% CI=0.59–0.86, Ptrend=0.001) than for melanomas occurred on the body sites with lower continuous sun exposure (trunk including shoulder, back, hip, abdomen and chest) (HR=0.90, 95% CI=0.70–1.16, Ptrend=0.60). This pattern of association was similar to that for caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. Conclusions Increasing caffeine intake and caffeinated coffee consumption may be protective against cutaneous malignant melanomas. PMID:26172864

Anti-albuminuric effect of losartan versus amlodipine in hypertensive Japanese patients with type 2 diabetes mellitus: A prospective, open-label, randomized, comparative study

PubMed Central

Ohno, Yasuhiro; Nishimura, Akiyoshi; Iwai, Hiroshi; Hirota, Noriyuki; Yamauchi, Takaaki; Fujimoto, Mika; Miyatake, Toshiyuki; Arai, Hiroshi; Aoki, Norihiko

2007-01-01

Abstract Background The antiproteinuric effect of the angiotensin II receptor-antagonist losartan has been observed in patients with type 2 diabetes mellitus (T2DM). Proteinuria is considered to be a predictor of the progression of kidney disease. Objective The aims of the present study were to compare and examine the ability of losartan and amlodipine to ameliorate albuminuria in hypertensive Japanese patients (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) with T2DM and whether the change in albuminuria was associated with a change in glomerular filtration rate (GFR). Methods This prospective, open-label, randomized, comparative study was conducted over 3 months at the Kinki University School of Medicine, Osaka-Sayama, Japan. Hypertensive patients with T2DM were enrolled and randomly assigned to 1 of 2 study groups receiving either losartan (25–100 mg/d) or the calcium channel-blocker amlodipine (2.5–5 mg/d). Urinary albumin excretion (UAE), creatinine clearance, and GFR were recorded at study initiation (baseline) and study end (month 3). The GFR was measured from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid. Adverse events (AEs) were monitored by a clinical research nurse during the examination. Results Fifty patients were asked to enroll and 38 returned the informed written consent. Thirty-five Japanese patients were included in the final study analysis. Seventeen patients were assigned to the losartan group (male sex, 10 [58.8%]; mean [SD] age, 58.1 [8.2] years) and 18 were assigned to the amlodipine group (male sex, 10 [55.6%]; mean [SD] age, 57.4 [8.9] years); no significant between-group difference in demographics was observed. A significant decrease from baseline to month 3 of mean (SD) UAE was observed in the losartan group (352.5 [556.6] mg/d vs 275.7 [466.1] mg/d; P = 0.048). No significant difference in mean (SD) UAE was observed in the amlodipine group for the same time period (298.2 [416.6] mg/d vs 322.7 [415.4] mg/d). There was a statistically significant difference found in the mean (SD) percent change of UAE from baseline to month 3 in the losartan group compared with the amlodipine group (−23.52 [28.42] vs +27.90 [63.51]; P = 0.004). Neither group was associated with a significant change in GFR during the course of the study. No patient discontinued the study due to AEs that were considered, by the investigator, to be possibly or probably associated with study treatment. Conclusions Treatment with losartan, but not amlodipine, was associated with a reduction in albuminuria in these hypertensive Japanese patients with T2DM within a period as short as 3 months. Neither drug was associated with a significant change in GFR. Therefore, the reduction of UAE was independent of a change in the GFR. PMID:24678123

Comparison of four proton pump inhibitors for the short-term treatment of esophagitis in elderly patients

PubMed Central

Pilotto, Alberto; Franceschi, Marilisa; Leandro, Gioacchino; Scarcelli, Carlo; D’Ambrosio, Luigi Piero; Paris, Francesco; Annese, Vito; Seripa, Davide; Andriulli, Angelo; Di Mario, Francesco

2007-01-01

AIM: To compare efficacy and tolerability of four proton pump inhibitors (PPIs) commonly used in the short-term therapy of esophagitis in elderly patients. METHODS: A total of 320 patients over 65 years with endoscopically diagnosed esophagitis were randomly assigned to one of the following treatments for 8 wk: (1) omeprazole 20 mg/d; (2) lansoprazole 30 mg/d; (3) pantoprazole 40 mg/d, or (4) rabeprazole 20 mg/d. Major symptoms, compliance, and adverse events were recorded. After 8 wk, endoscopy and clinical evaluation were repeated. RESULTS: Per protocol and intention to treat healing rates of esophagitis were: omeprazole = 81.0% and 75.0%, lansoprazole = 90.7% (P = 0.143 vs omeprazole) and 85.0%, pantoprazole = 93.5% (P = 0.04 vs omeprazole) and 90.0% (P = 0.02 vs omeprazole), rabeprazole = 94.6% (P = 0.02 vs omeprazole) and 88.8% (P = 0.04 vs omeprazole). Dividing patients according to the grades of esophagitis, omeprazole was significantly less effective than the three other PPIs in healing grade 1 esophagitis (healing rates: 81.8% vs 100%, 100% and 100%, respectively, P = 0.012). Pantoprazole and rabeprazole (100%) were more effective vs omeprazole (89.6%, P = 0.0001) and lansoprazole (82.4%, P = 0.0001) in decreasing heartburn. Pantoprazole and rabeprazole (92.2% and 90.1%, respectively) were also more effective vs lansoprazole (75.0%, P < 0.05) in decreasing acid regurgitation. Finally, pantoprazole and rabeprazole (95.2% and 100%) were also more effective vs lansoprazole (82.6%, P < 0.05) in decreasing epigastric pain. CONCLUSION: In elderly patients, pantoprazole and rabeprazole were significantly more effective than omeprazole in healing esophagitis and than omeprazole or lansoprazole in improving symptoms. H pylori infection did not influence the healing rates of esophagitis after a short-term treatment with PPI. PMID:17724802

[Treatment of idiopathic membranous nephropathy. Is the anti-CD20 antibody rituximab a reasonable option?].

PubMed

Busch, Martin; Gerth, Jens; Ott, Undine; Schip, Andre; Haufe, Christoph C; Gröne, Hermann-Josef; Wolf, Gunter

2008-07-15

Membranous nephropathy (MN) is characterized by proteinuria and other symptoms of the nephrotic syndrome. In many cases, the etiology is unknown. Whether and how to treat MN is still a controversial question. Despite the use of corticosteroids and alkylating agents, up to 40% of patients still progress to end-stage renal failure. A 40-year-old male patient with biopsy-proven idiopathic MN was initially treated with prednisolone and chlorambucil because of a proteinuria of 22 g/d. Treatment with cyclosporine was started because the nephrotic syndrome failed to improve. Proteinuria was reduced to a minimum of 4 g/d. Cyclosporine was stopped after 17 months leading to a fast relapse. Therapy with an ACE inhibitor and AT(1) receptor antagonist and retreatment with cyclosporine improved proteinuria. Cyclosporine was terminated after a total of 24 months. 5 months later, relapse occurred with a high proteinuria of 34 g/d. The monoclonal anti-CD20 antibody rituximab (375 mg/m(2)) was given four times every 4 weeks. 4 weeks and 4 months after the end of treatment, proteinuria decreased to 780 mg/d and <150 mg/d, but renal function remained impaired (creatinine clearance 65 ml/min, stage 2 according to K/DOQI). Now, remission of proteinuria (<150 mg/d) has been stable for almost 2 years. However, renal insufficiency progressed further (creatinine clearance 45 ml/min, stage 3 according to K/DOQI). Rituximab offers the possibility for a targeted treatment of idiopathic MN. Based on the existing evidence and experience from this case, rituximab can be recommended as a new treatment option for MN, possibly before starting any treatment with cytotoxic agents and high-dose prednisolone carrying the risk of severe side effects. However, long-term results of this treatment are still lacking.

Long-Term (3 Year) Effects of a Single Thermal Pulsation System Treatment on Meibomian Gland Function and Dry Eye Symptoms.

PubMed

Greiner, Jack V

2016-03-01

The present study examined the long-term (3 years) effects of a single (12 min) thermal pulsation system (TPS) treatment on symptomatic patients with evaporative dry eye disease (DED) secondary to meibomian gland dysfunction (MGD). In this prospective, cohort, observational, single-center study design, signs (meibomian gland secretion [MGS] scores and tear film breakup time [TBUT]) and symptoms (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED] questionnaires) were determined in 20 patients (40 eyes) with MGD and dry eye symptoms at baseline (BL), 1 month, and 3 years post-TPS treatment using LipiFlow. Meibomian gland secretion scores increased from BL (4.5±0.8) to 1 month (12.0±1.1, P≤0.001). Improvement persisted at 3 years (18.4±1.4) relative to BL (P≤0.001). Meibomian gland secretion scores in all regions of the lower eyelid were improved over BL at 1 month (nasal [P≤0.001], central [P≤0.001], temporal [P≤0.01]) and 3 years (nasal [P≤0.001], central [P≤0.001], temporal [P≤0.001]). TBUT increased from BL (4.1±0.4) to 1 month (7.9±1.4, P≤0.05) but was not significantly different than BL at 3 years (4.5±0.6, P>0.05). The OSDI scores decreased from BL (26.0±4.6) to 1 month (14.7±4.3, P≤0.001) but returned to BL levels at 3 years (22.5±5.4, P>0.05). The SPEED scores decreased from BL (13.4±1.0) to 1 month (6.5±1.3, P≤0.001), and this improvement persisted at 3 years (9.5±1.6, P≤0.001). Thermal pulsation may be a uniquely efficacious treatment option for DED secondary to MGD in that a single 12-min procedure is associated with significant improvement in MGS and SPEED scores for up to 3 years.

Potential development and recharge of ground water in Mill Creek Valley, Butler and Hamilton Counties, Ohio, based on analog model analysis

USGS Publications Warehouse

Fidler, Richard E.

1971-01-01

Mill Creek valley is part of the greater Cincinnati industrial area in southwestern Ohio. In 1964, nearly 30 percent of the water supply in the study area of about 27 square miles was obtained from wells in the glacial-outwash aquifer underlying the valley. Ground-water demand has increased steadily since the late 1800's, and excessive pumpage during the years of World War II caused water levels to decline to critical levels. Natural recharge to the aquifer, from precipitation, is about 8.5 mgd (million gallons per day). In 1964, the total water use was about 30 mgd, of which 8.1 mgd was obtained from wells in Mill Creek valley, and the remainder was imported from outside the basin. With rapid industrial expansion and population growth, demand for ground water is continuing to increase. By the year 2000 ground-water pumpage is expected to exceed 25 mgd. At a public hearing before the Ohio Water Commission in 1961, artificial recharge of the aquifer through injection wells was proposed as a possible solution to the Mill Creek valley water-supply problem. The present study attempts to determine the feasibility of injection-well recharge systems in the Mill Creek valley. Although basically simple, the hydrologic system in Mill Creek valley is complex in detail and is difficult to evaluate using conventional quantitative methods. Because of this complexity, an electric analog model was used to test specific development plans. Three hypothetical pumping plans were developed by projecting past pumpage data to the years 1980 and 2000. Various combinations of injection wells were tested on the model under different hypothetical conditions of pumpage. Based on analog model analysis, from three to eight inject-ion wells, with an approximate input of 2 mgd each, would reverse the trend in declining groundwater levels and provide adequate water to meet anticipated future demands.

Clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis caused by antithyroid drugs.

PubMed

Noh, Jaeduk Yoshimura; Yasuda, Shigemitu; Sato, Shotaro; Matsumoto, Masako; Kunii, Yo; Noguchi, Yoshihiko; Mukasa, Koji; Ito, Kunihiko; Ito, Koichi; Sugiyama, Osamu; Kobayashi, Hiroshi; Nihojima, Shigeru; Okazaki, Masaru; Yokoyama, Shunji

2009-08-01

The clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis caused by antithyroid drugs are still unclear because most reports describe only a small number of patients. The objective was to analyze a large number of patients with MPO-ANCA-associated vasculitis to determine the time of onset, the drug and dose taken, the clinical symptoms, the relationship between the clinical symptoms and the MPO-ANCA titer, and the incidence. We analyzed 92 patients in whom the adverse reaction of MPO-ANCA-associated vasculitis was reported to Chugai Pharmaceutical, a company that markets antithyroid drugs. Of the 92 patients, 41 (44.6%) had single-organ failure, 32 (34.8%) had two-organ failure, 13 (14.1%), had three-organ failure, and two (2.2%) had four-organ failure. The number of organs involved was unknown in the other four patients (4.3%). The median time of onset was 42 months (range, 1-372 months) after starting drug treatment. The median dose at onset of MPO-ANCA-associated vasculitis was 15 mg/d (range, 2.5-45 mg/d) for methimazole and 200 mg/d (50-450 mg/d) for propylthiouracil. The severity and number of organs involved were not correlated with the MPO-ANCA titer. The incidence was between 0.53 and 0.79 patients per 10,000, and the ratio of the estimated incidences for methimazole and propylthiouracil was 1:39.2. The time of onset of MPO-ANCA-associated vasculitis and the dose at onset varied. The severity and number of organs involved were not correlated with the MPO-ANCA titer, indicating a need for vigilance even when the MPO-ANCA titer is only weakly positive.

The effect of hormone therapy on plasma homocysteine levels: a randomized clinical trial.

PubMed

Tutuncu, Levent; Ergur, Ali Rustu; Mungen, Ercument; Gun, Ismet; Ertekin, Aktug; Yergok, Yusuf Ziya

2005-03-01

An elevated plasma homocysteine level is a risk factor for cardiovascular diseases. Hormone therapy (HT) may reduce fasting plasma homocysteine levels. We studied 80 postmenopausal women to determine the effect of medroxyprogesterone acetate (MPA) combined with conjugated equine estrogens (CEE) on fasting plasma homocysteine levels. In a randomized, double blind, prospective, placebo-controlled study, we randomly assigned 80 healthy postmenopausal women between CEE 0.625 mg/d combined with MPA 2.5 mg/d (n = 20), CEE 0.625 mg/d combined with MPA 5 mg/d (n = 20), unopposed CEE 0.625 mg/d (n = 20), and placebo (n = 20) all given for a duration of 6 months. Fasting plasma homocysteine levels were measured before and at the end of the treatment. Before treatment, plasma homocysteine concentrations were similar in all groups. After 6 months of unopposed CEE, the mean fasting plasma homocysteine levels decreased by 19.02% when compared with baseline levels (P < 0.05). The mean fasting plasma homocysteine concentrations decreased by 17.63% and 19.56% from baseline in both the CEE plus MPA 2.5 mg/d and CEE plus MPA 5 mg/d groups, respectively (P < 0.05 for each group). In contrast, plasma homocysteine levels increased by 11.66% in the placebo group. The homocysteine lowering effect did not differ significantly among the three groups of women receiving unopposed CEE alone and CEE plus MPA at two different doses. Six months of estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) significantly lower fasting plasma homocysteine levels in healthy postmenopausal women with equal efficacy.

The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis.

PubMed

Fu, Jie; Peng, Lilei; Li, Xiaogang

2016-01-01

Vortioxetine is a novel antidepressant approved for the treatment of major depressive disorder by the US Food and Drug Administration in September 2013. This meta-analysis assessed the efficacy and safety of different doses of vortioxetine for generalized anxiety disorder of adults. PubMed, Cochrane Library, PsycINFO, and Clinical Trials databases were searched from 2000 through 2015. The abstracts of the annual meetings of the American Psychiatric Association and previous reviews were searched to identify additional studies. The search was limited to individual randomized controlled trials (RCTs), and there was no language restriction. Four RCTs met the selection criteria. These studies included 1,843 adult patients. Results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The data were pooled with a random-effects or fixed-effects model. The results showed that multiple doses (2.5, 5, and 10 mg/d) of vortioxetine did not significantly improve the generalized anxiety disorder symptoms compared to placebo (OR=1.16, 95% CI=0.84-1.60, Z=0.89, P=0.38; OR=1.41, 95% CI=0.82-2.41, Z=1.25, P=0.21; OR=1.05, 95% CI=0.76-1.46, Z=0.32, P=0.75, respectively). We measured the efficacy of 2.5 mg/d vortioxetine compared to 10 mg/d, and no significant differences were observed. The common adverse effects included nausea and headache. With increased dose, nausea was found to be more frequent in the vortioxetine (5 and 10 mg/d) group (OR=2.99, 95% CI=1.31-6.84, Z=2.60, P=0.009; OR=2.80, 95% CI=1.85-4.25, Z=4.85, P<0.00001, respectively), but no significant differences were observed for headache. The results showed no significant improvement in the treatment of generalized anxiety disorder for vortioxetine compared to placebo, and nausea was more frequent with higher doses. So the current evidences do not support using vortioxetine for the treatment of generalized anxiety disorder. Few RCTs were included in our meta-analysis, and more studies are needed to verify our results in the future.

A dose-up of ursodeoxycholic acid decreases transaminases in hepatitis C patients

PubMed Central

Sato, Shuichi; Miyake, Tatsuya; Tobita, Hiroshi; Oshima, Naoki; Ishine, Junichi; Hanaoka, Takuya; Amano, Yuji; Kinoshita, Yoshikazu

2009-01-01

AIM: To examine whether a dose-up to 900 mg of ursodeoxycholic acid (UDCA) decreases transaminases in hepatitis C patients. METHODS: From January to December 2007, patients with chronic hepatitis C or compensated liver cirrhosis with hepatitis C virus (HCV) (43-80 years old) showing positive serum HCV-RNA who had already taken 600 mg/d of UDCA were recruited into this study. Blood parameters were examined at 4, 8 and 24 wk after increasing the dose of oral UDCA from 600 to 900 mg/d. RESULTS: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) levels were significantly decreased following the administration of 900 mg/d as compared to 600 mg/d. The decrease in ALT from immediately before the dose-up of UDCA to 8 wk after the dose-up was 14.3 IU/L, while that for AST was 10.5 IU/L and for GGT was 9.8 IU/L. Platelet count tended to increase after the dose-up of UDCA, although it did not show a statistically significant level (P = 0.05). Minor adverse events were observed in 3 cases, although no drop-outs from the study occurred. CONCLUSION: Oral administration of 900 mg/d of UDCA was more effective than 600 mg/d for reducing ALT, AST, and GGT levels in patients with HCV-related chronic liver disease. PMID:19522030

Single, binary and multi-component adsorption of some anions and heavy metals on environmentally friendly Carpobrotus edulis plant.

PubMed

Chiban, Mohamed; Soudani, Amina; Sinan, Fouad; Persin, Michel

2011-02-01

A low-cost adsorbent and environmentally friendly adsorbent from Carpobrotus edulis plant was used for the removal of NO(3)(-), H(2)PO(4)(-), Pb(2+) and Cd(2+) ions from single, binary and multi-component systems. The efficiency of the adsorbent was studied using batch adsorption technique under different experimental conditions by varying parameters such as pH, initial concentration and contact time. In single component systems, the dried C. edulis has the highest affinity for Pb(2+), followed by NO(3)(-), Cd(2+) and H(2)PO(4)(-), with adsorption capacities of 175mg/g, 125mg/g, 28mg/g and 26mg/g, respectively. These results showed that the adsorption of NO(3)(-) and H(2)PO(4)(-) ions from single and binary component systems can be successfully described by Langmuir and Freundlich isotherms. Freundlich adsorption model, showed the best fit to the single and binary experimental adsorption data. These results also indicated that the adsorption yield of Pb(2+) ion was reduced by the presence of Cd(2+) ion in binary metal mixture. The competitive adsorption of NO(3)(-), H(2)PO(4)(-), Pb(2+) and Cd(2+) ions on dried C. edulis plant shows that NO(3)(-) and H(2)PO(4)(-) anions are able to adsorb on different free binding sites and Pb(2+) and Cd(2+) cations are able to adsorb on the same active sites of C. edulis particles. The dried C. edulis was found to be efficient in removing nitrate, phosphate, cadmium and lead from aqueous solution as compared to other adsorbents already used for the removal of these ions. Copyright © 2010 Elsevier B.V. All rights reserved.

Theoretical Assessment on the Phase Transformation Kinetic Pathways of Multi-component Ti Alloys: Application to Ti-6Al- 4V

DOE PAGES

Ji, Yanzhou; Heo, Tae Wook; Zhang, Fan; ...

2015-12-21

Here we present our theoretical assessment of the kinetic pathways during phase transformations of multi-component Ti alloys. Employing the graphical thermodynamic approach and an integrated free energy function based on the realistic thermodynamic database and assuming that a displacive structural transformation occurs much faster than long-range diffusional processes, we analyze the phase stabilities of Ti-6Al -4V (Ti-6wt.%Al -4wt.%V). Our systematic analyses predict a variety of possible kinetic pathways for β to (α + β) transformations leading to different types of microstructures under various heat treatment conditions. In addition, the possibility of unconventional kinetic pathways is discussed. Lastly, we also brieflymore » discuss the application of our approach to general multicomponent/multiphase alloy systems.« less

Multicomponent, Multiphase Thermodynamics of Swelling Porous Media With Electroquasistatics. 1. Macroscale Field Equations

DTIC Science & Technology

2001-08-08

entropy inequality with independent variables consistent with several natural systems and apply the resulting constitutive theory near equi- librium...1973. [3] L. S. Bennethum and J. H. Cushman. Multiscale , hybrid mixture theory for swelling systems - I: Balance laws. International Journal of...Engineering Science, 34(2):125–145, 1996. [4] L. S. Bennethum and J. H. Cushman. Multiscale , hybrid mixture theory for swelling systems - II: Constitutive

Modeling of a complex, polar system with a modified Soave-Redlich-Kwong equation

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

Sturnfield, E.A.; Matherne, J.L.

1988-01-01

It is computationally feasible to use a simple equation of state (like a Redlich-Kwong) to calculate liquid fugacity but the simpler equations work well only for moderately non-ideal systems. More complex equations (like Ghemling-Lui-Prausnitz) predict system behavior more accurately but are much more complicated to use and can require fitting many parameters to data. This paper illustrates success in using a modified Redlich-Kwong to model a complex system including water, hydrogen, sub and supercritical ammonia, and amines. The binary interaction parameter ({Kappa}/sub ij/) of the Soave-Redlich-Kwong equation has been modified to be both asymmetric and temperature dependent. Further, the aimore » constant was determined by fitting vapor pressure data. Predicted model results are compared to literature (example 1) or plant data (examples 2-4) for four systems: 1. The ammonia-water binary over a wide range of pressure and temperature including ammonia above its critical. 2. A multicomponent Vapor-Liquid equilibrium flash tank and condenser containg hydrogen, amonia, water, and other heavier compounds. 3. A multicomponent vapor-liquid equilibrium flash tank containing water, heavier mines, and the amine salts. 4. A Liquid-Liquid-Vapor equilibrium decanter system containing water, ammonia, and an organic chloride.« less

Atomic force microscopy and Langmuir–Blodgett monolayer technique to assess contact lens deposits and human meibum extracts☆

PubMed Central

Hagedorn, Sarah; Drolle, Elizabeth; Lorentz, Holly; Srinivasan, Sruthi; Leonenko, Zoya; Jones, Lyndon

2015-01-01

Purpose The purpose of this exploratory study was to investigate the differences in meibomian gland secretions, contact lens (CL) lipid extracts, and CL surface topography between participants with and without meibomian gland dysfunction (MGD). Methods Meibum study: Meibum was collected from all participants and studied via Langmuir–Blodgett (LB) deposition with subsequent Atomic Force Microscopy (AFM) visualization and surface roughness analysis. CL Study: Participants with and without MGD wore both etafilcon A and balafilcon A CLs in two different phases. CL lipid deposits were extracted and analyzed using pressure-area isotherms with the LB trough and CL surface topographies and roughness values were visualized using AFM. Results Meibum study: Non-MGD participant meibum samples showed larger, circular aggregates with lower surface roughness, whereas meibum samples from participants with MGD showed more lipid aggregates, greater size variability and higher surface roughness. CL Study: Worn CLs from participants with MGD had a few large tear film deposits with lower surface roughness, whereas non-MGD participant-worn lenses had many small lens deposits with higher surface roughness. Balafilcon A pore depths were shallower in MGD participant worn lenses when compared to non-MGD participant lenses. Isotherms of CL lipid extracts from MGD and non-MGD participants showed a seamless rise in surface pressure as area decreased; however, extracts from the two different lens materials produced different isotherms. Conclusions MGD and non-MGD participant-worn CL deposition were found to differ in type, amount, and pattern of lens deposits. Lipids from MGD participants deposited irregularly whereas lipids from non-MGD participants showed more uniformity. PMID:25620317

Risk of Progression of Nonalbuminuric CKD to End-Stage Kidney Disease in People With Diabetes: The CRIC (Chronic Renal Insufficiency Cohort) Study.

PubMed

Koye, Digsu N; Magliano, Dianna J; Reid, Christopher M; Jepson, Christopher; Feldman, Harold I; Herman, William H; Shaw, Jonathan E

2018-05-18

Reduced glomerular filtration rate (GFR) in the absence of albuminuria is a common manifestation of chronic kidney disease (CKD) in diabetes. However, the frequency with which it progresses to end-stage kidney disease (ESKD) is unknown. Multicenter prospective cohort study. We included 1,908 participants with diabetes and reduced GFR enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. Urinary albumin and protein excretion. Incident ESKD, CKD progression (ESKD or ≥50% reduction in estimated GFR [eGFR] from baseline), and annual rate of decline in kidney function. ESKD was ascertained by self-report and by linkage to the US Renal Data System. We used Cox proportional hazards modeling to estimate the association of albuminuria and proteinuria with incident ESKD or CKD progression and linear mixed-effects models to assess differences in eGFR slopes among those with and without albuminuria. Mean eGFR at baseline was 41.2mL/min/1.73m 2 . Normal or mildly increased 24-hour urinary albumin excretion (<30mg/d) at baseline was present in 28% of participants, but in only 5% of those progressing to ESKD. For those with baseline normal or mildly increased albuminuria, moderately increased albuminuria (albumin excretion, 30-299mg/d), and 2 levels of severely increased albuminuria (albumin excretion, 300-999 and ≥1,000mg/d): crude rates of ESKD were 7.4, 34.8, 78.7, and 178.7 per 1,000 person-years, respectively; CKD progression rates were 17.0, 61.4, 130.5, and 295.1 per 1,000 person-years, respectively; and annual rates of eGFR decline were -0.17, -1.35, -2.74, and -4.69mL/min/1.73m 2 , respectively. We were unable to compare the results with healthy controls. In people with diabetes with reduced eGFRs, the absence of albuminuria or proteinuria is common and carries a much lower risk for ESKD, CKD progression, or rapid decline in eGFR compared with those with albuminuria or proteinuria. The rate of eGFR decline in normoalbuminuric CKD was similar to that reported for the general diabetic population. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome.

PubMed

Sullivan, David A; Dana, Reza; Sullivan, Rose M; Krenzer, Kathleen L; Sahin, Afsun; Arica, Beril; Liu, Yang; Kam, Wendy R; Papas, Athena S; Cermak, Jennifer M

2018-01-01

We hypothesized that women with primary (pSS) and secondary Sjögren syndrome (sSS; with systemic lupus erythematosus [SLE] or rheumatoid arthritis [RA]) have meibomian gland dysfunction (MGD). We sought to test our hypothesis. Subjects with pSS, sSS + SLE, sSS + RA, and non-SS-related MGD were recruited from the Sjögren's Syndrome Foundation or outpatient clinics at Tufts University School of Dental Medicine or Brigham and Women's Hospital. The control population was recruited from the Greater Boston area. After providing written informed consent, the subjects underwent an eye examination and/or completed two questionnaires that assess symptoms of dry eye disease (DED). Our results demonstrate that pSS and sSS patients have MGD. These subjects had meibomian gland orifice metaplasia, an increased number of occluded meibomian gland orifices, and a reduced quality of meibomian gland secretions. Further, patients with pSS, sSS + SLE, sSS + RA, and MGD had significant alterations in their tear film, lid margin, cornea, and conjunctiva. Symptoms of DED were increased ∼10-fold in all pSS, sSS, and MGD groups relative to controls. Our findings support our hypothesis and show that individuals with pSS, sSS + SLE, and sSS + RA have MGD. In addition, our study indicates that patients with pSS and sSS have both aqueous-deficient and evaporative DED. © 2018 S. Karger AG, Basel.

Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males

PubMed Central

Shi, Hongliang; Faessel, Hélène M.; Saad, Fred

2015-01-01

Context: TAK-385 is a highly selective, oral, nonpeptide GnRH antagonist being investigated as a possible prostate cancer treatment. Objective: The objectives were to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-385 on LH and testosterone. Design, Setting, and Participants: This was a three-part, randomized, double-blind, placebo-controlled, phase 1 dose-escalation study in 176 healthy male UK volunteers. Interventions: Part 1, single doses of TAK-385 (0 [placebo], 80, 120, 180, or 360 mg). Part 2, 14-day TAK-385 (0, 20, 40, 80, or 180 mg) daily. Part 3, 28-day TAK-385 (40 [with loading dose], 60, 80, or 160 mg) or placebo daily. Parts 2 and 3 included men aged 40–75 years. Main Outcome Measures: Main outcome measures included plasma concentrations of TAK-385, LH, and testosterone. Results: Oral TAK-385 was readily absorbed, and steady state was reached in ≤14 days. Food reduced TAK-385 systemic exposure by 47–52%. Mean serum testosterone levels declined ≤6 hours after TAK-385 administration. Loading doses up to 360 mg on day 1 or 360 mg on day 1 followed by 240 mg on day 2 reduced the time to achieve castrate testosterone levels from ≥7 to <3 days. TAK-385 doses ≥80 mg/d achieved sustained medical castration and trough TAK-385 concentrations >4 ng/mL. After discontinuation of TAK-385 on day 28, testosterone levels normalized in most subjects in ≤ 28 days. Common adverse events included bradycardia, headache, and hot flush (all grade ≤2). Conclusions: Oral TAK-385 (40–180 mg/d) was well tolerated and effectively lowered testosterone in healthy men. Planned phase 2 doses in men with hormone-sensitive prostate cancer are 80 and 120 mg/d. PMID:26502357

Multi-component hybrid hydrogels – understanding the extent of orthogonal assembly and its impact on controlled release† †Electronic supplementary information (ESI) available: Full experimental methods and further data from assays. See DOI: 10.1039/c7sc03301j Click here for additional data file.

PubMed Central

Vieira, Vânia M. P.; Hay, Laura L.

2017-01-01

This paper reports self-assembled multi-component hybrid hydrogels including a range of nanoscale systems and characterizes the extent to which each component maintains its own unique functionality, demonstrating that multi-functionality can be achieved by simply mixing carefully-chosen constituents. Specifically, the individual components are: (i) pH-activated low-molecular-weight gelator (LMWG) 1,3;2,4-dibenzylidenesorbitol-4′,4′′-dicarboxylic acid (DBS–COOH), (ii) thermally-activated polymer gelator (PG) agarose, (iii) anionic biopolymer heparin, and (iv) cationic self-assembled multivalent (SAMul) micelles capable of binding heparin. The LMWG still self-assembles in the presence of PG agarose, is slightly modified on the nanoscale by heparin, but is totally disrupted by the micelles. However, if the SAMul micelles are bound to heparin, DBS–COOH self-assembly is largely unaffected. The LMWG endows hybrid materials with pH-responsive behavior, while the PG provides mechanical robustness. The rate of heparin release can be controlled through network density and composition, with the LMWG and PG behaving differently in this regard, while the presence of the heparin binder completely inhibits heparin release through complexation. This study demonstrates that a multi-component approach can yield exquisite control over self-assembled materials. We reason that controlling orthogonality in such systems will underpin further development of controlled release systems with biomedical applications. PMID:29147525

Atomic force microscopy and Langmuir-Blodgett monolayer technique to assess contact lens deposits and human meibum extracts.

PubMed

Hagedorn, Sarah; Drolle, Elizabeth; Lorentz, Holly; Srinivasan, Sruthi; Leonenko, Zoya; Jones, Lyndon

2015-01-01

The purpose of this exploratory study was to investigate the differences in meibomian gland secretions, contact lens (CL) lipid extracts, and CL surface topography between participants with and without meibomian gland dysfunction (MGD). Meibum study: Meibum was collected from all participants and studied via Langmuir-Blodgett (LB) deposition with subsequent Atomic Force Microscopy (AFM) visualization and surface roughness analysis. CL Study: Participants with and without MGD wore both etafilcon A and balafilcon A CLs in two different phases. CL lipid deposits were extracted and analyzed using pressure-area isotherms with the LB trough and CL surface topographies and roughness values were visualized using AFM. Meibum study: Non-MGD participant meibum samples showed larger, circular aggregates with lower surface roughness, whereas meibum samples from participants with MGD showed more lipid aggregates, greater size variability and higher surface roughness. CL Study: Worn CLs from participants with MGD had a few large tear film deposits with lower surface roughness, whereas non-MGD participant-worn lenses had many small lens deposits with higher surface roughness. Balafilcon A pore depths were shallower in MGD participant worn lenses when compared to non-MGD participant lenses. Isotherms of CL lipid extracts from MGD and non-MGD participants showed a seamless rise in surface pressure as area decreased; however, extracts from the two different lens materials produced different isotherms. MGD and non-MGD participant-worn CL deposition were found to differ in type, amount, and pattern of lens deposits. Lipids from MGD participants deposited irregularly whereas lipids from non-MGD participants showed more uniformity. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Competitive adsorption of As(III), As(V), Sb(III) and Sb(V) onto ferrihydrite in multi-component systems: Implications for mobility and distribution.

PubMed

Qi, Pengfei; Pichler, Thomas

2017-05-15

The simultaneous adsorption behavior and competitive interactions between As(III), As(V), Sb(III) and Sb(V) by ferrihydrite were evaluated in multi-component (binary, ternary, quaternary) systems. In binary systems, Sb(III) had a stronger inhibitory influence on As(III) adsorption than Sb(V) did, and As(V) had a stronger inhibitory effect on Sb(V) adsorption than As(III) did. In ternary systems, NO 3 - , PO 4 3- and SO 4 2- did not compete with the adsorption of As(III) and Sb(III). NO 3 - and SO 4 2- also had no distinct effect on the adsorption of As(V) and Sb(V), while PO 4 3- competed with As(V) and Sb(V) for surface sites. In quaternary systems, the simultaneous adsorption behavior of the four redox species was pH dependent. Sb(III) always showed the strongest adsorption affinity regardless of pH. At pH 3.5 As(III) showed the lowest affinity could be due to the presence and negative effect of Sb(III) and As(V). The Freundlich model provided a good fit for the simultaneous adsorption data under quaternary conditions. The study of competitive/simultaneous adsorption of the four possible redox species onto ferrihydrite contributed to a better understanding of their distribution, mobility and fate in the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Formation and characterization of a multicomponent equilibrium system derived from cis- and trans-1-aminomethylcyclohexane-1,2-diol.

PubMed

Hetényi, Anasztázia; Szakonyi, Zsolt; Klika, Karel D; Pihlaja, Kalevi; Fülöp, Ferenc

2003-03-21

Both cis and trans isomers of amino diols 3-6 were prepared stereoselectively. In the reactions between 3-6 and phenyl isothiocyanate, the ring closure proceeded regioselectively and resulted only in spiro derivatives of 2-phenyliminooxazolidines 9, 10, 13, and 14. The reaction of cis- (or trans-)1-aminomethylcyclohexane-1,2-diol 4 (or 6) with 1 equiv of an aromatic aldehyde 15a-g in EtOH at room temperature resulted in a complex, multicomponent equilibrium mixture of 16a-g and 18a-g (or 17a-g and 19a-g), in each case consisting of a five-component, ring-chain tautomeric system 16A-E (or 17A-E), involving the Schiff base, two epimeric spirooxazolidines, two epimeric condensed 1,3-oxazines, and some of the four tricyclic compounds 18A-D (or 19A-D). The five-component, ring-chain equilibria were found to be adequately described by the Hammett-Brown linear free energy equation.

The incidence of elevations in urine 5-hydroxyindoleacetic acid.

PubMed

Nuttall, K L; Pingree, S S

1998-01-01

A 24-hour urine collection for 5-hydroxyindoleacetic acid (HIAA) is commonly performed to evaluate patients with suspected carcinoid syndrome. However, carcinoids are rare, and elevated results are common even when using an analytically specific method. To characterize this problem, the incidence of elevated results was examined in a population of 947 patient specimens received in a clinical reference laboratory setting. Using a reference limit of 15 mg/d identified 7.9 percent of the results as elevated, with 3 percent > 100 mg/d, and about 1 percent > 350 mg/d. Males showed 14 percent > 15 mg/d compared to 5.2 percent for females. Characterization of incomplete and excess 24-hr urine collections is facilitated by use of a creatinine ratio, with a reference limit of 14 mg/g creatinine equivalent to 15 mg/d. Given the frequency of elevated results, HIAA should be used to support the diagnoses of carcinoid only when consistent with other objective findings.

Estimated dietary intake and major food sources of polyphenols in the Polish arm of the HAPIEE study☆

PubMed Central

Grosso, Giuseppe; Stepaniak, Urszula; Topor-Mądry, Roman; Szafraniec, Krystyna; Pająk, Andrzej

2014-01-01

Objective The aim of this study was to estimate the intake of known individual polyphenols and their major dietary sources in the Polish arm of the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study. Methods A total of 10,477 random sample (45–69 y) of urban population of Krakow, Poland, completed a validated 148-item food frequency questionnaire. Polyphenol intake was calculated by matching food consumption data with the recently developed Phenol-Explorer database. Results The mean intake of polyphenols was 1756.5 ± 695.8 mg/d (median = 1662.5 mg/d). The main polyphenol groups were flavonoids (897 mg/d) and phenolic acids (800 mg/d). A total of 347 polyphenols from 19 polyphenol subclasses were found. The individual compounds with the highest intakes were isomers of chlorogenic acid (i.e., 5-caffeoylquinic acid and 4-caffeoylquinic acid) among hydroxycinnamic acids (average intake 150 mg/d), that largely originated from coffee, and compounds belonging to the catechin chemical family (i.e., [+]-gallocatechin, [-]-epigallocatechin 3-O-gallate, and [-]-epicatechin) among flavanols (average intake 50 mg/d), that mostly originated from tea and cocoa products. Conclusions The current study provides the most updated data for individual polyphenols intake in the diet of a well-established nutritional cohort. These findings will be useful to assess potential beneficial role on health of specific foods with high polyphenol content and characterize the effects of individual phenolic compounds. PMID:25280419

75 FR 72857 - Notice of Public Hearing and Commission Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... certain water resources projects; (2) compliance matters involving two projects; and (3) the rescission of... surface water withdrawal of up to 0.990 mgd. 10. Project Sponsor and Facility: Ultra Resources, Inc. (Pine...), Watson Township, Lycoming County, Pa. Application for surface water withdrawal of up to 0.720 mgd. 2...

Multicomponent synthesis of 4,4-dimethyl sterol analogues and their effect on eukaryotic cells.

PubMed

Alonso, Fernando; Cirigliano, Adriana M; Dávola, María Eugenia; Cabrera, Gabriela M; García Liñares, Guadalupe E; Labriola, Carlos; Barquero, Andrea A; Ramírez, Javier A

2014-06-01

Most sterols, such as cholesterol and ergosterol, become functional only after the removal of the two methyl groups at C-4 from their biosynthetic precursors. Nevertheless, some findings suggest that 4,4-dimethyl sterols might be involved in specific physiological processes. In this paper we present the synthesis of a collection of analogues of 4,4-dimethyl sterols with a diamide side chain and a preliminary analysis of their in vitro activity on selected biological systems. The key step for the synthesis involves an Ugi condensation, a versatile multicomponent reaction. Some of the new compounds showed antifungal and cytotoxic activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of a photoacoustic system through neural networks to determine multicomponent samples

NASA Astrophysics Data System (ADS)

Zajarevich, N. M.; Peuriot, A. L.; Slezak, V. B.

2016-07-01

Photoacoustic spectroscopy for trace gases detection, based on a CO2 laser, can be used in a wide range of applications. The tunability of this laser in the mid-infrared (9.4-10.6 μm) allows the quantitative determination of different substances in multicomponent samples. In general, at traces level, the total photoacoustic amplitude at a certain wavelength may be approximated by a linear superposition of the amplitudes given by each of the species absorbing at that wavelength. However, in some cases, the sum of the individual signals is no longer valid. In particular, it is known the presence of CO2 delays the acoustic signal in relation to the laser excitation due to the exchange of vibrational energy between CO2 and N2. This phenomenon generates a slow V-T energy relaxation from a metastable N2 vibrational level and the sum of individual contributions may no longer be valid. Moreover, the resolution of a linear equation system has limitations, so the possibility to determine concentrations in photoacoustics based on neural network is proposed in this work. This procedure is tried in a particular case of a volatile organic compound, such as C2H4, and CO2 in air. The results are compared with the ones obtained with a model based on rate equations.

R/V Kilo Moana's New Geophysical Instrumentation, Processing Methods, and Online Data Repository

NASA Astrophysics Data System (ADS)

Miller, J. E.; Chandler, M. T.; Taylor, B.; Shor, A.; Ferguson, J. S.; Wessel, P.

2012-12-01

In 2012 several upgrades were made to the underway geophysical systems on R/V Kilo Moana, which the University of Hawaii School of Ocean and Earth Science and Technology (SOEST) operates as part of the University-National Oceanographic Laboratory System (UNOLS) fleet. New instrumentation includes a Bell BGM-3 forced feedback-type gravimeter, a Kongsberg EM 122 12-kHz receiver array, and a high resolution 70-100 kHz EM 710 multibeam echo sounder. Multibeam acceptance trials carried out in June by the Multibeam Advisory Committee, Gates Acoustic Services and UH-SOEST found that both sonars are performing within expected levels with ~5x water depth (WD) for the EM 710 system in shallow water and ~19 km swath width at 4,700 m depth (~4x WD) for the EM 122 deep water system. UH-SOEST also took steps this year to fulfill its obligation to make Kilo Moana's geophysical data more accessible to the public. After an audit of Kilo Moana data at SOEST, Lamont's Rolling Deck to Repository (R2R) and the National Geophysical Data Center (NGDC), as of July 2012 all National Science Foundation-funded Kilo Moana multibeam, gravity, magnetics, center beam depth and Acoustic Doppler Current Profiler (ADCP) data have been submitted to R2R and any multibeam data over 2 years old is being transferred to NGDC. Because it had previously been difficult to access some of SOEST's geophysical data, updated data processing routines have been developed for converting raw gravity, magnetics, and centerbeam depth data to NGDC's standard marine data exchange format (MGD77) for archival and dissemination by NGDC. MGD77 files are being generated and inspected using rigorous along-track analytical techniques for ~270 surveys dating from 2002 to the present and are being submitted to NGDC. We are also developing an online data portal to further facilitate access to SOEST data.

Optimization of a dual-energy contrast-enhanced technique for a photon-counting digital breast tomosynthesis system: I. A theoretical model

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

Carton, Ann-Katherine; Ullberg, Christer; Lindman, Karin

2010-11-15

Purpose: Dual-energy (DE) iodine contrast-enhanced x-ray imaging of the breast has been shown to identify cancers that would otherwise be mammographically occult. In this article, theoretical modeling was performed to obtain optimally enhanced iodine images for a photon-counting digital breast tomosynthesis (DBT) system using a DE acquisition technique. Methods: In the system examined, the breast is scanned with a multislit prepatient collimator aligned with a multidetector camera. Each detector collects a projection image at a unique angle during the scan. Low-energy (LE) and high-energy (HE) projection images are acquired simultaneously in a single scan by covering alternate collimator slits withmore » Sn and Cu filters, respectively. Sn filters ranging from 0.08 to 0.22 mm thickness and Cu filters from 0.11 to 0.27 mm thickness were investigated. A tube voltage of 49 kV was selected. Tomographic images, hereafter referred to as DBT images, were reconstructed using a shift-and-add algorithm. Iodine-enhanced DBT images were acquired by performing a weighted logarithmic subtraction of the HE and LE DBT images. The DE technique was evaluated for 20-80 mm thick breasts. Weighting factors, w{sub t}, that optimally cancel breast tissue were computed. Signal-difference-to-noise ratios (SDNRs) between iodine-enhanced and nonenhanced breast tissue normalized to the square root of the mean glandular dose (MGD) were computed as a function of the fraction of the MGD allocated to the HE images. Peak SDNR/{radical}(MGD) and optimal dose allocations were identified. SDNR/{radical}(MGD) and dose allocations were computed for several practical feasible system configurations (i.e., determined by the number of collimator slits covered by Sn and Cu). A practical system configuration and Sn-Cu filter pair that accounts for the trade-off between SDNR, tube-output, and MGD were selected. Results: w{sub t} depends on the Sn-Cu filter combination used, as well as on the breast thickness; to optimally cancel 0% with 50% glandular breast tissue, w{sub t} values were found to range from 0.46 to 0.72 for all breast thicknesses and Sn-Cu filter pairs studied. The optimal w{sub t} values needed to cancel all possible breast tissue glandularites vary by less than 1% for 20 mm thick breasts and 18% for 80 mm breasts. The system configuration where one collimator slit covered by Sn is alternated with two collimator slits covered by Cu delivers SDNR/{radical}(MGD) nearest to the peak value. A reasonable compromise is a 0.16 mm Sn-0.23 mm Cu filter pair, resulting in SDNR values between 1.64 and 0.61 and MGD between 0.70 and 0.53 mGy for 20-80 mm thick breasts at the maximum tube current. Conclusions: A DE acquisition technique for a photon-counting DBT imaging system has been developed and optimized.« less

Validation and use of three complementary analytical methods (LC-FLS, LC-MS/MS and ICP-MS) to evaluate the pharmacokinetics, biodistribution and stability of motexafin gadolinium in plasma and tissues.

PubMed

Miles, Dale R; Mesfin, Mimi; Mody, Tarak D; Stiles, Mark; Lee, Jean; Fiene, John; Denis, Bernie; Boswell, Garry W

2006-05-01

Liquid chromatography-fluorescence (LC-FLS), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS) methods were developed and validated for the evaluation of motexafin gadolinium (MGd, Xcytrin) pharmacokinetics and biodistribution in plasma and tissues. The LC-FLS method exhibited the greatest sensitivity (0.0057 microg mL(-1)), and was used for pharmacokinetic, biodistribution, and protein binding studies with small sample sizes or low MGd concentrations. The LC-MS/MS method, which exhibited a short run time and excellent selectivity, was used for routine clinical plasma sample analysis. The ICP-MS method, which measured total Gd, was used in conjunction with LC methods to assess MGd stability in plasma. All three methods were validated using human plasma. The LC-FLS method was also validated using plasma, liver and kidneys from mice and rats. All three methods were shown to be accurate, precise and robust for each matrix validated. For three mice, the mean (standard deviation) concentration of MGd in plasma/tissues taken 5 hr after dosing with 23 mg kg(-1) MGd was determined by LC-FLS as follows: plasma (0.025+/-0.002 microg mL(-1)), liver (2.89+/-0.45 microg g(-1)), and kidney (6.09+/-1.05 microg g(-1)). Plasma samples from a subset of patients with brain metastases from extracranial tumors were analyzed using both LC-MS/MS and ICP-MS methods. For a representative patient, > or = 90% of the total Gd in plasma was accounted for as MGd over the first hour post dosing. By 24 hr post dosing, 63% of total Gd was accounted for as MGd, indicating some metabolism of MGd.

Phase I study of continuous MKC-1 in patients with advanced or metastatic solid malignancies using the modified Time-to-Event Continual Reassessment Method (TITE-CRM) dose escalation design.

PubMed

Tevaarwerk, Amye; Wilding, George; Eickhoff, Jens; Chappell, Rick; Sidor, Carolyn; Arnott, Jamie; Bailey, Howard; Schelman, William; Liu, Glenn

2012-06-01

MKC-1 is an oral cell-cycle inhibitor with broad antitumor activity in preclinical models. Clinical studies demonstrated modest antitumor activity using intermittent dosing schedule, however additional preclinical data suggested continuous dosing could be efficacious with additional effects against the mTor/AKT pathway. The primary objectives were to determine the maximum tolerated dose (MTD) and response of continuous MKC-1. Secondary objectives included characterizing the dose limiting toxicities (DLTs) and pharmacokinetics (PK). Patients with solid malignancies were eligible, if they had measurable disease, ECOG PS ≤1, and adequate organ function. Exclusions included brain metastases and inability to receive oral drug. MKC-1 was dosed twice daily, continuously in 28-day cycles. Other medications were eliminated if there were possible drug interactions. Doses were assigned using a TITE-CRM algorithm following enrollment of the first 3 pts. Disease response was assessed every 8 weeks. Between 5/08-9/09, 24 patients enrolled (15 M/9 F, median 58 years, range 44-77). Patients 1-3 received 120 mg/d of MKC-1; patients 4-24 were dosed per the TITE-CRM algorithm: 150 mg [n = 1], 180 [2], 200 [1], 230 [1], 260 [5], 290 [6], 320 [5]. The median time on drug was 8 weeks (range 4-28). The only DLT occurred at 320 mg (grade 3 fatigue). Stable disease occurred at 150 mg/d (28 weeks; RCC) and 320 mg/d (16 weeks; breast, parotid). Escalation halted at 320 mg/d. Day 28 pharmacokinetics indicated absorption and active metabolites. Continuous MKC-1 was well-tolerated; there were no RECIST responses, although clinical benefit occurred in 3/24 pts. Dose escalation stopped at 320 mg/d, and this is the MTD as defined by the CRM dose escalation algorithm; this cumulative dose/cycle exceeds that determined from intermittent dosing studies. A TITE-CRM allowed for rapid dose escalation and was able to account for late toxicities with continuous dosing via a modified algorithm.

[Mathematic modeling and experimental validation of macrostate quality expression for multicomponent in Chinese materia medica].

PubMed

He, Fuyuan; Deng, Kaiwen; Shi, Jilian; Liu, Wenlong; Pi, Fengjuan

2011-11-01

To establish the unitive multicomponent quality system bridged macrostate mathematic model parameters of material quality and microstate component concentration for Chinese materia medica (CMM). According to law of biologic laws of thermodynamics, the state functions of macrostate qulity of the CMM were established. The validation test was carried out as modeling drug as alcohol extract of Radix Rhozome (AERR), their enthalpy of combustion was determined, and entropy and the capability of information by chromatographic fingerprint were assayed, and then the biologic apparent macrostate parameters were calculated. The biologic macrostate mathematic models, for the CMM quality controll, were established as parameters as the apparent equilibrium constant, biologic enthalpy, Gibbs free energy and biologic entropy etc. The total molarity for the 10 batchs of AERR were 0.153 4 mmol x g(-1) with 28.26% of RSD, with the average of apparent equilibrium constants, biologic enthalpy, Gibbs free energy and biologic entropy were 0.039 65, 8 005 J x mol(-1), -2.408 x 10(7) J x mol(-1) and - 8.078 x 10(4) J x K(-1) with RSD as 6.020%, 1.860%, 42.32% and 42.31%, respectively. The macrostate quality models for CMM can represent their intrinsic quality for multicomponent dynamic system such as the CMM, to manifest out as if the forest away from or tree near from to see it.

Galantamine for Alzheimer's disease.

PubMed

Olin, J; Schneider, L

2001-01-01

Galantamine (also called galanthamine, marketed as Reminyl (Janssen)) can be isolated from several plants, including daffodil bulbs, and now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer's disease, and recently several multicentre clinical trials have been published with positive findings. Galantamine has received regulatory approval in Sweden, is available in Austria, and awaits marketing approval in the United States, Europe, and other countries. The objective of this review is to assess the clinical effects of galantamine in patients with probable Alzheimer's disease, and to investigate potential moderators of an effect. The Cochrane Dementia Group specialized register of clinical trials was searched using the terms 'galantamine,' and 'galanthamine' (15 February 2000) as was the Cochrane Controlled Trials Register (2000, Issue 2). These terms were also used to search the following databases: EMBASE, MEDLINE, PsychLit; Combined Health Information Database, NRR (National Research Register), ADEAR (Alzheimer's Disease Education and Referral Centre clinical database, BIOMED (Biomedicine and Health), Glaxo-Wellcome Clinical Trials Register, National Institutes of Health Clinical Trials Databases, Current Controlled Trials, Dissertation Abstracts (mainly North American dissertations) 1961-1994, Index to UK Theses (British dissertations) 1970-1994. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. Trials selected were randomized, double-blind, parallel-group, and unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in people with Alzheimer's disease. Data were extracted independently by the reviewers and pooled where appropriate and possible. The pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Intention-to-treat and observed cases data were both reported, if the data were available to be reported. -Outcomes of interest include the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), clinical global impression of change (CIBIC-plus or CGIC), Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL), Disability Assessment for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI). - Potential moderating variables of a treatment effect included trial duration and dose. Seven trials were identified that met criteria for entry, with 6 being Phase II or III industry-sponsored multicentre trials. One was of 12 weeks duration; one of 5 months; one of 29 weeks; and the rest of 6 months duration. Trials of 5 months or more were aggregated in the analyses as '6 months'. Overall, galantamine showed significant treatment effects at daily doses of 16-32 mg/d for trials of 3- to 6-months duration. For global ratings, trials of 3 months duration with doses of 24-32mg/d (Odds Ratio (OR) 2.2; 95%CI 1.4 to 3.7) and 36mg/d (OR 3.3; 95%CI 1.2 to 9.3) were statistically significant in favour of treatment. For trials of 6 months duration (5-months to 29 weeks), only doses of 8mg/d failed to be statistically significant (24mg: OR 2.0; 95%CI 1.5 to2.5; 32mg: OR 1.9; 95%CI 1.4 to 2.5). For cognitive function over 6 months duration: at a 24mg/d, improvements measured -3.5 points (k=3; 95%CI -4.3 to -2.8) on weighted mean difference on the ADAS-Cog scale, and -4.0 points at 32mg/d (k=2; 95%CI -5.0 to -3.0). Both observed cases (WMD 3.8; 95%CI 0.3 to 7.3) and intention to treat analyses using the Disability Assessment of Dementia gave statistically significant results in favour of treatment for daily doses of 32mg for 6 months duration. The small number of trials available for analysis, however, limited the power of analyses to detect differences. Galantamine consistently failed to show statistically significant treatment effects at doses of 8mg/day. Galantamine's adverse effects appear similar to those of other cholinesterase inhibitors, in that it tends to produce gastrointestinal effects acutely and with dosage increases. Overall, people treated with galantamine at doses of 24-32 mg/d were more likely to discontinue participation in most trials than were people treated with lower doses or placebo, but in the one trial with a slower rate of titration the discontinuation rate was not significantly greater than placebo for the 16 mg/day dose. (ABSTRACT TRUNCATED)

Effects of a behavioral intervention that emphasizes spices and herbs on adherence to recommended sodium intake: results of the SPICE randomized clinical trial12

PubMed Central

Anderson, Cheryl AM; Cobb, Laura K; Miller, Edgar R; Woodward, Mark; Hottenstein, Annette; Chang, Alex R; Mongraw-Chaffin, Morgana; White, Karen; Charleston, Jeanne; Tanaka, Toshiko; Thomas, Letitia; Appel, Lawrence J

2015-01-01

Background: For decades, dietary sodium intake in the United States has remained high, and few studies have examined strategies for maintaining recommended intakes. Objective: We examined the effects of a behavioral intervention, which emphasized spices and herbs, on the maintenance of sodium intake at the recommended intake of 1500 mg/d in individuals to whom the US Dietary Guidelines for Americans apply. Design: We conducted a 2-phase study that included adults ≥18 y of age for whom Dietary Guidelines for Americans recommends 1500 mg Na/d. The study was conducted in Baltimore, Maryland, from 2012 to 2014. In phase 1, 55 individuals consumed a low-sodium diet for 4 wk. Participants were provided all foods, snacks, and calorie-containing drinks. In phase 2, 40 participants from phase 1 were randomly assigned to either a behavioral intervention to reduce sodium intake (n = 20) or a self-directed control group (n = 20) for 20 wk. The primary study outcome was the change in mean 24-h urinary sodium excretion during phase 2. Linear regression analyses were used to determine intervention effects on urinary sodium excretion. Results: Participant characteristics were as follows: women: 65%; African American: 88%; hypertension: 63%; diabetes: 18%; mean age: 61 y; and mean body mass index (in kg/m2): 30. At the end of phase 2, mean 24-h sodium excretion was lower in the behavioral intervention than in the self-directed group (mean difference: −956.8 mg/d; 95% CI: −1538.7, −374.9 mg/d) after sodium intake at screening was controlled for (P = 0.002). These findings persisted in sensitivity analyses that excluded potentially incomplete urine collections [Mage’s equation mean difference: −1090 mg/d (P = 0.001); Joosens’ equation mean difference: −796 mg/d (P = 0.04)]. Conclusions: A multifactorial behavioral intervention emphasizing spices and herbs significantly reduced sodium intake. Because of the ubiquity of sodium in the US food supply, multilevel strategies addressing individual behaviors and the food supply are needed to improve adherence to recommendations. This trial was registered at clinicaltrials.gov as NCT01615159. PMID:26269371

Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment.

PubMed

Mantovani, Giovanni; Madeddu, Clelia; Macciò, Antonio; Gramignano, Giulia; Lusso, Maria Rita; Massa, Elena; Astara, Giorgio; Serpe, Roberto

2004-10-01

Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease. On the basis of our previously published studies and clinical experience, we have developed an innovative approach consisting of diet with high polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n - 3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each) per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for 16 weeks. The following variables are evaluated: (a) clinical variables (stage and Eastern Cooperative Oncology Group performance status); (b) nutritional variables (lean body mass, appetite, and resting energy expenditure); (c) laboratory variables (serum levels of proinflammatory cytokines, C-reactive protein, and leptin and blood levels of reactive oxygen species and antioxidant enzymes); and (d) quality of life variables (European Organization for Research and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II nonrandomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress. As of January 2004, 28 patients have been enrolled: 25 patients were evaluable and 14 of them have completed the treatment (20 patients have completed 2 months of treatment). As for clinical response, five patients improved, three patients remained unchanged, and six patients worsened. The Eastern Cooperative Oncology Group performance status (grade) 1 remained unchanged. As for nutritional/functional variables, the lean body mass increased significantly at 2 and 4 months. As for laboratory variables, reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha decreased significantly. As for quality of life, it comprehensively improved after treatment. The treatment has been shown to be effective for clinical response, increase of lean body mass, decrease of reactive oxygen species and proinflammatory cytokines, and improvement of quality of life. The treatment has been shown to be safe with good compliance of patients. The study is in progress (14 further patients will be included).

The relationship between adverse events during selective serotonin reuptake inhibitor treatment for major depressive disorder and nonremission in the suicide assessment methodology study.

PubMed

Daly, Ella J; Trivedi, Madhukar H; Fava, Maurizio; Shelton, Richard; Wisniewski, Stephen R; Morris, David W; Stegman, Diane; Preskorn, Sheldon H; Rush, A John

2011-02-01

Little is known about the association between antidepressant treatment-emergent adverse events and symptom nonremission in major depressive disorder. The objective of the current analysis was to determine whether particular baseline symptoms or treatment-emergent symptoms (adverse events) during the first 2 weeks are associated with nonremission after 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).Outpatients clinically diagnosed with nonpsychotic major depressive disorder were recruited from 6 primary and 9 psychiatric care sites. Participants (n = 206) were treated with an SSRI antidepressant (citalopram [20-40 mg/d], escitalopram [10-20 mg/d], fluoxetine [20-40 mg/d], paroxetine [20-40 mg/d], paroxetine CR [25-37.5 mg/d], or sertraline [50-150 mg/d]) for 8 weeks. Remission was defined as having a score of 5 or less on the 16-item Quick Inventory of Depressive Symptomatology-Clinician-Rated at week 8, or using last observation carried forward. Adverse events were identified using the 55-item Systematic Assessment for Treatment Emergent Events-Systematic Inquiry completed by participants at baseline and week 2.Findings indicated that the emergence of adverse events of weakness/fatigue, strange feeling, and trouble catching breath/hyperventilation at week 2 were independently associated with lack of remission even after controlling for the potential confounders of baseline depressive severity, anxious symptoms, antidepressant medication, chronic depression, race, burden of general medical comorbidity, and time in study. Hearing/seeing things appeared to have a protective effect. In conclusion, during SSRI treatment, the adverse events of weakness/fatigue, feeling strange, and trouble catching breath/hyperventilation are associated with nonremission, possibly due to lower adherence, early attrition, difficulty increasing the dose, and reduced efficacy.

Novel Reagents for Multi-Component Reactions

NASA Astrophysics Data System (ADS)

Wang, Yanguang; Basso, Andrea; Nenajdenko, Valentine G.; Gulevich, Anton V.; Krasavin, Mikhail; Bushkova, Ekaterina; Parchinsky, Vladislav; Banfi, Luca; Basso, Andrea; Cerulli, Valentina; Guanti, Giuseppe; Riva, Renata; Rozentsveig, Igor B.; Rozentsveig, Gulnur N.; Popov, Aleksandr V.; Serykh, Valeriy J.; Levkovskaya, Galina G.; Cao, Song; Shen, Li; Liu, Nianjin; Wu, Jingjing; Li, Lina; Qian, Xuhong; Chen, Xiaopeng; Wang, Hongbo; Feng, Jinwu; Wang, Yanguang; Lu, Ping; Heravi, Majid M.; Sadjadi, Samaheh; Kazemizadeh, Ali Reza; Ramazani, Ali; Kudyakova, Yulia S.; Goryaeva, Marina V.; Burgart, Yanina V.; Saloutin, Victor I.; Mossetti, Riccardo; Pirali, Tracey; Tron, Gian Cesare; Rozhkova, Yulia S.; Mayorova, Olga A.; Shklyaev, Yuriy V.; Zhdanko, Alexander G.; Nenajdenko, Valentine G.; Stryapunina, Olga G.; Plekhanova, Irina V.; Glushkov, Vladimir A.; Shklyaev, Yurii V.

Ketenimines are a class of versatile and highly reactive intermediates that can participate in a variety of organic reactions, such as nucleophilic additions, radical additions, [2 + 2] and [2 + 4] cycloadditions, and sigmatropic rearrangements. In this presentation, we report on a series of multi-component reactions that involve a ketenimine intermediate. These reactions could furnish diverse heterocyclic compounds, including functionalized iminocoumarin, iminodihydroqunolines, iminothiochromens, pyrrolines, isoquinolines, pyridines, β-lactams, imino-1,2-dihydrocoumarins, and benzimidazoles.

Impact of multicomponent ionic transport on pH fronts propagation in saturated porous media

NASA Astrophysics Data System (ADS)

Muniruzzaman, Muhammad; Rolle, Massimo

2016-04-01

Multicomponent ionic interactions have been increasingly recognized as important factors for the displacement of charged species in porous media under both diffusion- [1,2] and advection-dominated flow regimes [3,4]. In this study we investigate the propagation of pH fronts during multicomponent ionic transport in saturated porous media under flow-through conditions. By performing laboratory bench-scale experiments combined with numerical modeling we show the important influence of Coulombic effects on proton transport in the presence of ionic admixtures. The experiments were performed in a quasi two-dimensional flow-through setup under steady-state flow and transport conditions. Dilute solutions of hydrochloric acid with MgCl2 (1:2 strong electrolyte) were used as tracer solutions to experimentally test the effect of electrochemical cross-coupling on the migration of diffusive/dispersive pH fronts. We focus on two experimental scenarios, with different composition of tracer solutions, causing remarkably different effects on the propagation of the acidic fronts with relative differences in the penetration depth of pH fronts of 36% between the two scenarios and of 25% and 15% for each scenario with respect to the transport of ions at liberated state (i.e., without considering the charge effects). Also significant differences in the dilution of the distinct ionic plumes, quantified using the flux-related dilution index at the laboratory bench scale [5], were measured at the outflow of the flow-through system. The dilution of the pH plumes also changed considerably (26% relative difference) in the two flow-through experiments only due to the different composition of the pore water solution and to the electrostatic coupling of the ions in the flow-through setups. Numerical transport simulations were performed to interpret the laboratory experiments. The simulations were based on a multicomponent ionic formulation accurately capturing the Coulombic interactions between the transported ions in the flow-through system. The results of purely forward simulations show a very good agreement with the high-resolution measurements performed at the outlet of the flow-through setup and illustrate the importance of charge effects on pH fronts propagation in porous media. [1] Giambalvo, E. R., C. I. Steefel, A. T. Fisher, N. D. Rosenberg, and C. G. Wheat (2002), Effect of fluid-sediment reaction on hydrothermal fluxes of major elements, eastern flank of the Juan de Fuca Ridge, Geochim. Cosmochim. Acta, 66, 1739-1757. [2] Appelo, C. A. J., and P. Wersin (2007), Multicomponent diffusion modeling in clay systems with application to the diffusion of tritium, iodide, and sodium in opalinus clay, Environ. Sci. Technol., 41, 5002-5007. [3] Rolle, M., M. Muniruzzaman, C. M. Haberer, and P. Grathwohl (2013), Coulombic effects in advection-dominated transport of electrolytes in porous media: Multicomponent ionic dispersion, Geochim. Cosmochim. Acta, 120, 195-205. [4] Muniruzzaman, M., C. M. Haberer, P. Grathwohl, and M. Rolle (2014), Multicomponent ionic dispersion during transport of electrolytes in heterogeneous porous media: Experiments and model-based interpretation, Geochim. Cosmochim. Acta, 141, 656-669. [5] Rolle, M., G. Chiogna, D. L. Hochstetler, and P. K. Kitanidis (2013), On the importance of diffusion and compound-specific mixing for groundwater transport: An investigation from pore to field scale, J. Contam. Hydrol., 153, 51-68.

Multicomponent Dark Matter in Radiative Seesaw Models

NASA Astrophysics Data System (ADS)

Aoki, Mayumi; Kaneko, Daiki; Kubo, Jisuke

2017-11-01

We discuss radiative seesaw models, in which an exact Z_2¥times Z_2' symmetry is imposed. Due to the exact Z_2¥times Z_2' symmetry, neutrino masses are generated at a two-loop level and at least two extra stable electrically neutral particles are predicted. We consider two models: one has a multi-component dark matter system and the other one has a dark radiation in addition to a dark matter. In the multi-component dark matter system, non-standard dark matter annihilation processes exist. We find that they play important roles in determining the relic abundance and also responsible for the monochromatic neutrino lines resulting from the dark matter annihilation process. In the model with the dark radiation, the structure of the Yukawa coupling is considerably constrained and gives an interesting relationship among cosmology, lepton flavor violating decay of the charged leptons and the decay of the inert Higgs bosons.

Fatal sepsis and systemic inflammatory response syndrome after off-label prasugrel: a case report.

PubMed

Serebruany, Victor L; Kipshidze, Nodar; Pershukov, Igor V; Kuliczkowski, Wiktor; Carnes, Judy; Atar, Dan

2014-01-01

Aggressive dual antiplatelet therapy is associated not only with more bleeding, impaired wound healing, and potentially more solid cancer rates but it also causes higher infection risks including sepsis, and systemic inflammatory response syndrome (SIRS). This may be especially true considering the alarming off-label use of prasugrel. A 65-year-old white male patient with a history of myocardial infarction treated with percutaneous coronary intervention and implantation of 2 bare metal stents, was treated with off-label clopidogrel for 4 years, including a double daily dose (150 mg) for the initial 13 months. Still on clopidogrel, the patient was hospitalized with suspected pneumonia. A diagnostic cardiac catheterization revealed a 60%-70% blockage of the mid left anterior descending, but there was no need for coronary intervention. At discharge, clopidogrel 75 mg/d was switched over to off-label prasugrel 10 mg/d on top of aspirin (81 mg/d). On day 3 after prasugrel was given, a football-sized bruise appeared on the patient's lower right abdomen, but computed tomography results were unremarkable. On day 6 after administration of prasugrel, the patient became dizzy, disoriented, confused, experienced difficulty breathing, severe headache, weakness, intensive petechial rash covering the entire body, and breathing difficulty requiring ventilation. Within 24 hours, the patient was unable to correctly identify his age; his eyes were pale in color to almost colorless and when hearing a sound he would turn his entire head toward the sound and he appeared to be blind. His lungs, liver, and kidneys began to show signs of failure over the next 5-9 days. Sixteen days after the administration of the first prasugrel dose, the patient died of sepsis complicated with SIRS. Aggressive off-label use of clopidogrel (double dose for 13 months, and >4 years overall duration), followed by off-label switchover to the highest daily dose (10 mg) prasugrel may trigger sepsis and fatal SIRS. The mechanism responsible for such harmful association is probably indirect, and involves the weakening of platelet-neutrophil-endothelial crosstalk necessary to combat infections, and/or keep inflammation from spreading.

Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

PubMed Central

Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

1996-01-01

Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations. PMID:8935328

Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

PubMed

Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

1996-05-01

Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations.

Catalysis and Multi-Component Reactions

NASA Astrophysics Data System (ADS)

Shibasaki, Masakatsu; Yus, Miguel; Bremner, Stacy; Comer, Eamon; Shore, Gjergji; Morin, Sylvie; Organ, Michael G.; van der Eycken, Erik; Merkul, Eugen; Dorsch, Dieter; Müller, Thomas J. J.; Ryabukhin, Sergey V.; Ostapchuk, Eugeniy N.; Plaskon, Andrey S.; Volochnyuk, Dmitriy M.; Shivanyuk, Alexander N.; Tolmachev, Andrey A.; Sheibani, Hassan; Babaie, Maryam; Behzadi, Soheila; Dabiri, Minoo; Bahramnejad, Mahboobeh; Bashiribod, Sahareh; Hekmatshoar, Rahim; Sadjadi, Sodeh; Khorasani, Mohammad; Polyakov, Anatoliy I.; Eryomina, Vera A.; Medvedeva, Lidiya A.; Tihonova, Nadezhda I.; Listratova, Anna V.; Voskressensky, Leonid G.; Merkul, Eugen; Dorsch, Dieter; Müller, Thomas J. J.; Sheibani, Hassan; Esfandiarpoor, Zeinab; Behzadi, Soheila; Titova, Julia A.; Fedorova, Olga V.; Ovchinnikova, Irina G.; Valova, Marina S.; Koryakova, Olga V.; Rusinov, Gennady L.; Charushin, Valery N.; Hekmatshoar, Rahim; Sadjadi, Sodeh

We have been studying the development of new asymmetric two-center catalysis using rare earth alkoxides and bifunctional sugar and related ligands. In The Fourth International Conference on Multi-Component Reactions and Related Chemistry (MCR 2009), new catalytic asymmetric reactions using catalysts 1 and 2 and catalytic asymmetric syntheses of ranirestat 3 and tamiflu 4 will be presented.

A unique combination of anatomy and physiology in cells of the rat paralaminar thalamic nuclei adjacent to the medial geniculate body

PubMed Central

Smith, Philip H.; Bartlett, Edward L.; Kowalkowski, Anna

2010-01-01

The medial geniculate body (MGB) has three major subdivisions - ventral (MGV), dorsal (MGD) and medial (MGM). MGM is linked with paralaminar nuclei that are situated medial and ventral to MGV/MGD. Paralaminar nuclei have unique inputs and outputs when compared with MGV and MGD and have been linked to circuitry underlying some important functional roles. We recorded intracellularly from cells in the paralaminar nuclei in vitro. We found that they possess an unusual combination of anatomical and physiological features when compared to those reported for “standard” thalamic neurons seen in the MGV/MGD and elsewhere in the thalamus. Compared to MGV/MGD neurons, anatomically, 1) paralaminar cell dendrites can be long, branch sparingly and encompass a much larger area. 2) their dendrites may be smooth but can have well defined spines and 3) their axons can have collaterals that branch locally within the same or nearby paralaminar nuclei. When compared to MGV/MGD neurons physiologically 1) their spikes are larger in amplitude and can be shorter in duration and 2) can have dual afterhyperpolarizations with fast and slow components and 3) they can have a reduction or complete absence of the low threshold, voltage-sensitive calcium conductance that reduces or eliminates the voltage-dependent burst response. We also recorded from cells in the parafascicular nucleus, a nucleus of the posterior intralaminar nuclear group, because they have unusual anatomical features that are similar to some of our paralaminar cells. Like the labeled paralaminar cells, parafascicular cells had physiological features distinguishing them from typical thalamic neurons. PMID:16566009

Effect of topical 3% diquafosol sodium on eyes with dry eye disease and meibomian gland dysfunction.

PubMed

Amano, Shiro; Inoue, Kenji

2017-01-01

To prospectively evaluate the effect of topical diquafosol sodium on eyes with dry eye disease (DED) and meibomian gland dysfunction (MGD). The subjects were consecutive patients diagnosed with both DED and MGD at Inouye Eye Hospital between March and September of 2016. The subjects were administered topical 3% diquafosol sodium ophthalmic solution six times a day for 3 months. At each study visit, subjects underwent slit-lamp examination and completed MGD symptoms and dry eye-related quality of life score (DEQS) questionnaires. Meibum quality (meibum score) and meibomian gland loss (meiboscore) were evaluated. Tear lipid layer thickness was measured in both eyes with an ocular surface interferometer immediately after clinic arrival and 20 minutes after instillation of one drop of topical diquafosol. Thirteen patients (3 men, 10 women) with a mean age of 69.5±8.3 years completed the 3-month study. The number of telangiectasia and plugged meibomian gland orifices significantly decreased from baseline after 1 month of diquafosol use. The meibum score and the meiboscore significantly decreased from baseline at 3 months. Also, the lipid layer thickness was greater after diquafosol administration than before administration at baseline and 1, 2, and 3 months by 12.2, 11.5, 9.5, and 17.0 nm, respectively, but this difference was only significant at 3 months ( p =0.039). The DEQS ocular symptom ( p =0.065) and MGD questionnaire ( p =0.081) scores tended to be lower than baseline at 3 months. Diquafosol sodium ophthalmic solution improves DED- and MGD-related signs in eyes with MGD.

Iron supplementation has minor effects on gut microbiota composition in overweight and obese women in early pregnancy.

PubMed

Dekker Nitert, Marloes; Gomez-Arango, Luisa F; Barrett, Helen L; McIntyre, H David; Anderson, Gregory J; Frazer, David M; Callaway, Leonie K

2018-05-23

Fe is an essential nutrient for many bacteria, and Fe supplementation has been reported to affect the composition of the gut microbiota in both Fe-deficient and Fe-replete individuals outside pregnancy. This study examined whether the dose of Fe in pregnancy multivitamin supplements affects the overall composition of the gut microbiota in overweight and obese pregnant women in early pregnancy. Women participating in the SPRING study with a faecal sample obtained at 16 weeks' gestation were included in this substudy. For each subject, the brand of multivitamin used was recorded. Faecal microbiome composition was assessed by 16S rRNA sequencing and analysed with the QIIME software suite. Dietary intake of Fe was assessed using a FFQ at 16 weeks' gestation. Women were grouped as receiving low (<60 mg/d, n 94) or high (≥60 mg/d; n 65) Fe supplementation. The median supplementary Fe intake in the low group was 10 (interquartile range (IQR) 5-10) v. 60 (IQR 60-60) mg/d in the high group (P<0·001). Dietary Fe intake did not differ between the groups (10·0 (IQR 7·4-13·3) v. 9·8 (IQR 8·2-13·2) mg/d). Fe supplementation did not significantly affect the composition of the faecal microbiome at any taxonomic level. Network analysis showed that the gut microbiota in the low Fe supplementation group had a higher predominance of SCFA producers. Pregnancy multivitamin Fe content has a minor effect on the overall composition of the gut microbiota of overweight and obese pregnant women at 16 weeks' gestation.

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

PubMed Central

2016-01-01

A new way of developing novel synthesis strategies for the construction of monocyclic rings found in organic molecules is presented. The method is based on the visual application of integer partitioning to chemical structures. Two problems are addressed: (1) the determination of the total number of possible ways to construct a given ring by 2-, 3-, and 4-component couplings; and (2) the systematic enumeration of those possibilities. The results of the method are illustrated using cyclohexanone, pyrazole, and the Biginelli adduct as target ring systems with a view to discover new and greener strategies for their construction using multicomponent reactions. The application of the method is also extended to various heterocycles found in many natural products and pharmaceuticals. PMID:28144310

A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress.

PubMed

Mantovani, Giovanni; Macciò, Antonio; Madeddu, Clelia; Gramignano, Giulia; Lusso, Maria Rita; Serpe, Roberto; Massa, Elena; Astara, Giorgio; Deiana, Laura

2006-05-01

To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants, and drugs, all given orally, in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress. An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d alpha-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: (a) clinical (Eastern Cooperative Oncology Group performance status); (b) nutritional [lean body mass (LBM), appetite, and resting energy expenditure]; (c) laboratory [proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes]; (d) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF). From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable. Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha, and a negative relationship worthy of note was only found between LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D(VAS), and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were "responders" or "high responders." The minimum required was 21; therefore, the treatment was effective and more importantly was shown to be safe. The efficacy and safety of the treatment have been shown by the study; therefore, a randomized phase III study is warranted.

The electric dipole moment of magnesium deuteride, MgD.

PubMed

Steimle, Timothy C; Zhang, Ruohan; Wang, Hailing

2014-06-14

The (0,0) A(2)Π-X (2)Σ(+) band of a cold molecular beam sample of magnesium monodeuteride, MgD, has been recorded field-free and in the presence of a static electric field of up to 11 kV/cm. The lines associated with the lowest rotational levels are detected for the first time. The field-free spectrum was analyzed to produce an improved set of fine structure parameters for the A(2)Π (v = 0) state. The observed electric field induced splittings and shifts were analyzed to produce permanent electric dipole moments, μ(el) of 2.567(10)D and 1.31(8)D for A(2)Π (v = 0) and X(2)Σ(+)(v = 0) states, respectively. The recommended value for μ(el)(X(2)Σ(+) (v = 0)) for MgH, based upon the measured value for MgD, is 1.32(8)D.

Evaluation of the adhesive properties of the cornea by means of optical coherence tomography in patients with meibomian gland dysfunction and lacrimal tear deficiency.

PubMed

Napoli, Pietro Emanuele; Coronella, Franco; Satta, Giovanni Maria; Galantuomo, Maria Silvana; Fossarello, Maurizio

2014-01-01

The aim was to determine the influence of meibomian gland dysfunction (MGD) and aqueous tear deficiency dry eye (ADDE) on the adhesive properties of the central cornea by means of optical coherence tomography (OCT), and to investigate the relationship between corneal adhesiveness and classical tear tests, as well as the reliability of results, in these lacrimal functional unit disorders. Prospective, case-control study. Twenty-eight patients with MGD and 27 patients with ADDE were studied. A group of 32 healthy subjects of similar age and gender distribution served as a control group. The adhesive properties of the anterior corneal surface were measured by OCT, based on the retention time of adhesion marker above it, in all participants. An excellent (≥5 minutes), borderline (within 3-5 minutes), fair (within 1-3 minutes) and poor (<1 minute) values of corneal adhesiveness were found, respectively, in 0%, 7.1%, 64.3% and 28.6% of MGD, in 0%, 7.4%, 63% and 29.6% of ADDE, and in 31.3%, 65.6%, 3.1% and 0% of healthy patients. The differences in time of corneal adhesiveness between MGD and healthy patients, as well as between ADDE and healthy patients, were found to be statistically significant (p<0.001; p<0.001; respectively). Conversely, no statistical significant differences between MGD and ADDE were found (p = 0.952). Data analysis revealed a statistically significant correlation between corneal adhesiveness and clinical tests of dry eye, as well as an excellent degree of inter-rater reliability and reproducibility for OCT measurements (p<0.001). ADDE and MGD share similar abnormalities on OCT imaging. Decreased adhesive properties of the anterior cornea were identified as a common feature of MGD and ADDE. This simple OCT approach may provide new clues into the mechanism and evaluation of dry eye syndrome.

Explaining the variability in recommended intakes of folate, vitamin B12, iron and zinc for adults and elderly people.

PubMed

Doets, Esmée L; Cavelaars, Adrienne E J M; Dhonukshe-Rutten, Rosalie A M; van 't Veer, Pieter; de Groot, Lisette C P G M

2012-05-01

To signal key issues for harmonising approaches for establishing micronutrient recommendations by explaining observed variation in recommended intakes of folate, vitamin B12, Fe and Zn for adults and elderly people. We explored differences in recommended intakes of folate, vitamin B12, Fe and Zn for adults between nine reports on micronutrient recommendations. Approaches used for setting recommendations were compared as well as eminence-based decisions regarding the selection of health indicators indicating adequacy of intakes and the consulted evidence base. In nearly all reports, recommendations were based on the average nutrient requirement. Variation in recommended folate intakes (200-400 μg/d) was related to differences in the consulted evidence base, whereas variation in vitamin B12 recommendations (1.4-3.0 μg/d) was due to the selection of different CV (10-20 %) and health indicators (maintenance of haematological status or basal losses). Variation in recommended Fe intakes (men 8-10 mg/d, premenopausal women 14.8-19.6 mg/d, postmenopausal women 7.5-10.0 mg/d) was explained by different assumed reference weights and bioavailability factors (10-18 %). Variation in Zn recommendations (men 7-14 mg/d, women 4.9-9.0 mg/d) was also explained by different bioavailability factors (24-48 %) as well as differences in the consulted evidence base. For the harmonisation of approaches for setting recommended intakes of folate, vitamin B12, Fe and Zn across European countries, standardised methods are needed to (i) select health indicators and define adequate biomarker concentrations, (ii) make assumptions about inter-individual variation in requirements, (iii) derive bioavailability factors and (iv) collate, select, interpret and integrate evidence on requirements.

Dosimetric characterization and organ dose assessment in digital breast tomosynthesis: Measurements and Monte Carlo simulations using voxel phantoms

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

Baptista, Mariana, E-mail: marianabaptista@ctn.ist.utl.pt; Di Maria, Salvatore; Barros, Sílvia

2015-07-15

Purpose: Due to its capability to more accurately detect deep lesions inside the breast by removing the effect of overlying anatomy, digital breast tomosynthesis (DBT) has the potential to replace the standard mammography technique in clinical screening exams. However, the European Guidelines for DBT dosimetry are still a work in progress and there are little data available on organ doses other than to the breast. It is, therefore, of great importance to assess the dosimetric performance of DBT with respect to the one obtained with standard digital mammography (DM) systems. The aim of this work is twofold: (i) to studymore » the dosimetric properties of a combined DBT/DM system (MAMMOMAT Inspiration Siemens{sup ®}) for a tungsten/rhodium (W/Rh) anode/filter combination and (ii) to evaluate organs doses during a DBT examination. Methods: For the first task, measurements were performed in manual and automatic exposure control (AEC) modes, using two homogeneous breast phantoms: a PMMA slab phantom and a 4 cm thick breast-shaped rigid phantom, with 50% of glandular tissue in its composition. Monte Carlo (MC) simulations were performed using Monte Carlo N-Particle eXtended v.2.7.0. A MC model was implemented to mimic DM and DBT acquisitions for a wide range of x-ray spectra (24 –34 kV). This was used to calculate mean glandular dose (MGD) and to compute series of backscatter factors (BSFs) that could be inserted into the DBT dosimetric formalism proposed by Dance et al. Regarding the second aim of the study, the implemented MC model of the clinical equipment, together with a female voxel phantom (“Laura”), was used to calculate organ doses considering a typical DBT acquisition. Results were compared with a standard two-view mammography craniocaudal (CC) acquisition. Results: Considering the AEC mode, the acquisition of a single CC view results in a MGD ranging from 0.53 ± 0.07 mGy to 2.41 ± 0.31 mGy in DM mode and from 0.77 ± 0.11 mGy to 2.28 ± 0.32 mGy in DBT mode. Regarding the BSF, the results achieved may lead to a MGD correction of about 6%, contributing to the improvement of the current guidelines used in these applications. Finally, considering the MC results obtained for the organ dose study, the radiation doses found for the tissues of the body other than the breast were in the range of tens of μSv, and are in part comparable to the ones obtained in standard DM. Nevertheless, in a single DBT examination, some organs (such as lung and thyroid) receive higher doses (of about 9% and 21%, respectively) with respect to the CC DM acquisition. Conclusions: Taking into account an average breast with a thickness of 4.5 cm, the MGDs for DM and DBT acquisitions were below the achievable value (2.0 mGy) defined by the European protocol. Additionally, in the case of a fusion imaging study (DM + DBT), the MGD for a 4.5 cm thick breast is of the order of 1.88 ± 0.36 mGy. Finally, organ dose evaluations underline the need to improve awareness concerning dose estimation of DBT exams for some organs, especially when radiation risk is assessed by using the effective dose.« less

The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

PubMed

Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

2015-01-01

The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Considerations Regarding Neuropsychiatric Nutritional Requirements for Omega-3 Long Chain Fatty Acids Intakes

PubMed Central

Hibbeln, Joseph R.; Davis, John M.

2009-01-01

Background Adverse neurodevelopmental and neuropsychiatric outcomes have been established as signs of nutrient deficiencies and may be applicable to insufficient dietary intakes of omega-3 long chain fatty acids (n-3 LCFAs). Objective Consider if statistical definitions for Daily Reference Intakes can be applied to n-3 LCFAs intakes during pregnancy for maternal and neurodevelopmental deficiencies. Design Data was prospectively collected from women during pregnancy and children up to age 8 y participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Statistical analyses took social and lifestyle factors into account. Results During pregnancy, n-3 LCFA intakes from seafood that putatively meet statistical definitions of an Estimated Average Requirement ranged from 0.05 –0.06 en % (111–139 mg/d/2,000 Cal) for suboptimal fine motor control at 42 m and 0.065-0.08 en% (114–181 mg/d/2,000 Cal) for suboptimal verbal IQ at age 8 y and 0.18–0.22 en% (389–486 mg/d/2,000 Cal) for maternal depression at 32 w. Intakes of n-3 ranging from 0.2–0.41 en% (445 – 917 mg/d/2,000 Cal) prevented both increased risk of maternal depression and adverse neurodevelopmental outcomes for children among 97.5% of the population. No upper limit for safety was found. Conclusion During pregnancy, a n-3 LCFA intake of 0.40 en% (900 mg/d/2,000 Cal) from seafood is likely to meet the nutritional requirements for 97.5 % of the mothers and children of this population. These considerations do not constitute DRI’s for docosahexaenoic acid and n-3 LCFAs, but may contribute to their formulation. PMID:19619995

Dietary sodium content, mortality, and risk for cardiovascular events in older adults: the Health, Aging, and Body Composition (Health ABC) Study.

PubMed

Kalogeropoulos, Andreas P; Georgiopoulou, Vasiliki V; Murphy, Rachel A; Newman, Anne B; Bauer, Douglas C; Harris, Tamara B; Yang, Zhou; Applegate, William B; Kritchevsky, Stephen B

2015-03-01

Additional information is needed about the role of dietary sodium on health outcomes in older adults. To examine the association between dietary sodium intake and mortality, incident cardiovascular disease (CVD), and incident heart failure (HF) in older adults. We analyzed 10-year follow-up data from 2642 older adults (age range, 71-80 years) participating in a community-based, prospective cohort study (inception between April 1, 1997, and July 31, 1998). Dietary sodium intake at baseline was assessed by a food frequency questionnaire. We examined sodium intake as a continuous variable and as a categorical variable at the following levels: less than 1500 mg/d (291 participants [11.0%]), 1500 to 2300 mg/d (779 participants [29.5%]), and greater than 2300 mg/d (1572 participants [59.5%]). Adjudicated death, incident CVD, and incident HF during 10 follow-up years. Analysis of incident CVD was restricted to 1981 participants without prevalent CVD at baseline. The mean (SD) age of participants was 73.6 (2.9) years, 51.2% were female, 61.7% were of white race, and 38.3% were black. After 10 years, 881 participants had died, 572 had developed CVD, and 398 had developed HF. In adjusted Cox proportional hazards regression models, sodium intake was not associated with mortality (hazard ratio [HR] per 1 g, 1.03; 95% CI, 0.98-1.09; P = .27). Ten-year mortality was nonsignificantly lower in the group receiving 1500 to 2300 mg/d (30.7%) than in the group receiving less than 1500 mg/d (33.8%) and the group receiving greater than 2300 mg/d (35.2%) (P = .07). Sodium intake of greater than 2300 mg/d was associated with nonsignificantly higher mortality in adjusted models (HR vs 1500-2300 mg/d, 1.15; 95% CI, 0.99-1.35; P = .07). Indexing sodium intake for caloric intake and body mass index did not materially affect the results. Adjusted HRs for mortality were 1.20 (95% CI, 0.93-1.54; P = .16) per milligram per kilocalorie and 1.11 (95% CI, 0.96-1.28; P = .17) per 100 mg/kg/m2 of daily sodium intake. In adjusted models accounting for the competing risk for death, sodium intake was not associated with risk for CVD (subHR per 1 g, 1.03; 95% CI, 0.95-1.11; P = .47) or HF (subHR per 1 g, 1.00; 95% CI, 0.92-1.08; P = .92). No consistent interactions with sex, race, or hypertensive status were observed for any outcome. In older adults, food frequency questionnaire-assessed sodium intake was not associated with 10-year mortality, incident CVD, or incident HF, and consuming greater than 2300 mg/d of sodium was associated with nonsignificantly higher mortality in adjusted models.

Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder

PubMed Central

2013-01-01

Background Despite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD. Methods In a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an “optimal” LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission. Results Four hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days (P<.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits. Conclusion In the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months. Trial registration Clinical Trial Numbers: NCT00334880 and NCT01070394 Clinical Trial Registry: clinicaltrials.gov URLs http://www.clinicaltrials.gov/show/NCT00334880 http://www.clinicaltrials.gov/ct2/show/NCT01070394?term=NCT01070394&rank=1 PMID:23356790

Challenges in Diagnosis and Treatment of Wernicke Encephalopathy: Report of 2 Cases.

PubMed

Infante, Maria Teresa; Fancellu, Roberto; Murialdo, Alessandra; Barletta, Laura; Castellan, Lucio; Serrati, Carlo

2016-04-01

Wernicke encephalopathy (WE) is a medical emergency caused by thiamine deficiency, characterized by cerebellar ataxia, ophthalmoplegia, and cognitive disturbances that may progress to Korsakoff amnesia. We describe 2 patients with WE who needed high-dose and long-term treatment with thiamine to obtain neurological improvement and recovery. The first patient was a woman diagnosed with non-Hodgkin lymphoma. After a gastrointestinal infection, she developed depression, memory loss, disorientation, behavioral changes, and ataxic paraplegia. Brain magnetic resonance imaging (MRI) showed bilateral alterations in thalamic, frontal, and periaqueductal regions, suggestive of WE. The second patient was a man who lost 10 kg after surgical gastrectomy; he developed diplopia, ophthalmoplegia, cerebellar ataxia, lower limb paresthesias, and amnesia. A brain MRI demonstrated contrast enhancement of mammillary bodies, compatible with WE. The patients were treated with intramuscular (IM) thiamine (1200 mg/d for 2 months and 900 mg/d for a month, respectively) with gradual cognitive and behavioral improvement and brain MRI normalization, while ataxia and oculomotion improved in following months. In both patients, thiamine was gradually reduced to IM 200 mg/d and continued for a year, without clinical relapses. There is no consensus about dosage, frequency, route, and duration of thiamine administration in WE treatment. Based on our cases, we recommend treating patients with WE with higher doses of IM thiamine for a longer time than suggested (900-1200 mg/d for 1-2 months, in our cases) and to gradually reduce dosage after clinical and radiological improvement, maintaining IM 200 mg/d dosage for at least 1 year. © 2016 American Society for Parenteral and Enteral Nutrition.

Multicomponent Synthesis of a N-Protected Alpha-Amino Ester: Ethyl 2-((4-Methoxyphenyl)Amino)-3-Phenylpropanoate

ERIC Educational Resources Information Center

Le Gall, Erwan; Pignon, Antoine

2012-01-01

This laboratory experiment describes the preparation of a N-protected phenylalanine ethyl ester by a zinc-mediated Mannich-like multicomponent reaction between benzyl bromide, "p"-anisidine, and ethyl glyoxylate. The one-step reaction involves the in situ metallation of benzyl bromide into a benzylzinc reagent and its addition onto imine (Barbier…

Quality assurance in mammography: College of Radiology Survey in Malaysia.

PubMed

Ho, E L M; Ng, K H; Wong, J H D; Wang, H B

2006-06-01

Malaysia's mammography QA practice was surveyed based on the Malaysian Ministry of Health and the American College of Radiology (ACR) requirements. Data on mammography unit, processor, image receptor, exposure factors, mean glandular dose (MGD), sensitometry, image quality and viewbox luminance were obtained. Mean developer temperature and cycle time were 34.1 +/- 1.8degreesC and 107.7 +/- 33.2 seconds. Mean base+fog level, speed index and contrast index were 0.20+/-0.01, 1.20+/-0.01 and 1.33+/-0.26 respectively. Eighty-six percent of the fifty centres passed the image quality test while 12.5% complied with ACR recommended viewbox luminance. Average MGD was 1.0+/-0.4 mGy. Malaysia is on the right track for QA but with room for total quality improvement.

Polyelectrolyte Multicomponent Colloidosomes Loaded with Nisin Z for Enhanced Antimicrobial Activity against Foodborne Resistant Pathogens

PubMed Central

Niaz, Taskeen; Shabbir, Saima; Noor, Tayyaba; Abbasi, Rashda; Raza, Zulfiqar A.; Imran, Muhammad

2018-01-01

Food grade micro- or nano-carrier systems (NCS) are being developed to improve the controlled release of antimicrobial agents. To augment the stability of liposomal NCS and to overcome the limitations associated with the use of free bacteriocin (nisin) in the food system, multi-component colloidosomes (MCCS) were developed by electrostatic interactions between anionic alginate and cationic chitosan (multilayer) around phospholipids based liposomes (core). Zeta-sizer results revealed the average diameter of 145 ± 2 nm, 596 ± 3 nm, and 643 ± 5 nm for nano-liposome (NL), chitosomes (chitosan coated NL) and MCCS, respectively. Zeta potential values of NCS varied from −4.37 ± 0.16 mV to 33.3 ± 6 mV, thus both chitosomes (CS) and MCCS were positively charged. Microstructure analysis by scanning electron microscope (SEM) revealed relatively higher size of MCCS with smooth and round morphology. TGA and DSC based experiments revealed that MCCS were thermally more stable than uncoated liposomes. Encapsulation efficiency of nisin in MCCS was observed to be 82.9 ± 4.1%, which was significantly higher than NL (56.5 ± 2.5%). FTIR analyses confirmed the cross-linking between sodium alginate and chitosan layer. Both qualitative (growth kinetics) and quantitative (colony forming unit) antimicrobial assays revealed that nisin loaded MCCS have superior potential to control resistant foodborne pathogens including Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis, (5.8, 5.4, and 6.1 Log CFUmL−1 reduction, respectively) as compared to free nisin, loaded NL or CS. Controlled release kinetics data fitted with Korsmeyer–Peppas model suggested that nisin release from MCCS followed Fickian diffusion. Cytotoxic studies on human blood cells and HepG2 cell lines revealed hemocompatibility and non-toxicity of MCCS. Thus, due to enhanced controlled release, stability and biocompatibility; these multi-component colloidosomes can be useful for incorporating antimicrobial agents into functional foods, beverages and pharmaceutical products to combat pathogenic and spoilage bacteria. PMID:29379490

Fortification of Yogurts with Vitamin D and Calcium Enhances the Inhibition of Serum Parathyroid Hormone and Bone Resorption Markers: A Double Blind Randomized Controlled Trial in Women over 60 Living in a Community Dwelling Home.

PubMed

Bonjour, J-P; Benoit, V; Atkin, S; Walrand, S

2015-05-01

To evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum parathyroid hormone (PTH) and bone resorption markers (BRM) as compared to iso-caloric and iso-protein dairy products in aged white women at risk of fragility fractures. A randomized double-blind controlled trial. A community dwelling home. Forty-eight women over 60 years (mean age 73.4). Consumption during 84 days of two 125 g servings of either vitamin D and calcium-fortified yogurts (FY) at supplemental levels of 10 µg vitamin D3/d and 520 mg/d of calcium (total=800 mg/d), or non fortified control yogurts (CY) providing 280 mg/d of calcium. Serum changes from baseline (D0) to D28, D56 and D84 in 25OHD, PTH and in two BRM: Tartrate-resistant-acid-phosphatase-isoform-5b (TRAP5b) and carboxy-terminal-cross-linked-telopeptide of type-I-collagen (CTX). The 10 years risk of major and hip fractures were 13.1 and 5.0%, and 12.9 and 4.2 %, in FY and CY groups, respectively. From D0 to D84, serum 25OHD increased (mean±SE) from 34.3±2.4 to 56.3±2.4 nmol/L in FY (n=24) and from 35.0±2.5 to 41.3±3.0 nmol/L in CY (n=24), (P=0.00001). The corresponding changes in PTH were from 64.1±5.1 to 47.4±3.8 ng/L in FY and from 63.5±4.6 to 60.7±4.2 ng/L in CY (P=0.0011). After D84, TRAP5b was reduced significantly (P=0.0228) and CTX fell though not significantly (P=0.0773) in FY compared to CY. This trial in aged white women living in a community dwelling home at risk for osteoporotic fractures confirms that fortification of dairy products with vitamin D3 and calcium should provide a greater prevention of secondary hyperparathyroidism and accelerated bone resorption as compared to non-fortified equivalent foods.

Automated Measurement of Tear Film Dynamics and Lipid Layer Thickness for Assessment of Non-Sjögren Dry Eye Syndrome With Meibomian Gland Dysfunction.

PubMed

Ji, Yong Woo; Lee, Jeihoon; Lee, Hun; Seo, Kyoung Yul; Kim, Eung Kweon; Kim, Tae-Im

2017-02-01

To investigate automated values from an advanced corneal topographer with a built-in real keratometer, color camera, and ocular surface interferometer for the evaluation of non-Sjögren dry eye syndrome (NSDES) with meibomian gland dysfunction (MGD). Sixty-four patients (64 eyes) diagnosed with NSDES with MGD were enrolled. All eyes were evaluated using the Ocular Surface Disease Index (OSDI), fluorescence staining score, tear film breakup time (TBUT), Schirmer test, and MGD grade. Noninvasive Keratograph average tear film breakup time (NIKBUTav), tear meniscus height (TMHk), meibomian gland (MG) dropout grade, and lipid layer thickness (LLT) using interferometry were measured. Among automated indexes, NIKBUTav (mean 7.68 ± 4.07 s) and the MG dropout grade (mean 1.0 ± 0.5) significantly correlated with the OSDI (mean 40.6 ± 22.9) (r = -0.337, P = 0.006; and r = 0.201, P = 0.023, respectively), as did all conventional indicators, except the Schirmer score (mean 9.1 ± 5.9 mm). TMHk (mean 0.21 ± 0.18 mm) had significant correlation with the Schirmer score, the staining score (mean 1.2 ± 0.7), TBUT (mean 3.8 ± 1.8 s), and NIKBUTav (r = 0.298, P = 0.007; r = -0.268, P = 0.016; r = 0.459, P < 0.001; and r = 0.439, P < 0.001, respectively), but not any MGD indicator, even the MG dropout grade. NIKBUTav showed significant correlations with all clinical parameters and other automated values, except the Schirmer score and LLT (mean 83.94 ± 20.82 nm) (all (Equation is included in full-text article.)≥ 0.25 and P < 0.01). The MG dropout grade highly correlated with all indexes except TMHk (all (Equation is included in full-text article.)≥ 0.25 and P < 0.05). LLT was significantly associated with TBUT, MGD grade (mean 2.0 ± 0.7), and MG dropout grade (r = 0.219, P = 0.047; r = -0.221, P = 0.039; and r = 0.433, P < 0.001, respectively), although it was not related to patient symptoms. Automated noninvasive measurements using an advanced corneal topographer and LLT measured with an ocular surface interferometer can be alternatives to conventional methods to evaluate tear conditions on the ocular surface; the former device can provide information about conformational MG changes in NSDES with MGD.

Synthesis of water-dispersed magnetic nanoparticles (H2O-DMNPs) of β-cyclodextrin modified Fe3O4 and its catalytic application in Kabachnik-Fields multicomponent reaction

NASA Astrophysics Data System (ADS)

Rostamnia, Sadegh; Doustkhah, Esmail

2015-07-01

Water-dispersed magnetic nanoparticles (H2O-DMNPs) of β-cyclodextrin modified Fe3O4 were successfully synthesized. β-Cyclodextrin acts as stabilizer and structure directing agent of Fe3O4. Subsequently, the dispersion of Fe3O4@β-CD was applied for the Kabachnik-Fields multicomponent reaction through three-component synthesis of an amine, aldehyde, and dimethylphosphonate. β-CD had also a drastic effect in accelerating the catalysis of phosphonate synthesis. By this protocol, phosphonate derivatives were synthesized in high yields and the catalyst was recycled for 10 successful runs.

Estimated daily intake of Fe, Cu, Ca and Zn through common cereals in Tehran, Iran.

PubMed

Kashian, S; Fathivand, A A

2015-06-01

This paper presents the findings of study undertaken to estimate the dietary intake of iron (Fe), copper (Cu), calcium (Ca) and zinc (Zn) through common cereals in Tehran, Iran. 100 samples of rice, wheat and barley were collected from various brands between August and October 2013. The samples were analyzed performing instrumental neutron activation analysis (INAA). The dietary intake for adults was estimated by a total cereal study. Calculations were carried out on the basis of the reported adults' average food consumption rate data. The total daily intake estimated in mgd(-1) for Tehran population were 3.6 (Fe), 10.2 (Zn), 0.3 (Cu) and 234.5 (Ca). Wheat showed the highest contribution to Zn, Cu and Ca intakes. Furthermore, intakes were compared with recommended dietary allowance (RDA). Zn total intake (10.2mgd(-1)) was comparable with RDA values for males (11mgd(-1)) and was higher than recommended value for females (8mgd(-1)). The intakes of other studied elements were below the respective RDAs. Copyright © 2014 Elsevier Ltd. All rights reserved.

The millimeter-wave spectrum of the MgH and MgD radicals

NASA Technical Reports Server (NTRS)

Ziurys, L. M.; Barclay, W. L., Jr.; Anderson, M. A.

1993-01-01

The pure rotational spectrum of MgH radical (X 2 Sigma (+)) in its ground state v = 0 and v = 1 vibrational modes has been observed in the laboratory using millimeter/submillimeter direct absorption spectroscopy. The rotational spectra of two isotopically substituted species, MgD and (Mg-26)H, have been detected as well. All six hyperfine components of the N = 0 -1 transition of MgH in its v = 0 and v = 1 states have been directly measured to an accuracy of +/-50 kHz, and the five components have been observed for (Mg-26)H. The N = 0 +/-1 and N = 1 -2 transitions of MgD have also been detected. Rotational, fine structure, and hyperfine constants were determined for all species from a nonlinear least-squared fit to the data using a 2 Sigma Hamiltonian.

The COMT Val158Met Polymorphism Is Associated With Response to Add-on Dextromethorphan Treatment in Bipolar Disorder.

PubMed

Lee, Sheng-Yu; Chen, Shiou-Lan; Wang, Tzu-Yun; Chang, Yun-Hsuan; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Chen, Kao Ching; Yang, Yen Kuang; Lu, Ru-Band

2017-02-01

We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD. In the current study, we investigated whether the COMT Val158Met polymorphism predicts treatment response to VPA + add-on DM and to VPA + placebo. Patients with BD (n = 309) undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (30 mg/d) (n = 102), DM (60 mg/d) (n = 101), or placebo (n = 106) for 12 weeks. The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to evaluate clinical response during weeks 0, 1, 2, 4, 8, and 12. The genotypes of the COMT Val158Met polymorphism were determined using polymerase chain reaction plus restriction fragment length polymorphism analysis. To adjust for within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used. When stratified by the COMT Val158Met genotypes, significantly greater decreases in Hamilton Depression Rating Scale scores were found in the VPA + DM (30 mg/d) group in patients with the Val/Met genotype (P = 0.008). We conclude that the COMT Val158Met polymorphism may influence responses to DM (30 mg/d) by decreasing depressive symptoms in BD patients.

A prospective study of caffeine intake and risk of incident tinnitus.

PubMed

Glicksman, Jordan T; Curhan, Sharon G; Curhan, Gary C

2014-08-01

Caffeine is a commonly consumed substance that has been thought to play a role in the development of tinnitus, but prospective data are lacking. We prospectively evaluated the association between caffeine intake and self-reported tinnitus in a female cohort. Participants were 65,085 women in the Nurses' Health Study II, aged 30 to 44 years and without tinnitus at baseline in 1991, who completed questionnaires about lifestyle and medical history every 2 years and food frequency questionnaires every 4 years. Information on self-reported tinnitus and date of onset was obtained from the 2009 questionnaire, with cases defined as those reporting experiencing symptoms "a few days/week" or "daily." Multivariable adjusted hazard ratios were calculated using Cox proportional hazards regression models. At baseline, the mean age of the cohort was 36.3 years and the mean caffeine intake was 242.3 mg/d. After 18 years of follow-up, 5289 incident cases of tinnitus were reported. There was a significant inverse association between caffeine intake and the incidence of tinnitus. Compared with women with caffeine intake less than 150 mg/d (150 mg corresponds to ∼ one 8-ounce cup of coffee), the multivariable adjusted hazard ratios were 0.85 (95% confidence interval, 0.76-0.95) for those who consumed 450 to 599 mg/d and 0.79 (0.68-0.91) for those who consumed 600 mg/d or more. In this prospective study, higher caffeine intake was associated with a lower risk of incident tinnitus in women. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of calcium and vitamin D supplementation on obesity in postmenopausal women: secondary analysis for a large-scale, placebo controlled, double-blind, 4-year longitudinal clinical trial.

PubMed

Zhou, Jiapeng; Zhao, Lan-Juan; Watson, Patrice; Zhang, Qin; Lappe, Joan M

2010-07-23

It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women. The purpose of the study is to detect the effect of calcium supplementation on indices of obesity and body composition. This is a secondary analysis of data from a population-based, double-blind, placebo-controlled, randomized trial designed to determine the effects of calcium and vitamin D on osteoporotic fractures. The cohort included 1179 postmenopausal women who were randomly assigned into one of three groups: 1) supplemental calcium (1400 mg/d or 1500 mg/d) plus vitamin D placebo (Ca-only group); 2) supplemental calcium (1400 mg/d or 1500 mg/d) plus supplemental vitamin D3 (1100 IU/d) (Ca + D group); or, 3) two placebos (placebo group). After applying the exclusion criteria for this analysis, 870 subjects were included in this study. The primary outcomes for the present study were changes in body mass index, trunk fat, trunk lean, and percentage of trunk fat after calcium supplementation. Changes in trunk fat, trunk lean, and percentage of trunk fat were significantly different between the calcium intervention groups (Ca-only group or Ca + D group) and the placebo group during the trial (P < 0.05). The calcium intervention groups gained less trunk fat and maintained more trunk lean when compared to the placebo group. No significant difference was observed for body mass index between groups. Calcium supplementation over four years has a beneficial effect on body composition in postmenopausal women.

76 FR 72023 - Public Hearing and Commission Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-21

... County, Pa. Application for groundwater withdrawal of up to 0.715 mgd (30-day average) from Well PW-11. 2...) action on certain water resources projects; and (3) a request for partial fee waiver from SWEPI LP... water; (3) presentation of the Commission's William Jeanes Award; (4) a report on hydrologic conditions...

75 FR 38590 - Notice of Actions Taken at June 11, 2010, Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

... County, PA. Surface water withdrawal of up to 0.216 mgd. 4. Project Sponsor and Facility: East Resources... regular business meeting. At the public hearing, the Commission: (1) Approved and tabled certain water resources projects, including approval of two projects involving diversions into the basin; and (2) approved...

An adaptive supramolecular hydrogel comprising self-sorting double nanofibre networks

NASA Astrophysics Data System (ADS)

Shigemitsu, Hajime; Fujisaku, Takahiro; Tanaka, Wataru; Kubota, Ryou; Minami, Saori; Urayama, Kenji; Hamachi, Itaru

2018-02-01

Novel soft materials should comprise multiple supramolecular nanostructures whose responses (for example, assembly and disassembly) to external stimuli can be controlled independently. Such multicomponent systems are present in living cells and control the formation and break-up of a variety of supramolecular assemblies made of proteins, lipids, DNA and RNA in response to external stimuli; however, artificial counterparts are challenging to make. Here, we present a hybrid hydrogel consisting of a self-sorting double network of nanofibres in which each network responds to an applied external stimulus independent of the other. The hydrogel can be made to change its mechanical properties and rates of release of encapsulated proteins by adding Na2S2O4 or bacterial alkaline phosphatase. Notably, the properties of the gel depend on the order in which the external stimuli are applied. Multicomponent hydrogels comprising orthogonal stimulus-responsive supramolecular assemblies would be suitable for designing novel adaptive materials.

Thermal equation of state of (Mg 0.9Fe 0.1) 2SiO 4 olivine

NASA Astrophysics Data System (ADS)

Liu, Wei; Li, Baosheng

2006-08-01

In situ synchrotron X-ray diffraction measurements have been carried out on San Carlos olivine (Mg 0.9Fe 0.1) 2SiO 4 up to 8 GPa and 1073 K. Data analysis using the high-temperature Birch-Murnaghan (HTBM) equation of state (EoS) yields the temperature derivative of the bulk modulus (∂ KT/∂ T) P = -0.019 ± 0.002 GPa K -1. The thermal pressure (TH) approach gives αKT = 4.08 ± 0.10 × 10 -3 GPa K -1, from which (∂ KT/∂ T) P = -0.019 ± 0.001 GPa K -1 is derived. Fitting the present data to the Mie-Grüneisen-Debye (MGD) formalism, the Grüneisen parameter at ambient conditions γ0 is constrained to be 1.14 ± 0.02 with fixed volume dependence q = 1. Combining the present data with previous results on iron-bearing olivine and fitting to MGD EoS, we obtain γ0 = 1.11 ± 0.01 and q = 0.54 ± 0.36. In this study the thermoelastic parameters obtained from various approaches are in good agreement with one another and previous results.

Dietary calcium intake and risk of cardiovascular disease, stroke, and fracture in a population with low calcium intake.

PubMed

Kong, Sung Hye; Kim, Jung Hee; Hong, A Ram; Cho, Nam H; Shin, Chan Soo

2017-07-01

Background: The role of dietary calcium intake in cardiovascular disease (CVD), stroke, and fracture is controversial. Most previous reports have evaluated populations with high calcium intake. Objective: We aimed to evaluate whether high dietary calcium intake was associated with the risk of CVD, stroke, and fracture in a population with low calcium intake. Design: In a prospective cohort study beginning in 2001 in Ansung-Ansan, Korea, 2158 men and 2153 women aged >50 y were evaluated for all-cause mortality, CVD, stroke, and fractures over a median 9-y follow-up. Results: During follow-up, 242 and 100 deaths, 149 and 150 CVD events, 58 and 82 stroke events, and 211 and 292 incident fractures occurred in men and women, respectively. The first quartiles of energy-adjusted dietary calcium intake were 249 mg/d (IQR: 169 mg/d) in men and 209 mg/d (IQR: 161 mg/d) in women. Both men and women with higher dietary calcium intake tended to have higher fat, protein, sodium, phosphorus, fruit, and vegetable intakes. In men, outcomes were not significantly associated with dietary calcium intake with or without adjustments, and CVD risk tended to increase with increasing energy-adjusted dietary calcium intake, but this was not statistically significant ( P = 0.078 and P = 0.093 with and without adjustment, respectively). In women, CVD risk and dietary calcium intake showed a U-shaped association; the HRs (95% CIs) without adjustment relative to the first quartile were 0.71 (0.47, 1.07), 0.57 (0.36, 0.88), and 0.52 (0.33, 0.83) for quartiles 2, 3, and 4, respectively, and the values after adjustment were 0.70 (0.45, 1.07), 0.51 (0.31, 0.81), and 0.49 (0.29, 0.83) for quartiles 2, 3, and 4, respectively. Conclusion: In Korean women, increased dietary calcium intake was associated with a decreased CVD risk, but it did not influence the risk of stroke or fracture. © 2017 American Society for Nutrition.

High dietary phosphorus intake is associated with all-cause mortality: results from NHANES III.

PubMed

Chang, Alex R; Lazo, Mariana; Appel, Lawrence J; Gutiérrez, Orlando M; Grams, Morgan E

2014-02-01

Elevated serum phosphorus is associated with all-cause mortality, but little is known about risk associated with dietary phosphorus intake. We investigated the association between phosphorus intake and mortality in a prospective cohort of healthy US adults (NHANES III; 1998-1994). Study participants were 9686 nonpregnant adults aged 20-80 y without diabetes, cancer, or kidney or cardiovascular disease. Exposure to dietary phosphorus, which was assessed by using a 24-h dietary recall, was expressed as the absolute intake and phosphorus density (phosphorus intake divided by energy intake). All-cause and cardiovascular mortality was assessed through 31 December 2006. Median phosphorus intake was 1166 mg/d (IQR: 823-1610 mg/d); median phosphorus density was 0.58 mg/kcal (0.48-0.70 mg/kcal). Individuals who consumed more phosphorus-dense diets were older, were less often African American, and led healthier lifestyles (smoking, physical activity, and Healthy Eating Index). In analyses adjusted for demographics, cardiovascular risk factors, kidney function, and energy intake, higher phosphorus intake was associated with higher all-cause mortality in individuals who consumed >1400 mg/d [adjusted HR (95% CI): 2.23 (1.09, 4.5) per 1-unit increase in ln(phosphorus intake); P = 0.03]. At <1400 mg/d, there was no association. A similar association was seen between higher phosphorus density and all-cause mortality at a phosphorus density amount >0.35 mg/kcal [adjusted HR (95% CI): 2.27 (1.19, 4.33) per 0.1-mg/kcal increase in phosphorus density; P = 0.01]. At <0.35 mg/kcal (approximately the fifth percentile), lower phosphorus density was associated with increased mortality risk. Phosphorus density was associated with cardiovascular mortality [adjusted HR (95% CI): 3.39 (1.43, 8.02) per 0.1 mg/kcal at >0.35 mg/kcal; P = 0.01], whereas no association was shown in analyses with phosphorus intake. Results were similar by subgroups of diet quality and in analyses adjusted for sodium and saturated fat intakes. High phosphorus intake is associated with increased mortality in a healthy US population. Because of current patterns in phosphorus consumption in US adults, these findings may have important public health implications.

Grand Forks - East Grand Forks Urban Water Resources Study. Wastewater Management Appendix.

DTIC Science & Technology

1981-07-01

SLUIGES FROM AEROBIC DIGESTION . 2. LOADING RATE OF 20 LB/FT 2/YR APPLICABLE TO BIOLOGICAL SLUDGES FROM ANAEROBIC DIGESTION. 3. EXPECTED PERFORMANCE...plant size as follows: Sludge Handling Facilities Flow Range Biological Sludge Lime Sludge Flow <_ 3 MCD Flotation thickening, Gravity thicken & aerobic ... digestion , & drying beds. drying beds. 3 MGD < Mot; < 10 MGD Flotation thickening, Gravity thicken & anaerobic digestion, & vacuum filter. vacuum

Computer Program for the Calculation of Multicomponent Convective Diffusion Deposition Rates from Chemically Frozen Boundary Layer Theory

NASA Technical Reports Server (NTRS)

Gokoglu, S. A.; Chen, B. K.; Rosner, D. E.

1984-01-01

The computer program based on multicomponent chemically frozen boundary layer (CFBL) theory for calculating vapor and/or small particle deposition rates is documented. A specific application to perimter-averaged Na2SO4 deposition rate calculations on a cylindrical collector is demonstrated. The manual includes a typical program input and output for users.

A randomized, controlled comparison of different intensive lipid-lowering therapies in Chinese patients with non-ST-elevation acute coronary syndrome (NSTE-ACS): Ezetimibe and rosuvastatin versus high-dose rosuvastatin.

PubMed

Ran, Dan; Nie, Hui-Juan; Gao, Yu-Lin; Deng, Song-Bai; Du, Jian-Lin; Liu, Ya-Jie; Jing, Xiao-Dong; She, Qiang

2017-05-15

Statin combined with ezetimibe demonstrates significant benefit in lowering low density lipid cholesterol (LDL-C) and cardiovascular events abroad, but whether intermediate intensity statins combined with ezetimibe is superior to high-intensity statin monotherapy in Chinese people is unknown. A total of 125 patients were randomly assigned to a intermediate intensity rosuvastatin group (rosuvastatin 10mg/d, n=42), high-dose rosuvastatin group (rosuvastatin 20mg/d, n=41) or combination therapy group (ezetimibe 10mg/d and rosuvastatin 10mg/d, n=42) with a 12-week follow-up. The primary end point was the proportion of patients who achieved the 2011 ESC/EAS LDL-C goal <70mg/dL (1.8mmol/L) at week 12. Secondary end points included changes from baseline in lipids, the occurrence of all cardiovascular events, high-sensitivity C-reactive protein and safety markers. The combination therapy group in the primary end point was significantly higher than rosuvastatin (20mg) and rosuvastatin (10mg) at week 12 (81.0% vs 68.3% vs 33.3%, P<0.001). And the similar change was observed in reducing LDL-C levels at week 12 (67.28% vs 52.80% vs 43.89%, P<0.001). The incidence of drug-related adverse events was much higher in the rosuvastatin 20mg group than the rosuvastatin 10mg group and the combination therapy group (17.0% vs 2.4% vs 4.8%, P<0.05). The combination of rosuvastatin 10mg/ezetimibe 10mg was an effectively alternative therapy superior to rosuvastatin 20mg or 10mg with a greater effect on lowering LDL-C and a lower incidence of drug-related adverse events in Chinese patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Genes of the N-Methylglutamate Pathway Are Essential for Growth of Methylobacterium extorquens DM4 with Monomethylamine

PubMed Central

Gruffaz, Christelle; Muller, Emilie E. L.; Louhichi-Jelail, Yousra; Nelli, Yella R.; Guichard, Gilles

2014-01-01

Monomethylamine (MMA, CH3NH2) can be used as a carbon and nitrogen source by many methylotrophic bacteria. Methylobacterium extorquens DM4 lacks the MMA dehydrogenase encoded by mau genes, which in M. extorquens AM1 is essential for growth on MMA. Identification and characterization of minitransposon mutants with an MMA-dependent phenotype showed that strain DM4 grows with MMA as the sole source of carbon, energy, and nitrogen by the N-methylglutamate (NMG) pathway. Independent mutations were found in a chromosomal region containing the genes gmaS, mgsABC, and mgdABCD for the three enzymes of the pathway, γ-glutamylmethylamide (GMA) synthetase, NMG synthase, and NMG dehydrogenase, respectively. Reverse transcription-PCR confirmed the operonic structure of the two divergent gene clusters mgsABC-gmaS and mgdABCD and their induction during growth with MMA. The genes mgdABCD and mgsABC were found to be essential for utilization of MMA as a carbon and nitrogen source. The gene gmaS was essential for MMA utilization as a carbon source, but residual growth of mutant DM4gmaS growing with succinate and MMA as a nitrogen source was observed. Plasmid copies of gmaS and the gmaS homolog METDI4690, which encodes a protein 39% identical to GMA synthetase, fully restored the ability of mutants DM4gmaS and DM4gmaSΔmetdi4690 to use MMA as a carbon and nitrogen source. Similarly, chemically synthesized GMA, the product of GMA synthetase, could be used as a nitrogen source for growth in the wild-type strain, as well as in DM4gmaS and DM4gmaSΔmetdi4690 mutants. The NADH:ubiquinone oxidoreductase respiratory complex component NuoG was also found to be essential for growth with MMA as a carbon source. PMID:24682302

Decomposition of water-soluble mononitrosyl iron complexes with dithiocarbamates and of dinitrosyl iron complexes with thiol ligands in animal organisms.

PubMed

Serezhenkov, Vladimir A; Timoshin, Alexander A; Orlova, Tsvetina R; Mikoyan, Vasak D; Kubrina, Lioudmila N; Poltorakov, Alexander P; Ruuge, Enno K; Sanina, Natalia A; Vanin, Anatoly F

2008-05-01

EPR studies have shown that water-soluble mononitrosyl iron complexes with N-methyl-d-glucamine dithiocarbamate (MNIC-MGD) (3 micromol) injected to intact mice were decomposed virtually completely within 1h. The total content of MNIC-MGD in animal urine did not exceed 30 nmol/ml. In the liver, a small amount of MNIC-MGD were converted into dinitrosyl iron complexes (30 nmol/g of liver tissue). The same was observed in intact rabbits in which MNIC-MGD formation was induced by endogenous or exogenous NO binding to NO traps, viz., iron complexes with MGD. In mice, the content of MNIC-MGD in urine samples did not change after bacterial lipopolysaccharide-induced expression of iNOS. It was supposed that MNIC-MGD decomposition in intact animals was largely due to the release of NO from the complexes and its further transfer to other specific acceptors. In mice with iNOS expression, the main contribution to MNIC-MGD decomposition was made by superoxide ions whose destructive effect is mediated by an oxidative mechanism. This effect could fully compensate the augmented synthesis of MNIC-MGD involving endogenous NO whose production was supported by iNOS. Water-soluble dinitrosyl iron complexes (DNIC) with various thiol-containing ligands and thiosulfate injected to intact mice were also decomposed; however, in this case the effect was less pronounced than in the case of MNIC-MGD. It was concluded that DNIC decomposition was largely due to the oxidative effect of superoxide ions on these complexes.

Demographic, dietary, and urinary factors and 24-h urinary calcium excretion.

PubMed

Taylor, Eric N; Curhan, Gary C

2009-12-01

Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values < or =0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend < or =0.01). Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium.

Optimization of tungsten x-ray spectra for digital mammography: a comparison of model to experiment

NASA Astrophysics Data System (ADS)

Andre, Michael P.; Spivey, Brett A.

1997-05-01

Tungsten (W) target x-rays tubes are being studied for use in digital mammography to improve x-ray flux, reduce noise and increase tube heat capacity. A parametric model was developed for digital mammography to evaluate optimization of x-ray spectra for a particular sensor. The model computes spectra and mean glandular doses (MGD) for combinations of W target, beam filters, kVp, breast type and thickness. Two figures of merit were defined: (signal/noise)2/MGD and spectral quantum efficiency; these were computed as a means to approach optimization of object contrast. The model is derived from a combination of classic equations, XCOM from NBS, and published data. X-ray spectra were calculated and measured for filters of Al, Sn, Rh, Mo and Ag on a Eureka tube. (Signal/noise)2/MGD was measured for a filtered W target tube and a digital camera employing CsI scintillator optically coupled to a CCD for which the detective quantum efficiency (DQE) was known. A 3-mm thick acrylic disk was imaged on thickness of 3-8 cm of acrylic and the results were compared to the predictions of the model. The relative error between predicted and measured spectra was +/- 2 percent from 24 to 34 kVp. Calculated MGD as a function of breast thickness, half-value layer and beam filter compares very well to published data. Best performance was found for the following combinations: Mo filter with 30 mm breast, Ag filter with 45 mm, Sn filter for 60 mm, and Al filter for 75 mm thick breast. The parametric model agrees well with measurement and provides a means to explore optimum combinations of kVp and beam filter. For a particular detector, this data may be used with the DQE to estimate total system signal-to-noise ratio for a particular imaging task.

Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction.

PubMed

Liu, Ruixing; Rong, Bei; Tu, Ping; Tang, Yun; Song, Wenjing; Toyos, Rolando; Toyos, Melissa; Yan, Xiaoming

2017-11-01

To investigate the change from baseline of inflammatory markers in tears of dry eye disease (DED) subjects owing to meibomian gland dysfunction (MGD) after intense pulsed light (IPL) treatment and meibomian gland expression (MGE) compared to sham treatment, and the correlations with ocular surface parameters. Randomized, double-masked, controlled study. Those randomized into the active treatment arm received 3 consecutive treatments (14∼16 J/cm 2 ) approximately 4 weeks apart in the periocular region. Control eyes received 3 treatments in the same intervals of 0 J/cm 2 . Tear samples in all eyes were collected and analyzed at baseline, week 12, and/or week 4 for interleukin (IL)-17A, IL-6, and prostaglandin E2 (PGE2). The correlations between cytokines and ocular surface parameters were analyzed before and after IPL treatment. All of the inflammatory markers declined in value compared to baselines. IL-17A and IL-6 showed statistically significant decreases compared to sham treatment at each measured time point. PGE2 showed statistically significant decreases compared to sham at week 12. Results showed that the expressions of IL-17A and IL-6 correlated well with ocular surface parameters of the lower eyelid before IPL. The changed values of IL-6 and PGE2 in tears correlated with the changed values of partial ocular surface parameters after IPL treatment in study eyes, respectively. The study results suggest that IPL can significantly reduce inflammatory markers in tears of patients suffering with DED owing to MGD after IPL treatment. These findings indicate that IL-17A and IL-6 play roles in the pathogenesis of DED owing to MGD, and the reduction of the inflammatory factors is consistent with the improvement of partial clinical symptoms and signs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Degradative pathways for p-toluenecarboxylate and p-toluenesulfonate and their multicomponent oxygenases in Comamonas testosteroni strains PSB-4 and T-2.

PubMed

Junker, F; Saller, E; Schläfli Oppenberg, H R; Kroneck, P M; Leisinger, T; Cook, A M

1996-09-01

Three multicomponent oxygenases involved in the degradation of p-toluenesulfonate and p-toluenecarboxylate and the regulation of their synthesis have been examined in three strains (T-2, PSB-4 and TER-1) of Comamonas testosteroni. Strain T-2 utilizes p-toluenesulfonate as a source of carbon and energy for growth via p-sulfobenzoate and protocatechuate, and p-toluenecarboxylate via terephthalate and protocatechuate, and has the unusual property of requiring the reductase (TsaB) of the toluenesulfonate methyl monooxygenase system (TsaMB) in an incompletely expressed sulfobenzoate dioxygenase system (PsbAC) [Schläfli Oppenberg, H.R., Chen, G., Leisinger, T. & Cook, A. M. (1995). Microbiology 141, 1891-1899]. The independently isolated C. testosteroni PSB-4 utilized only sulfobenzoate and terephthalate via protocatechuate. Mutant TER-1, derived from strain T-2, utilized only terephthalate via protocatechuate. We detected no enzymes of the pathway from toluenesulfonate to sulfobenzoate in strains PSB-4 and TER-1, and confirmed by PCR and Southern blot analysis that the genes (tsaMB) encoding toluenesulfonate monooxygenase were absent. We concluded that, in strain PSB-4, the regulatory unit encoding the genes for the conversion of toluenesulfonate to sulfobenzoate was missing, and that generation of mutant TER-1 involved deletion of this regulatory unit and of the regulatory unit encoding desulfonation of sulfobenzoate. The degradation of sulfobenzoate in strain PSB-4 was catalysed by a fully inducible sulfobenzoate dioxygenase system (PsbACPSB-4), which, after purification of the oxygenase component (PsbAPSB-4), turned out to be indistinguishable from the corresponding component from strain T-2 (PsbAT-2). Reductase PsbCPSB-4, which we could separate but not purify, was active with oxygenase PsbAPSB-4 and PsbAT-2. Oxygenase PsbAPSB-4 was shown by electron paramagnetic resonance spectroscopy to contain a Rieske [2Fe-2S] centre. The enzyme system oxygenating terephthalate was examined and the oxygenase component purified and characterized. The oxygenase component in strains T-2 (and mutant TER-1) and PSB-4 were indistinguishable. The reductase component, which we separated but failed to purify, was active with the oxygenase from all strains. Gains and losses of blocks of genes in evolution is discussed.

The influence of precipitation kinetics on trace element partitioning between solid and liquid solutions: A coupled fluid dynamics/thermodynamics framework to predict distribution coefficients

NASA Astrophysics Data System (ADS)

Kavner, A.

2017-12-01

In a multicomponent multiphase geochemical system undergoing a chemical reaction such as precipitation and/or dissolution, the partitioning of species between phases is determined by a combination of thermodynamic properties and transport processes. The interpretation of the observed distribution of trace elements requires models integrating coupled chemistry and mechanical transport. Here, a framework is presented that predicts the kinetic effects on the distribution of species between two reacting phases. Based on a perturbation theory combining Navier-Stokes fluid flow and chemical reactivity, the framework predicts rate-dependent partition coefficients in a variety of different systems. We present the theoretical framework, with applications to two systems: 1. species- and isotope-dependent Soret diffusion of species in a multicomponent silicate melt subjected to a temperature gradient, and 2. Elemental partitioning and isotope fractionation during precipitation of a multicomponent solid from a multicomponent liquid phase. Predictions will be compared with results from experimental studies. The approach has applications for understanding chemical exchange in at boundary layers such as the Earth's surface magmatic systems and at the core/mantle boundary.

Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.

PubMed

Mattingly, Greg W; Weisler, Richard H; Young, Joel; Adeyi, Ben; Dirks, Bryan; Babcock, Thomas; Lasser, Robert; Scheckner, Brian; Goodman, David W

2013-01-29

Despite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD. In a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an "optimal" LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission. Four hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days (P<.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits. In the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months. Clinical Trial Numbers: NCT00334880 and NCT01070394CLINICAL TRIAL REGISTRY: clinicaltrials.gov.

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

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

Chinnaiyan, Prakash, E-mail: prakash.chinnaiyan@moffitt.org; Won, Minhee; Wen, Patrick Y.

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

Ionic liquid catalyzed one-pot multi-component synthesis, characterization and antibacterial activity of novel chromeno[2,3-d]pyrimidin-8-amine derivatives

NASA Astrophysics Data System (ADS)

Kanakaraju, Sankari; Prasanna, Bethanamudi; Basavoju, Srinivas; Chandramouli, G. V. P.

2012-06-01

An efficient, simple and convenient method for the one-pot multi-component synthesis of novel chromeno[2,3-d]pyrimidin-8-amine derivatives has been accomplished by starting from α-naphthol, aryl aldehydes, malononitrile and NH4Cl. The reaction has been catalyzed by 1-butyl-3-methylimidazolium tetrafluoroborate [bmim]BF4 ionic liquid. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, mass spectra, and elemental analysis. The structure of compound 4a was confirmed by single-crystal X-ray diffraction. All the synthesized compounds were evaluated for their in vitro antibacterial activity.

Demographic, Dietary, and Urinary Factors and 24-h Urinary Calcium Excretion

PubMed Central

Curhan, Gary C.

2009-01-01

Background and objectives: Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Design, setting, participants, & measurements: Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Results: Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values ≤0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend ≤0.01). Conclusions: Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium. PMID:19820135

Serosal-to-mucosal urea flux across the isolated ruminal epithelium is mediated via urea transporter-B and aquaporins when Holstein calves are abruptly changed to a moderately fermentable diet.

PubMed

Walpole, M E; Schurmann, B L; Górka, P; Penner, G B; Loewen, M E; Mutsvangwa, T

2015-02-01

Urea transport (UT-B) proteins are known to facilitate urea movement across the ruminal epithelium; however, other mechanisms may be involved as well because inhibiting UT-B does not completely abolish urea transport. Of the aquaporins (AQP), which are a family of membrane-spanning proteins that are predominantly involved in the movement of water, AQP-3, AQP-7, and AQP-10 are also permeable to urea, but it is not clear if they contribute to urea transport across the ruminal epithelium. The objectives of this study were to determine (1) the functional roles of AQP and UT-B in the serosal-to-mucosal urea flux (Jsm-urea) across rumen epithelium; and (2) whether functional adaptation occurs in response to increased diet fermentability. Twenty-five Holstein steer calves (n=5) were assigned to a control diet (CON; 91.5% hay and 8.5% vitamin and mineral supplement) or a medium grain diet (MGD; 41.5% barley grain, 50% hay, and 8.5% vitamin and mineral) that was fed for 3, 7, 14, or 21 d. Calves were killed and ruminal epithelium was collected for mounting in Ussing chambers under short-circuit conditions and for analysis of mRNA abundance of UT-B and AQP-3, AQP-7, and AQP-10. To mimic physiologic conditions, the mucosal buffer (pH 6.2) contained no urea, whereas the serosal buffer (pH 7.4) contained 1 mM urea. The fluxes of (14)C-urea (Jsm-urea; 26 kBq/10 mL) and (3)H-mannitol (Jsm-mannitol; 37 kBq/10 mL) were measured, with Jsm-mannitol being used as an indicator of paracellular or hydrophilic movement. Serosal addition of phloretin (1 mM) was used to inhibit UT-B-mediated urea transport, whereas NiCl2 (1 mM) was used to inhibit AQP-mediated urea transport. Across treatments, the addition of phloretin or NiCl2 reduced the Jsm-urea from 116.5 to 54.0 and 89.5 nmol/(cm(2) × h), respectively. When both inhibitors were added simultaneously, Jsm-urea was further reduced to 36.8 nmol/(cm(2) × h). Phloretin-sensitive and NiCl2-sensitive Jsm-urea were not affected by diet. The Jsm-urea tended to increase linearly as the duration of adaptation to MGD increased, with the lowest Jsm-urea being observed in animals fed CON [107.7 nmol/(cm(2) × h)] and the highest for those fed the MGD for 21 d [144.2 nmol/(cm(2) × h)]. Phloretin-insensitive Jsm-urea tended to increase linearly as the duration of adaptation to MGD increased, whereas NiCl2-insensitive Jsm-urea tended to be affected by diet. Gene transcript abundance for AQP-3 and UT-B in ruminal epithelium increased linearly as the duration of MGD adaptation increased. For AQP-7 and AQP-10, gene transcript abundance in animals that were fed the MGD was greater compared with that of CON animals. These results demonstrate that both AQP and UT-B play significant functional roles in urea transport, and they may play a role in urea transport during dietary adaptation to fermentable carbohydrates. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Thermodynamics and Phase Behavior of Miscible Polymer Blends in the Presence of Supercritical Carbon Dioxide

NASA Astrophysics Data System (ADS)

Young, Nicholas Philip

The design of environmentally-benign polymer processing techniques is an area of growing interest, motivated by the desire to reduce the emission of volatile organic compounds. Recently, supercritical carbon dioxide (scCO 2) has gained traction as a viable candidate to process polymers both as a solvent and diluent. The focus of this work was to elucidate the nature of the interactions between scCO2 and polymers in order to provide rational insight into the molecular interactions which result in the unexpected mixing thermodynamics in one such system. The work also provides insight into the nature of pairwise thermodynamic interactions in multicomponent polymer-polymer-diluent blends, and the effect of these interactions on the phase behavior of the mixture. In order to quantify the strength of interactions in the multicomponent system, the binary mixtures were characterized individually in addition to the ternary blend. Quantitative analysis of was made tractable through the use of a model miscible polymer blend containing styrene-acrylonitrile copolymer (SAN) and poly(methyl methacrylate) (dPMMA), a mixture which has been considered for a variety of practical applications. In the case of both individual polymers, scCO2 is known to behave as a diluent, wherein the extent of polymer swelling depends on both temperature and pressure. The solubility of scCO 2 in each polymer as a function of temperature and pressure was characterized elsewhere. The SAN-dPMMA blend clearly exhibited lower critical solution temperature behavior, forming homogeneous mixtures at low temperatures and phase separating at elevated temperature. These measurements allowed the determination of the Flory-Huggins interaction parameter chi23 for SAN (species 2) and dPMMA (species 3) as a function of temperature at ambient pressure, in the absence of scCO2 (species 1). Characterization of the phase behavior of the multicomponent (ternary) mixture was also carried out by SANS. An in situ SANS environment was developed to allow measurement of blend miscibility in the presence of scCO2. The pressure-temperature phase behavior of the system could be mapped by approaching the point of phase separation by spinodal decomposition through pressure increases at constant temperature. For a roughly symmetric mixture of SAN and dPMMA, the temperature at which phase separation occurred could be decreased by over 125 °C. The extent to which the phase behavior of the multicomponent system could be tuned motivated further investigation into the interactions present within the homogeneous mixtures. Analysis of the SANS results for homogeneous mixtures was undertaken using a new multicomponent formalism of the random phase approximation theory. The scattering profiles obtained from the scCO2-SAN-dPMMA system could be predicted with reasonable success. The success of the theoretical predictions was facilitated by directly employing the interactions found in the binary experiments. Exploitation of the condition of homogeneity with respect to chemical potential allowed determination of interaction parameters for scCO2-SAN and 2-dPMMA within the multicomponent mixture (chi12 and chi13, respectively). Studying this system over a large range of the supercritical regime yielded insight on the nature of interactions in the system. Near the critical point of scCO 2, chi12 and chi13 increase monotonically as a function of pressure. Conversely, at elevated temperature away from the critical point, the interaction parameters are found to go through a minimum as a pressure increases. Analysis of the critical phenomenon associated with scCO2 suggests that the observed dependence of chi12 and chi13 on pressure are related to the magnitude of scCO 2 density fluctuations and the proximity of the system to the so-called density fluctuation ridge. By tuning the system parameters of the multicomponent mixture, the phase behavior can be altered through the balance of pairwise interactions been the constituent species. The presence of scCO2 in the mixtures appears to eliminate the existence of the metastable state that epitomizes most polymer-polymer mixtures. Thus it is shown that knowledge of the individual pairwise interactions in such multicomponent mixtures can greatly influence the resulting phase behavior, and provide insight into the design of improved functional materials with decreased environmental impacts.

76 FR 9758 - Notice of Commission Meeting and Public Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... River) Municipal Utilities Authority, D- 1971-094 CP-4. An application for renewal of the Belvidere... Borough Authority, D-1987-054 CP-3. An application to renew the approval for discharge of up to 0.7 mgd of... Richmond Township, Berks County, Pennsylvania. 3. Village of Monticello, D-1981-038 CP-2. An application to...

Lamotrigine in binge-eating disorder associated with bipolar II depression and treatment-resistant type 2 diabetes mellitus: a case report.

PubMed

Yamamoto, Tetsuya; Kanahara, Nobuhisa; Hirai, Aizan; Watanabe, Hiroyuki; Iyo, Masaomi

2013-01-01

Lamotrigine (LMG) is an anticonvulsant currently registered for the treatment of bipolar disorder (BP) depression. We report the case of a 61-year-old woman with comorbid binge-eating disorder (BED), BP depression, and treatment-resistant type 2 diabetes mellitus (T2DM), in which LMG showed significant efficacy against BED and BP depression and resulted in a drastic decrease in plasma glucose levels. The patient had had untreated BP depression, BED, and T2DM for more than 30 years. We prescribed LMG at 25 mg/d for BP depression and titrated it up to 50 mg/d over 4 weeks, then maintained this dose for the next 16 weeks. At follow-up after the first 4-week period, she reported a significant decrease in compulsive eating impulses and depressive mood, and her positive reports were consistent in the following months. Hemoglobin A1c levels at National Glycohemoglobin Standardization Program decreased drastically from 9.6% to 7.1% over the 20 weeks after initiating treatment. This case suggests that LMG might be beneficial for BED with concomitant BP depression, and potentially for treatment-resistant T2DM, if this refractoriness is identified to result from comorbidity of BED and BP.

Meibomian Gland Dysfunction Determines the Severity of the Dry Eye Conditions in Visual Display Terminal Workers

PubMed Central

Dong, Nuo; Yang, Fan; Lin, Zhirong; Shang, Xumin; Li, Cheng

2014-01-01

Objective To explore meibomian gland dysfunction (MGD) may determine the severity of dry eye conditions in visual display terminal (VDT) workers. Methodology Prospective, case-control study carried out in China.106 eyes of 53 patients (VDT work time >4 hour per day) were recruited as the Long time VDT group; 80 eyes of 40 control subjects (VDT work time ≤4 hour per day) served as the Short time VDT group. A questionnaire of Ocular Surface Disease Index (OSDI) and multiple tests were performed. Three dry eye tests: tear film breakup time (BUT), corneal fluorescein staining, Schirmer I test; and three MGD parameters: lid margin abnormality score, meibum expression assessment (meibum score), and meibomian gland dropout degree (meiboscore) using Keratograph 5 M. Principal Findings OSDI and corneal fluorescein score were significantly higher while BUT was dramatically shorter in the long time VDT group than the short time VDT group. However, the average of Schirmer tear volumes was in normal ranges in both groups. Interestingly, the three MGD parameters were significantly higher in the long time VDT group than the short time one (P<0.0001). When 52 eyes with Schirmer <10 mm and 54 eyes with Schirmer ≥10 mm were separated from the long time VDT workers, no significant differences were found between the two subgroups in OSDI, fluorescein staining and BUT, as well as the three MGD parameters. All three MGD parameters were positively correlated with VDT working time (P<0.0001) and fluorescein scores (P<0.0001), inversely correlated with BUT (P<0.05), but not correlated with Schirmer tear volumes in the VDT workers. Conclusions Our findings suggest that a malfunction of meibomian glands is associated with dry eye patients in long term VDT workers with higher OSDI scores whereas some of those patients presenting a normal tear volume. PMID:25144638

Large area CMOS active pixel sensor x-ray imager for digital breast tomosynthesis: Analysis, modeling, and characterization.

PubMed

Zhao, Chumin; Kanicki, Jerzy; Konstantinidis, Anastasios C; Patel, Tushita

2015-11-01

Large area x-ray imagers based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been proposed for various medical imaging applications including digital breast tomosynthesis (DBT). The low electronic noise (50-300 e-) of CMOS APS x-ray imagers provides a possible route to shrink the pixel pitch to smaller than 75 μm for microcalcification detection and possible reduction of the DBT mean glandular dose (MGD). In this study, imaging performance of a large area (29×23 cm2) CMOS APS x-ray imager [Dexela 2923 MAM (PerkinElmer, London)] with a pixel pitch of 75 μm was characterized and modeled. The authors developed a cascaded system model for CMOS APS x-ray imagers using both a broadband x-ray radiation and monochromatic synchrotron radiation. The experimental data including modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were theoretically described using the proposed cascaded system model with satisfactory consistency to experimental results. Both high full well and low full well (LFW) modes of the Dexela 2923 MAM CMOS APS x-ray imager were characterized and modeled. The cascaded system analysis results were further used to extract the contrast-to-noise ratio (CNR) for microcalcifications with sizes of 165-400 μm at various MGDs. The impact of electronic noise on CNR was also evaluated. The LFW mode shows better DQE at low air kerma (Ka<10 μGy) and should be used for DBT. At current DBT applications, air kerma (Ka∼10 μGy, broadband radiation of 28 kVp), DQE of more than 0.7 and ∼0.3 was achieved using the LFW mode at spatial frequency of 0.5 line pairs per millimeter (lp/mm) and Nyquist frequency ∼6.7 lp/mm, respectively. It is shown that microcalcifications of 165-400 μm in size can be resolved using a MGD range of 0.3-1 mGy, respectively. In comparison to a General Electric GEN2 prototype DBT system (at MGD of 2.5 mGy), an increased CNR (by ∼10) for microcalcifications was observed using the Dexela 2923 MAM CMOS APS x-ray imager at a lower MGD (2.0 mGy). The Dexela 2923 MAM CMOS APS x-ray imager is capable to achieve a high imaging performance at spatial frequencies up to 6.7 lp/mm. Microcalcifications of 165 μm are distinguishable based on reported data and their modeling results due to the small pixel pitch of 75 μm. At the same time, potential dose reduction is expected using the studied CMOS APS x-ray imager.

High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

PubMed

Taguchi, Isao; Iimuro, Satoshi; Iwata, Hiroshi; Takashima, Hiroaki; Abe, Mitsuru; Amiya, Eisuke; Ogawa, Takanori; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Miyauchi, Katsumi; Yamazaki, Tsutomu; Ito, Hiroshi; Otsuji, Yutaka; Kimura, Kazuo; Takahashi, Jun; Hirayama, Atsushi; Yokoi, Hiroyoshi; Kitagawa, Kazuo; Urabe, Takao; Okada, Yasushi; Terayama, Yasuo; Toyoda, Kazunori; Nagao, Takehiko; Matsumoto, Masayasu; Ohashi, Yasuo; Kaneko, Tetsuji; Fujita, Retsu; Ohtsu, Hiroshi; Ogawa, Hisao; Daida, Hiroyuki; Shimokawa, Hiroaki; Saito, Yasushi; Kimura, Takeshi; Inoue, Teruo; Matsuzaki, Masunori; Nagai, Ryozo

2018-05-08

Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group ( P <0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P =0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; P =0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730. © 2018 The Authors.

Rogue waves in the multicomponent Mel'nikov system and multicomponent Schrödinger-Boussinesq system

NASA Astrophysics Data System (ADS)

Sun, Baonan; Lian, Zhan

2018-02-01

By virtue of the bilinear method and the KP hierarchy reduction technique, exact explicit rational solutions of the multicomponent Mel'nikov equation and the multicomponent Schrödinger-Boussinesq equation are constructed, which contain multicomponent short waves and single-component long wave. For the multicomponent Mel'nikov equation, the fundamental rational solutions possess two different behaviours: lump and rogue wave. It is shown that the fundamental (simplest) rogue waves are line localised waves which arise from the constant background with a line profile and then disappear into the constant background again. The fundamental line rogue waves can be classified into three: bright, intermediate and dark line rogue waves. Two subclasses of non-fundamental rogue waves, i.e., multirogue waves and higher-order rogue waves are discussed. The multirogue waves describe interaction of several fundamental line rogue waves, in which interesting wave patterns appear in the intermediate time. Higher-order rogue waves exhibit dynamic behaviours that the wave structures start from lump and then retreat back to it. Moreover, by taking the parameter constraints further, general higher-order rogue wave solutions for the multicomponent Schrödinger-Boussinesq system are generated.

Hemocompatible ɛ-polylysine-heparin microparticles: A platform for detecting triglycerides in whole blood.

PubMed

Xu, Tingting; Chi, Bo; Chu, Meilin; Zhang, Qicheng; Zhan, Shuyue; Shi, Rongjia; Xu, Hong; Mao, Chun

2018-01-15

Triglycerides are clinically important marker for atherosclerosis, heart disease and hypertension. Here, a platform for detecting triglycerides in whole blood directly was developed based on hemocompatible ɛ-polylysine-heparin microparticles. The obtained products of ɛ-polylysine-heparin microparticles were characterized by fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM) and ζ-potential. Moreover, the blood compatibility of ɛ-polylysine-heparin microparticles was characterized by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Considering of uniform particle size, good dispersibility and moderate long-term anticoagulation capability of the microparticles, a Lipase-(ɛ-polylysine-heparin)-glassy carbon electrode (GCE) was constructed to detect triglycerides. The proposed biosensor had good electrocatalytic activity towards triglycerides, in which case the sensitivity was 0.40μAmg -1 dLcm -2 and the detection limit was 4.67mgdL -1 (S/N = 3). Meanwhile, the Lipase-(ɛ-polylysine-heparin)-GCE electrode had strong anti-interference ability as well as a long shelf-life. Moreover, for the detection of triglycerides in whole blood directly, the detection limit was as low as 5.18mgdL -1 . The new constructed platform is suitable for detecting triglycerides in whole blood directly, which provides new analytical systems for clinical illness diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

[Efficacy of combination therapy with pegylated-interferon alfa-2a plus ribavirin in autoantibody-positive chronic hepatitis C patients].

PubMed

Li, Ya-xin; Yang, Yan-jia; Yang, Mei; Chen, Li-yu; Lu, Jia-jie; Ma, Yuan-ji; Liu, Kai; Lei, Xue-zhong; Tang, Hong

2013-05-01

To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.

ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

PubMed

Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

2006-12-01

The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

Theory and Simulation of Multicomponent Osmotic Systems

PubMed Central

Karunaweera, Sadish; Gee, Moon Bae; Weerasinghe, Samantha; Smith, Paul E.

2012-01-01

Most cellular processes occur in systems containing a variety of components many of which are open to material exchange. However, computer simulations of biological systems are almost exclusively performed in systems closed to material exchange. In principle, the behavior of biomolecules in open and closed systems will be different. Here, we provide a rigorous framework for the analysis of experimental and simulation data concerning open and closed multicomponent systems using the Kirkwood-Buff (KB) theory of solutions. The results are illustrated using computer simulations for various concentrations of the solutes Gly, Gly2 and Gly3 in both open and closed systems, and in the absence or presence of NaCl as a cosolvent. In addition, KB theory is used to help rationalize the aggregation properties of the solutes. Here one observes that the picture of solute association described by the KB integrals, which are directly related to the solution thermodynamics, and that provided by more physical clustering approaches are different. It is argued that the combination of KB theory and simulation data provides a simple and powerful tool for the analysis of complex multicomponent open and closed systems. PMID:23329894

Associations between plasma lipid parameters and APOC3 and APOA4 genotypes in a healthy population are independent of dietary cholesterol intake.

PubMed

Herron, Kristin L; Lofgren, Ingrid E; Adiconis, Xian; Ordovas, Jose M; Fernandez, Maria Luz

2006-01-01

To determine whether APOC3 and APOA4 genotypes influence plasma cholesterol fluctuations following a high cholesterol diet, a healthy population of 40 men and 51 women were studied. The crossover intervention randomly assigned participants to an EGG (640 mg/d cholesterol) or placebo (0 mg/d cholesterol) diet for 30 days, with a 3-week washout between periods. Allele-specific oligonucleotide hybridization was utilized to determine the presence or absence of APOC3 and APOA4 polymorphisms. Differences in plasma cholesterol between hyper- and hypo-responders were not influenced by genotype. However, an interaction (P < 0.0001) did exist between APOA4 allele, diet and gender with regard to triglycerides (TG). While female carriers of the APOA4(347) S allele had lower TG concentrations than those with the common T/T allele, males with the S allele had higher concentrations. The APOC3 SstI polymorphism analysis revealed that heterozygous carriers of the S2 allele had higher (P < 0.05) plasma apo C-III and TG concentrations, regardless of gender or dietary period. In addition, carriers of the S2 allele had smaller LDL peak particle diameter than those having the common APOC3 genotype. The presence of individual alleles in this population was associated with differences in plasma lipids and LDL size. However, these relationships were independent of dietary cholesterol.

Efficacy of an artificial tear emulsion in patients with dry eye associated with meibomian gland dysfunction.

PubMed

Sindt, Christine W; Foulks, Gary N

2013-01-01

The aim of the study reported here was to assess the efficacy of an artificial tear emulsion for the treatment of dry eye associated with meibomian gland dysfunction (MGD). At five clinics, patients completed a 1-week treatment with their habitual topical therapy and then a 4-week treatment with open-label study medication: Systane® Balance Lubricant Eye Drops (Alcon, Alcon Inc, Fort Worth, TX, USA). Subjective assessments included a preference survey, the Impact of Dry Eye in Everyday Life questionnaire, and the Work Productivity and Activity Impairment questionnaire. Objective assessments by unmasked investigators included visual acuity, meibomian gland expression and dropout, tear film breakup time, corneal staining, and dosing frequency. At baseline, the 49 patients had mean meibomian gland expression grades and gland dropout that indicated mild to moderate MGD. Patients administered their habitual therapy 2.5 ± 1.3 times per day. After 4 weeks of study medication, the Impact of Dry Eye in Everyday Life questionnaire results indicated statistically and clinically significant improvements. Fewer than half of the participants were employed, limiting the usefulness of the Work Productivity and Activity Impairment questionnaire. Visual acuity remained statistically similar, while corneal staining and tear film breakup time improved significantly (P < 0.05) but modestly. The outcomes were achieved with 1.9 ± 1.1 doses per day of study medication, a significantly lower frequency than the habitual frequency (P < 0.001). The most common medication-related adverse event was blurred vision (3/49 patients, 6.1%). At study conclusion, 27/44 (61.4%) survey respondents preferred the study medication to their habitual therapy. The artificial tear emulsion was effective for treating the signs and symptoms of dry eye in MGD patients.

A single LipiFlow® Thermal Pulsation System treatment improves meibomian gland function and reduces dry eye symptoms for 9 months.

PubMed

Greiner, Jack V

2012-04-01

To evaluate the effect of a single treatment with the LipiFlow(®) Thermal Pulsation System on signs of meibomian gland dysfunction (MGD) and dry eye symptoms over a 9-month period. Patients (n = 42 eyes, 21 subjects) diagnosed with MGD and dry eye symptoms were recruited for a non-significant risk, prospective, open-label, 1-month clinical trial. Patients received a single 12-minute treatment using the LipiFlow(®) Thermal Pulsation System on each eye. The LipiFlow(®) device applies heat to the conjunctival surfaces of the upper and lower inner eyelids while simultaneously applying pulsatile pressure to the outer eyelid surfaces to express the meibomian glands. Patient symptoms were evaluated using the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation for Eye Dryness (SPEED) dry eye questionnaires; tear break-up time was measured with the dry eye test (DET™); and meibomian gland function was evaluated using a standardized diagnostic expression technique. Data are presented for patient's pre-treatment (baseline) and at 1-month and 9-month post-treatment. Meibomian gland secretion scores improved significantly from baseline (4.4 ± 4.0) to 1-month post-treatment (11.3 ± 6.2; p < 0.0001) and this improvement was maintained with no significant regression at 9 months (11.7 ± 5.9). Similarly, baseline tear break-up time (4.8 ± 3.2) was significantly increased at 1 month (9.6 ± 7.6; p < 0.001) and this increase was maintained with no significant regression at 9 months (7.1 ± 5.6). Symptom scores on both OSDI and SPEED questionnaires improved significantly at 1 month (p < 0.0001) and this improvement was maintained at 9 months. With such prolonged improvement in signs and symptoms of dry eye disease, the LipiFlow(®) Thermal Pulsation System offers a technological advancement for the treatment of dry eye disease secondary to meibomian gland dysfunction. A single 12-minute LipiFlow(®) treatment results in up to 9 months of sustained improvement of meibomian gland function, tear break-up time and dry eye symptoms that are unparalleled with current dry eye treatments.

Coulombic interactions during advection-dominated transport of ions in porous media

NASA Astrophysics Data System (ADS)

Muniruzzaman, Muhammad; Stolze, Lucien; Rolle, Massimo

2017-04-01

Solute transport of charged species in porous media is significantly affected by the electrochemical migration term resulting from the charge-induced interactions among dissolved ions and with solid surfaces. Therefore, the characterization of such Coulombic interactions and their effect on multicomponent ionic transport is of critical importance for assessing the fate of charged solutes in porous media. In this work we present a detailed investigation of the electrochemical effects during conservative multicomponent ionic transport in homogeneous and heterogeneous domains by means of laboratory bench-scale experiments and numerical simulations. The investigation aims at quantifying the key role of small-scale electrostatic interactions in flow-through systems, especially when advection is the dominant mass-transfer process. Considering dilute solutions of strong electrolytes (e.g., MgCl2 and NaBr) we report results showing the important role of Coulombic interactions in the lateral displacement of the different ionic species for steady-state transport scenarios in which the solutions are continuously injected through different portions of the flow-through chamber [1, 2]. Successively, we focus our attention on transient transport and pulse injection of the electrolytes. In these experiments high-resolution spatial and temporal monitoring of the ions' concentrations (600 samples; 1800 concentration measurements), at closely spaced outlet ports (5 mm), allowed us resolving the effects of charge interactions on the temporal breakthrough and spatial profiles of the cations and anions [3]. The interpretation of the experimental results requires a multicomponent modeling approach with an accurate description of local hydrodynamic dispersion, as well as the explicit quantification of the dispersive fluxes' cross-coupling due to the Coulombic interactions between the charged species. A new 2-D simulator [4], coupling the solution of the multicomponent ionic transport problem with the geochemical code PHREEQC has been developed and used to quantitatively interpret the experimental results. References [1] Rolle M., Muniruzzaman M., Haberer C.M. and P. Grathwohl (2013). Geochim. Cosmochim. Acta 120, 195-205. [2] Muniruzzaman M., Haberer C.M., Grathwohl P. and M. Rolle (2014). Geochim. Cosmochim. Acta 141, 656-669. [3] Muniruzzaman M. and M. Rolle (2017). Water Resour. Res. (in press). [4] Muniruzzaman M. and M. Rolle (2016). Adv. Water Resour. 98, 1-15.

The dubious effect of milnacipran for the treatment of burning mouth syndrome.

PubMed

Sugimoto, Koreaki

2011-01-01

Burning mouth syndrome (BMS) is a condition accompanied by oral burning symptoms, including glossal pain (glossodynia) without a detectable cause. Although BMS is a chronic-pain syndrome, only one self-controlled pilot study and some case reports have reported that milnacipran is effective for the treatment of chronic pain, including that caused by BMS. However, these papers assessed only pain, and the dosage of prescribed milnacipran varied from 30 to 150 mg/d in each patient. In this study, the dosage of prescribed milnacipran was set at 60 mg/d for 12 weeks for all patients, and depression and quality of life (QOL) were assessed in addition to pain. Twelve patients with glossodynia participated in this study. Milnacipran was initiated at a dosage of 15 mg/d and then raised gradually to 60 mg/d after 4 weeks of treatment; this dose was continued until the end of the study (total of 12 weeks). The evaluation included the Hamilton Rating Scale for Depression, the Visual Analog Scale score for pain evaluation, the General Oral Health Assessment Index for oral-related QOL evaluation, and the Medical Outcomes Study's 36-Item Short-Form Health Survey (SF-36) for whole QOL evaluation. The Hamilton Rating Scale for Depression score decreased significantly after treatment with a 60-mg/d dosage of milnacipran for 12 weeks. However, the Visual Analog Scale pain, General Oral Health Assessment Index, and SF-36 scores did not change. A randomized, double-blind, placebo-controlled multi-institution trial of milnacipran will be essential to determine its effectiveness for the treatment of BMS.

Methylphenidate side effects in advanced cancer: a retrospective analysis.

PubMed

Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Davis, Mellar P; Rivera, Nilo; Khoshknabi, Dilara Seyidova

2010-02-01

Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults. To evaluate MP-associated symptoms or side effects (S/E). Data was collected from 2 published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All 3 reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5, and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. 62 patients were enrolled. Fifty completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most (96%) had improvement in depression and/or fatigue. Among the 62 patients, new symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before MP showed significant improvement during MP therapy. (1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with MP appeared to improve spontaneously despite continued MP therapy. (3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. (4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.

Effect of dietary copper on the copper content of urine, parotid saliva, and sweat in humans

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

Turnlund, J.R.

Eleven young men were confined to a metabolic research unit to study the effect of the level of dietary copper (Cu) on Cu metabolism. They were fed a constant diet containing the following three levels of dietary Cu: adequate Cu (1.68 mg/d) for 24 days (MP1), low Cu (0.785 mg/d) for 42 days (MP2), and high Cu (7.53 mg/d) for 24 days (MP3). Urine was collected throughout the study and Cu was determined in 6-day pools from the beginning of the study, the end of each MP, and the midpoint of MP2. Parotid saliva was collected near the end ofmore » each MP. Sweat was collected from the upper arm and ancillary area of three subjects for 2-day periods near the end of each MP. Urinary Cu averaged 0.34, 0.34 and 0.33 {mu}mol/d for MP 1, 2, and 3, respectively. Individual averages ranged from 0.16 to 0.39 {mu}mol/d. Parotid saliva Cu averaged 13.4, 13.0, and 12.0 nmol/L for MP 1, 2 and 3, respectively. Individual averages ranged from 6.9 to 17.8 nmol/L. Sweat Cu levels were very low and did not appear to be affected by dietary Cu. The limited data suggest that sweat losses would have little effect on Cu balance. Neither urinary nor salivary Cu was affected by dietary Cu or related to indices of Cu status (serum Cu, ceruloplasmin, or erythrocyte superoxide dismutase). Urinary and salivary Cu differed significantly among individuals. Results suggest that urinary, salivary, and sweat Cu do not play a role in regulating Cu retention or affect Cu status of humans.« less

Activation of mineralocorticoid receptors by exogenous glucocorticoids and the development of cardiovascular inflammatory responses in adrenalectomized rats.

PubMed

Young, Morag J; Morgan, James; Brolin, Kim; Fuller, Peter J; Funder, John W

2010-06-01

Activation of the mineralocorticoid receptor (MR) in the context of a high salt intake produces cardiovascular inflammation plus cardiac fibrosis and failure. Inactivation of vascular 11beta-hydroxysteroid dehydrogenase type 2 activity in intact animals by carbenoxolone (CBX) produces a similar pathology, presumably reflecting coronary vascular MR activation by endogenous glucocorticoids. To test this hypothesis, we have used adrenalectomized rats, without endogenous corticosteroids, and examined the consequences of corticosterone (CORT) replacement on a series of cardiovascular disease parameters. Uninephrectomized adrenalectomized Sprague Dawley rats given 1% NaCl/0.3% KCl to drink were treated for 8 d as follows: control; 20 mg deoxycorticosterone (DOC); 2 mg/d CORT; 2.5 mg/d CBX; CORT plus CBX (CORT/CBX); and CORT/CBX plus 100 mg/kg.d eplerenone. Markers of cardiac oxidative stress (p22(phox) and NOX4 mRNA) were up-regulated in the DOC and CORT/CBX groups; in contrast, inflammatory cell infiltration was increased and endothelial nitric oxide synthase down-regulated by CORT as well as by DOC and CORT/CBX. In the kidney, connective tissue growth factor mRNA levels were increased by DOC and CORT/CBX; in contrast, DOC had no effect on mRNA levels for channel inducing factor or endothelin 3, which were elevated only by CORT/CBX. All changes noted were reversed by eplerenone. Rats given 10-fold lower CORT (0.2 mg/d) with or without CBX showed no change in any parameter. These results suggest that there exist distinct but overlapping ligand-specific MR-mediated tissue responses to a classic mineralocorticoid (DOC) and to the glucocorticoid CORT, in the presence and absence of CBX to block vascular 11beta-hydroxysteroid dehydrogenase type 2.

Effect of aripiprazole 2 to 15 mg/d on health-related quality of life in the treatment of irritability associated with autistic disorder in children: a post hoc analysis of two controlled trials.

PubMed

Varni, James W; Handen, Benjamin L; Corey-Lisle, Patricia K; Guo, Zhenchao; Manos, George; Ammerman, Diane K; Marcus, Ronald N; Owen, Randall; McQuade, Robert D; Carson, William H; Mathew, Suja; Mankoski, Raymond

2012-04-01

There are limited published data on the impact of treatment on the health-related quality of life (HRQOL) in individuals with autistic disorder. The aim of this study was to evaluate the impact of aripiprazole on HRQOL in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder. This post hoc analysis assessed data from two 8-week, double-blind, randomized, placebo-controlled studies that compared the efficacy of aripiprazole (fixed-dose study, 5, 10, and 15 mg/d; flexible-dose study, 2-15 mg/d) with placebo in the treatment of irritability associated with autistic disorder. HRQOL was assessed at baseline and week 8 using 3 Pediatric Quality of Life Inventory (PedsQL™) scales. Clinically relevant improvement in HRQOL was determined using an accepted distribution-based criterion-1 standard error of measurement. In total, 316 patients were randomly assigned to receive treatment with aripiprazole (fixed-dose study, 166; flexible-dose study, 47) or placebo (fixed-dose study, 52; flexible-dose study, 51). Aripiprazole was associated with significantly greater improvement than placebo in PedsQL combined-scales total score (difference, 7.8; 95% CI, 3.8-11.8; P < 0.001) and in 3 PedsQL scale scores (differences [95% CI]: Emotional Functioning, 7.8 [3.4-12.2]; Social Functioning, 6.2 [0.7-11.8]; Cognitive Functioning, 9.3 [3.8-14.9]; all, P < 0.05). Patients who received aripiprazole were significantly more likely than those who received placebo to have a clinically meaningful improvement on the combined-scales total score (odds ratio [OR] = 1.9; 95% CI, 1.0-3.3; P < 0.05), Emotional Functioning scale (OR = 2.2; 95% CI, 1.2-4.0; P < 0.05) and Social Functioning scale (OR = 2.2; 95% CI, 1.2-4.1; P < 0.05), and were significantly less likely to experience deterioration (OR: 0.3, 95% CI: 0.1-0.8; P < 0.05) when "Stable" was used as the reference group. The findings from the present post hoc analysis suggest that aripiprazole was associated with improved HRQOL, as assessed using 3 PedsQL scales, in pediatric patients with irritability associated with autistic disorder. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Cu2O-based solar cells using oxide semiconductors

NASA Astrophysics Data System (ADS)

Minami, Tadatsugu; Nishi, Yuki; Miyata, Toshihiro

2016-01-01

We describe significant improvements of the photovoltaic properties that were achieved in Al-doped ZnO (AZO)/n-type oxide semiconductor/p-type Cu2O heterojunction solar cells fabricated using p-type Cu2O sheets prepared by thermally oxidizing Cu sheets. The multicomponent oxide thin film used as the n-type semiconductor layer was prepared with various chemical compositions on non-intentionally heated Cu2O sheets under various deposition conditions using a pulsed laser deposition method. In Cu2O-based heterojunction solar cells fabricated using various ternary compounds as the n-type oxide thin-film layer, the best photovoltaic performance was obtained with an n-ZnGa2O4 thin-film layer. In most of the Cu2O-based heterojunction solar cells using multicomponent oxides composed of combinations of various binary compounds, the obtained photovoltaic properties changed gradually as the chemical composition was varied. However, with the ZnO-MgO and Ga2O3-Al2O3 systems, higher conversion efficiencies (η) as well as a high open circuit voltage (Voc) were obtained by using a relatively small amount of MgO or Al2O3, e.g., (ZnO)0.91-(MgO)0.09 and (Ga2O3)0.975-(Al2O3)0.025, respectively. When Cu2O-based heterojunction solar cells were fabricated using Al2O3-Ga2O3-MgO-ZnO (AGMZO) multicomponent oxide thin films deposited with metal atomic ratios of 10, 60, 10 and 20 at.% for the Al, Ga, Mg and Zn, respectively, a high Voc of 0.98 V and an η of 4.82% were obtained. In addition, an enhanced η and an improved fill factor could be achieved in AZO/n-type multicomponent oxide/p-type Cu2O heterojunction solar cells fabricated using Na-doped Cu2O (Cu2O:Na) sheets that featured a resistivity controlled by optimizing the post-annealing temperature and duration. Consequently, an η of 6.25% and a Voc of 0.84 V were obtained in a MgF2/AZO/n-(Ga2O3-Al2O3)/p-Cu2O:Na heterojunction solar cell fabricated using a Cu2O:Na sheet with a resistivity of approximately 10 Ω·cm and a (Ga0.975Al0.025)2O3 thin film with a thickness of approximately 60 nm. In addition, a Voc of 0.96 V and an η of 5.4% were obtained in a MgF2/AZO/n-AGMZO/p-Cu2O:Na heterojunction solar cell.

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

Ji, Yanzhou; Heo, Tae Wook; Zhang, Fan

Here we present our theoretical assessment of the kinetic pathways during phase transformations of multi-component Ti alloys. Employing the graphical thermodynamic approach and an integrated free energy function based on the realistic thermodynamic database and assuming that a displacive structural transformation occurs much faster than long-range diffusional processes, we analyze the phase stabilities of Ti-6Al -4V (Ti-6wt.%Al -4wt.%V). Our systematic analyses predict a variety of possible kinetic pathways for β to (α + β) transformations leading to different types of microstructures under various heat treatment conditions. In addition, the possibility of unconventional kinetic pathways is discussed. Lastly, we also brieflymore » discuss the application of our approach to general multicomponent/multiphase alloy systems.« less

[Ethyl 4-methyloctanoate, major component of male pherome in Oryctes rhinoceros (L.) (Coleoptera, Dynastidae)].

PubMed

Morin, J P; Rochat, D; Malosse, C; Lettere, M; de Chenon, R D; Wibwo, H; Descoins, C

1996-07-01

Ethyl 4-methyloctanoate, which has already been described in Oryctes monoceros, has been identified, using extracts of effluvia collected from males, as being a major component of the male pheromone of O. rhinoceros. Field trials have been carried out in North Sumatra, Indonesia. Ethyl 4-methyloctanoate synthesized in the laboratory and released at 10 mg/d resulted in the capture of 6.8 insects per week per trap, whereas ethyl chrysanthemate (40 mg/d), an allelochemical compound once used as an attractant, only led to the capture of 0.3 insects, and the control none at all. The insects captured with the pheromone were 81% females, the majority being sexually mature. Discovery of this compound opens up new prospects for O. rhinoceros control.

Equivalence of Brownian dynamics and dynamic Monte Carlo simulations in multicomponent colloidal suspensions.

PubMed

Cuetos, Alejandro; Patti, Alessandro

2015-08-01

We propose a simple but powerful theoretical framework to quantitatively compare Brownian dynamics (BD) and dynamic Monte Carlo (DMC) simulations of multicomponent colloidal suspensions. By extending our previous study focusing on monodisperse systems of rodlike colloids, here we generalize the formalism described there to multicomponent colloidal mixtures and validate it by investigating the dynamics in isotropic and liquid crystalline phases containing spherical and rodlike particles. In order to investigate the dynamics of multicomponent colloidal systems by DMC simulations, it is key to determine the elementary time step of each species and establish a unique timescale. This is crucial to consistently study the dynamics of colloidal particles with different geometry. By analyzing the mean-square displacement, the orientation autocorrelation functions, and the self part of the van Hove correlation functions, we show that DMC simulation is a very convenient and reliable technique to describe the stochastic dynamics of any multicomponent colloidal system. Our theoretical formalism can be easily extended to any colloidal system containing size and/or shape polydisperse particles.

Effects of a New Eyelid Shampoo on Lid Hygiene and Eyelash Length in Patients with Meibomian Gland Dysfunction: A Comparative Open Study.

PubMed

Kobayashi, Asuka; Ide, Takeshi; Fukumoto, Teruki; Miki, Emiko; Tsubota, Kazuo; Toda, Ikuko

2016-01-01

Purpose . Meibomian gland dysfunction (MGD) can lead to abnormalities in the composition and function of tear film, resulting in dry eye. Eyelid hygiene is a key to management of MGD. We tested a novel eyelid shampoo (Eye Shampoo Long, ESL) for its ability to maintain lid hygiene. This shampoo is nonirritating and can potentially lengthen eyelashes. This study was aimed to evaluate the efficacy of ESL in the treatment of MGD and its effects on eyelash length. Methods . Ten patients with MGD and 10 healthy subjects without MGD applied ESL twice daily for 8 weeks. Patients were examined for lid margin and dry eye before and after the trial. Subjective symptoms were evaluated. Eyelash length was measured at baseline and at the end of the trial. Results . In the MGD group, significant improvements were observed in subjective symptoms obstruction of the meibomian orifice, secretion of meibum, eyelashes contamination, eyelid margin foam, and SPK. Eyelash length became significantly longer. Conclusions . Maintaining eyelid hygiene using ESL improved the eyelid margins and symptoms of dry eye in MGD patients and increased eyelash length. These findings are promising and warrant confirmation in a larger randomized controlled study.

Application of a High-Throughput Analyzer in Evaluating Solid Adsorbents for Post-Combustion Carbon Capture via Multicomponent Adsorption of CO2, N-2, and H2O

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

Mason, JA; McDonald, TM; Bae, TH

Despite the large number of metal-organic frameworks that have been studied in the context of post-combustion carbon capture, adsorption equilibria of gas mixtures including CO2, N-2, and H2O, which are the three biggest components of the flue gas emanating from a coal- or natural gas-fired power plant, have never been reported. Here, we disclose the design and validation of a high-throughput multicomponent adsorption instrument that can measure equilibrium adsorption isotherms for mixtures of gases at conditions that are representative of an actual flue gas from a power plant. This instrument is used to study 15 different metal-organic frameworks, zeolites, mesoporousmore » silicas, and activated carbons representative of the broad range of solid adsorbents that have received attention for CO2 capture. While the multicomponent results presented in this work provide many interesting fundamental insights, only adsorbents functionalized with alkylamines are shown to have any significant CO2 capacity in the presence of N-2 and H2O at equilibrium partial pressures similar to those expected in a carbon capture process. Most significantly, the amine-appended metal organic framework mmen-Mg-2(dobpdc) (mmen = N,N'-dimethylethylenediamine, dobpdc (4-) = 4,4'-dioxido-3,3'-biphenyldicarboxylate) exhibits a record CO2 capacity of 4.2 +/- 0.2 mmol/g (16 wt %) at 0.1 bar and 40 degrees C in the presence of a high partial pressure of H2O.« less

Application of a high-throughput analyzer in evaluating solid adsorbents for post-combustion carbon capture via multicomponent adsorption of CO2, N2, and H2O.

PubMed

Mason, Jarad A; McDonald, Thomas M; Bae, Tae-Hyun; Bachman, Jonathan E; Sumida, Kenji; Dutton, Justin J; Kaye, Steven S; Long, Jeffrey R

2015-04-15

Despite the large number of metal-organic frameworks that have been studied in the context of post-combustion carbon capture, adsorption equilibria of gas mixtures including CO2, N2, and H2O, which are the three biggest components of the flue gas emanating from a coal- or natural gas-fired power plant, have never been reported. Here, we disclose the design and validation of a high-throughput multicomponent adsorption instrument that can measure equilibrium adsorption isotherms for mixtures of gases at conditions that are representative of an actual flue gas from a power plant. This instrument is used to study 15 different metal-organic frameworks, zeolites, mesoporous silicas, and activated carbons representative of the broad range of solid adsorbents that have received attention for CO2 capture. While the multicomponent results presented in this work provide many interesting fundamental insights, only adsorbents functionalized with alkylamines are shown to have any significant CO2 capacity in the presence of N2 and H2O at equilibrium partial pressures similar to those expected in a carbon capture process. Most significantly, the amine-appended metal organic framework mmen-Mg2(dobpdc) (mmen = N,N'-dimethylethylenediamine, dobpdc (4-) = 4,4'-dioxido-3,3'-biphenyldicarboxylate) exhibits a record CO2 capacity of 4.2 ± 0.2 mmol/g (16 wt %) at 0.1 bar and 40 °C in the presence of a high partial pressure of H2O.

SU-F-R-27: Use Local Shape Descriptor Based On Geodesic Distance to Predict Survival in Non-Small Cell Lung Cancer After Radiotherapy

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

Zhang, H; Yan, L; Huang, K

2016-06-15

Purpose: The shape of the Positron Emission Tomography (PET) image represents the heterogeneity of tumor growth in various directions, and thus could be associated with tumor malignancy. We have proposed a median geodesic distance (MGD) to represent the local complexity of the shape and use a normalized MGD (NMGD) to quantify the shape, and found a potential correlation of NMGD to survival in a 20-patient pilot study. This study was to verify the finding in a larger patient cohort. Methods: Geodesic distance of two vertices on a surface is defined as the shortest path on the surface connecting the twomore » vertices. The MGD was calculated for each vertex on the surface to display the local complexity of the shape. The NMGD was determined as: NMGD = 100*standard deviation(MGDs)/mean(MGDs). We applied the NMGD to 40 NSCLC patients who were enrolled in prospective PET image protocols and received radiotherapy. Each patient had a pre-treatment PET scan with the resolution of 4mm*4mm*5mm. Tumors were contoured by a professional radiation oncologist and triangulation meshes were built up based on the contours. Results: The mean and standard deviation of NMGD was 6.4±3.0. The OS was 33.1±16.9 months for low NMGD group, and 15.4±15.6 months for the high NMGD group. The low NMGD group had significant better OS than the high NMGD group (p=0.0013). Conclusion: NMGD could be used as a shape biomarker to predict survival and the MGD could be combined with image texture in future to increase prediction accuracy. This study was supported by Award Number 1R01CA166948 from the NIH and National Cancer Institute.« less

Optimising decision making on illness absenteeism due to fever and common infections within childcare centres: development of a multicomponent intervention and study protocol of a cluster randomised controlled trial.

PubMed

Peetoom, K K B; Crutzen, R; Bohnen, J M H A; Verhoeven, R; Nelissen-Vrancken, H J M G; Winkens, B; Dinant, G J; Cals, J W L

2017-07-26

Evidence has shown that children 0-4 year-old attending childcare are prone to acquire infections compared to children cared for at home, with fever being the most common symptom. Illness absenteeism due to fever and common infections is substantial and mostly driven by unrealistic concerns and negative attitude towards fever of both childcare staff and parents, resulting in illness absenteeism from childcare, work absenteeism among parents and healthcare service use. The objective of this study is to optimise decision making among childcare staff on illness absenteeism due to fever and common infections in childcare. Underlying determinants of behavioural change were targeted by means of a multicomponent intervention. A multicomponent intervention was developed to improve decision making, using the stepwise approach of Intervention Mapping, and in close collaboration with stakeholders and experts. The intervention consisted of 1) a two-hour educational session on fever among childcare staff; 2) an online video for childcare staff and parents emphasising key information of the educational session; 3) a decision tool for childcare staff and parents in the format of a traffic light system to estimate the severity of illness and corresponding advices for childcare staff and parents; 4) an information booklet regarding childhood fever, common infections, and self-management strategies for childcare staff and parents. The multicomponent intervention will be evaluated in a cluster randomised trial with a 12-week follow-up period and absenteeism due to illness (defined as the percentage of childcare days absent due to illness on the total of childcare days during a 12-week period) as primary outcome measure. Secondary outcome measures are: incidence rate and duration of illness episodes, knowledge, attitude, self-efficacy, and risk perception on fever and common infections of childcare staff and parents, healthcare service use in general and paracetamol use, and work absenteeism of parents. This study aims to develop a multicomponent intervention and to evaluate to what extent illness absenteeism due to fever and common infections can be affected by implementing a multicomponent intervention addressing decision making and underlying determinants among childcare staff and parents of children attending daycare. NTR6402 (registered on 21-apr-2017).

Delirium Associated With Fluoxetine Discontinuation: A Case Report.

PubMed

Fan, Kuang-Yuan; Liu, Hsing-Cheng

Withdrawal symptoms on selective serotonin reuptake inhibitor (SSRI) discontinuation have raised clinical attention increasingly. However, delirium is rarely reported in the SSRI discontinuation syndrome. We report a case of delirium developing after fluoxetine discontinuation in a 65-year-old female patient with major depressive disorder. She experienced psychotic depression with limited response to treatment of fluoxetine 40 mg/d and quetiapine 100 mg/d for 3 months. After admission, we tapered fluoxetine gradually in 5 days because of its limited effect. However, delirious pictures developed 2 days after we stopped fluoxetine. Three days later, we added back fluoxetine 10 mg/d. Her delirious features gradually improved, and the clinical presentation turned into previous psychotic depression state. We gradually increased the medication to fluoxetine 60 mg/d and olanzapine 20 mg/d in the following 3 weeks. Her psychotic symptoms decreased, and there has been no delirious picture noted thereafter. Delirium associated with fluoxetine discontinuation is a much rarer complication in SSRI discontinuation syndrome. The symptoms of SSRI discontinuation syndrome may be attributable to a rapid decrease in serotonin availability. In general, the shorter the half-life of any medication, the greater the likelihood patients will experience discontinuation symptoms. Genetic vulnerability might be a potential factor to explain that SSRI discontinuation syndrome also occurred rapidly in people taking long-half-life fluoxetine. The genetic polymorphisms of both pharmacokinetic and pharmacodynamic pathways might be potentially associated with SSRI discontinuation syndrome.

Water resources of the Mobile area, Alabama, with a section on salinity of the Mobile River

USGS Publications Warehouse

Robinson, W.H.; Powell, William J.; Brown, Eugene; Corps of Engineers, U.S. Army

1956-01-01

Water is an abundant resource of the Mobile area. The Mobile River has an estimated average flow of 60, 000 cubic feet per second (cfs), or about 39,000 million gallons per day (mgd). It is the largest single source of water. Water is available in substantial quantities from the many local streams and extensive water-bearing formations almost anywhere in the area. Surface water is low in dissolved mineral matter and is extremely soft. Salt water moving up the Mobile River from Mobile Bay during periods of low river flow, however, limits the use of that stream as a source of supply. The principal water-bearing formations are the alluvium and sediments of Miocene age. The Miocene strata dip toward the southwest, forming an artesian basin in the downtown area of Mobile. Small groundwater supplies can be developed practically everywhere, and supplies for industrial or other large-scale uses are available north of Mobile. The average use of water from all sources in the area during 1954 was about 356 mgd, of which about 20 mgd was used for domestic supplies and 336 mgd was used by industry. An estimated 42 mgd of ground water is used in the Mobile area. The discharge from wells used by industry ranges from 10 to 1,500 gallons per minute (gpm}, and the specific capacity of the large-capacity wells ranges from less than 6 to about 6 3 gpm per foot of drawdown. Concentrated pumping in the downtown area of Mobile between 1941 and 1945 resulted in encroachment of salt water from the Mobile River into the alluvium. Because of a decrease in pumping in that vicinity, the sodium chloride content of the water has decreased substantially since 1945. The quality of ground water is variable. Hardness of waters sampled ranged from 1 to 2, 190 parts per million (ppm}, the dissolved solids from 27 to 13, 000 ppm, and the chloride from 2.2 to 6,760 ppm. The water of best quality occurs between McIntosh and Prichard, and the water of poorest quality occurs in the downtown area of Mobile. The water-supply systems presently developed in the metropolitan area could furnish a moderate increase without taxing their facilities; with some increase in plant and pumping facilities, they could support a substantial increase. Industries outside the metropolitan area must develop their own supplies from local streams or wells.

"Self-Shaping" of Multicomponent Drops.

PubMed

Cholakova, Diana; Valkova, Zhulieta; Tcholakova, Slavka; Denkov, Nikolai; Smoukov, Stoyan K

2017-06-13

In our recent study we showed that single-component emulsion drops, stabilized by proper surfactants, can spontaneously break symmetry and transform into various polygonal shapes during cooling [ Denkov Nature 2015 , 528 , 392 - 395 ]. This process involves the formation of a plastic rotator phase of self-assembled oil molecules beneath the drop surface. The plastic phase spontaneously forms a frame of plastic rods at the oil drop perimeter which supports the polygonal shapes. However, most of the common substances used in industry appear as mixtures of molecules rather than pure substances. Here we present a systematic study of the ability of multicomponent emulsion drops to deform upon cooling. The observed trends can be summarized as follows: (1) The general drop-shape evolution for multicomponent drops during cooling is the same as with single-component drops; however, some additional shapes are observed. (2) Preservation of the particle shape upon freezing is possible for alkane mixtures with chain length difference Δn ≤ 4; for greater Δn, phase separation within the droplet is observed. (3) Multicomponent particles prepared from alkanes with Δn ≤ 4 plastify upon cooling due to the formation of a bulk rotator phase within the particles. (4) If a compound, which cannot induce self-shaping when pure, is mixed with a certain amount of a compound which induces self-shaping, then drops prepared from this mixture can also self-shape upon cooling. (5) Self-emulsification phenomena are also observed for multicomponent drops. In addition to the three recently reported mechanisms of self-emulsification [ Tcholakova Nat. Commun. 2017 , ( 8 ), 15012 ], a new (fourth) mechanism is observed upon freezing for alkane mixtures with Δn > 4. It involves disintegration of the particles due to a phase separation of alkanes upon freezing.

Advanced Environmental Barrier Coatings Development for Si-Based Ceramics

NASA Technical Reports Server (NTRS)

Zhu, Dong-Ming; Choi, R. Sung; Robinson, Raymond C.; Lee, Kang N.; Bhatt, Ramakrishna T.; Miller, Robert A.

2005-01-01

Advanced environmental barrier coating concepts based on multi-component HfO2 (ZrO2) and modified mullite systems are developed for monolithic Si3N4 and SiC/SiC ceramic matrix composite (CMC) applications. Comprehensive testing approaches were established using the water vapor cyclic furnace, high pressure burner rig and laser heat flux steam rig to evaluate the coating water vapor stability, cyclic durability, radiation and erosion resistance under simulated engine environments. Test results demonstrated the feasibility and durability of the environmental barrier coating systems for 2700 to 3000 F monolithic Si3N4 and SiC/SiC CMC component applications. The high-temperature-capable environmental barrier coating systems are being further developed and optimized in collaboration with engine companies for advanced turbine engine applications.

Adequate intake of potassium does not cause hyperkalemia in hypertensive individuals taking medications that antagonize the renin angiotensin aldosterone system.

PubMed

Malta, Daniela; Arcand, JoAnne; Ravindran, Anju; Floras, Vanessa; Allard, Johane P; Newton, Gary E

2016-10-01

Reduced potassium excretion caused by angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) may increase the risk of hyperkalemia (serum potassium concentration >5 mmol/L) in the setting of increased potassium intake. The purpose of this study was to assess the effect of increasing dietary potassium on serum potassium concentration in hypertensive individuals with normal renal function treated with an ACEi or ARB. We hypothesized that an increase in dietary potassium would not provoke hyperkalemia in this population despite treatment with either an ACEi or ARB. We conducted a controlled, parallel-design clinical trial in 20 hypertensive subjects with normal renal function treated with an ACEi or ARB, with random assignment to a usual diet or a high-potassium diet (HKD). Fruit and vegetable intake was used to increase potassium intake. Serum potassium concentration, 3-d food records, and 24-h urine collections were completed at baseline and 4 wk. In the usual-diet group there were no statistically significant differences for potassium excretion, intake, or serum levels at end of study compared with baseline. The HKD group had significant differences in urinary potassium excretion (83 ± 26 mmol/d at baseline compared with 109 ± 35 mmol/d at 4 wk, P = 0.01) and dietary potassium intake (3775 ± 1189 mg/d at baseline compared with 5212 ± 1295 mg/d at 4 wk, P = 0.02). Despite increased potassium intake in the HKD group, serum potassium concentrations did not significantly increase from baseline at midpoint or end of study (4.1 ± 0.6, 4.3 ± 0.3, and 4.2 ± 0.4 mmol/L, respectively). This study demonstrates that an increase in dietary potassium over a 4-wk period is safe in hypertensive subjects who have normal renal function and are receiving ACEi and/or ARB therapy. This trial was registered at www.clinicaltrials.gov as NCT02759367. © 2016 American Society for Nutrition.

A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus.

PubMed

Suckfüll, Markus; Althaus, Michael; Ellers-Lenz, Barbara; Gebauer, Alexander; Görtelmeyer, Roman; Jastreboff, Pawel J; Moebius, Hans J; Rosenberg, Tanja; Russ, Hermann; Wirth, Yvonne; Krueger, Hagen

2011-01-11

Neramexane is a new substance that exhibits antagonistic properties at α9α10 cholinergic nicotinic receptors and N-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus. A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12). Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (p = 0.098 for 50 mg/d; p = 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with p values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence. This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies. ClinicalTrials.gov NCT00405886.

Water resources of the Grand Rapids area, Michigan

USGS Publications Warehouse

Stramel, G.J.; Wisler, C.O.; Laird, L.B.

1954-01-01

The Grand Rapids area, Michigan, has three sources from which to obtain its water supply: Lake Michigan, the Grand River and its tributaries, and ground water. Each of the first two and possibly the third is capable of supplying the entire needs of the area.This area is now obtaining a part of its supply from each of these sources. Of the average use of 50 mgd (million gallons per day) during 1951, Lake Michigan supplied 29 mgd; the Grand River and its tributaries supplied 1 mgd; and ground water supplied 20 mgd.Lake Michigan offers a practically unlimited source of potable water. However, the cost of delivery to the Grand Rapids area presents an economic problem in the further development of this source. Even without storage the Grand River can provide an adequate supply for the city of Grand Rapids. The present average use of the city of Grand Rapids is about 30 mgd and the maximum use is about 60 mgd, while the average flow of the Grand River is 2, 495 mgd or 3, 860 cfs (cubic feet per second) and the minimum daily flow recorded is 246 mgd. The quality and temperature of water in the Grand River is less desirable than Lake Michigan water. However, with proper treatment its chemical quality can be made entirely satisfactory.The city of Grand Rapids is actively engaged in a study that will lead to the expansion of its present water-supply facilities to meet the expected growth in population in Grand Rapids and its environs.Ground-water aquifers in the area are a large potential source of supply. The Grand Rapids area is underlain by glacial material containing a moderately hard to very hard water of varying chemical composition but suitable for most uses. The glacial outwash and lacustrine deposits bordering principal streams afford the greatest potential for the development of large supplies of potable ground water. Below the glacial drift, bedrock formations contain water that is extremely hard and moderately to highly mineralized. Thus the major sources of usable ground water are the glacial drift and some parts of the bedrock. Wherever the bedrock yields large quantities of water, the water is generally of inferior quality. Any development should be preceded by test drilling and careful hydrologic and geologic studies of the area under consideration and chemical analysis of the water found.

Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess.

PubMed

Ghavanini, Amer A; Kimpinski, Kurt

2014-09-01

Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine based on questionable evidence. However, neurological practitioners frequently discourage patients from taking pyridoxine in excess of 50 mg/d given concerns around the development of a toxic sensory neuronopathy. There is no systematic review to support either of the 2 practices. To address this gap in knowledge, we reviewed the available literature on neuropathy attributed to pyridoxine deficiency and excess. Based on the current limited data, it can be concluded that very low doses of daily pyridoxine are required to prevent peripheral neuropathy. There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system. Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged.

Nutritional intake of French soccer players at the clairefontaine training center.

PubMed

Leblanc, J Ch; Le Gall, F; Grandjean, V; Verger, Ph

2002-09-01

Young, French male athletes undergoing intensive elite sports training at the National Training Centre in Clairefontaine served as the subjects (N = 180; age range: 13 to 16 years) in a 3-year dietary survey aimed at characterizing their nutritional intake in terms of energy, macronutrients, calcium, and iron. Each year, the subjects were grouped by level into 3 promotions so that 9 groups could be studied. Dietary intake data were collected each year for each subject in the 9 groups, using a 5-day food record. The results showed that their total energy intake (TEI) was insufficient for athletes (ranging from 2352 454 to 3395 396 kcal/d as opposed to the recommended range of between 3819 and 5185 kcal/d). Furthermore, their diet was unbalanced, with too great an emphasis upon fatty foods (29.1 2.8 to 34.1 3.1% TEI vs. the 20% recommended), to the detriment of carbohydrates (48.5 4.3 to 56.6 3.1% TEI vs. the 55 to 60% recommended). The calcium intake was too low in 5 of the 9 groups while, in contrast, the iron intake was satisfactory in all groups. Furthermore, during this 3-year period at the Clairefontaine Centre, the subjects significantly (p <.05) improved their calcium and iron intakes (1021 197 and 12 2 mg/d in 1996, 1299 155 and 16 2 mg/d in 1997, and 1252 184 and 17 2 mg/d in 1998). This rise in micronutrient intakes may have been due to a physiological adaptation to growth or to the positive effects of courses on nutrition given during their stay at the Centre.

THE SPITZER SURVEY OF STELLAR STRUCTURE IN GALAXIES (S{sup 4}G): MULTI-COMPONENT DECOMPOSITION STRATEGIES AND DATA RELEASE

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

Salo, Heikki; Laurikainen, Eija; Laine, Jarkko

The Spitzer Survey of Stellar Structure in Galaxies (S{sup 4}G) is a deep 3.6 and 4.5 μm imaging survey of 2352 nearby (<40 Mpc) galaxies. We describe the S{sup 4}G data analysis pipeline 4, which is dedicated to two-dimensional structural surface brightness decompositions of 3.6 μm images, using GALFIT3.0. Besides automatic 1-component Sérsic fits, and 2-component Sérsic bulge + exponential disk fits, we present human-supervised multi-component decompositions, which include, when judged appropriate, a central point source, bulge, disk, and bar components. Comparison of the fitted parameters indicates that multi-component models are needed to obtain reliable estimates for the bulge Sérsicmore » index and bulge-to-total light ratio (B/T), confirming earlier results. Here, we describe the preparations of input data done for decompositions, give examples of our decomposition strategy, and describe the data products released via IRSA and via our web page (www.oulu.fi/astronomy/S4G-PIPELINE4/MAIN). These products include all the input data and decomposition files in electronic form, making it easy to extend the decompositions to suit specific science purposes. We also provide our IDL-based visualization tools (GALFIDL) developed for displaying/running GALFIT-decompositions, as well as our mask editing procedure (MASK-EDIT) used in data preparation. A detailed analysis of the bulge, disk, and bar parameters derived from multi-component decompositions will be published separately.« less

Transport-induced shifts in condensate dew-point and composition in multicomponent systems with chemical reaction

NASA Technical Reports Server (NTRS)

Rosner, D. E.; Nagarajan, R.

1985-01-01

Partial heterogeneous condensation phenomena in multicomponent reacting systems are analyzed taking into consideration the chemical element transport phenomena. It is demonstrated that the dew-point surface temperature in chemically reactive systems is not a purely thermodynamic quantity, but is influenced by the multicomponent diffusion and Soret-mass diffusion phenomena. Several distinct dew-points are shown to exist in such systems and, as a result of transport constraints, the 'sharp' locus between two chemically distinct condensates is systematically moved to a difference mainstream composition.

Armodafinil for fatigue associated with menopause: an open-label trial.

PubMed

Meyer, Fremonta; Freeman, Marlene P; Petrillo, Laura; Barsky, Maria; Galvan, Thania; Kim, Semmie; Cohen, Lee; Joffe, Hadine

2016-02-01

This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life. Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence. Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120 mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P = 0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P = 0.0001). Median hot flashes for 24 hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P = 0.0005). Improvements in MENQOL total score (49%; P = 0.0001), cognitive function (59.2%; P = 0.0002), depressive symptoms (64.7%; P = 0.0006), insomnia (72.7%; P = 0.0012), and excessive sleepiness (57.1%; P = 0.0006) were noted. Randomized continuation (n = 10) or discontinuation (n = 10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events. These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms.

Laser ultrasonic multi-component imaging

DOEpatents

Williams, Thomas K [Federal Way, WA; Telschow, Kenneth [Des Moines, WA

2011-01-25

Techniques for ultrasonic determination of the interfacial relationship of multi-component systems are discussed. In implementations, a laser energy source may be used to excite a multi-component system including a first component and a second component at least in partial contact with the first component. Vibrations resulting from the excitation may be detected for correlation with a resonance pattern indicating if discontinuity exists at the interface of the first and second components.

Effects of a New Eyelid Shampoo on Lid Hygiene and Eyelash Length in Patients with Meibomian Gland Dysfunction: A Comparative Open Study

PubMed Central

Miki, Emiko

2016-01-01

Purpose. Meibomian gland dysfunction (MGD) can lead to abnormalities in the composition and function of tear film, resulting in dry eye. Eyelid hygiene is a key to management of MGD. We tested a novel eyelid shampoo (Eye Shampoo Long, ESL) for its ability to maintain lid hygiene. This shampoo is nonirritating and can potentially lengthen eyelashes. This study was aimed to evaluate the efficacy of ESL in the treatment of MGD and its effects on eyelash length. Methods. Ten patients with MGD and 10 healthy subjects without MGD applied ESL twice daily for 8 weeks. Patients were examined for lid margin and dry eye before and after the trial. Subjective symptoms were evaluated. Eyelash length was measured at baseline and at the end of the trial. Results. In the MGD group, significant improvements were observed in subjective symptoms obstruction of the meibomian orifice, secretion of meibum, eyelashes contamination, eyelid margin foam, and SPK. Eyelash length became significantly longer. Conclusions. Maintaining eyelid hygiene using ESL improved the eyelid margins and symptoms of dry eye in MGD patients and increased eyelash length. These findings are promising and warrant confirmation in a larger randomized controlled study. PMID:28078136

Multimodal imaging of ocular surface of dry eye subjects

NASA Astrophysics Data System (ADS)

Zhang, Aizhong; Salahura, Gheorghe; Kottaiyan, Ranjini; Yoon, Geunyoung; Aquavella, James V.; Zavislan, James M.

2016-03-01

To study the relationship between the corneal lipid layer and the ocular surface temperature (OST), we conducted a clinical trial for 20 subjects. Subjects were clinically screened prior to the trial. Of the 20 subjects, 15 have Meibomian gland dysfunction (MGD), and 5 have aqueous-deficient dry eye (ADDE). A custom, circularly polarized illumination video tearscope measured the lipid layer thickness of the ocular tear film. A long-wave infrared video camera recorded the dynamic thermal properties of the ocular team film. The results of these two methods were analyzed and compared. Using principal component analysis (PCA) of the lipid layer distribution, we find that the 20 subjects could be categorized into five statistically significant groups, independent of their original clinical classification: thin (6 subjects), medium (5 subjects), medium and homogenous (3 subjects), thick (4 subjects), and very thick (2 subjects) lipids, respectively. We also conducted PCA of the OST data, and recategorized the subjects into two thermal groups by k-means clustering: one includes all ADDE subjects and some MGD subjects; the other includes the remaining MGD subjects. By comparing these two methods, we find that dry eye subjects with thin (<= 40 nm) lipids have significantly lower OST, and a larger OST drop range, potentially due to more evaporation. However, as long as the lipid layer is not thin (> 40 nm), there is no strong correlation between the lipid layer thickness and heterogeneity and the OST patterns.

The influence of different sub-bandage pressure values on venous leg ulcers healing when treated with compression therapy.

PubMed

Milic, Dragan J; Zivic, Sasa S; Bogdanovic, Dragan C; Jovanovic, Milan M; Jankovic, Radmilo J; Milosevic, Zoran D; Stamenkovic, Dragan M; Trenkic, Marija S

2010-03-01

Venous leg ulcers (VLU) have a huge social and economic impact. An estimated 1.5% of European adults will suffer a venous ulcer at some point in their lives. Despite the widespread use of bandaging with high pressure in the treatment of this condition, recurrence rates range between 25% to 70%. Numerous studies have suggested that the compression system should provide sub-bandage pressure values in the range from 35 mm Hg to 45 mm Hg in order to achieve the best possible healing results. An open, randomized, prospective, single-center study was performed in order to determine the healing rates of VLU when treated with different compression systems and different sub-bandage pressure values. One hundred thirty-one patients (72 women, 59 men; mean age, 59-years-old) with VLU (ulcer surface >3 cm(2); duration >3 months) were randomized into three groups: group A - 42 patients who were treated using an open-toed, elastic, class III compression device knitted in tubular form (Tubulcus, Laboratoires Innothera, Arcueil, France); group B - 46 patients treated with the multi-component bandaging system comprised of Tubulcus and one elastic bandage (15 cm wide and 5 cm long with 200% stretch, Niva, Novi Sad, Serbia); and group C - forty-three patients treated with the multi-component bandaging system comprised of Tubulcus and two elastic bandages. Pressure measurements were taken with the Kikuhime device (TT MediTrade, Soro, Denmark) at the B1 measuring point in the supine, sitting, and standing positions under the three different compression systems. The median resting values in the supine and standing positions in examined study groups were as follows: group A - 36.2 mm Hg and 43.9 mm Hg; group B - 53.9 mm Hg and 68.2 mm Hg; group C - 74.0 mm Hg and 87.4 mm Hg. The healing rate during the 26-week treatment period was 25% (13/42) in group A, 67.4% (31/46) in group B, and 74.4% (32/43) in group C. The success of compression treatment in group A was strongly associated with the small ulcer surface (<5 cm(2)) and smaller calf circumference (CC; <38 cm). On the other hand, compliance in group A was good. In groups B and C, compliance was poor in patients with small CC, but the healing rate was high, especially in patients with large ulcers and a large CC (>43 cm). The results obtained in this study indicate that better healing results are achieved with two or multi-component compression systems than with single-component compression systems and that a compression system should be individually determined for each patient according to individual characteristics of the leg and CC. Target sub-bandage pressure value (B1 measuring point in the sitting position) of the compression system needed for the ulcer healing could be determined according to a simple formula, CC + CC/2.

Scaled Particle Theory for Multicomponent Hard Sphere Fluids Confined in Random Porous Media.

PubMed

Chen, W; Zhao, S L; Holovko, M; Chen, X S; Dong, W

2016-06-23

The formulation of scaled particle theory (SPT) is presented for a quite general model of fluids confined in a random porous media, i.e., a multicomponent hard sphere (HS) fluid in a multicomponent hard sphere or a multicomponent overlapping hard sphere (OHS) matrix. The analytical expressions for pressure, Helmholtz free energy, and chemical potential are derived. The thermodynamic consistency of the proposed theory is established. Moreover, we show that there is an isomorphism between the SPT for a multicomponent system and that for a one-component system. Results from grand canonical ensemble Monte Carlo simulations are also presented for a binary HS mixture in a one-component HS or a one-component OHS matrix. The accuracy of various variants derived from the basic SPT formulation is appraised against the simulation results. Scaled particle theory, initially formulated for a bulk HS fluid, has not only provided an analytical tool for calculating thermodynamic properties of HS fluid but also helped to gain very useful insight for elaborating other theoretical approaches such as the fundamental measure theory (FMT). We expect that the general SPT for multicomponent systems developed in this work can contribute to the study of confined fluids in a similar way.

Multi-component sorption of Pb(II), Cu(II) and Zn(II) onto low-cost mineral adsorbent.

PubMed

Prasad, Murari; Xu, Huan-yan; Saxena, Sona

2008-06-15

Multi-component sorption studies were carried out for attenuation of divalent heavy metal cations (Pb2+, Cu2+ and Zn2+) by a low-cost mineral adsorbent from the aqueous solution. Kinetic and equilibrium batch-type sorption experiments were conducted under variable conditions for multi-component using low-grade (<12%P2O5) phosphate rock. Percentage of multiple heavy metal species removal increases with decreasing initial metals concentration and particle size. The equilibrium data were well described to a lesser extent by Freundlich model but Langmuir model seemed to be more appropriate with the fixation capacity obtained at room temperature for Pb2+, Cu2+ and Zn2+ was 227.2, 769.2 and 666.6 micromol g(-1), respectively. Two simple kinetic models were tested to investigate the adsorption mechanism. Rate constants have been found nearly constant at all metal concentrations for first order. The comparison of adsorption capacity of low-grade phosphate rock decreases in multi-component system as compared to single component due to ionic interactions. X-ray powder diffraction (XRPD) technique was used to ascertain the formation of new metal phases followed by surface complexation. Used adsorbents have been converted into a value added product by utilizing innovative Zero-waste concept to solve the used adsorbents disposal problem and thus protecting the environment.

Meibomian gland dysfunction and ocular discomfort in video display terminal workers.

PubMed

Fenga, C; Aragona, P; Cacciola, A; Spinella, R; Di Nola, C; Ferreri, F; Rania, L

2008-01-01

Meibomian gland dysfunction (MGD) is one of the most common ocular disorders encountered in clinical practice. The clinical manifestations of MGD are related to the changes in the tear film and ocular surface with symptoms of ocular discomfort. In recent years, many surveys have evaluated symptoms associated with the use of Video Display Terminals (VDT), and VDT use is recognized as a risk factor for eye discomfort. The aim of the present study was to determine if the presence of MGD contributes to the signs and symptoms of ocular discomfort during the use of VDT. In course of a routine health surveillance programme, a group of 70 subjects fulfilled the inclusion criteria and responded to a questionnaire about symptoms of ocular discomfort. The following ocular tests were performed: tear break-up time, fluorescein corneal stain, and basal tear secretion test. A total of 52 subjects out of 70 (74.3%) had MGD. A statistically significant correlation between the symptoms of ocular discomfort and hours spent on VDT work was observed in the total population (r=0.358; P=0.002; 95% CI 0.13-0.54) and in the group of subjects with MGD (r=0.365; P=0.009; 95% CI 0.103-0.58). Such correlation was not shown in subjects without MGD. The high prevalence of MGD among the subjects with symptoms of ocular discomfort suggests that this diagnosis should be considered when occupational health practitioners encounter ocular complaints among VDT operators. It appears that MGD can contribute to the development of ocular discomfort in VDT operators.

Liquid scintillators for optical fiber applications

DOEpatents

Franks, Larry A.; Lutz, Stephen S.

1982-01-01

A multicomponent liquid scintillator solution for use as a radiation-to-light converter in conjunction with a fiber optic transmission system. The scintillator includes a quantity of 1, 2, 4, 5, 3H, 6H, 1 OH, tetrahydro-8-trifluoromethyl (1) benzopyrano (9, 9a, 1-gh) quinolizin-10-one (Coumarin) as a solute in a fluor solvent such as benzyl alcohol or pseudo-cumene. The use of BIBUQ as an additional or primary solute is also disclosed.

Large area CMOS active pixel sensor x-ray imager for digital breast tomosynthesis: Analysis, modeling, and characterization

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

Zhao, Chumin; Kanicki, Jerzy, E-mail: kanicki@eecs.umich.edu; Konstantinidis, Anastasios C.

Purpose: Large area x-ray imagers based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been proposed for various medical imaging applications including digital breast tomosynthesis (DBT). The low electronic noise (50–300 e{sup −}) of CMOS APS x-ray imagers provides a possible route to shrink the pixel pitch to smaller than 75 μm for microcalcification detection and possible reduction of the DBT mean glandular dose (MGD). Methods: In this study, imaging performance of a large area (29 × 23 cm{sup 2}) CMOS APS x-ray imager [Dexela 2923 MAM (PerkinElmer, London)] with a pixel pitch of 75 μm was characterizedmore » and modeled. The authors developed a cascaded system model for CMOS APS x-ray imagers using both a broadband x-ray radiation and monochromatic synchrotron radiation. The experimental data including modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were theoretically described using the proposed cascaded system model with satisfactory consistency to experimental results. Both high full well and low full well (LFW) modes of the Dexela 2923 MAM CMOS APS x-ray imager were characterized and modeled. The cascaded system analysis results were further used to extract the contrast-to-noise ratio (CNR) for microcalcifications with sizes of 165–400 μm at various MGDs. The impact of electronic noise on CNR was also evaluated. Results: The LFW mode shows better DQE at low air kerma (K{sub a} < 10 μGy) and should be used for DBT. At current DBT applications, air kerma (K{sub a} ∼ 10 μGy, broadband radiation of 28 kVp), DQE of more than 0.7 and ∼0.3 was achieved using the LFW mode at spatial frequency of 0.5 line pairs per millimeter (lp/mm) and Nyquist frequency ∼6.7 lp/mm, respectively. It is shown that microcalcifications of 165–400 μm in size can be resolved using a MGD range of 0.3–1 mGy, respectively. In comparison to a General Electric GEN2 prototype DBT system (at MGD of 2.5 mGy), an increased CNR (by ∼10) for microcalcifications was observed using the Dexela 2923 MAM CMOS APS x-ray imager at a lower MGD (2.0 mGy). Conclusions: The Dexela 2923 MAM CMOS APS x-ray imager is capable to achieve a high imaging performance at spatial frequencies up to 6.7 lp/mm. Microcalcifications of 165 μm are distinguishable based on reported data and their modeling results due to the small pixel pitch of 75 μm. At the same time, potential dose reduction is expected using the studied CMOS APS x-ray imager.« less

(n, N) type maintenance policy for multi-component systems with failure interactions

NASA Astrophysics Data System (ADS)

Zhang, Zhuoqi; Wu, Su; Li, Binfeng; Lee, Seungchul

2015-04-01

This paper studies maintenance policies for multi-component systems in which failure interactions and opportunistic maintenance (OM) involve. This maintenance problem can be formulated as a Markov decision process (MDP). However, since an action set and state space in MDP exponentially expand as the number of components increase, traditional approaches are computationally intractable. To deal with curse of dimensionality, we decompose such a multi-component system into mutually influential single-component systems. Each single-component system is formulated as an MDP with the objective of minimising its long-run average maintenance cost. Under some reasonable assumptions, we prove the existence of the optimal (n, N) type policy for a single-component system. An algorithm to obtain the optimal (n, N) type policy is also proposed. Based on the proposed algorithm, we develop an iterative approximation algorithm to obtain an acceptable maintenance policy for a multi-component system. Numerical examples find that failure interactions and OM pose significant effects on a maintenance policy.

Nonequilibrium Contribution to the Rate of Reaction. III. Isothermal Multicomponent Systems

DOE R&D Accomplishments Database

Shizgal, B.; Karplus, M.

1970-10-01

The nonequilibrium contribution to the reaction rate of an isothermal multicomponent system is obtained by solution of the appropriate Chapman-Enskog equation; the system is composed of reactive species in contact with a heat bath of inert atoms M.

Rapid correction of electron microprobe data for multicomponent metallic systems

NASA Technical Reports Server (NTRS)

Gupta, K. P.; Sivakumar, R.

1973-01-01

This paper describes an empirical relation for the correction of electron microprobe data for multicomponent metallic systems. It evaluates the empirical correction parameter, a for each element in a binary alloy system using a modification of Colby's MAGIC III computer program and outlines a simple and quick way of correcting the probe data. This technique has been tested on a number of multicomponent metallic systems and the agreement with the results using theoretical expressions is found to be excellent. Limitations and suitability of this relation are discussed and a model calculation is also presented in the Appendix.

Acidic mammalian chitinase in dry eye conditions.

PubMed

Musumeci, Maria; Aragona, Pasquale; Bellin, Milena; Maugeri, Francesco; Rania, Laura; Bucolo, Claudio; Musumeci, Salvatore

2009-07-01

An acidic mammalian chitinase (AMCase) seems to be implicated in allergic asthma and allergic ocular pathologies. The aim of this work was to investigate the role of AMCase during Sjögren's Syndrome (SS) and Meibomian Gland Dysfunction (MGD) dry eye diseases. Six patients with MGD dry eye (20-58 years, median 40) and six patients with dry eye associated to SS (32-60 years, median 47) were enrolled in this study. AMCase activity was measured in tears and AMCase mRNA expression was evaluated by real-time polymerase chain reaction from RNA extracted from epithelial cells of the conjunctiva. Six healthy adult subjects of the same age (34-44 years, median 39) were also studied as the control group. AMCase activity was significantly increased in patients affected by MGD dry eye (18.54 +/- 1.5 nmol/ml/h) and SS dry eye (8.94 +/- 1.0 nmol/ml/h) respectively, compared to healthy controls (1.6 +/- 0.2 nmol/ml/h). AMCase activity was higher in the tears of subjects with MGD dry eye (P < 0.001). AMCase mRNA was detected in conjunctival epithelial cells and the expression was significantly higher in MGD dry eye than SS dry eye. A significant correlation between AMCase activity in the tears and mRNA in conjunctival epithelial cells was found. AMCase may be an important marker in the pathogenesis of dry eye, suggesting the potential role of AMCase as a therapeutic target in these frequent pathologies.

A technology-enabled adherence enhancement system for people with bipolar disorder: results from a feasibility and patient acceptance analysis

PubMed Central

Sajatovic, Martha; Davis, Michael S; Cassidy, Kristin A; Nestor, Joseph; Sams, Johnny; Fuentes-Casiano, Edna

2015-01-01

Objective As poor medication adherence is common in bipolar disorder (BD), technology-assisted approaches may help to monitor and enhance adherence. This study evaluated preliminary feasibility, patient satisfaction and effects on adherence, BD knowledge, and BD symptoms associated with the use of a multicomponent technology-assisted adherence enhancement system. Methods This prospective study tested the system in five BD patients over a 15-day period. System components included: 1) an automated pill cap with remote monitoring sensor; 2) a multimedia adherence enhancement program; and 3) a treatment incentive program. This study evaluated system usability, patient satisfaction and effects on adherence (Morisky scale), knowledge (treatment knowledge test [TKT]), and symptoms (internal state scale [ISS]). Results Mean age of the sample was 62 years, 4/5 (80%) Caucasian, and 4/5 (80%) single/divorced or widowed. Most participants (4/5, 80%) were on a single BD medication. Participants had BD for an average of 21 years. Challenges included attaching the pill sensor to standard pharmacy bottles for individuals using very large pill containers or those with multiday pill boxes. Three of five (60%) individuals completed the full 15-day period. Usability scores were high overall. Mean Morisky scores improved. Means on all four subscales of the ISS were all in the direction of improvement. On the TKT, there was a 40% increase in mean scores. Conclusion A multicomponent technology-assisted BD adherence enhancement system is feasible. Challenges include accommodating multiple types of pill containers and monitoring multiple drugs simultaneously. The system can also generate adherence information that is potentially useful for treatment planning. PMID:26089652

76 FR 51876 - Medical Devices; Ophthalmic Devices; Classification of the Eyelid Thermal Pulsation System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... meibomian gland dysfunction (MGD), also known as evaporative dry eye or lipid deficiency dry eye. The system... evaporative dry eye or lipid deficiency dry eye. The system consists of a component that is inserted around...

Optimization of the crystal growth of the superconductor CaKFe4As4 from solution in the FeAs -CaFe2As2-KFe2As2 system

NASA Astrophysics Data System (ADS)

Meier, W. R.; Kong, T.; Bud'ko, S. L.; Canfield, P. C.

2017-06-01

Measurements of the anisotropic properties of single crystals play a crucial role in probing the physics of new materials. Determining a growth protocol that yields suitable high-quality single crystals can be particularly challenging for multicomponent compounds. Here we present a case study of how we refined a procedure to grow single crystals of CaKFe4As4 from a high temperature, quaternary liquid solution rich in iron and arsenic ("FeAs self-flux"). Temperature dependent resistance and magnetization measurements are emphasized, in addition to the x-ray diffraction, to detect intergrown CaKFe4As4 , CaFe2As2 , and KFe2As2 within what appear to be single crystals. Guided by the rules of phase equilibria and these data, we adjusted growth parameters to suppress formation of the impurity phases. The resulting optimized procedure yielded phase-pure single crystals of CaKFe4As4 . This optimization process offers insight into the growth of quaternary compounds and a glimpse of the four-component phase diagram in the pseudoternary FeAs -CaFe2As2-KFe2As2 system.

The two novel DLL4-targeting antibody-drug conjugates MvM03 and MGD03 show potent anti-tumour activity in breast cancer xenograft models.

PubMed

Wang, Shijing; Zhou, Rihong; Sun, Fumou; Li, Renjie; Wang, Min; Wu, Min

2017-11-28

The anti-human Delta-like 4 (DLL4) monoclonal antibody MMGZ01 has a high affinity to hrDLL4 and arrests the DLL4-mediated human umbilical vein endothelial cell (HUVEC) phenotype, promotes immature vessels, and effectively reduces breast cancer cell growth in vivo. To develop a much more effective therapy, we conjugated MMGZ01 with two small-molecule cytotoxic agents, i.e., monomethyl auristatin E (MMAE) and doxorubicin (DOX), with different linkers to generate antibody-drug conjugates (ADCs), i.e., MMGZ01-vc-MMAE (named MvM03) and MMGZ01-GMBS-DOX (named MGD03), that are more potent therapeutic agents than naked antibody therapeutic agents. The produced anti-DLL4 ADCs can be effectively directed against DLL4 and internalized. Then, the release of MMAE or DOX into the cytosol can induce G2/M or G0/G1 phase growth arrest and cell death through the induction of apoptosis. In vitro, MvM03 was highly potent and selective against DLL4 cell lines. The anti-DLL4 ADCs, particularly MvM03, showed more potent anti-tumour activity than Docetaxel, which is an inhibitor of the depolymerisation of microtubules, in two xenograft breast cancer tumour models. Our findings indicate that anti-DLL4 ADCs have promising potential as an effective therapy for breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

75 FR 62176 - Notice of Projects Approved for Consumptive Uses of Water

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-07

... Hipple Pad A, ABR- 201008021, Gamble Township, Lycoming County, Pa.; Consumptive Use of up to 3.000 mgd..., Gamble Township, Lycoming County, Pa.; Consumptive Use of up to 3.000 mgd; Approval Date: August 6, 2010..., Gamble Township, Lycoming County, Pa.; Consumptive Use of up to 3.000 mgd; Approval Date: August 11, 2010...

The function and morphology of Meibomian glands in patients with thyroid eye disease: a preliminary study.

PubMed

Wang, Chia-Yu; Ho, Ren-Wen; Fang, Po-Chiung; Yu, Hun-Ju; Chien, Chun-Chih; Hsiao, Chang-Chun; Kuo, Ming-Tse

2018-04-12

To investigate function and morphology of the meibomian gland (MG) in patients with thyroid eye disease (TED). In this prospective case series study, patients with unilateral or bilateral TED were consecutively enrolled. The diagnosis of TED was based on the typical orbital findings and/or radiographic evidence. The disease activity of TED was classified according to the clinical activity score (CAS). Degrees of lagophthalmos and exophthalmos, blinking rates, and results of the Schirmer test 1 were also recorded. All patients completed the SPEED questionnaire and underwent MG assessment, including lipid layer thickness (LLT), MG dropout (MGd), and MG expression. In total 31 eyes from 17 patients with unilateral or bilateral TED were included. Patients were divided into inactive TED (CAS 0-1; 20 eyes from 11 patients) and active TED (CAS 2-3, 11 eyes from 6 patients) groups. MGd was significantly more severe in the active TED than the inactive TED group [Median (Inter-quartile region): 3.0 (2.0-3.0) vs. 2.0 (1.0-2.0) degree, P = 0.04]. However, patients with active TED had thicker LLT than those with inactive TED (90.0 [80.0-100.0] vs. 65.0 [47.8-82.5] nm, P = 0.02), and LLT was positively correlated with lagophthalmos (r = 0.37, P = 0.04). Patients with active TED had more severe MGd, but thicker LLT. Active TED may cause periglandular inflammation of MGs, leading to MGd, but compensatory secretion from residual MGs and lagophthalmos-induced forceful blinking might temporarily release more lipids over the tear film.

Serum concentrations and effects of gabapentin and vigabatrin: observations from a dose titration study.

PubMed

Lindberger, Martin; Luhr, Owe; Johannessen, Svein I; Larsson, Sirkku; Tomson, Torbjörn

2003-08-01

To explore possible concentration-effect relationships, gabapentin (GBP) and vigabatrin (VGB) serum concentrations were obtained from patients participating in an add-on dose-titration trial comparing GBP and VGB in partial epilepsy. Patients randomized to GBP started on 1800 mg/d and could have their dosage increased stepwise to 2400 and 3600 mg/d if seizures persisted. Those randomised to VGB started on 1000 mg/d, and the dose could be increased to 2000 and 4000 mg/d. Blood samples were obtained at steady state, at a nonstandardized time, from 27 patients randomized to GBP and from 36 randomized to VGB. Serum samples were analyzed using high-performance liquid chromatography. The treatment effect was expressed as percentage reduction in number of seizures from baseline. In addition, patients were classified as responders (>50% reduction in number of seizures from baseline) or nonresponders. There was no significant correlation between serum concentrations of GBP and seizure reduction at the lowest dosage, 1800 mg/d (r = -0.02, P = 0.94, Spearman-rank), nor between VGB serum levels and seizure reduction at 1000 mg/d of VGB (r = -0.14, P = 0.44). The serum GBP concentrations among responders to GBP 1800 mg/d were 26 +/- 12 micro mol/L (mean +/- SD), which was not different from serum concentrations in nonresponders, 28+/-13 micro mol/L. Nor was there a difference between serum concentrations of responders and nonresponders to VGB 1000 mg/d (32 +/- 23 and 44 +/- 36 micro mol/L, respectively). Hence, with the present study design we were unable to identify specific target ranges of GBP and VGB serum concentrations.

Ethinyl estradiol-cyproterone acetate versus low-dose pioglitazone-flutamide-metformin for adolescent girls with androgen excess: divergent effects on CD163, TWEAK receptor, ANGPTL4, and LEPTIN expression in subcutaneous adipose tissue.

PubMed

Díaz, Marta; Chacón, Matilde R; López-Bermejo, Abel; Maymó-Masip, Elsa; Salvador, Cristina; Vendrell, Joan; de Zegher, Francis; Ibáñez, Lourdes

2012-10-01

The aim was to compare the effects of a traditional therapy (an oral estroprogestagen) to those of a novel treatment (a low-dose combination of generics) in adolescent girls with androgen excess. In an open-label trial over 1 yr, 34 adolescents (age, 16 yr; body mass index, 23 kg/m2) with hyperinsulinemic androgen excess and without pregnancy risk were randomized to receive daily ethinyl estradiol-cyproterone acetate (EE-CA; Diane 35 Diario) or a low-dose combination of pioglitazone 7.5 mg/d, flutamide 62.5 mg/d, and metformin 850 mg/d (PioFluMet). Markers of androgen excess, C-reactive protein, high molecular weight adiponectin, lipids, carotid intima media thickness, body composition (absorptiometry), abdominal fat partitioning (magnetic resonance imaging), and gene expression in longitudinal biopsies of sc adipose tissue at the abdominal level (RT-PCR) were assessed at baseline and after 1 yr. EE-CA and low-dose PioFluMet reduced androgen excess comparably, but had divergent effects on C-reactive protein, high molecular weight adiponectin, lipids, carotid intima media thickness, lean mass, abdominal and visceral fat, and on the expression of CD163, leptin, TNF-like weak inducer of apoptosis receptor, and angiopoietin-like protein 4, respectively, related to macrophage activation, fat accretion, inflammation, and lipoprotein metabolism in adipose tissue. All these divergences pointed to a healthier condition on low-dose PioFluMet. EE-CA and PioFluMet are similarly effective in reversing androgen excess over 1 yr, but low-dose PioFluMet is superior in reversing inflammatory, metabolic, and cardiovascular anomalies that are often associated with androgen excess.

Desensitization to clopidogrel: a tailor-made protocol.

PubMed

Barreira, P; Cadinha, S; Malheiro, D; Moreira da Silva, J P

2014-01-01

Clopidogrel is an antiplatelet drug widely used for treatment and prevention of a variety of cardiovascular diseases. We report a successful desensitization to clopidogrel in a 70-year-old Caucasian man with delayed hypersensitivity (HS) reaction. He developed lip, hand and foot swelling, erythematous papular non-pruritic lesions and arthralgias 2 weeks after starting treatment with clopidogrel 75 mg/d. A 3-hour desensitization protocol was started, achieving a cumulative dose of 154 mg without any reaction, and a daily dose of 75 mg was recommended. On the 4th day, the patient developed skin lesions similar to the previously described. He was treated with topical steroids and oral antihistamines, and the daily dose of clopidogrel was reduced to 20 mg. A new desensitization protocol was established, with a slow dose increment, according to the patient's response. It was only possible to achieve the dose of 75 mg/d after 2 months. Although well tolerated by most patients, HS reactions with clopidogrel may occur and desensitization is rising as a safe alternative in those patients. In delayed reactions with cutaneous lesions, a slower desensitization protocol may be necessary, as in this case.

Dosimetry in x-ray-based breast imaging

PubMed Central

Dance, David R; Sechopoulos, Ioannis

2016-01-01

The estimation of the mean glandular dose to the breast (MGD) for x-ray based imaging modalities forms an essential part of quality control and is needed for risk estimation and for system design and optimisation. This review considers the development of methods for estimating the MGD for mammography, digital breast tomosynthesis (DBT) and dedicated breast CT (DBCT). Almost all of the methodology used employs Monte Carlo calculated conversion factors to relate the measurable quantity, generally the incident air kerma, to the MGD. After a review of the size and composition of the female breast, the various mathematical models used are discussed, with particular emphasis on models for mammography. These range from simple geometrical shapes, to the more recent complex models based on patient DBCT examinations. The possibility of patient-specific dose estimates is considered as well as special diagnostic views and the effect of breast implants. Calculations using the complex models show that the MGD for mammography is overestimated by about 30% when the simple models are used. The design and uses of breast-simulating test phantoms for measuring incident air kerma are outlined and comparisons made between patient and phantom-based dose estimates. The most widely used national and international dosimetry protocols for mammography are based on different simple geometrical models of the breast, and harmonisation of these protocols using more complex breast models is desirable. PMID:27617767

Dosimetry in x-ray-based breast imaging

NASA Astrophysics Data System (ADS)

Dance, David R.; Sechopoulos, Ioannis

2016-10-01

The estimation of the mean glandular dose to the breast (MGD) for x-ray based imaging modalities forms an essential part of quality control and is needed for risk estimation and for system design and optimisation. This review considers the development of methods for estimating the MGD for mammography, digital breast tomosynthesis (DBT) and dedicated breast CT (DBCT). Almost all of the methodology used employs Monte Carlo calculated conversion factors to relate the measurable quantity, generally the incident air kerma, to the MGD. After a review of the size and composition of the female breast, the various mathematical models used are discussed, with particular emphasis on models for mammography. These range from simple geometrical shapes, to the more recent complex models based on patient DBCT examinations. The possibility of patient-specific dose estimates is considered as well as special diagnostic views and the effect of breast implants. Calculations using the complex models show that the MGD for mammography is overestimated by about 30% when the simple models are used. The design and uses of breast-simulating test phantoms for measuring incident air kerma are outlined and comparisons made between patient and phantom-based dose estimates. The most widely used national and international dosimetry protocols for mammography are based on different simple geometrical models of the breast, and harmonisation of these protocols using more complex breast models is desirable.

Archive of U.S. Geological Survey selected single-beam bathymetry datasets, 1969-2000

USGS Publications Warehouse

Schreppel, Heather A.; Degnan, Carolyn H.; Dadisman, Shawn V.; Metzger, Dan R.

2013-01-01

New national programs, as well as natural and man-made disasters, have raised awareness about the need to find new and improved ways to share information about the coastal and marine environment with a wide-ranging public audience. The U.S. Geological Survey (USGS) Coastal and Marine Geology Program (CMGP) has begun a large-scale effort to incorporate the program's published, digital geophysical data into a single point of access known as the Coastal and Marine Geoscience Data System (CMGDS) (http://cmgds.marine.usgs.gov/). To aid in data discovery, work is also being done to import CMGP data into highly visible data and information resources, such as the National Oceanic and Atmospheric Administration's (NOAA) National Geophysical Data Center (NGDC) and two widely used Earth-science tools, GeoMapApp (GMA) (http://www.geomapapp.org) and Virtual Ocean (VO) (http://www.virtualocean.org/). This task of the CMGP Integrated Data Management System project will help support information exchange with partners, regional planning groups, and the public, as well as facilitate integrated spatial-data analysis. Sharing USGS-CMGP geophysical data via CMGDS, NGDC, GMA, and VO will aid data discovery and enable the data to support new purposes beyond those for which the data were originally intended. In order to make data available to NGDC, and from there into GMA and VO, the data must be reformatted into a standard exchange format and published. In 1977, a group of geophysical data managers from the public and private sectors developed the MGD77 format as the standard exchange format for geophysical data. In 2010, a tab-delimited version of the format was added as MGD77T (Hittelman and others, 1977). The MGD77T geophysical data format can include bathymetry, magnetics, gravity, and seismic navigation data. It is used for the transmission of data between marine institutions, data centers, and can be used by various software programs as an exchange format. A header (documentation) file and data file are created for each survey (Hittelman and others, 1977). More details about the MGD77T format are available at http://www.ngdc.noaa.gov/mgg/dat/geodas/docs/mgd77.pdf (74MB PDF). This archive describes the detailed steps used to convert single-beam bathymetry and navigation files into the MGD77T format (Hittelman and others, 1977) for submission to NGDC and formal Federal Geographic Data Committee (FGDC) (http://www.fgdc.gov/metadata) metadata as a publication of these single-beam bathymetry datasets.

Elevated International Normalized Ratio in a Patient Taking Warfarin and Mauby: A Case Report.

PubMed

Sorbera, Maria; Joseph, Tina; DiGregorio, Robert V

2017-10-01

We describe a 70-year-old Haitian man who had been taking warfarin for 5 years for atrial fibrillation and pulmonary hypertension. This patient had his international normalized ratio (INR) checked in the pharmacist-run anticoagulation clinic and was followed monthly. Prior to the interaction, his INR was therapeutic for 5 months while taking warfarin 10.5 mg/d. The patient presented with an INR > 8.0. Patient held 4 days of warfarin and restarted on warfarin 8.5 mg/d. Two weeks later, his INR was 2.5. After continuing dose, patient presented 2 weeks later and INR was 4.8. Upon further questioning, the patient stated he recently began ingesting mauby. Mauby is a bitter dark liquid extracted from the bark of the mauby tree that is commonly used in the Caribbean population as a folk remedy with many health benefits. This case report illustrates that mauby may have a probable drug-herb interaction (Naranjo Algorithm Score of 6) when given with warfarin. There is a lack of published literature and unclear information on the Internet describing the interaction of mauby and warfarin. Health professionals should be cautious regarding interactions between warfarin and mauby until the interaction is fully elucidated.

A retrospective Aliskiren and Losartan study in non-diabetic chronic kidney disease.

PubMed

Woo, Keng-Thye; Choong, Hui-Lin; Wong, Kok-Seng; Tan, Han-Kim; Foo, Marjorie; Stephanie, Fook-Chong; Lee, Evan Jc; Anantharaman, Vathsala; Lee, Grace Sl; Chan, Choong-Meng

2013-11-06

To assess the efficacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease (CKD). This is a retrospective study of 143 patients with non-diabetic CKD comparing combined Aliskiren (150 mg/d) with Losartan (100 mg/d) therapy vs High dose Angiotensin receptor blockers (ARB) (Losartan 200 mg/d) and the third group Aliskiren (150 mg/d) alone. This study involved only patient medical records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate (eGFR) < 15 mL/min or end stage renal failure. Patients treated with high dose ARB compared to the other two treatment groups had significantly less proteinuria at the end of 36 mo (P < 0.007). All 3 groups had significant reduction of proteinuria (P < 0.043, P < 0.001). Total urinary protein was significantly different between the 3 groups over the 3-year study period (P = 0.008), but not eGFR. The changes in eGFR from baseline to each year were not significantly different between the 3 therapeutic groups (P < 0.119). There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia (> 5.5 mmol/L) was 14.2% (7/49) in the Combined Aliskiren and ARB group, 8.7% (4/46) in the Aliskiren alone group and 6.3% (3/48) in the High dose ARB group (P < 0.001). This study in non-diabetic CKD patients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was associated with a high prevalence of hyperkalaemia.

TELMISARATAN PROVIDES BETTER RENAL PROTECTION THAN VALSARTAN IN A RAT MODEL OF METABOLIC SYNDROME

PubMed Central

Khan, Abdul Hye; Imig, John D.

2013-01-01

BACKGROUND Angiotension receptor blockers (ARB), telmisartan and valsartan were compared for renal protection in spontaneously hypertensive rats (SHR) fed high fat diet. We hypothesized that in cardiometabolic syndrome, telmisartan an ARB with PPAR-γ activity will offer better renal protection. METHODS SHR were fed either normal (SHR-NF, 7% fat) or high fat (SHR-HF, 36% fat) diet and treated with an ARB for 10 weeks. RESULTS Blood pressure was similar between SHR-NF (190±3 mmHg) and SHR-HF (192±4 mmHg) at the end of the 10 week period. Telmisartan and valsartan decreased blood pressure to similar extents in SHR-NF and SHR-HF groups. Body weight was significantly higher in SHR-HF (368±5g) compared to SHR-NF (328±7g). Telmisartan but not valsartan significantly reduced the body weight gain in SHR-HF. Telmisartan was also more effective than valsartan in improving glycemic and lipid status in SHR-HF. Monocyte chemoattractant protein-1 (MCP-1), an inflammatory marker, was higher in SHR-HF (24±2 ng/d) compared to SHR-NF (14±5 ng/d). Telmisartan reduced MCP-1 excretion in both SHR-HF and SHR-NF to a greater extent than valsartan. An indicator of renal injury, urinary albumin excretion increased to 85±8 mg/d in SHR-HF compared to 54±9 mg/d in SHR-NF. Telmisartan (23±5 mg/d) was more effective than valsartan (45±3 mg/d) in lowering urinary albumin excretion in SHR-HF. Moreover, telmisartan reduced glomerular damage to a greater extent than valsartan in the SHR-HF. CONCLUSIONS Collectively, our data demonstrate that telmisartan was more effective than valsartan in reducing body weight gain, renal inflammation, and renal injury in a rat model of cardiometabolic syndrome. PMID:21415842

[Comparison of the dietary phytosterols intake and serum lipids content in elderly women from three cities of China].

PubMed

Han, Jun-hua; Li, Yan-ping; Men, Jian-hua; Yu, Wen-tao; Yang, Yue-xin

2009-12-01

To investigate the dietary phytosterol intake of elderly women in three different cities of China, and to compare the main dietary sources, so that to discuss the relationship of dietary phytosterol intake and serum lipids. Based on the dietary pattern, women more than 50 years old from Beijing, Hefei and Urumchi were chosen as testers, 80 - 100 people for each city respectively. The dietary survey was done by continues 24 hours review of two days, the plant food were collected and the phytosterol content (include beta-sitosterol, campesterol, stigmasterol, sitostanol) were analyzed by GC methods, the total phytosterols content were calculated. The dietary phytosterol intake were calculated and serum lipids were also analyzed in all the testers. Testers from Beijing, Hefei and Urumchi were 100, 101 and 84 respectively. The average dietary phytosterol intake of people in Beijing and Hefei were 340.3 mg/d and 313.5 mg/d, the main sources were plant oil and cereals, while the average dietary phytosterol intake of people in Urumchi were 550.4 mg/d, higher than the other two cities (t values were 9.369, 10.420, respectively, both P values < 0.01), the main source in Urumchi was cereal (provide 53.1% of the total phytosterol intake). The laboratory results showed, testers in Urumchi had significantly lower serum TC content ((4.04 +/- 0.78) mmol/L) than that in Beijing ((4.89 +/- 0.91) mmol/L) and Hefei ((4.71 +/- 0.83) mmol/L) (t value were 6.766 and 5.401 respectively, both P values < 0.01); serum TG content in Urumchi((1.01 +/- 0.48) mmol/L) was also lower than that in Beijing ((1.31 +/- 0.53) mmol/L) and Hefei ((1.66 +/- 0.75) mmol/L) (t values were 3.343 and 7.293 respectively, both P values < 0.01); the serum glucose is also lower in testers in Urumchi ((5.02 +/- 2.18) mmol/L) compared with testers in Beijing ((5.69 +/- 1.53) mmol/L, t = 2.561, P < 0.05) and Hefei ((5.78 +/- 1.53) mmol/L, t = 2.934, P < 0.01). Different dietary pattern result in significantly different dietary phytosterol intake in elder women in three cities, higher, phytosterol intake seemed to contribute to lower serum lipids.

Assessment of the mean glandular dose using LiF:Mg,Ti, LiF:Mg,Cu,P, Li2B4O7:Mn and Li2B4O7:Cu TL detectors in mammography radiation fields

NASA Astrophysics Data System (ADS)

Fartaria, M. J.; Reis, C.; Pereira, J.; Pereira, M. F.; Cardoso, J. V.; Santos, L. M.; Oliveira, C.; Holovey, V.; Pascoal, A.; Alves, J. G.

2016-09-01

The aim of this paper is the characterization of four thermoluminescence detectors (TLD), namely, LiF:Mg,Ti, LiF:Mg,Cu,P, Li2B4O7:Mn and Li2B4O7:Cu for the measurement of the entrance surface air kerma (ESAK) and estimation of the mean glandular dose (MGD) in digital mammography examinations at hospitals and clinics. Low-energy x-ray beams in the typical energy ranges of mammography, produced with a tungsten target and additional 60 µm molybdenum filtration were implemented and characterized at the Laboratory of Metrology of Ionizing Radiation at Instituto Superior Técnico. These beams were used for the characterization of the TLDs in terms of sensitivity, linearity, reproducibility, energy dependence and fading at 40 °C. The energy dependence test was further extended using clinical beams produced by mammography units at hospitals and clinics. The method proposed by the International Atomic Energy Agency was used for the measurement of ESAK and assessment of MGD. The combined standard uncertainty for the measurement of ESAK (and MGD) was determined in accordance to the Guide to the expression of uncertainty in measurement. The x-ray beams generated in the 23-40 kVp range presented HVL values from 0.36 to 0.46 mm Al. The beam produced at 28 kVp (HVL 0.39 mm Al) was considered as reference. The radiation field defined a circle with 84 mm diameter with a maximum variation of the beam intensity of less than 1% at the top flat (plateau) within 4 cm of the central axis. The estimated total uncertainty for the measurement of air kerma was 0.42%. All the TL detectors tested showed good performance except the commercial Li2B4O7:Mn (or TLD-800) which was excluded due to its poor sensitivity in our experimental set up. Both lithium fluorides showed better linearity and reproducibility as well as lower energy dependence and fading when compared to lithium borates. The stable behaviour of LiF:Mg,Ti and LiF:Mg,Cu,P detectors is reflected in the low combined standard uncertainty of  ±5.6% and  ±4.3% respectively (or  ±5.1% and  ±3.6% if fading is neglected). In general a total combined uncertainty lower than  ±10% for the measurement of ESAK was obtained for the four TL materials studied.

Intake of selected bioactive compounds from plant food supplements containing fennel (Foeniculum vulgare) among Finnish consumers.

PubMed

Uusitalo, Liisa; Salmenhaara, Maija; Isoniemi, Merja; Garcia-Alvarez, Alicia; Serra-Majem, Lluís; Ribas-Barba, Lourdes; Finglas, Paul; Plumb, Jenny; Tuominen, Pirkko; Savela, Kirsti

2016-03-01

The purpose of this study was to estimate the intake of selected bioactive compounds from fennel-containing plant food supplements (PFS) among Finnish consumers. The estimated average intake of estragole was 0.20mg/d, of trans-anethole 1.15mg/d, of rosmarinic acid 0.09mg/d, of p-coumaric acid 0.0068mg/d, of kaempferol 0.0034mg/d, of luteolin 0.0525μg/d, of quercetin 0.0246mg/d, of matairesinol 0.0066μg/d and of lignans 0.0412μg/d. The intakes of kaempferol, quercetin, luteolin, matairesinol and lignans from PFS were low in comparison with their dietary supply. The intake of estragole was usually moderate, but a heavy consumption of PFS may lead to a high intake of estragole. The intake of trans-anethole did not exceed the acceptable daily intake, but PFS should be taken into account when assessing the total exposure. To our knowledge, this study provided the first intake estimates of trans-anethole, p-coumaric acid and rosmarinic acid in human populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diffusion Coefficients from Molecular Dynamics Simulations in Binary and Ternary Mixtures

NASA Astrophysics Data System (ADS)

Liu, Xin; Schnell, Sondre K.; Simon, Jean-Marc; Krüger, Peter; Bedeaux, Dick; Kjelstrup, Signe; Bardow, André; Vlugt, Thijs J. H.

2013-07-01

Multicomponent diffusion in liquids is ubiquitous in (bio)chemical processes. It has gained considerable and increasing interest as it is often the rate limiting step in a process. In this paper, we review methods for calculating diffusion coefficients from molecular simulation and predictive engineering models. The main achievements of our research during the past years can be summarized as follows: (1) we introduced a consistent method for computing Fick diffusion coefficients using equilibrium molecular dynamics simulations; (2) we developed a multicomponent Darken equation for the description of the concentration dependence of Maxwell-Stefan diffusivities. In the case of infinite dilution, the multicomponent Darken equation provides an expression for [InlineEquation not available: see fulltext.] which can be used to parametrize the generalized Vignes equation; and (3) a predictive model for self-diffusivities was proposed for the parametrization of the multicomponent Darken equation. This equation accurately describes the concentration dependence of self-diffusivities in weakly associating systems. With these methods, a sound framework for the prediction of mutual diffusion in liquids is achieved.

A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus

PubMed Central

2011-01-01

Background Neramexane is a new substance that exhibits antagonistic properties at α9α10 cholinergic nicotinic receptors and N-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus. Methods A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12). Results Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (p = 0.098 for 50 mg/d; p = 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with p values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence. Conclusions This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies. Trial Registration ClinicalTrials.gov NCT00405886 PMID:21223542

Modeling and forecasting of the under-five mortality rate in Kermanshah province in Iran: a time series analysis.

PubMed

Rostami, Mehran; Jalilian, Abdollah; Hamzeh, Behrooz; Laghaei, Zahra

2015-01-01

The target of the Fourth Millennium Development Goal (MDG-4) is to reduce the rate of under-five mortality by two-thirds between 1990 and 2015. Despite substantial progress towards achieving the target of the MDG-4 in Iran at the national level, differences at the sub-national levels should be taken into consideration. The under-five mortality data available from the Deputy of Public Health, Kermanshah University of Medical Sciences, was used in order to perform a time series analysis of the monthly under-five mortality rate (U5MR) from 2005 to 2012 in Kermanshah province in the west of Iran. After primary analysis, a seasonal auto-regressive integrated moving average model was chosen as the best fitting model based on model selection criteria. The model was assessed and proved to be adequate in describing variations in the data. However, the unexpected presence of a stochastic increasing trend and a seasonal component with a periodicity of six months in the fitted model are very likely to be consequences of poor quality of data collection and reporting systems. The present work is the first attempt at time series modeling of the U5MR in Iran, and reveals that improvement of under-five mortality data collection in health facilities and their corresponding systems is a major challenge to fully achieving the MGD-4 in Iran. Studies similar to the present work can enhance the understanding of the invisible patterns in U5MR, monitor progress towards the MGD-4, and predict the impact of future variations on the U5MR.

First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype

PubMed Central

Saito, Yoshimasa; Serizawa, Hiroshi; Kato, Yukako; Nakano, Masaru; Nakamura, Masahiko; Saito, Hidetsugu; Suzuki, Hidekazu; Kanai, Takanori

2015-01-01

AIM: To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication. METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or 13C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642). RESULTS: The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population. CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs. PMID:26730167

Changes in the evaporation rate of tear film after digital expression of meibomian glands in patients with and without dry eye.

PubMed

Arciniega, Juan Carlos; Wojtowicz, Jadwiga Cristina; Mohamed, Engy Mostafa; McCulley, James Parker

2011-08-01

To evaluate the effect of excess meibum on tear evaporation rate in patients with and without dry eye. Eleven healthy subjects and 16 patients with dry eye were tested. The dry eye group was divided into 2 subgroups: classic keratoconjunctivitis sicca (KCS) with clear and easily expressed meibum and KCS with meibomian gland dysfunction (MGD) with turbid secretions and difficult-to-express meibum. Evaporative measurements were performed at baseline and after digital expression of meibomian glands at 12, 24, 36, and 48 minutes. Two ranges of relative humidity were used, 25% to 35% and 35% to 45%. The data were expressed as microliters per square centimeter per minute. An increase in the evaporation rate of the tear film was noted for all measurements at both relative humidities in the classic KCS and KCS with MGD groups compared with healthy subjects (P < 0.05). The average evaporation rates at relative humidities of 25% to 35% and 35% to 45% were 0.056 ± 0.016 and 0.040 ± 0.008 for the classic KCS group; 0.055 ± 0.026 and 0.037 ± 0.019 for the KCS with MGD group and 0.033 ± 0.012 and 0.023 ± 0.008 for the healthy group. Also, a decrease in the evaporation rate was observed in the healthy and KCS with MGD groups between baseline and the first measurement after digital expression for both relative humidities (P < 0.05). The classic KCS group did not show any changes after expression. Classic KCS and KCS with MGD groups showed an increase in tear evaporation rates compared with the healthy group. Aqueous tear evaporation diminished in the healthy and KCS with MGD groups after expression of meibomian glands. However, this effect was transient and negligible after the second measurement.

Everolimus with reduced-dose cyclosporine in de novo renal transplant recipients: Philippine experience.

PubMed

Li, J T; Danguilan, R A; Cabanayan-Casasola, C B; Talusan-Tomacruz, Y; Ona, E T

2008-09-01

The objective of this study was to describe the appropriate dose of everolimus to achieve target trough concentrations in standard-risk Filipino kidney transplant recipients. We reviewed all kidney transplant recipients from December 1, 2006 to June 15, 2007 who were given everolimus (1.5 mg/d) in combination with low-dose cyclosporine (5 mg/kg/d) and prednisone but without induction therapy for their immunosuppressive doses, trough levels, as well as hematologic and blood chemistry profiles. Target everolimus trough concentration was 3-8 ng/mL and C2 level was 1000-1400 ng/mL for the first 3 months. Among 148 patients who underwent transplantation during the study period, 26 comprised the study population but only 15 patients completed the 3-month follow-up and are the subject of this report. Their mean age was 33 years, average PRA 2%, and mean HLA mismatches 3. All were from living donors. At 7 days posttransplantation, all patients achieved or exceeded the target everolimus trough and cyclosporine C2 level. At 1 and 3 months posttransplantation the mean everolimus dose was 1.17 and 0.78 mg/d, respectively, whereas the cyclosporine dose was 195 and 148 mg/d, respectively. Three patients showed elevated alanine aminotransferase (ALT) and all patients had hypercholesterolemia after 1 month, which improved with everolimus dose reduction (half required statins). One patient experienced a Banff Grade IA acute rejection episode at 2 months posttransplantation with a serum creatinine value of 2 mg/dL after steroid pulsing. Most standard-risk Filipino kidney transplant recipients required a maintenance everolimus dose of 1 mg/d at 1 month. The cyclosporine dose requirement was also lower. A larger sample size is needed to provide a level of significance compared with other populations.

Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans.

PubMed

Navarro, Sandi L; White, Emily; Kantor, Elizabeth D; Zhang, Yuzheng; Rho, Junghyun; Song, Xiaoling; Milne, Ginger L; Lampe, Paul D; Lampe, Johanna W

2015-01-01

Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans. We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0-32.5 kg/m2) adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin. Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo. Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer. ClinicalTrials.gov NCT01682694.

[Effect of multicomponent environment on intestinal permeability of puerarin in biopharmaceutics classification system of Chinese materia medica].

PubMed

Liu, Yang; Wang, Gang; Dong, Ling; Tang, Ming-Min; Zhu, Mei-Ling; Dong, Hong-Huant; Hou, Cheng-Bo

2014-12-01

The evaluation of permeability in biopharmaceutics classification system of Chinese materia medica (CMMBCS) requires multicomponent as a whole in order to conduct research, even in the study of a specific component, should also be put in the multicomponent environment. Based on this principle, the high content components in Gegen Qinlian decoction were used as multicomponent environmental impact factors in the experiment, and the relevant parameters of intestinal permeability about puerarin were measured with using in situ single-pass intestinal perfusion model, to investigate and evaluate the intestinal permeability of puerarin with other high content components. The experimental results showed that different proportions of baicalin, glycyrrhizic acid and berberine had certain influence on intestinal permeability of puerarin, and glycyrrhizic acid could significantly inhibit the intestinal absorption of puerarin, moreover, high concentration of berberine could promote the absorption of puerarin. The research results indicated that the important research ideas of permeability evaluation in biopharmaceutics classification system of Chinese materia medica with fully considering the effects of other ingredients in multicomponent environment.

Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia.

PubMed

Tateno, Amane; Arakawa, Ryosuke; Okumura, Masaki; Fukuta, Hajime; Honjo, Kazuyoshi; Ishihara, Keiichi; Nakamura, Hiroshi; Kumita, Shin-ichiro; Okubo, Yoshiro

2013-04-01

Blonanserin is a novel antipsychotic with high affinities for dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D(2) receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]raclopride for the striatum and 1 with [(11)C]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D(2) receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D(2) receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

Battery-operated, portable, and flexible air microplasma generation device for fabrication of microfluidic paper-based analytical devices on demand.

PubMed

Kao, Peng-Kai; Hsu, Cheng-Che

2014-09-02

A portable microplasma generation device (MGD) operated in ambient air is introduced for making a microfluidic paper-based analytical device (μPAD) that serves as a primary healthcare platform. By utilizing a printed circuit board fabrication process, a flexible and lightweight MGD can be fabricated within 30 min with ultra low-cost. This MGD can be driven by a portable power supply (less than two pounds), which can be powered using 12 V-batteries or ac-dc converters. This MGD is used to perform maskless patterning of hydrophilic patterns with sub-millimeter spatial resolution on hydrophobic paper substrates with good pattern transfer fidelity. Using this MGD to fabricate μPADs is demonstrated. With a proper design of the MGD electrode geometry, μPADs with 500-μm-wide flow channels can be fabricated within 1 min and with a cost of less than $USD 0.05/device. We then test the μPADs by performing quantitative colorimetric assay tests and establish a calibration curve for detection of glucose and nitrite. The results show a linear response to a glucose assay for 1-50 mM and a nitrite assay for 0.1-5 mM. The low cost, miniaturized, and portable MGD can be used to fabricate μPADs on demand, which is suitable for in-field diagnostic tests. We believe this concept brings impact to the field of biomedical analysis, environmental monitoring, and food safety survey.

An 8-Week Randomized, Double-Blind Trial Comparing Efficacy, Safety, and Tolerability of 3 Vilazodone Dose-Initiation Strategies Following Switch From SSRIs and SNRIs in Major Depressive Disorder

PubMed Central

Rele, Shilpa; Millet, Robert; Kim, Sungman; Paik, Jong-Woo; Kim, Seonghwan; Masand, Prakash S.

2015-01-01

Introduction: Vilazodone, a selective and potent 5-HT1A partial agonist and 5-HT reuptake inhibitor, has been approved for treatment of major depressive disorder (MDD) in adults. The primary objective of the study was to compare the efficacy and tolerability of switching to 3 different doses of vilazodone from an equivalent dose range of generic selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in adult subjects with MDD. Method: This was an 8-week, randomized, double-blind, parallel-group, 3-arm trial to compare vilazodone 10 mg/d, 20 mg/d, and 40 mg/d as starting doses. Data were collected from December 2012 to December 2013. There was no washout phase, prior medications were stopped at the baseline visit, and vilazodone was started the next day in adults with MDD (DSM-IV criteria). The 10-mg/d and 20-mg/d dose was increased to 40 mg/d by week 3 and week 1, respectively, and the 40-mg/d initiation dose continued unchanged. The primary efficacy measure was change in Montgomery-Asberg Depression Rating Scale (MADRS) score between the 3 dose groups. The secondary efficacy measures were changes in Clinical Global Impressions–Severity (CGI-S), CGI-Improvement (CGI-I), and Hamilton Anxiety Rating Scale (HARS) scores. Safety measures were obtained by spontaneously reported adverse events, vital signs recording, and laboratory tests. Multivariate tests were used for statistical analysis. Results: Seventy subjects were randomized, and 60 subjects completed the study (n = 20 in each group). Overall, there was a significant reduction in MADRS score from baseline (26.08 ± 1.1) to week 8 (9.86 ± 1.2) in the entire sample (P < .001). Similarly, there was a significant improvement in CGI-S (P < .001), CGI-I (P < .001) and HDRS (P < .001) scores from baseline to the end of the trial. There were no significant differences between the 3 vilazodone dose-initiation groups in changes in MADRS scores (P = .95) or changes in CGI-S (P = .83), CGI-I (P = .51), or HARS scores (P = .61). Dry mouth (n = 55), nausea (n = 10), and diarrhea (n = 5) were the most common side effects, with diarrhea reported in 5 subjects in the 40-mg/d initiation group. No serious adverse events were reported. Conclusions: The present study indicates the potential benefit of switching to vilazodone in patients with MDD who are inadequate responders to SSRIs or SNRIs. There were no meaningful differences in efficacy or tolerability between the 3 different dose-initiation strategies with vilazodone; however, diarrhea appeared to be more frequently reported with the 40-mg/d dose. Given the modest sample size, larger studies are required to confirm our findings. Trial Registration: ClinicalTrials.gov identifiers: NCT02015546 and NCT01473381 PMID:26693034

General Model for Multicomponent Ablation Thermochemistry

NASA Technical Reports Server (NTRS)

Milos, Frank S.; Marschall, Jochen; Rasky, Daniel J. (Technical Monitor)

1994-01-01

A previous paper (AIAA 94-2042) presented equations and numerical procedures for modeling the thermochemical ablation and pyrolysis of thermal protection materials which contain multiple surface species. This work describes modifications and enhancements to the Multicomponent Ablation Thermochemistry (MAT) theory and code for application to the general case which includes surface area constraints, rate limited surface reactions, and non-thermochemical mass loss (failure). Detailed results and comparisons with data are presented for the Shuttle Orbiter reinforced carbon-carbon oxidation protection system which contains a mixture of sodium silicate (Na2SiO3), silica (SiO2), silicon carbide (SiC), and carbon (C).

Urine sodium excretion increased slightly among U.S. adults between 1988 and 2010.

PubMed

Pfeiffer, Christine M; Hughes, Jeffery P; Cogswell, Mary E; Burt, Vicki L; Lacher, David A; Lavoie, Donna J; Rabinowitz, Daniel J; Johnson, Clifford L; Pirkle, James L

2014-05-01

Little information is available on temporal trends in sodium intake in the U.S. population using urine sodium excretion as a biomarker. Our aim was to assess 1988-2010 trends in estimated 24-h urine sodium (24hUNa) excretion among U.S. adults (age 20-59 y) participating in the cross-sectional NHANES. We used subsamples from a 1988-1994 convenience sample, a 2003-2006 one-third random sample, and a 2010 one-third random sample to comply with resource constraints. We estimated 24hUNa excretion from measured sodium concentrations in spot urine samples by use of calibration equations (for men and women) derived from the International Cooperative Study on Salt, Other Factors, and Blood Pressure study. Estimated 24hUNa excretion increased over the 20-y period [1988-1994, 2003-2006, and 2010; means ± SEMs (n): 3160 ± 38.4 mg/d (1249), 3290 ± 29.4 mg/d (1235), and 3290 ± 44.4 mg/d (525), respectively; P-trend = 0.022]. We observed significantly higher mean estimated 24hUNa excretion in each survey period (P < 0.001) for men compared with women (31-33%) and for persons with a higher body mass index (BMI; 32-35% for obese vs. normal weight) or blood pressure (17-26% for hypertensive vs. normal blood pressure). After adjusting for age, sex, and race-ethnicity, temporal trends in mean estimated 24hUNa excretion remained significant (P-trend = 0.004). We observed no temporal trends in mean estimated 24hUNa excretion among BMI subgroups, nor after adjusting for BMI. Although several limitations apply to this analysis (the use of a convenience sample in 1988-1994 and using estimated 24hUNa excretion as a biomarker of sodium intake), these first NHANES data suggest that mean estimated 24hUNa excretion increased slightly in U.S. adults over the past 2 decades, and this increase may be explained by a shift in the distribution of BMI.

Effects of Direct Renin Blockade on Renal & Systemic Hemodynamics and on RAAS Activity, in Weight Excess and Hypertension: A Randomized Clinical Trial.

PubMed

Kwakernaak, A J; Roksnoer, L C; Lambers Heerspink, H J; van den Berg-Garrelds, I; Lochorn, G A; van Embden Andres, J H; Klijn, M A; Kobori, H; Danser, A H J; Laverman, G D; Navis, G J

2017-01-01

The combination of weight excess and hypertension significantly contributes to cardiovascular risk and progressive kidney damage. An unfavorable renal hemodynamic profile is thought to contribute to this increased risk and may be ameliorated by direct renin inhibition (DRI). The aim of this trial was to assess the effect of DRI on renal and systemic hemodynamics and on RAAS activity, in men with weight excess and hypertension. A randomized, double-blind, cross-over clinical trial to determine the effect of DRI (aliskiren 300 mg/day), with angiotensin converting enzyme inhibition (ACEi; ramipril 10 mg/day) as a positive control, on renal and systemic hemodynamics, and on RAAS activity (n = 15). Mean (SEM) Glomerular filtration rate (101 (5) mL/min/1.73m2) remained unaffected by DRI or ACEi. Effective renal plasma flow (ERPF; 301 (14) mL/min/1.73m2) was increased in response to DRI (320 (14) mL/min/1.73m2, P = 0.012) and ACEi (317 (15) mL/min/1.73m2, P = 0.045). Filtration fraction (FF; 34 (0.8)%) was reduced by DRI only (32 (0.7)%, P = 0.044). Mean arterial pressure (109 (2) mmHg) was reduced by DRI (101 (2) mmHg, P = 0.008) and ACEi (103 (3) mmHg, P = 0.037). RAAS activity was reduced by DRI and ACEi. Albuminuria (20 [9-42] mg/d) was reduced by DRI only (12 [5-28] mg/d, P = 0.030). In men with weight excess and hypertension, DRI and ACEi improved renal and systemic hemodynamics. Both DRI and ACEi reduced RAAS activity. Thus, DRI provides effective treatment in weight excess and hypertension. Dutch trial register, registration number: 2532 www.trialregister.nl.

Gels and gel-derived glasses in the Na2O-B2O3-SiO2 system. [containerless melting in space

NASA Technical Reports Server (NTRS)

Mukherjee, S. P.

1982-01-01

The containerless melting of high-purity multicomponent homogeneous gels and gel-monoliths offers a unique approach to making ultrapure multicomponent optical glasses in the reduced gravity environment of space. Procedures for preparing and characterizing gels and gel-derived glasses in the Na2O-B2O3-SiO2 system are described. Preparation is based on the polymerization reactions of alkoxysilane with trimethyl borate or boric acid and a suitable sodium compound. The chemistry of the gelling process is discussed in terms of process parameters and the gel compositions. The physicochemical nature of gels prepared by three different procedures were found to be significantly different. IR absorption spectra indicate finite differences in the molecular structures of the different gels. The melting of the gel powders and the transformation of porous gel-monoliths to transparent 'glass' without melting are described.

Gels and gel-derived glasses in the system Na2O-B2O3-SiO2

NASA Technical Reports Server (NTRS)

Mukherjee, S. P.

1983-01-01

The containerless melting of high-purity multicomponent homogeneous gels and gel monoliths offers a unique approach to making ultrapure multicomponent optical glasses in the reduced gravity environment of space. Procedures for preparing and characterizing gels and gel-derived glasses in the system Na2O-B2O3-SiO2 are described. Preparation is based on the polymerization reactions of alkoxysilane with trimethyl borate or boric acid and a suitable sodium compound. The chemistry of the gelling process is discussed in terms of process parameters and the gel compositions. The physicochemical nature of gels prepared by three different procedures was found to be significantly different. Infrared absorption spectra indicate finite differences in the molecular structures of the different gels. The melting of the gel powders and the transformation of porous gel monoliths to transparent 'glass' without melting are described.

Smart spectroscopy sensors: II. Narrow-band laser systems

NASA Astrophysics Data System (ADS)

Matharoo, Inderdeep; Peshko, Igor

2013-03-01

This paper describes the principles of operation of a miniature multifunctional optical sensory system based on laser technology and spectroscopic principles of analysis. The operation of the system as a remote oxygen sensor has been demonstrated. The multi-component alarm sensor has been designed to recognise gases and to measure gas concentration (O2, CO2, CO, CH4, N2O, C2H2, HI, OH radicals and H2O vapour, including semi-heavy water), temperature, pressure, humidity, and background radiation from the environment. Besides gas sensing, the same diode lasers are used for range-finding and to provide sensor self-calibration. The complete system operates as an inhomogeneous sensory network: the laser sensors are capable of using information received from environmental sensors for improving accuracy and reliability of gas concentration measurement. The sources of measurement errors associated with hardware and algorithms of operation and data processing have been analysed in detail.

General multicomponent Yajima-Oikawa system: Painlevé analysis, soliton solutions, and energy-sharing collisions.

PubMed

Kanna, T; Sakkaravarthi, K; Tamilselvan, K

2013-12-01

We consider the multicomponent Yajima-Oikawa (YO) system and show that the two-component YO system can be derived in a physical setting of a three-coupled nonlinear Schrödinger (3-CNLS) type system by the asymptotic reduction method. The derivation is further generalized to the multicomponent case. This set of equations describes the dynamics of nonlinear resonant interaction between a one-dimensional long wave and multiple short waves. The Painlevé analysis of the general multicomponent YO system shows that the underlying set of evolution equations is integrable for arbitrary nonlinearity coefficients which will result in three different sets of equations corresponding to positive, negative, and mixed nonlinearity coefficients. We obtain the general bright N-soliton solution of the multicomponent YO system in the Gram determinant form by using Hirota's bilinearization method and explicitly analyze the one- and two-soliton solutions of the multicomponent YO system for the above mentioned three choices of nonlinearity coefficients. We also point out that the 3-CNLS system admits special asymptotic solitons of bright, dark, anti-dark, and gray types, when the long-wave-short-wave resonance takes place. The short-wave component solitons undergo two types of energy-sharing collisions. Specifically, in the two-component YO system, we demonstrate that two types of energy-sharing collisions-(i) energy switching with opposite nature for a particular soliton in two components and (ii) similar kind of energy switching for a given soliton in both components-result for two different choices of nonlinearity coefficients. The solitons appearing in the long-wave component always exhibit elastic collision whereas those of short-wave components exhibit standard elastic collisions only for a specific choice of parameters. We have also investigated the collision dynamics of asymptotic solitons in the original 3-CNLS system. For completeness, we explore the three-soliton interaction and demonstrate the pairwise nature of collisions and unravel the fascinating state restoration property.

Multicomponent long-wave-short-wave resonance interaction system: Bright solitons, energy-sharing collisions, and resonant solitons.

PubMed

Sakkaravarthi, K; Kanna, T; Vijayajayanthi, M; Lakshmanan, M

2014-11-01

We consider a general multicomponent (2+1)-dimensional long-wave-short-wave resonance interaction (LSRI) system with arbitrary nonlinearity coefficients, which describes the nonlinear resonance interaction of multiple short waves with a long wave in two spatial dimensions. The general multicomponent LSRI system is shown to be integrable by performing the Painlevé analysis. Then we construct the exact bright multisoliton solutions by applying the Hirota's bilinearization method and study the propagation and collision dynamics of bright solitons in detail. Particularly, we investigate the head-on and overtaking collisions of bright solitons and explore two types of energy-sharing collisions as well as standard elastic collision. We have also corroborated the obtained analytical one-soliton solution by direct numerical simulation. Also, we discuss the formation and dynamics of resonant solitons. Interestingly, we demonstrate the formation of resonant solitons admitting breather-like (localized periodic pulse train) structure and also large amplitude localized structures akin to rogue waves coexisting with solitons. For completeness, we have also obtained dark one- and two-soliton solutions and studied their dynamics briefly.

The mechanism of ureido-pyrimidinone:2,7-diamido-naphthyridine complexation and the presence of kinetically controlled pathways in multicomponent hydrogen-bonded systems.

PubMed

de Greef, Tom F A; Ligthart, G B W L; Lutz, Martin; Spek, Anthony L; Meijer, E W; Sijbesma, Rint P

2008-04-23

The kinetics of association of ureido-pyrimidinone (U) dimers, present either in the 4[1H]-keto form or in the pyrimidin-4-ol form, with 2,7-diamido-1,8-naphthyridine (N) into a complementary heterodimer have been investigated. The formation of heterodimers with 2,7-diamido-1,8-naphthyridine from pyrimidin-4-ol dimers is much faster than from 4[1H]-pyrimidinone dimers. Using a combination of simple measurements and simulations, evidence for a bimolecular tautomerization step is presented. Finally, the acquired kinetic knowledge of the different pathways leading from ureido-pyrimidinone homodimers to ureido-pyrimidinone:diamido-naphthyridine (U:N) heterodimers allows the prediction and observation of kinetically determined ureido-pyrimidinone heterodimers which slowly convert back to the corresponding homodimers.

Longitudinal Changes in Tear Evaporation Rates After Eyelid Warming Therapies in Meibomian Gland Dysfunction.

PubMed

Yeo, Sharon; Tan, Jen Hong; Acharya, U Rajendra; Sudarshan, Vidya K; Tong, Louis

2016-04-01

Lid warming is the major treatment for meibomian gland dysfunction (MGD). The purpose of the study was to determine the longitudinal changes of tear evaporation after lid warming in patients with MGD. Ninety patients with MGD were enrolled from a dry eye clinic at Singapore National Eye Center in an interventional trial. Participants were treated with hot towel (n = 22), EyeGiene (n = 22), or Blephasteam (n = 22) twice daily or a single 12-minute session of Lipiflow (n = 24). Ocular surface infrared thermography was performed at baseline and 4 and 12 weeks after the treatment, and image features were extracted from the captured images. The baseline of conjunctival tear evaporation (TE) rate (n = 90) was 66.1 ± 21.1 W/min. The rates were not significantly different between sexes, ages, symptom severities, tear breakup times, Schirmer test, corneal fluorescein staining, or treatment groups. Using a general linear model (repeat measures), the conjunctival TE rate was reduced with time after treatment. A higher baseline evaporation rate (≥ 66 W/min) was associated with greater reduction of evaporation rate after treatment. Seven of 10 thermography features at baseline were predictive of reduction in irritative symptoms after treatment. Conjunctival TE rates can be effectively reduced by lid warming treatment in some MGD patients. Individual baseline thermography image features can be predictive of the response to lid warming therapy. For patients that do not have excessive TE, additional therapy, for example, anti-inflammatory therapy, may be required.

Synthesis, crystal structures and luminescence properties of new multi-component co-crystals of isostructural Co(II) and Zn(II) complexes

NASA Astrophysics Data System (ADS)

Tella, Adedibu C.; Owalude, Samson O.; Omotoso, Mary F.; Olatunji, Sunday J.; Ogunlaja, Adeniyi S.; Alimi, Lukman O.; Popoola, Olugbenga K.; Bourne, Susan A.

2018-04-01

Two novel isostructural compounds containing multi-component co-crystals [M(C6H4NO2)2(H2O)2](C9H6O6)2 (M = Co (1), Zn (2), C6H4NO2 = Picolinic acid, C9H6O6 = Trimesic acid) have been synthesized. The compounds were characterized by elemental analysis, FT-IR, UV-Visible and 1H NMR spectroscopies as well as thermal and single crystal X-ray diffraction analyses. Single crystal X-ray diffraction analysis reveals that 1 and 2 are isostructural. Compound 1 crystallizes in triclinic space group (P-1, with a = 5.154 (10) Å, b = 11.125 (2) Å, c = 14.113 (3) Å, α = 91.01 (3)°, β = 100.54 (3)°, and γ = 102.71 (3)°). In a similar fashion, compound 2 crystallizes in triclinic space group (P-1, with a = 5.1735 (3) Å, b = 11.0930 (10) Å, c = 14.1554 (8) Å, α = 91.70 (3)°, β = 100.26 (3)°, γ = 102.90 (3)°). The metal (II) cation presents distorted MN2O4 octahedral geometry with H2O molecules coordinated to the metal in equatorial position while the picolinic acid molecules are axially coordinated through the pyridine N atom. The two trimesic acid molecules are not part of the first coordination sphere. Compounds 1 and 2 constitute an example of a class of coordination compound of multicomponent crystals having trimesic acid outside the coordination sphere where it is neither protonated or deprotonated. The two compounds were investigated for luminiscence properties.

Gauge transformation and symmetries of the commutative multicomponent BKP hierarchy

NASA Astrophysics Data System (ADS)

Li, Chuanzhong

2016-01-01

In this paper, we defined a new multi-component B type Kadomtsev-Petviashvili (BKP) hierarchy that takes values in a commutative subalgebra of {gl}(N,{{C}}). After this, we give the gauge transformation of this commutative multicomponent BKP (CMBKP) hierarchy. Meanwhile, we construct a new constrained CMBKP hierarchy that contains some new integrable systems, including coupled KdV equations under a certain reduction. After this, the quantum torus symmetry and quantum torus constraint on the tau function of the commutative multi-component BKP hierarchy will be constructed.

Mouse Genome Database: From sequence to phenotypes and disease models

PubMed Central

Richardson, Joel E.; Kadin, James A.; Smith, Cynthia L.; Blake, Judith A.; Bult, Carol J.

2015-01-01

Summary The Mouse Genome Database (MGD, www.informatics.jax.org) is the international scientific database for genetic, genomic, and biological data on the laboratory mouse to support the research requirements of the biomedical community. To accomplish this goal, MGD provides broad data coverage, serves as the authoritative standard for mouse nomenclature for genes, mutants, and strains, and curates and integrates many types of data from literature and electronic sources. Among the key data sets MGD supports are: the complete catalog of mouse genes and genome features, comparative homology data for mouse and vertebrate genes, the authoritative set of Gene Ontology (GO) annotations for mouse gene functions, a comprehensive catalog of mouse mutations and their phenotypes, and a curated compendium of mouse models of human diseases. Here, we describe the data acquisition process, specifics about MGD's key data areas, methods to access and query MGD data, and outreach and user help facilities. genesis 53:458–473, 2015. © 2015 The Authors. Genesis Published by Wiley Periodicals, Inc. PMID:26150326

Testing the accuracy of correlations for multicomponent mass transport of adsorbed gases in metal-organic frameworks: diffusion of H2/CH4 mixtures in CuBTC.

PubMed

Keskin, Seda; Liu, Jinchen; Johnson, J Karl; Sholl, David S

2008-08-05

Mass transport of chemical mixtures in nanoporous materials is important in applications such as membrane separations, but measuring diffusion of mixtures experimentally is challenging. Methods that can predict multicomponent diffusion coefficients from single-component data can be extremely useful if these methods are known to be accurate. We present the first test of a method of this kind for molecules adsorbed in a metal-organic framework (MOF). Specifically, we examine the method proposed by Skoulidas, Sholl, and Krishna (SSK) ( Langmuir, 2003, 19, 7977) by comparing predictions made with this method to molecular simulations of mixture transport of H 2/CH 4 mixtures in CuBTC. These calculations provide the first direct information on mixture transport of any species in a MOF. The predictions of the SSK approach are in good agreement with our direct simulations of binary diffusion, suggesting that this approach may be a powerful one for examining multicomponent diffusion in MOFs. We also use our molecular simulation data to test the ideal adsorbed solution theory method for predicting binary adsorption isotherms and a method for predicting mixture self-diffusion coefficients.

Dietary Sodium Content, Mortality, and Risk for Cardiovascular Events in Older Adults: The Health, Aging, and Body Composition Study

PubMed Central

Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Murphy, Rachel A.; Newman, Anne B.; Bauer, Douglas C.; Harris, Tamara B.; Yang, Zhou; Applegate, William B.; Kritchevsky, Stephen B.

2016-01-01

Importance Additional information is needed on the role of dietary sodium on health outcomes in older adults. Objective To examine the association between dietary sodium intake and mortality, incident cardiovascular disease (CVD), and incident heart failure (HF) in older adults. Design, Setting, and Participants We analyzed 10-year follow-up data from 2,642 older adults (age 71-80) participating in a community-based, prospective cohort study (inception 1997-98). Exposure Dietary sodium intake at baseline was assessed by a food frequency questionnaire (FFQ). We examined sodium intake both as a continuous and as a categorical variable (<1500mg/d [N=291; 11.0%]; 1500–2300mg/d [N=779; 29.5%]; and >2300mg/d [N=1572; 59.5%]. Main Outcomes Adjudicated death, incident CVD, and incident HF over 10-years of follow-up. Analysis of incident CVD was restricted to those without prevalent CVD (N=1981) at baseline. Results Average age of participants was 73.6±2.9 years; 51.2% were women; 61.7% white; and 38.3% black. After 10 years, 881 participants had died, 572 developed CVD and 398 developed HF. In adjusted Cox proportional hazards models, sodium intake was not associated with mortality (HR per 1g, 1.03; 95%CI 0.98–1.09; P=0.27). Ten-year mortality was nonsignificantly lower in the 1500–2300-mg group (30.7%) compared to the <1500-mg (33.8%) and >2300-mg (35.2%) groups; P=0.074. Sodium intake >2300mg/d was associated with nonsignificantly higher mortality in adjusted models (HR vs. 1500–2300 mg/d, 1.15; 95%CI 0.99–1.35; P=0.072). Indexing sodium intake for caloric intake and body mass index did not materially affect the results. Adjusted HR for mortality was 1.20 (95%CI 0.93–1.54; P=0.16) per mg/kcal sodium and 1.11 (95%CI 0.96–1.28; P=0.17) per 100mg/kg/m2 sodium. In adjusted models accounting for the competing risk of death, sodium intake was not associated with risk for CVD (HR per 1g, 1.03; 95%CI 0.95–1.11; P=0.47) or HF (HR per 1g, 1.00; 95%CI 0.92–1.08; P=0.92). There were no consistent interactions with gender, race, or hypertensive status for any outcome. Conclusions In older adults, FFQ-assessed sodium intake was not associated with 10-year mortality, incident CVD, or incident HF, albeit there was a trend towards higher mortality among those consuming >2300 mg/d sodium. PMID:25599120

New Pb(Mg1/3Nb2/3)O3-Pb(In1/2Nb1/2)O3-PbZrO3-PbTiO3 Quaternary Ceramics: Morphotropic Phase Boundary Design and Electrical Properties.

PubMed

Luo, Nengneng; Zhang, Shujun; Li, Qiang; Xu, Chao; Yang, Zhanlue; Yan, Qingfeng; Zhang, Yiling; Shrout, Thomas R

2016-06-22

Four series of Pb(Mg1/3Nb2/3)O3-Pb(In1/2Nb1/2)O3-PbZrO3-PbTiO3 (PMN-PIN-PZ-PT) quaternary ceramics with compositions located at the morphotropic phase boundary (MPB) regions were prepared. The MPBs of the multicomponent system were predicted using a linear combination rule and experimentally confirmed by X-ray powder diffraction and electrical measurement. The positions of MPBs in multicomponent systems were found in linear correlation with the tolerance factor and ionic radii of non-PT end-members. The phase structure, piezoelectric coefficient, electromechanical coupling coefficient, unipolar strains, and dielectric properties of as-prepared ceramics were systematically investigated. The largest d33s were obtained at S36.8, L37.4, M39.6, and N35.8, with the corresponding values of 580, 450, 420, and 530 pC/N, respectively, while the largest kps were found at S34.8, L37.4, M39.6, and N35.8, with the respective values of 0.54, 0.50, 0.47, and 0.53. The largest unipolar strain Smax and high-field piezoelectric strain coefficients d33* were also observed around the respective MPB regions. The rhombohedral-to-tetragonal phase transition temperature Trt increased with increasing PIN and PZ contents. Of particular importance is that high Trt of 140-197 °C was achieved in the M series with PZ and PIN contents being around 0.208 and 0.158, which will broaden the temperature usage range.

The Solidification of Multicomponent Alloys

PubMed Central

Boettinger, William J.

2017-01-01

Various topics taken from the author’s research portfolio that involve multicomponent alloy solidification are reviewed. Topics include: ternary eutectic solidification and Scheil-Gulliver paths in ternary systems. A case study of the solidification of commercial 2219 aluminum alloy is described. Also described are modifications of the Scheil-Gulliver analysis to treat dendrite tip kinetics and solid diffusion for multicomponent alloys. PMID:28819348

GROUNDWATER MASS TRANSPORT AND EQUILIBRIUM CHEMISTRY MODEL FOR MULTICOMPONENT SYSTEMS

EPA Science Inventory

A mass transport model, TRANQL, for a multicomponent solution system has been developed. The equilibrium interaction chemistry is posed independently of the mass transport equations which leads to a set of algebraic equations for the chemistry coupled to a set of differential equ...

Efficacy and safety of long-term treatment with the combination of amlodipine besylate and olmesartan medoxomil in patients with hypertension.

PubMed

Chrysant, Steven G; Oparil, Suzanne; Melino, Michael; Karki, Sulekha; Lee, James; Heyrman, Reinilde

2009-09-01

J Clin Hypertens (Greenwich). 2009;11:475-482. (c) 2009 Wiley Periodicals, Inc.The authors report on the 44-week open-label extension of the 8-week, double-blind Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial in 1684 patients. Initial therapy was amlodipine (AML) plus olmesartan medoxomil (OM) 5+40 mg/d, up-titrated to AML+OM 10+40 mg/d plus hydrochlorothiazide (HCTZ) 12.5 mg then 25 mg if patients did not achieve blood pressure (BP) goal (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes). Baseline mean BP decreased from 164/102 mm Hg to 131/82 mm Hg at end of study, with an overall 66.7% of patients, including those with diabetes, achieving BP goal. The BP goal achievement was 80% for AML+OM 5+40 mg/d, 70.6% for AML+OM 10+40 mg/d, 66.6% for AML+OM+HCTZ 10+40+12.5 mg/d, and 46.3% for AML+OM+HCTZ 10+40+25 mg/d. Study medication was safe and well tolerated. Combination antihypertensive therapy with AML+OM+/-HTCZ, up-titrated as necessary, allowed a majority of patients to achieve BP goal.

Primary and Secondary Prevention of Cardiovascular Disease

PubMed Central

Vandvik, Per Olav; Lincoff, A. Michael; Gore, Joel M.; Gutterman, David D.; Sonnenberg, Frank A.; Alonso-Coello, Pablo; Akl, Elie A.; Lansberg, Maarten G.; Guyatt, Gordon H.

2012-01-01

Background: This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: We present 23 recommendations for pertinent clinical questions. For primary prevention of cardiovascular disease, we suggest low-dose aspirin (75-100 mg/d) in patients aged > 50 years over no aspirin therapy (Grade 2B). For patients with established coronary artery disease, defined as patients 1-year post-acute coronary syndrome, with prior revascularization, coronary stenoses > 50% by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing, we recommend long-term low-dose aspirin or clopidogrel (75 mg/d) (Grade 1A). For patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI) with stent placement, we recommend for the first year dual antiplatelet therapy with low-dose aspirin in combination with ticagrelor 90 mg bid, clopidogrel 75 mg/d, or prasugrel 10 mg/d over single antiplatelet therapy (Grade 1B). For patients undergoing elective PCI with stent placement, we recommend aspirin (75-325 mg/d) and clopidogrel for a minimum duration of 1 month (bare-metal stents) or 3 to 6 months (drug-eluting stents) (Grade 1A). We suggest continuing low-dose aspirin plus clopidogrel for 12 months for all stents (Grade 2C). Thereafter, we recommend single antiplatelet therapy over continuation of dual antiplatelet therapy (Grade 1B). Conclusions: Recommendations continue to favor single antiplatelet therapy for patients with established coronary artery disease. For patients with acute coronary syndromes or undergoing elective PCI with stent placement, dual antiplatelet therapy for up to 1 year is warranted. PMID:22315274

Chemically frozen multicomponent boundary layer theory of salt and/or ash deposition rates from combustion gases

NASA Technical Reports Server (NTRS)

Rosner, D. E.; Chen, B.-K.; Fryburg, G. C.; Kohl, F. J.

1979-01-01

There is increased interest in, and concern about, deposition and corrosion phenomena in combustion systems containing inorganic condensible vapors and particles (salts, ash). To meet the need for a computationally tractable deposition rate theory general enough to embrace multielement/component situations of current and future gas turbine and magnetogasdynamic interest, a multicomponent chemically 'frozen' boundary layer (CFBL) deposition theory is presented and its applicability to the special case of Na2SO4 deposition from seeded laboratory burner combustion products is demonstrated. The coupled effects of Fick (concentration) diffusion and Soret (thermal) diffusion are included, along with explicit corrections for effects of variable properties and free stream turbulence. The present formulation is sufficiently general to include the transport of particles provided they are small enough to be formally treated as heavy molecules. Quantitative criteria developed to delineate the domain of validity of CFBL-rate theory suggest considerable practical promise for the present framework, which is characterized by relatively modest demands for new input information and computer time.

Examination of new chiral smectics with four aromatic rings

NASA Astrophysics Data System (ADS)

Żurowska, Magdalena; Czerwiński, Michał; Dziaduszek, Jerzy; Filipowicz, Marek

2018-05-01

This paper presents the results of the study of four chiral mesogens with the acronym (4X1X2). The investigated compounds might be of interest for use as components of multicomponent mixtures useful in technical devices. The compounds have high chemical stability. Their mesomorphic properties were tested by means of polarizing optical microscopy and differential scanning calorimetry. The helical pitch of the prepared compounds and mixtures was estimated using the selective reflection method. Their phase smectic layer structure and usefulness for formulation of multicomponent antiferroelectric mixtures were then reported.

Treatment Practices and Outcomes of Meibomian Gland Dysfunction at a Tertiary Center in Southern India.

PubMed

Lee, Ling; Garrett, Qian; Flanagan, Judith L; Vaddavalli, Pravin K; Papas, Eric B

2016-12-19

To describe the current treatment practices for meibomian gland dysfunction (MGD) at a tertiary eye center, together with the subjective outcomes and compliance behaviors of patients. This retrospective cohort study reviewed medical records for MGD severity grading, treatment prescribed, and follow-up schedule. In addition, participants were surveyed to gauge subjective outcomes and treatment adherence. Eight hundred ten patients were diagnosed with "MGD" or "meibomitis" and had a total of 14 different treatment combinations prescribed. In 3.0% of cases, there was no treatment specified. As MGD severity increased, it became more likely that management would be applied and this was also associated with significantly longer treatment durations (P=0.02) and shorter follow-up periods (P<0.001). Posttreatment subjective outcomes and treatment adherence surveys had a response rate of 36.7% and 24.1% respectively. Overall, 53.5% reported sustained improvement, 40.7% no improvement, and 5.7% experienced temporary relief. Although no treatment regimen seemed to be more efficacious than others, patients showed greater adherence when using topical reagents compared with lid hygiene measures (P≤0.002). Clinicians, in this large tertiary eye center, use a wide range of treatment regimens to manage MGD. This suggests the need for development of standard management protocols. Whether alone, or in combination, no MGD treatment significantly improved subjective symptoms, a result that may be influenced by compliance behaviors. Use of topical reagents (eye drops or ointment) seemed to be associated with the best compliance. Future focus on more effective MGD treatments is needed to improve practical outcomes.

Baclofen add-on to citalopram in treatment of posttraumatic stress disorder.

PubMed

Manteghi, Ali Akhoundpour; Hebrani, Paria; Mortezania, Mohammad; Haghighi, Mehri Baghban; Javanbakht, Arash

2014-04-01

Posttraumatic stress disorder (PTSD) is a chronic disabling illness, resulting from exposure to extreme traumatic event. Although different pharmacologic agents are suggested for treatment of PTSD, none have been completely effective in eliminating symptoms. The purpose of this study was to assess the use of baclofen as an add-on to citalopram in treatment of PTSD. In this double-blind clinical trial, 40 Iranian combat veterans with PTSD were randomly assigned to 2 groups. The first group received a combination treatment of 20 to 60 mg/d citalopram and 40 mg/d baclofen, and the second group received 20 to 60 mg/d citalopram plus placebo. Symptom severity was assessed by Clinician-Administered PTSD Scale at the beginning of the study and after 2, 4, 6, and 8 weeks. Global Assessment of Functioning and Hamilton Rating Scale for Anxiety and Depression were also used at the same periods. Data were analyzed with independent t test and paired t test using SPSS software version 13 (IBM, Armonk, NY). Twenty-three male patients (baclofen group, 13 patients; placebo group, 10 patients) completed the study. Dropout from the treatment was not caused by adverse effects of the new medications in any of the subjects. Baclofen group showed significantly larger improvement in Clinician-Administered PTSD Scale total (P = 0.040), hyperarousal (P = 0.020), and avoidance (0.020) scores, Global Assessment of Functioning score (0.001), depression (P = 0.000), and anxiety (P = 0.000) after 8 weeks of treatment. No intergroup difference was found in improvement of reexperience symptoms (P = 0.740). Baclofen showed to be an effective add-on to selective serotonin reuptake inhibitors in treatment of PTSD for better symptom recovery and functional improvement.

Growth hormone treatment of adults with Prader-Willi syndrome and growth hormone deficiency improves lean body mass, fractional body fat, and serum triiodothyronine without glucose impairment: results from the United States multicenter trial.

PubMed

Mogul, Harriette R; Lee, Phillip D K; Whitman, Barbara Y; Zipf, William B; Frey, Michael; Myers, Susan; Cahan, Mindy; Pinyerd, Belinda; Southren, A Louis

2008-04-01

GH replacement in Prader-Willi syndrome (PWS) children has well-defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multisite studies. Our objective was to evaluate the effectiveness and safety of GH in GH-deficient genotype-positive PWS adults. We conducted a 12-month open-label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods. The study was conducted at outpatient treatment facilities at four U.S. academic medical centers. Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements were recruited from clinical populations. Human recombinant GH (Genotropin) was initiated at 0.2 mg/d with monthly 0.2-mg increments to a maximum 1.0 mg/d, as tolerated. Lean body mass and percent fat were measured by dual-energy x-ray absorptiometry. Lean body mass increased from 42.65 +/- 2.25 (se) to 45.47 +/- 2.31 kg (P < or = 0.0001), and percent fat decreased from 42.84 +/- 1.12 to 39.95 +/- 1.34% (P = 0.025) at a median final dose of 0.6 mg/d in 30 study subjects who completed 6-12 months of GH. Mean fasting glucose of 85.3 +/- 3.4 mg/dl, hemoglobin A1c of 5.5 +/- 0.2%, fasting insulin of 5.3 +/- 0.6 microU/ml, area under the curve for insulin of 60.4 +/- 7.5 microU/ml, and homeostasis model assessment of insulin resistance of 1.1 +/- 0.2 were normal at baseline in 38 study initiators, including five diabetics, and remained in normal range. Total T(3) increased 26.7% from 127.0 +/- 7.8 to 150.5 +/- 7.8 ng/dl (P = 0.021) with normalization in all subjects, including six (20%) with baseline T(3) values at least 2 sd below the mean. Mildly progressive ankle edema was the most serious treatment-emergent adverse event (five patients). This multicenter study demonstrates that GH improves body composition, normalizes T(3), and is well tolerated without glucose impairment in PWS genotype adults.

Phosphorus Balance in Adolescent Girls and the Effect of Supplemental Dietary Calcium.

PubMed

Vorland, Colby J; Martin, Berdine R; Weaver, Connie M; Peacock, Munro; Gallant, Kathleen M Hill

2018-03-01

There are limited data on phosphorus balance and the effect of dietary calcium supplements on phosphorus balance in adolescents. The purpose of this study was to determine phosphorus balance and the effect of increasing dietary calcium intake with a supplement on net phosphorus absorption and balance in healthy adolescent girls. This study utilized stored urine, fecal, and diet samples from a previously conducted study that focused on calcium balance. Eleven healthy girls ages 11 to 14 years participated in a randomized crossover study, which consisted of two 3-week periods of a controlled diet with low (817 ± 19.5 mg/d) or high (1418 ± 11.1 mg/d) calcium, separated by a 1-week washout period. Phosphorus intake was controlled at the same level during both placebo and calcium supplementation (1435 ± 23.5 and 1453 ± 28.0 mg/d, respectively, p = 0.611). Mean phosphorus balance was positive by about 200 mg/d and was unaffected by the calcium supplement ( p = 0.826). Urinary phosphorus excretion was lower with the calcium supplement (535 ± 42 versus 649 ± 41 mg/d, p = 0.013), but fecal phosphorus and net phosphorus absorption were not significantly different between placebo and calcium supplement (553 ± 60 versus 678 ± 63 versus mg/d, p = 0.143; 876 ± 62 versus 774 ± 64 mg/d, p = 0.231, respectively). Dietary phosphorus underestimates using a nutrient database compared with the content measured chemically from meal composites by ~40%. These results show that phosphorus balance is positive in girls during adolescent growth and that a calcium dietary supplement to near the current recommended level does not affect phosphorus balance when phosphorus intake is at 1400 mg/d, a typical US intake level. © 2017 American Society for Bone and Mineral Research.

Life Cycle Assessment and Cost Analysis of Water and ...

EPA Pesticide Factsheets

changes in drinking and wastewater infrastructure need to incorporate a holistic view of the water service sustainability tradeoffs and potential benefits when considering shifts towards new treatment technology, decentralized systems, energy recovery and reuse of treated wastewater. The main goal of this study is to determine the influence of scale on the energy and cost performance of different transitional membrane bioreactors (MBR) in decentralized wastewater treatment (WWT) systems by performing a life cycle assessment (LCA) and cost analysis. LCA is a tool used to quantify sustainability-related metrics from a systems perspective. The study calculates the environmental and cost profiles of both aerobic MBRs (AeMBR) and anaerobic MBRs (AnMBR), which not only recover energy from waste, but also produce recycled water that can displace potable water for uses such as irrigation and toilet flushing. MBRs represent an intriguing technology to provide decentralized WWT services while maximizing resource recovery. A number of scenarios for these WWT technologies are investigated for different scale systems serving various population density and land area combinations to explore the ideal application potentials. MBR systems are examined from 0.05 million gallons per day (MGD) to 10 MGD and serve land use types from high density urban (100,000 people per square mile) to semi-rural single family (2,000 people per square mile). The LCA and cost model was built with ex

Four-week effects of allopurinol and febuxostat treatments on blood pressure and serum creatinine level in gouty men.

PubMed

Kim, Hyun Ah; Seo, Young-Il; Song, Yeong W

2014-08-01

The aim of this study was to observe the effects of uric acid lowering therapy (UALT), febuxostat and allopurinol, on blood pressure (BP) and serum creatinine level. Post-hoc data were derived from a phase-III, randomised, double-blind, 4-week trial of male gouty patients that compared the safety and efficacy of febuxostat and allopurinol in adults with gout. The subjects were randomly assigned to one of five groups, 35-37 in each group (febuxostat: 40, 80, 120 mg/d; allopurinol: 300 mg/d; control group: placebo). Blood pressure and serum creatinine level were measured at baseline and at weeks 2 and 4. Diastolic BP and creatinine level had decreased significantly in the UALT groups compared to the control group at week 4. Diastolic BP had decreased significantly in the allopurinol group and serum creatinine level had decreased significantly in the febuxostat groups at week 4. After adjusting for confounding variables, serum uric acid changes were found to be significantly correlated with changes in serum creatinine level but were not associated with changes in systolic or diastolic BP. UALT in gouty subjects significantly decreased diastolic BP and serum creatinine level. Changes in uric acid were significantly correlated with those in serum creatinine level, suggesting the feasibility of renal function improvement through UALT in gouty men.

Report of the River Master of the Delaware River for the period of December 1, 1980 to November 30, 1981

USGS Publications Warehouse

Schaefer, Francis T.; Fish, Robert E.

1982-01-01

Water supply conditions at the beginning of the year were marginal in marked contrast to those for the preceeding nine years. Discharge of the Delaware River at Montague, New Jersey, was only 72% of median as compared to 68% in excess of median the previous year. In December, with reservoir storage again declining, further reductions in both diversions and releases were imposed. With consent of all the parties, reductions were effected on December 20 limiting New York City diversions to 560 mgd, New Jersey to 65 mgd, and the required discharge at Montague was targeted at 1550 cfs. To conserve supplies, additional reductions were imposed in January when the Delaware River basin Commission formally declared a drought. New York City 's limitations was set at 520 mgd and that for New Jersey at 62 mgd. Montague flows were targeted between 1100 cfs, depending upon the location of the salt front in the estuary. Water quality of the Delaware River and Estuary was monitored on a continuous basis at eight sites for most of the year and on a monthly basis at ten sites to accurately locate the salt front. Highest concentrations observed at the Benjamin Franklin Bridge site was 133 mg/l (milligram per liter) on February 2. (USGS)

Neither Folic Acid Supplementation nor Pregnancy Affects the Distribution of Folate Forms in the Red Blood Cells of Women1–3

PubMed Central

Hartman, Brenda A.; Fazili, Zia; Pfeiffer, Christine M.; O’Connor, Deborah L.

2016-01-01

It is not known whether folate metabolism is altered during pregnancy to support increased DNA and RNA biosynthesis. By using a state-of-the-art LC tandem mass spectrometry technique, the aim of this study was to investigate differences in RBC folate forms between pregnant and nonpregnant women and between nonpregnant women consuming different concentrations of supplemental folic acid. Forms of folate in RBCs were used to explore potential shifts in folate metabolism during early erythropoiesis. Total RBC folate and folate forms [tetrahydrofolate; 5-methyltetrahydrofolate (5-methyl-THF); 4α-hydroxy-5-methyl-tetrahydrofolate (an oxidation product of 5-methyl-THF); 5-formyl-tetrahydrofolate; and 5,10-methenyl-tetrahydrofolate] were measured in 4 groups of women (n = 26): pregnant women (PW) (30–36 wk of gestation) consuming 1 mg/d of folic acid, and nonpregnant women consuming 0 mg/d (NPW-0), 1 mg/d (NPW-1), and 5 mg/d (NPW-5) folic acid. The mean ± SD RBC folate concentration of the NPW-0 group (890 ± 530 nmol/L) was lower than the NPW-1 (1660 ± 350 nmol/L) and NPW-5 (1980 ± 570 nmol/L) groups as assessed by microbiologic assay (n = 26, P < 0.0022). No difference was found between the NPW-1 and NPW-5 groups. We detected 5-methyl-THF [limit of detection (LOD) = 0.06 nmol/L] in all groups and tetrahydrofolate (LOD = 0.2 nmol/L) in most women regardless of methylenetetrahydrofolate reductase genotype. Most women consuming folic acid supplements had detectable concentrations of 5,10-methenyl-tetrahydrofolate (LOD = 0.31 nmol/L). However, there was no difference in the relative distribution of 5-methyl-THF (83–84%), sum of non-methyl folates (0.6–3%), or individual non-methyl folate forms in RBCs across groups. We conclude that although folic acid supplementation in nonpregnant women increases RBC total folate and the concentration of individual folate forms, it does not alter the relative distribution of folate forms. Similarly, distribution of RBC folate forms did not differ between pregnant and nonpregnant women. This trial was registered at clinicaltrials.gov as NCT01741077. PMID:24991041

Neither folic acid supplementation nor pregnancy affects the distribution of folate forms in the red blood cells of women.

PubMed

Hartman, Brenda A; Fazili, Zia; Pfeiffer, Christine M; O'Connor, Deborah L

2014-09-01

It is not known whether folate metabolism is altered during pregnancy to support increased DNA and RNA biosynthesis. By using a state-of-the-art LC tandem mass spectrometry technique, the aim of this study was to investigate differences in RBC folate forms between pregnant and nonpregnant women and between nonpregnant women consuming different concentrations of supplemental folic acid. Forms of folate in RBCs were used to explore potential shifts in folate metabolism during early erythropoiesis. Total RBC folate and folate forms [tetrahydrofolate; 5-methyltetrahydrofolate (5-methyl-THF); 4α-hydroxy-5-methyl-tetrahydrofolate (an oxidation product of 5-methyl-THF); 5-formyl-tetrahydrofolate; and 5,10-methenyl-tetrahydrofolate] were measured in 4 groups of women (n = 26): pregnant women (PW) (30-36 wk of gestation) consuming 1 mg/d of folic acid, and nonpregnant women consuming 0 mg/d (NPW-0), 1 mg/d (NPW-1), and 5 mg/d (NPW-5) folic acid. The mean ± SD RBC folate concentration of the NPW-0 group (890 ± 530 nmol/L) was lower than the NPW-1 (1660 ± 350 nmol/L) and NPW-5 (1980 ± 570 nmol/L) groups as assessed by microbiologic assay (n = 26, P < 0.0022). No difference was found between the NPW-1 and NPW-5 groups. We detected 5-methyl-THF [limit of detection (LOD) = 0.06 nmol/L] in all groups and tetrahydrofolate (LOD = 0.2 nmol/L) in most women regardless of methylenetetrahydrofolate reductase genotype. Most women consuming folic acid supplements had detectable concentrations of 5,10-methenyl-tetrahydrofolate (LOD = 0.31 nmol/L). However, there was no difference in the relative distribution of 5-methyl-THF (83-84%), sum of non-methyl folates (0.6-3%), or individual non-methyl folate forms in RBCs across groups. We conclude that although folic acid supplementation in nonpregnant women increases RBC total folate and the concentration of individual folate forms, it does not alter the relative distribution of folate forms. Similarly, distribution of RBC folate forms did not differ between pregnant and nonpregnant women. This trial was registered at clinicaltrials.gov as NCT01741077. © 2014 American Society for Nutrition.

Improved Cook-off Modeling of Multi-component Cast Explosives

NASA Astrophysics Data System (ADS)

Nichols, Albert

2017-06-01

In order to understand the hazards associated with energetic materials, it is important to understand their behavior in adverse thermal environments. These processes have been relatively well understood for solid explosives, however, the same cannot be said for multi-component melt-cast explosives. Here we describe the continued development of ALE3D, a coupled thermal/chemical/mechanical code, to improve its description of fluid explosives. The improved physics models include: 1) Chemical potential driven species segregation. This model allows us to model the complex flow fields associated with the melting and decomposing Comp-B, where the denser RDX tends to settle and the decomposing gasses rise, 2) Automatically scaled stream-wise diffusion model for thermal, species, and momentum diffusion. These models add sufficient numerical diffusion in the direction of flow to maintain numerical stability when the system is under resolved, as occurs for large systems. And 3) a slurry viscosity model, required to properly define the flow characteristics of the multi-component fluidized system. These models will be demonstrated on a simple Comp-B system. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344.

Coffee, Caffeine, and Risk of Depression Among Women

PubMed Central

Lucas, Michel; Mirzaei, Fariba; Pan, An; Okereke, Olivia I.; Willett, Walter C; O’Reilly, Éilis J; Koenen, Karestan; Ascherio, Alberto

2012-01-01

Background Caffeine is the world’s most widely used central nervous system stimulant, with about 80% consumed in form of coffee. However, studies that analyzed prospectively the relation of coffee or caffeine consumption and depression risk are scarce. Methods A total of 50,739 U.S. women (mean age=63 years) free from depressive symptoms at baseline (1996) were prospectively followed until 2006. Caffeine and coffee consumption, and other caffeinated and decaffeinated beverages, were obtained from validated questionnaires completed between 1980 through 2002 and computed as cumulative average of consumption with a 2-year latency applied. Clinical depression was defined as reporting both physician-diagnosed depression and antidepressant use. Relative risks of clinical depression were estimate using Cox proportional hazards regression models. Results During 10 years of follow-up (1996–2006), 2,607 incident cases of depression were identified. Compared to women consuming caffeinated coffee less frequently (≤1 cup/wk), multivariate relative risk of depression was 0.85 (95% confidence interval [CI], 0.75 to 0.95) for those consuming 2–3 cups/d and 0.80 (95%CI, 0.64 to 0.99; P trend <0.001) for those consuming ≥4 cups/d. Multivariate relative risk for depression was 0.80 (95%CI, 0.68 to 0.95; P trend=0.02) for women in the highest (≥550 mg/d) vs. lowest (<100 mg/d) of the 5 caffeine consumption categories. Decaffeinated coffee was not associated with depression risk. Conclusions In this large longitudinal study we found that depression risk decreases with increasing caffeinated coffee consumption. Further investigations are needed to confirm this finding and to determine whether usual caffeinated coffee consumption may contribute to depression prevention. PMID:21949167

Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers.

PubMed

Takayama, Masaki; Matsui, Shigenaga; Kawasaki, Masanori; Asakuma, Yutaka; Sakurai, Toshiharu; Kashida, Hiroshi; Kudo, Masatoshi

2013-09-14

To prospectively compare the healing rates of endoscopic submucosal dissection (ESD)-induced ulcers treated with either a proton-pump inhibitor (PPI) or rebamipide. We examined 90 patients with early gastric cancer who had undergone ESD. All patients were administered an intravenous infusion of the PPI lansoprazole (20 mg) every 12 h for 2 d, followed by oral administration of lansoprazole (30 mg/d, 5 d). After 7-d treatment, the patients were randomly assigned to 2 groups and received either lansoprazole (30 mg/d orally, n = 45; PPI group) or rebamipide (300 mg orally, three times a day; n = 45; rebamipide group). At 4 and 8 wk after ESD, the ulcer outcomes in the 2 groups were compared. No significant differences were noted in patient age, underlying disease, tumor location, Helicobacter pylori infection rate, or ESD-induced ulcer size between the 2 groups. At both 4 and 8 wk, the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients (4 wk: PPI, 27.2%; rebamipide, 33.3%; P = 0.5341; 8 wk: PPI, 90.9%; rebamipide, 93.3%; P = 0.6710). At 8 wk, the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group (13.6%) than in the rebamipide-treated group (0.0%; P = 0.0103). Ulcer-related symptoms were similar in the 2 treatment groups at 8 wk. The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide. No ulcer bleeding or complications due to the drugs were observed in either treatment group. The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment; however, rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.

Integrated Personnel and Pay System-Army Increment 2 (IPPS-A Inc 2)

DTIC Science & Technology

2016-03-01

2016 Major Automated Information System Annual Report Integrated Personnel and Pay System-Army Increment 2 (IPPS-A Inc 2) Defense Acquisition...703-325-3747 DSN Phone: 865-2915 DSN Fax: 221-3747 Date Assigned: May 2, 2014 Program Information Program Name Integrated Personnel and Pay System...Program Description The Integrated Personnel and Pay System-Army (IPPS-A) will provide the Army with an integrated, multi-Component (Active, National

Multicomponent Supramolecular Systems: Self-Organization in Coordination-Driven Self-Assembly

PubMed Central

Zheng, Yao-Rong; Yang, Hai-Bo; Ghosh, Koushik; Zhao, Liang; Stang, Peter J.

2009-01-01

The self-organization of multicomponent supramolecular systems involving a variety of two-dimensional (2-D) polygons and three-dimensional (3-D) cages is presented. Nine self-organizing systems, SS1–SS9, have been studied. Each involving the simultaneous mixing of organoplatinum acceptors and pyridyl donors of varying geometry and their selective self-assembly into three to four specific 2-D (rectangular, triangular, and rhomboid) and/or 3-D (triangular prism and distorted and nondistorted trigonal bipyramidal) supramolecules. The formation of these discrete structures is characterized using NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). In all cases, the self-organization process is directed by: (1) the geometric information encoded within the molecular subunits and (2) a thermodynamically driven dynamic self-correction process. The result is the selective self-assembly of multiple discrete products from a randomly formed complex. The influence of key experimental variables – temperature and solvent – on the self-correction process and the fidelity of the resulting self-organization systems is also described. PMID:19544512

HIGHLY EFFECTIVE SYNTHESIS OF 4-HALO-TETRAHYDROPYRANS VIA A HIGHLY DIASTEREOSELECTIVE IN SITU PRINS-TYPE CYCLIZATION REACTION. (R822668)

EPA Science Inventory

Abstract

The reaction of aldehyde with homoallyl alcohols mediated by indium trichloride generated 4-chlorotetrahydropyrans in high yields and with high stereoselectivity. The same type of compounds can be generated through a single step, multi-component coupling be...