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Sample records for increasing treatment time

  1. Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review

    PubMed Central

    Neal, R D; Tharmanathan, P; France, B; Din, N U; Cotton, S; Fallon-Ferguson, J; Hamilton, W; Hendry, A; Hendry, M; Lewis, R; Macleod, U; Mitchell, E D; Pickett, M; Rai, T; Shaw, K; Stuart, N; Tørring, M L; Wilkinson, C; Williams, B; Williams, N; Emery, J

    2015-01-01

    Background: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. Methods: Systematic review of the literature and narrative synthesis. Results: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. Conclusions: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers. PMID:25734382

  2. Manipulation of progesterone to increase ovulatory response to the first GnRH treatment of an Ovsynch protocol in lactating dairy cows receiving first timed artificial insemination.

    PubMed

    Carvalho, P D; Wiltbank, M C; Fricke, P M

    2015-12-01

    Ovulation to the first GnRH (G1) treatment of the Ovsynch protocol improves synchronization rate and pregnancies per AI (P/AI). Elevated progesterone (P4) concentrations at G1 decrease the ovulatory response by decreasing the magnitude of the GnRH-induced LH surge. Therefore, our objective was to evaluate the effect of temporarily decreasing P4 concentrations before initiation of an Ovsynch protocol on ovulatory response to G1 and P/AI. Lactating Holstein cows (n=800) at 53±3 (herd A) or 51±3 (herd B) d in milk (DIM) were synchronized using a modified Double-Ovsynch protocol [pre-Ovsynch protocol (d 0, GnRH; d 7, PGF2?; d 10, GnRH) followed 7 d later by an Ovsynch-56 protocol (d 0, G1; d 7, PGF2?; d 8, PGF2?; d 9.5, GnRH)] to receive first timed artificial insemination (TAI; 80±3 DIM) 16h after the last GnRH treatment. Cows were randomly assigned to receive 12.5mg of PGF2? (a half-dose of dinoprost tromethamine) 2 d before G1 (low-P4) or serve as untreated controls (high-P4). Overall, high-P4 cows had greater P4 concentrations at G1 compared with low-P4 cows (3.0 vs. 1.3ng/mL, respectively). Ovulatory response to G1 was greater for low-P4 than high-P4 cows [81.1 vs. 60.3%, respectively]. Premature luteal regression during the second Ovsynch protocol did not differ between treatments [15.0% vs. 10.7%; for low-P4 vs. high-P4 cows, respectively]. Overall, P/AI did not differ between treatments 32 d after TAI [56.3 vs. 52.9%, for low-P4 vs. high-P4 cows, respectively] or 67 d after AI [50.5 vs. 47.6%, for low-P4 vs. high-P4 cows, respectively]. Pregnancy loss from 32 to 67 d after TAI did not differ between treatments [9.9 vs. 9.3%, for low-P4 vs. high-P4 cows, respectively]. Overall, cows that ovulated to G1 had more P/AI than cows that did not ovulate [58.2 vs. 41.8%, respectively]. The increase in P/AI for cows that ovulated to G1 (16.4%) combined with the observed increase in ovulation to G1 due to treatment (20.8%; low-P4 - high-P4) resulted in the expected numerical increase in P/AI of 3.4% in low-P4 versus high-P4 cows observed in this experiment. We conclude that administration of a half-dose of PGF2? 2 d before G1 during a Double-Ovsynch protocol decreased P4 at G1 and increased ovulatory response to G1. PMID:26454293

  3. Increasing nursing treatment for pediatric procedural pain.

    PubMed

    Bice, April A; Gunther, Mary; Wyatt, Tami

    2014-03-01

    Procedural pain management is an underused practice in children. Despite the availability of efficacious treatments, many nurses do not provide adequate analgesia for painful interventions. Complementary therapies and nonpharmacologic interventions are additionally essential to managing pain. Owing to the increasing awareness of inadequate nursing utilization of pharmacologic measures for procedural pain, this paper focuses only on analgesic treatments. The aim of this review was to examine how varying degrees of quality improvement affect nursing utilization of treatments for routine pediatric procedural pain. A comprehensive search of databases including Cinahl, Medline/Pubmed, Web of Science, Google Scholar, Psycinfo, and Cochrane Library was performed. Sixty-two peer-reviewed research articles were examined. Ten articles focusing on quality improvement in pediatric pain management published in English from 2001 to 2011 were included. Three themes emerged: 1) increasing nursing knowledge; 2) nursing empowerment; and 3) protocol implementation. Research critique was completed with the use of guidelines and recommendations from Creswell (2009) and Garrard (2011). The literature reveals that nurses still think that pediatric pain management is essential. Quality improvement increases nursing utilization of procedural pain treatments. Although increasing nursing knowledge improves pediatric pain management, it appears that nursing empowerment and protocol implementation increase nursing compliance more than just education alone. Nurses providing pain management can enhance their individual practice with quality improvement measures that may increase nursing adherence to institutional and nationally recommended pediatric procedural pain management guidelines. PMID:24602440

  4. Night-time sedating H1-antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial

    PubMed Central

    Staevska, M; Gugutkova, M; Lazarova, C; Kralimarkova, T; Dimitrov, V; Zuberbier, T; Church, MK; Popov, TA

    2014-01-01

    Background Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1-antihistamine in the morning and a sedating first-generation H1-antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded? Objectives To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria (CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy). Methods In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence. Results Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2oL scores (P < 0·001) without significant differences between the two. Compared with baseline, daytime somnolence was significantly reduced by levocetirizine monotherapy (P = 0·006) but not by levocetirizine plus hydroxyzine (P = 0·218). Direct comparison of the two treatment modalities in terms of daytime somnolence favoured levocetirizine monotherapy (P = 0·026). Conclusions The widespread belief that sleep is aided by the addition of a sedating first-generation H1-antihistamine, usually hydroxyzine, at night is not supported. These results are in line with the urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1-antihistamines only. PMID:24472058

  5. Early Diagnosis, Timely Treatment

    MedlinePLUS Videos and Cool Tools

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  6. Can treatment increase the epidemic size?

    PubMed

    Xiao, Yanyu; Brauer, Fred; Moghadas, Seyed M

    2016-01-01

    Antiviral treatment is one of the key pharmacological interventions against many infectious diseases. This is particularly important in the absence of preventive measures such as vaccination. However, the evolution of drug-resistance in treated patients and its subsequent spread to the population pose significant impediments to the containment of disease epidemics using treatment. Previous models of population dynamics of influenza infection have shown that in the presence of drug-resistance, the epidemic final size (i.e., the total number of infections throughout the epidemic) is affected by the treatment rate. These models, through simulation experiments, illustrate the existence of an optimal treatment rate, not necessarily the highest possible rate, for minimizing the epidemic final size. However, the conditions for the existence of such an optimal treatment rate have never been found. Here, we provide these conditions for a class of models covered in the literature previously, and investigate the combination effect of treatment and transmissibility of the drug-resistant pathogen strain on the epidemic final size. For the first time, we obtain the final size relations for an epidemic model with two strains of a pathogen (i.e., drug-sensitive and drug-resistant). We also discuss this model with specific functional forms of de novo resistance emergence, and illustrate the theoretical findings with numerical simulations. PMID:25925242

  7. Improvement of grafted watermelon transplant survival as a result of size and starch increases over time caused by rootstock fatty alcohol treatment Part II

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty alcohol treatments can be used to eliminate the meristem of cucurbit (Family Cucurbitaceae) rootstocks which prevents regrowth when grafting, but the effects of the treatment on the rootstock have not been documented. Two rootstock types, ‘Emphasis’ bottle gourd (Lagenaria siceraria) and ‘Car...

  8. Are mental disorders increasing over time?

    PubMed

    Häfner, H

    1985-01-01

    The impression that the prevalence of mental disorder has been increasing during the last decades is only partially justified. The considerable increase in the demand for psychiatric and psychotherapeutic help is influenced by quite a number of factors that vary in nature and direction. The most essential contribution was made by changes in the age composition of the population - and here primarily by the growing number of mentally ill elderly persons - and by the enormous increase in life expectancy. In milder psychiatric disorder the increase in the utilization of medical help is mainly due to new ways of treatment and to the great enlargement of psychiatric and psychotherapeutic services in most industrial countries, for which the zeitgeist of transition from a predominance of natural science to a more psychological understanding of life forms the background. Civilizational factors in a closer sense, like the raising of the achievement level for school beginners or alterations in the threshold of tolerance between mental illness needing medical intervention and mental suffering to be borne with submission to God's will, play an essential role particularly for the widening of the disease concept and thus for changes in the frequency of certain deficits of achievement and feeling, such as 'reading disorder' or depressive states. The fact that the age-corrected risk of falling ill with schizophrenia has remained stable over many decades - wherever it could be investigated - does not point to a relation with variable environmental factors like industrialization, civilization or social order. In contrast with this disease in a closer sense, the rates of psychiatrically relevant forms of deviant behaviour - suicidal attempts, drug- and alcohol-related disorders - show rapidly changing upward and downward variations. Thus, they are more comparable to criminality rates that vary over time and culture. There is obviously a relation between changes in the frequency of deviant behaviour and changing patterns of values in society, such as the reduction of educational intensity and the commitment of adolescents to norms and convictions of their parents. This is why the most distinct changes in these rates occur at the age most accessible to contemporary or fashionable influences: in youth and younger adult age. Except for age-related changes, we do not seem to have become more ill than the generation of our parents, but more pessimistic. PMID:4059492

  9. Wait Time for Treatment in Hospital Emergency Departments: 2009

    MedlinePLUS

    ... NCHS Data Brief Number 102, August 2012 Wait Time for Treatment in Hospital Emergency Departments: 2009 On ... emergency department crowding, ambulance diversion, boarding Has wait time for treatment in EDs increased? Between 2003 and ...

  10. Burns treatment in ancient times.

    PubMed

    Pe?anac, Marija; Janji?, Zlata; Komarcevi?, Aleksandar; Paji?, Milos; Dobanovacki, Dusanka; Miskovi?, Sanja Skeledzija

    2013-01-01

    Discovery of fire at the dawn of prehistoric time brought not only the benefits to human beings offering the light and heat, but also misfortune due to burns; and that was the beginning of burns treatment. Egyptian doctors made medicines from plants, animal products and minerals, which they combined with magic and religious procedures. The earliest records described burns dressings with milk from mothers of male babies. Goddess Isis was called upon to help. Some remedies and procedures proved so successful that their application continued for centuries. The Edwin Smith papyrus (1500 BC) mentioned the treatment of burns with honey and grease. Ebers Papyrus (1500 BC) contains descriptions of application of mud, excrement, oil and plant extracts. They also used honey, Aloe and tannic acid to heal burns. Ancient Egyptians did not know about microorganisms but they knew that honey, moldy bread and copper salts could prevent infections from dirt in burns healing. Thyme, opium and belladona were used for pain relief. In the 4th century BC, Hippocrates recorded that Greek and Roman doctors used rendered pig fat, resin and bitumen to treat burns. Mixture of honey and bran, or lotion of wine and myrrh were used by Celsus. Honey was also known in Ayurveda (Indian medicine) time. Ayurvedic records Characa and Sushruta included honey in their dressing aids to purify sores and promote the healing. Burn treatment in Chinese medicine was traditional. It was a compilation of philosophy, knowledge and herbal medicine. The successful treatment of burns started in recent time and it has been made possible by better knowledge of the pathophysiology of thermal injuries and their consequences, medical technology advances and improved surgical techniques. PMID:23888738

  11. [Health anxiety - increased knowledge and treatment options].

    PubMed

    Davidsdottir, Soley Drofn; Sveinsson, Olafur Arni

    2010-12-01

    Patients with hypochondriasis are preoccupied with the fear or belief that they have a serious, undiagnosed disease. This concern derives from misinterpretations of benign physical sensations, and persists despite appropriate reassurance to the contrary. They have, on average, disproportionately high rates of visits to physicians, specialty consultations, laboratory tests, and surgical procedures, as well as high health care costs. Despite this extensive medical attention, they find their care unsatisfactory, which is understandable, as convincing alternative explanations to their ailments are repeatedly delayed. Physicians, in turn, may feel discouraged and frustrated in relation to these individuals where their best efforts to help often prove ineffective or are even rejected. Recent scientific studies have shown that cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRI) are effective treatment options for health anxiety as demonstrated in clinical trials. PMID:21149871

  12. After treatment ends: neutral time.

    PubMed

    Hurt, G J; McQuellon, R P; Barrett, R J

    1994-01-01

    For persons diagnosed with cancer, the remission period may be marked by increased anxiety and distress. While the medical team may view remission as an eagerly anticipated milestone, the decreased medical surveillance during this time can cause a heightened fear of recurrence for the patient. One author has called this period of remission "neutral time," a time characterized by uncertainty. The safety signal hypothesis, developed by Martin Seligman, may help to explain the anxiety experienced by some patients during the remission period. Because cancer is frequently a silent disease with no overt symptoms, patients in remission often have no safety signal to indicate that the disease will not return. A case study is presented and discussed in light of these two concepts. PMID:7697080

  13. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  14. Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment.

    PubMed

    Coffeng, Luc E; Stolk, Wilma A; Hoerauf, Achim; Habbema, Dik; Bakker, Roel; Hopkins, Adrian D; de Vlas, Sake J

    2014-01-01

    The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently. PMID:25545677

  15. Increases in body mass index following initiation of methadone treatment.

    PubMed

    Fenn, Jennifer M; Laurent, Jennifer S; Sigmon, Stacey C

    2015-04-01

    Despite the clear efficacy of methadone for opioid dependence, one less desirable phenomenon associated with methadone may be weight gain. We examined changes in body mass index (BMI) among patients entering methadone treatment. A retrospective chart review was conducted for 96 patients enrolled in an outpatient methadone clinic for ? 6 months. The primary outcome of BMI was assessed at intake and a subsequent physical examination approximately 1.8 ± 0.95 years later. Demographic, drug use and treatment characteristics were also examined. There was a significant increase in BMI following intake (p<0.001). Mean BMIs increased from 27.2 ± 6.8 to 30.1 ± 7.7 kg/m(2), translating to a 17.8-pound increase (10% increase in body weight) in the overall patient sample. Gender was the strongest predictor of BMI changes (p < 0.001), with significantly greater BMI increases in females than males (5.2 vs. 1.7 kg/m(2), respectively). This translates to a 28-pound (17.5%) increase in females vs. a 12-pound (6.4%) increase in males. In summary, methadone treatment enrollment was associated with clinically significant weight gain, particularly among female patients. This study highlights the importance of efforts to help patients mitigate weight gain during treatment, particularly considering the significant health and economic consequences of obesity for individuals and society more generally. PMID:25441923

  16. Heat treatment procedure to increase ductility of degraded nickel alloy

    NASA Technical Reports Server (NTRS)

    Prager, M.

    1968-01-01

    Tests demonstrate the room temperature ductility of degraded Rene 41 can be increased to acceptable values by solution heat treatment at a temperature of 2050 degrees to 2150 degrees F /1 to 2 hours/ and cooling through a controlled temperature range followed by normal aging in air /16 hours at 1400 degrees F/.

  17. Thermal treatment for increasing magnetostrictive response of rare earth-iron alloy rods

    DOEpatents

    Verhoeven, J.D.; McMasters, O.D.

    1989-07-18

    Magnetostrictive rods formed from rare earth-iron alloys are subjected to a short time heat treatment to increase their magnetostrictive response under compression. The heat treatment is preferably carried out at a temperature of from 900 to 1,000 C for 20 minutes to six hours.

  18. Thermal treatment for increasing magnetostrictive response of rare earth-iron alloy rods

    DOEpatents

    Verhoeven, John D. (Ames, IA); McMasters, O. D. (Ames, IA)

    1989-07-18

    Magnetostrictive rods formed from rare earth-iron alloys are subjected to a short time heat treatment to increase their Magnetostrictive response under compression. The heat treatment is preferably carried out at a temperature of from 900.degree. to 1000.degree. C. for 20 minutes to six hours.

  19. Cow comfort in tie-stalls: increased depth of shavings or straw bedding increases lying time.

    PubMed

    Tucker, C B; Weary, D M; von Keyserlingk, M A G; Beauchemin, K A

    2009-06-01

    Over half of US dairy operations use tie-stalls, but these farming systems have received relatively little research attention in terms of stall design and management. The current study tested the effects of the amount of 2 bedding materials, straw and shavings, on dairy cattle lying behavior. The effects of 4 levels of shavings, 3, 9, 15, and 24 kg/stall (experiment 1, n = 12), and high and low levels of straw in 2 separate experiments: 1, 3, 5, and 7 kg/stall (experiment 2, n = 12) and 0.5, 1, 2, and 3 kg/stall (experiment 3, n = 12) were assessed. Treatments were compared using a crossover design with lactating cows housed in tie-stalls fitted with mattresses. Treatments were applied for 1 wk. Total lying time, number of lying bouts, and the length of each lying bout was recorded with data loggers. In experiment 1, cows spent 3 min more lying down for each additional kilogram of shavings (11.0, 11.7, 11.6, and 12.1 +/- 0.24 h/d for 3, 9, 15, and 24 kg/stall shavings, respectively). In experiment 2, cows increased lying time by 12 min for every additional kilogram of straw (11.2, 12.0, 11.8, and 12.4 +/- 0.24 h/d for 1, 3, 5, and 7 kg/stall of straw, respectively). There were no differences in lying behavior among the lower levels of straw tested in experiment 3 (11.7 +/- 0.32 h/d). These results indicated that additional bedding above a scant amount improves cow comfort, as measured by lying time, likely because a well-bedded surface is more compressible. PMID:19448001

  20. Prolonged Treatment Time Deteriorates Positioning Accuracy for Stereotactic Radiosurgery

    PubMed Central

    Wang, Chun-Wei; Lin, Yin-Chun; Tseng, Ham-Min; Xiao, Furen; Chen, Chang-Mu; Cheng, Wei-Li; Lu, Szu-Huai; Lan, Keng-Hsueh; Chen, Wan-Yu; Liang, Hsiang-Kuang; Kuo, Sung-Hsin

    2015-01-01

    Introduction The accuracy of radiation delivery is increasingly important as radiotherapy technology continues to develop. The goal of this study was to evaluate intrafractional motion during intracranial radiosurgery and the relationship between motion change and treatment time. Methods and Materials A total of 50 treatment records with 5988 images, all acquired during treatments with the CyberKnife Radiosurgery System, were retrospectively analyzed in this study. We measured translation and rotation motion including superior-inferior (SI), right-left (RL), anterior-posterior (AP), roll, tilt and yaw. All of the data was obtained during the first 45 minutes of treatment. The records were divided into 3 groups based on 15-min time intervals following the beginning of treatment: group A (0-15 min), group B (16-30 min) and group C (31-45 min). The mean deviations, systematic errors, random errors and margin for planning target volume (PTV) were calculated for each group. Results The mean deviations were less than 0.1 mm in all three translation directions in the first 15 minutes. Greater motion occurred with longer treatment times, especially in the SI direction. For the 3D vector, a time-dependent change was observed, from 0.34 mm to 0.77 mm (p=0.01). There was no significant correlation between the treatment time and deviations in the AP, LR and rotation axes. Longer treatment times were associated with increases in systematic error, but not in random error. The estimated PTV margin for groups A, B and C were 0.86 / 1.14 / 1.31 mm, 0.75 / 1.12 / 1.20 mm, and 0.43 / 0.54 / 0.81 mm in the SI, RL, and AP directions, respectively. Conclusions During intracranial radiosurgery, a consistent increase in the positioning deviation over time was observed, especially in the SI direction. If treatment time is greater than 15 minutes, we recommend increasing the PTV margins to ensure treatment precision. PMID:25894841

  1. High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People

    PubMed Central

    Kranz, Georg S.; Wadsak, Wolfgang; Kaufmann, Ulrike; Savli, Markus; Baldinger, Pia; Gryglewski, Gregor; Haeusler, Daniela; Spies, Marie; Mitterhauser, Markus; Kasper, Siegfried; Lanzenberger, Rupert

    2015-01-01

    Background Women are two times more likely to be diagnosed with depression than men. Sex hormones modulating serotonergic transmission are proposed to partly underlie these epidemiologic findings. Here, we used the cross-sex steroid hormone treatment of transsexuals seeking sex reassignment as a model to investigate acute and chronic effects of testosterone and estradiol on serotonin reuptake transporter (SERT) binding in female-to-male and male-to-female transsexuals. Methods Thirty-three transsexuals underwent [11C]DASB positron emission tomography before start of treatment, a subset of which underwent a second scan 4 weeks and a third scan 4 months after treatment start. SERT nondisplaceable binding potential was quantified in 12 regions of interest. Treatment effects were analyzed using linear mixed models. Changes of hormone plasma levels were correlated with changes in regional SERT nondisplaceable binding potential. Results One and 4 months of androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus. SERT binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, 4 months of antiandrogen and estrogen treatment in male-to-female transsexuals led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding, indicating a protective effect of estradiol against SERT loss. Conclusions Given the central role of the SERT in the treatment of depression and anxiety disorders, these findings may lead to new treatment modalities and expand our understanding of the mechanism of action of antidepressant treatment properties. PMID:25497691

  2. Combined ultrasonication and thermal pre-treatment of sewage sludge for increasing methane production.

    PubMed

    Trzcinski, Antoine Prandota; Tian, Xinbo; Wang, Chong; Lin, Li Leonard; Ng, Wun Jern

    2015-01-01

    This article focuses on the combination of ultrasonic and thermal treatment of sewage sludge (SS). The combination involved ultrasonicating a fraction of the sludge and thermal treatment at various temperatures and this resulted in solubilization of proteins and carbohydrates, and so contributing to increased COD solubilization. During the treatment, SCOD, soluble proteins and carbohydrates increased from 760 mg L(-1) to 10,200 mg L(-1), 110 mg L(-1) to 2,900 mg L(-1) and 60 mg L(-1) to 630 mg L(-1), respectively. It was found ultrasonication of only a fraction of the sludge (>20%) followed by thermal treatment led to significant improvement compared to thermal and ULS treatments applied on their own. At 65°C, the kinetic of solubilization was improved and the hyper-thermophilic treatment time could be reduced to a few hours when ultrasonication was used first. A linear correlation (R(2) = 95%) was found between the SCOD obtained after ultrasonication pre-treatment and anaerobic biodegradability. The combined treatment resulted in 20% increase in biogas production during the anaerobic digestion of the pre-treated sludge. PMID:25560267

  3. Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers

    PubMed Central

    Ishioka, Masamichi; Yasui-Furukori, Norio; Sugawara, Norio; Furukori, Hanako; Kudo, Shuhei; Nakamura, Kazuhiko

    2015-01-01

    Objective The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE) is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation. Method The participants included 182 patients with schizophrenia (male =89, female =93) who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex) and serum prolactin concentrations were measured. Results Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002) and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the thrombin–antithrombin complex level (r=0.117, ns) among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE. PMID:25750528

  4. Time-Dependent Increase in Network Response to Stimulation

    PubMed Central

    Hamilton, Franz; Graham, Robert; Luu, Lydia; Peixoto, Nathalia

    2015-01-01

    In vitro neuronal cultures have become a popular method with which to probe network-level neuronal dynamics and phenomena in controlled laboratory settings. One of the key dynamics of interest in these in vitro studies has been the extent to which cultured networks display properties indicative of learning. Here we demonstrate the effects of a high frequency electrical stimulation signal in training cultured networks of cortical neurons. Networks receiving this training signal displayed a time-dependent increase in the response to a low frequency probing stimulation, particularly in the time window of 20–50 ms after stimulation. This increase was found to be statistically significant as compared to control networks that did not receive training. The timing of this increase suggests potentiation of synaptic mechanisms. To further investigate this possibility, we leveraged the powerful Cox statistical connectivity method as previously investigated by our group. This method was used to identify and track changes in network connectivity strength. PMID:26545098

  5. Aggregation increases prey survival time in group chase and escape

    NASA Astrophysics Data System (ADS)

    Yang, Sicong; Jiang, Shijie; Jiang, Li; Li, Geng; Han, Zhangang

    2014-08-01

    Recently developed chase-and-escape models have addressed a fascinating pursuit-and-evasion problem that may have both theoretical significance and potential applications. We introduce three aggregation strategies for the prey in a group chase model on a lattice. Simulation results show that aggregation dramatically increases the group survival time, even allowing immortal prey. The average survival time ? and the aggregation probability P have a power-law dependence of \\tau \\sim {{(1-P)}^{-1}} for P\\in [0.9,0.997]. With increasing numbers of predators, there is still a phase transition. When the number of predators is less than the critical point value, the prey group survival time increases significantly.

  6. Does carbon reduction increase sustainability? A study in wastewater treatment.

    PubMed

    Sweetapple, Christine; Fu, Guangtao; Butler, David

    2015-12-15

    This study investigates the relationships between carbon reduction and sustainability in the context of wastewater treatment, focussing on the impacts of control adjustments, and demonstrates that reducing energy use and/or increasing energy recovery to reduce net energy can be detrimental to sustainability. Factorial sampling is used to derive 315 control options, containing two different control strategies and a range of sludge wastage flow rates and dissolved oxygen setpoints, for evaluation. For each, sustainability indicators including operational costs, net energy and multiple environmental performance measures are calculated. This enables identification of trade-offs between different components of sustainability which must be considered before implementing energy reduction measures. In particular, it is found that the impacts of energy reduction measures on sludge production and nitrogen removal must be considered, as these are worsened in the lowest energy solutions. It also demonstrates that a sufficiently large range of indicators need to be assessed to capture trade-offs present within the environmental component of sustainability. This is because no solutions provided a move towards sustainability with respect to every indicator. Lastly, it is highlighted that improving the energy balance (as may be considered an approach to achieving carbon reduction) is not a reliable means of reducing total greenhouse gas emissions. PMID:26152903

  7. IFN-gamma treatment increases insulin binding and MHC class I expression in erythroleukemia cells.

    PubMed

    Ferm, M; Grönberg, A; Tally, M

    1996-01-01

    We have investigated if interferon-gamma (IFN-gamma) treatment of human K562 tumor cells, which upregulates the expression of MHC class I antigens (MHC-I), simultaneously would influence insulin binding. Treatment of K562 cells with recombinant human IFN-gamma for 48 h caused a significant increase of insulin binding at 37 degrees C. Recombinant human tumor necrosis factor-alpha (TNF-alpha) alone had no effect but acted synergistically with IFN-gamma, leading to a two-fold increase of insulin binding. No change in affinity, number of binding sites or cell surface expression of insulin receptors (IR) after IFN-gamma treatment could be detected. The increased insulin binding observed at 37 degrees C was not seen at 4 degrees C, suggesting alteration of insulin internalization. The dose-response curve, as well as the time curve, for the increase in insulin binding after IFN-gamma treatment correlated with enhanced cell surface expression of MHC-I antigens. However, the correlation was not absolute. Our results show that IFN-gamma treatment alone or together with TNF-alpha, can alter the insulin binding to K562 cells without changing the expression or affinity of the IR. This correlates with the effect of IFN-gamma on MHC-I expression. These results support the findings that MHC-I molecules associate and interact with the IR at the cell surface. PMID:8675233

  8. Method for Predicting Which Customers' Time Deposit Balances Will Increase

    NASA Astrophysics Data System (ADS)

    Ono, Toshiyuki; Yoshikawa, Hiroshi; Morita, Masahiro; Komoda, Norihisa

    This paper proposes a method of predicting which customers' account balances will increase by using data mining to effectively and efficiently promote sales. Prediction by mining all the data in a business is difficult because of much time required to collect, process, and calculate it. The selection of which features are used for prediction is a critical issue. We propose a method of selecting features to improve the accuracy of prediction within practical time limits. It consists of three parts: (1) converting collected features into financial behavior features that reflect customer actions, (2) extracting features affecting increases in account balances from these collected and financial behavior features, and (3) predicting customers whose account balances will increase based on the extracted features. We found the accuracy of prediction in an experiment with our method to be higher than with other conventional methods.

  9. Using wastewater for cooling: Increasing water reuse poses treatment challenges

    SciTech Connect

    Lutey, R.W.

    1996-04-01

    Technologies for control of biofouling, scale, corrosion and microbiologically influenced corrosion (MIC) in cooling water systems are discussed. Techniques involving water reuse and using wastewater as makeup are emphasized, and associated problems are identified. Appropriate chemical treatments, including biocides and biostats, biodispersants, sludge dispersants, corrosion inhibitors, and supplementary chemical treatments, are outlined. New and developing technologies reviewed include microorganism control based on biodispersants and on enzymes.

  10. False recall and recognition of brand names increases over time.

    PubMed

    Sherman, Susan M

    2013-01-01

    Using the Deese-Roediger-McDermott (DRM) paradigm, participants are presented with lists of associated words (e.g., bed, awake, night). Subsequently, they reliably have false memories for related but nonpresented words (e.g., SLEEP). Previous research has found that false memories can be created for brand names (e.g., Morrisons, Sainsbury's, Waitrose, and TESCO). The present study investigates the effect of a week's delay on false memories for brand names. Participants were presented with lists of brand names followed by a distractor task. In two between-subjects experiments, participants completed a free recall task or a recognition task either immediately or a week later. In two within-subjects experiments, participants completed a free recall task or a recognition task both immediately and a week later. Correct recall for presented list items decreased over time, whereas false recall for nonpresented lure items increased. For recognition, raw scores revealed an increase in false memory across time reflected in an increase in Remember responses. Analysis of Pr scores revealed that false memory for lures stayed constant over a week, but with an increase in Remember responses in the between-subjects experiment and a trend in the same direction in the within-subjects experiment. Implications for theories of false memory are discussed. PMID:22963741

  11. This is an exciting time in the treatment of lymphoma.

    MedlinePLUS

    ... Cover Story: Leukemia/Lymphoma "This is an exciting time in the treatment of lymphoma." Past Issues / Summer ... best medication for each patient, indicates the best time for treatments, and sheds light on the patient's ...

  12. Treatment increases stress-corrosion resistance of aluminum alloys

    NASA Technical Reports Server (NTRS)

    Jacobs, A. J.

    1966-01-01

    Overaging during heat treatment of the aluminum alloys immediately followed by moderate plastic deformation, preferably by shock loading achieves near optimum values of both yield strength and resistance to stress corrosion. Similar results may be obtained by substituting a conventional deformation process for the shock loading step.

  13. A Role for Cognitive Rehabilitation in Increasing the Effectiveness of Treatment for Alcohol Use Disorders

    PubMed Central

    Bates, Marsha E.; Buckman, Jennifer F.; Nguyen, Tam T.

    2013-01-01

    Neurocognitive impairments are prevalent in persons seeking treatment for alcohol use disorders (AUDs). These impairments and their physical, social, psychological and occupational consequences vary in severity across persons, much like those resulting from traumatic brain injury; however, due to their slower course of onset, alcohol-related cognitive impairments are often overlooked both within and outside of the treatment setting. Evidence suggests that cognitive impairments can impede treatment goals through their effects on treatment processes. Although some recovery of alcohol-related cognitive impairments often occurs after cessation of drinking (time-dependent recovery), the rate and extent of recovery is variable across cognitive domains and individuals. Following a long hiatus in scientific interest, a new generation of research aims to facilitate treatment process and improve AUD treatment outcomes by directly promoting cognitive recovery (experience-dependent recovery). This review updates knowledge about the nature and course of cognitive and brain impairments associated with AUD, including cognitive effects of adolescent AUD. We summarize current evidence for indirect and moderating relationships of cognitive impairment to treatment outcome, and discuss how advances in conceptual frameworks of brain-behavior relationships are fueling the development of novel AUD interventions that include techniques for cognitive remediation. Emerging evidence suggests that such interventions can be effective in promoting cognitive recovery in persons with AUD and other substance use disorders, and potentially increasing the efficacy of AUD treatments. Finally, translational approaches based on cognitive science, neurophysiology, and neuroscience research are considered as promising future directions for effective treatment development that includes cognitive rehabilitation. PMID:23412885

  14. Timely diagnosis and treatment essential in glomerulonephritis.

    PubMed

    Lewis, Gareth; Maxwell, Alexander P

    2015-02-01

    Glomerulonephritis is an important cause of kidney disease and, in the UK, the most common diagnosis in patients receiving chronic dialysis or waiting for kidney transplantation. A key feature is the presence of urinary abnormalities (proteinuria ± haematuria). Patients with nephrotic syndrome typically present with peripheral oedema, massive urinary protein loss and associated low serum albumin levels. Blood pressure and renal function, as measured by eGFR, are usually normal initially. Patients presenting with nephritic syndrome tend to be hypertensive with dipstick-positive or visible haematuria. There may be rapidly progressive renal dysfunction and fall in eGFR. Many patients will have a background genetic susceptibility to glomerulonephritis which may be triggered by environmental, infective or autoimmune factors. Autoimmunity, in combination with genetic factors, is responsible for a significant proportion of cases of glomerulonephritis. Infective agents such as viruses can precipitate minimal change disease. NSAIDs, lithium, penicillamine and heroin can cause nephrotic syndrome. Timely diagnosis and treatment of glomerulonephritis can help to minimise both the occurrence and severity of complications. All patients with glomerulonephritis should be managed according to CKD guidelines with CKD stage-appropriate measurement of renal function, blood pressure, and proteinuria. PMID:25816500

  15. Providing Performance Feedback for Teachers to Increase Treatment Fidelity

    ERIC Educational Resources Information Center

    Stormont, Melissa; Reinke, Wendy M.

    2014-01-01

    This article reviewed a method for increasing teachers' use of behavior-specific praise, which is especially important for students with emotional and behavioral disabilities. The use of performance feedback has been researched fairly extensively and has yielded positive outcomes when compared with other forms of consultation. This article…

  16. Time-decreasing hazard and increasing time until the next earthquake

    SciTech Connect

    Corral, Alvaro

    2005-01-01

    The existence of a slowly always decreasing probability density for the recurrence times of earthquakes in the stationary case implies that the occurrence of an event at a given instant becomes more unlikely as time since the previous event increases. Consequently, the expected waiting time to the next earthquake increases with the elapsed time, that is, the event moves away fast to the future. We have found direct empirical evidence of this counterintuitive behavior in two worldwide catalogs as well as in diverse regional catalogs. Universal scaling functions describe the phenomenon well.

  17. Reducing video frame rate increases remote optimal focus time

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1993-01-01

    Twelve observers made best optical focus adjustments to a microscope whose high-resolution pattern was video monitored and displayed first on a National Television System Committee (NTSC) analog color monitor and second on a digitally compressed computer monitor screen at frame rates ranging (in six steps) from 1.5 to 30 frames per second (fps). This was done to determine whether reducing the frame rate affects the image focus. Reducing frame rate has been shown to be an effective and acceptable means of reducing transmission bandwidth of dynamic video imagery sent from Space Station Freedom (SSF) to ground scientists. Three responses were recorded per trial: time to complete the focus adjustment, number of changes of focus direction, and subjective rating of final image quality. It was found that: the average time to complete the focus setting increases from 4.5 sec at 30 fps to 7.9 sec at 1.5 fps (statistical probability = 1.2 x 10(exp -7)); there is no significant difference in the number of changes in the direction of focus adjustment across these frame rates; and there is no significant change in subjectively determined final image quality across these frame rates. These data can be used to help pre-plan future remote optical-focus operations on SSF.

  18. Reducing time limits: a means to increase behavior of retardates.

    PubMed Central

    Ayllon, T; Garber, S; Pisor, K

    1976-01-01

    A common assumption in special education is that temporal limits for a task should be expanded so that ample time is provided for completing the work. This study describes the opposite strategy of restricting temporal limits to augment academic performance. Three educable retarded children received token reinforcement contingent on the number of correct math problems answered during daily sessions. A reversal design was used to assess the effects of an abrupt reduction in time limits (20-5-20 min) and a graduated sequence of reductions (20-15-10-5-20 min). The graduated sequence resulted in rate increases of correct responding ranging from 125% to 266% and these gains endured when temporal limits were again expanded. In contrast, the abrupt shift produced interfering emotional behaviors and rate decreases in academic performance of 25% to 80%. The findings indicate that systematically restricting temporal limits for an academic task can further enhance the performance of slow learners already maintained by a token system. PMID:977515

  19. Treatment with iron increases weight gain and psychomotor development.

    PubMed Central

    Aukett, M A; Parks, Y A; Scott, P H; Wharton, B A

    1986-01-01

    Previous work at this hospital and elsewhere has shown that anaemia in toddlers is common and is associated with psychomotor delay. It seemed unclear, however, whether this association was cause and effect or merely due to the same underprivileged environment. A double blind randomised intervention study was, therefore, performed. After an initial assessment 97 children with anaemia (haemoglobin 8-11 g/dl) aged 17-19 months received either iron and vitamin C or vitamin C only (control group) for two months and were then reassessed. The children who received the iron had an increased rate of weight gain and more of them achieved the expected rate of development. While iron deficiency anaemia is unlikely to be the only factor in the slower development of children living in underprivileged circumstances, it can at least be easily identified and treated. Routine child health surveillance in such areas should include a haemoglobin determination. PMID:2429622

  20. INCREASED OIL RECOVERY FROM MATURE OIL FIELDS USING GELLED POLYMER TREATMENTS

    SciTech Connect

    G.P. Willhite; D.W. Green; C.S. McCool

    2003-05-01

    Gelled polymer treatments are applied to oil reservoirs to increase oil production and to reduce water production by altering the fluid movement within the reservoir. This report describes the results of a three-year research program aimed at reducing barriers to the widespread use of gelled polymer treatments by (1) developing methods to predict gel behavior during placement in matrix rock and fractures, (2) determining the persistence of permeability reduction after gel placement, and (3) developing methods to design production well treatments to control water production. The work focused on the gel system composed of polyacrylamide and chromium acetate. The molar mass of the polymer was about six million. Chromium(III) acetate reacted and formed crosslinks between polymer molecules. The crosslinked polymer molecules, or pre-gel aggregates, combine and grow to eventually form a 3-dimensional gel. A fundamental study to characterize the formation and growth of pre-gel aggregates was conducted. Two methods, flow field-flow fractionation (FFFF) and multi-angle laser light scattering (MALLS) were used. Studies using FFFF were inconclusive. Data taken using MALLS showed that at the gel time the average molar mass of gel aggregates increased by a factor of about three while the average size increase was approximately 50%. Increased acetate concentration in the gelant increases the gel time. The in situ performance of an added-acetate system was investigated to determine the applicability for in-depth treatments. Increased acetate concentrations delayed the development of increased flow resistance during gelant injection in short sandpacks. The development of increased flow resistance (in situ gelation) was extended from 2 to 34 days by increasing the acetate-to-chromium ratio from 38 to 153. In situ gelation occurred at a time that was approximately 22% of the bulk gelation time. When carbonate rocks are treated with gel, chromium retention in the rock may limit in-depth treatment. Chromium retention due to precipitation was investigated by flowing chromium acetate solutions through carbonate rock. Chromium precipitated faster in the rocks than in beaker experiments at similar conditions. A mathematical model previously developed fit the precipitation data reasonably well. The stability of gels when subjected to stress was investigated by experiments with gels placed in tubes and in laboratory-scale fractures. Rupture pressures for gels placed in small diameter tubes were correlated with the ratio of tube length to tube ID. In fractures, fluid leakoff from the fracture to adjacent matrix rock affected gel formation and gel stability in a positive way. Disproportionate permeability reduction (DPR) was studied in unconsolidated sandpacks and in Berea sandstone cores. A conceptual model was developed to explain the presence of DPR. The effect of a pressure gradient, imposed by injection of oil or brine, on the permeability of gel-treated cores was investigated. DPR increased significantly as the pressure gradient was decreased. The magnitude of the pressure gradient had a much larger effect on water permeability than on oil permeability.

  1. Does fertility treatment increase the risk of uterine cancer? A meta-analysis.

    PubMed

    Saso, Srdjan; Louis, Louay S; Doctor, Farah; Hamed, Ali Hassan; Chatterjee, Jayanta; Yazbek, Joseph; Bora, Shabana; Abdalla, Hossam; Ghaem-Maghami, Sadaf; Thum, Meen-Yau

    2015-12-01

    An ongoing debate over the last two decades has focused on whether fertility treatment in women may lead to an increased risk of developing uterine cancer over a period of time. Uterine cancer (including mainly endometrial carcinoma and the less common uterine sarcoma) is the commonest reproductive tract cancer and the fourth commonest cancer in women in the UK. Our objective was to assess the association between fertility drugs used in the treatment of female infertility (both as an independent therapy and during in vitro fertilization cycles) and the development of uterine cancer. A literature search was performed using Medline, Embase, Cochrane Library and Google Scholar databases for comparative studies until December 2014 to investigate a clinical significance of fertility treatment on the incidence of developing uterine cancer. General and MESH search headings, as well as the 'related articles' function were applied. All comparative studies of 'fertility treatment' versus 'non-fertility treatment' reporting the incidence of uterine cancer as an outcome were included. Uterine cancer incorporated the following terms: uterine cancer, uterine body tumours, uterine sarcomas and endometrial cancers. The primary outcome of interest was the uterine cancer incidence in all 'fertility treatment' versus 'non-fertility treatment' patient groups. Secondary outcomes of interest were: (a) uterine cancer incidence in 'IVF' versus 'non-IVF' patient groups; and (b) uterine cancer incidence according to type of fertility drug used. Odds ratio was the summary statistic. Random-effects modelling, graphical exploration and sensitivity analysis were used to evaluate the consistency of the calculated treatment effect. We included six studies in our final analysis, which comprised 776,224 patients in total. Of these, 103,758 had undergone fertility treatment and 672,466 had not. There was 100% agreement between the two reviewers regarding the data extraction. All the studies contained groups that were comparable in age, although the criteria of reporting age varied. Taking all studies into account, the incidence of uterine cancer was 0.14% (150 of 103,758) in the fertility treatment group and 2.22% (14,918 of 672,466) in the non-fertility treatment group. Using the random-effect model to analyze uterine cancer incidence, this difference was not found to be of statistical significance: OR 0.78 (95% CI, 0.39-1.57). The degree of heterogeneity was high (I(2)=68%). The risk for the development of uterine and in particular endometrial cancer posed by infertility and an unopposed oestrogen state is widely recognized. The present analysis aimed to perceive whether standard fertility drugs were also a risk to future uterine cancer development. The treatment does increase the concentrations of unopposed oestrogen for a short periods of time but if successful leads to fertility. This meta-analysis points to a non-deleterious effect of fertility drugs towards the development of uterine cancer, a conclusion strongly supported by our sub-group analysis. PMID:26476799

  2. Predictors and outcomes of increases in creatine phosphokinase concentrations or rhabdomyolysis risk during statin treatment

    PubMed Central

    van Staa, Tjeerd P; Carr, Daniel F; O’Meara, Helen; McCann, Gerry; Pirmohamed, Munir

    2014-01-01

    Aim The aim was to evaluate clinical risk factors associated with myotoxicity in statin users. Methods This was a cohort study of patients prescribed a statin in UK primary care practices contributing to the Clinical Practice Research Datalink. Outcomes of interest were creatine phosphokinase (CPK) concentrations and clinical records of rhabdomyolysis. Results The cohort comprised 641 703 statin users. Simvastatin was most frequently prescribed (66.3%), followed by atorvastatin (24.4%). CPK was measured in 127 209 patients: 81.4% within normal range and 0.7% above times the upper limit of normal (ULN). Rhabdomyolysis was recorded in 59 patients. Patients with concomitant prescribing of CYP3A4-interacting drugs had an increased odds ratio (OR) of rhabdomyolysis compared with controls (OR 3.71, 95% CI 1.18, 11.61) and >four times ULN CPK compared with normal CPK (OR 1.28, 95% CI 1.01, 1.60). Rosuvastatin users had higher risk of >four times ULN CPK (OR 1.62, 95% CI 1.22, 2.15) as did patients with larger daily doses of other statin types. A recent clinical record of myalgia was associated with an increased OR of >four times ULN CPK (OR 1.73, 95% CI 1.37, 2.18). In patients who were rechallenged to statins and had repeat CPK measurements after >four times ULN CPK abnormalities, 54.8% of the repeat CPK values were within normal range, 32.1% between one to three times and 13.0% >four times ULN. Conclusions The frequencies of substantive CPK increases and rhabdomyolysis during statin treatment were low, with highest risks seen in those on large daily doses or interacting drugs and on rosuvastatin. CPK measurements appeared to have been done in a haphazard manner and better guidance is needed. PMID:24602118

  3. The Effect of Increased Vocal Intensity on Interarticulator Timing in Speakers with Parkinson’s Disease: A Preliminary Analysis

    PubMed Central

    Richardson, Kelly; Sussman, Joan E.; Stathopoulos, Elaine T.; Huber, Jessica E.

    2014-01-01

    Purpose The purpose of the current study was to investigate the effect of increased vocal intensity on interarticulator timing in individuals with Parkinson’s disease (PD). Methods Ten individuals with mild to moderate hypophonia, secondary to PD, were selected for study. Over an 8-week treatment period, multi-talker babble noise was presented monaurally to the individuals with PD during everyday communication contexts to elicit increased vocal intensity (Lombard effect). Outcome measures included sound pressure level (SPL), voice onset time (VOT), VOT ratio, percent voicing, and speech intelligibility. Results Group and individual participant responses to the treatment are reported and discussed. Speakers with PD were shown to significantly increase SPL in response to treatment. Six of the ten speakers showed improved temporal coordination between the laryngeal and supralaryngeal mechanisms (interarticulator timing) in response to treatment. Four of the ten speakers, however, showed reduced laryngeal-supralaryngeal timing at the end of treatment. Group speech intelligibility scores were significantly higher post-treatment as compared to pre-treatment. Conclusions Voice treatment during everyday communication resulted in improved temporal coordination across the laryngeal and supralaryngeal mechanisms for the majority of speakers with PD and made them easier to understand. Further investigations are planned to explore individual differences in response to treatment. The identification of speaker-specific voicing and devoicing strategies is consistent with the heterogeneous nature of PD. PMID:25459460

  4. Evaluation of medical treatments to increase survival of ebullism in guinea pigs

    NASA Technical Reports Server (NTRS)

    Stegmann, Barbara J.; Pilmanis, Andrew A.; Wolf, E. G.; Derion, Toniann; Fanton, J. W.; Davis, H.; Kemper, G. B.; Scoggins, Terrell E.

    1993-01-01

    Spaceflight carriers run a constant risk of exposure to vacuum. Above 63,000 ft (47 mmHg), the ambient pressure falls below the vapor pressure of water at 37 C, and tissue vaporization (ebullism) begins. Little is know about appropriate resuscitative protocols after such an ebullism exposure. This study identified injury patterns and mortality rates associated with ebullism while verifying effectiveness of traditional pulmonary resuscitative techniques. Male Hartley guinea pigs were exposed to 87,000 ft for periods of 40 to 115 sec. After descent, those animals that did not breathe spontaneously were given artificial ventilation by bag and mask for up to 15 minutes. Those animals surviving were randomly assigned to one of three treatment groups--hyperbaric oxygen (HBO), ground-level oxygen (GLO2), and ground-level air (GLAIR). The HBO group was treated on a standard treatment table 6A while the GLO2 animals received O2 for an equivalent length of time. Those animals in the GLAIR group were observed only. All surviving animals were humanely sacrified at 48 hours. Inflation of the animal's lungs after the exposure was found to be difficult and, at times, impossible. This may be due to surfactant disruption at the alveolar lining. Electron microscopy identified a disruption of the surfactant layer in animals that did not survive initial exposure. Mortality was found to increase with exposure time: 40 sec--0 percent; 60 sec--6 percent; 70 sec--40 percent; 80 sec--13 percent; 100 sec--38 percent; 110 sec--40 percent; and 115 sec--100 percent. There was no difference in the delayed mortality among the treatment groups (HBO--15 percent, GLO2--11 percent, GLAIR--11 percent). However, since resuscitation was ineffective, the effectiveness of any post-exposure treatment was severely limited. Preliminary results indicate that reuscitation of guinea pigs following ebullism exposure is difficult, and that current techniques (such as traditional CPR) may not be appropriate.

  5. Increasing placebo responses over time in U.S. clinical trials of neuropathic pain.

    PubMed

    Tuttle, Alexander H; Tohyama, Sarasa; Ramsay, Tim; Kimmelman, Jonathan; Schweinhardt, Petra; Bennett, Gary J; Mogil, Jeffrey S

    2015-12-01

    Recent failures of clinical trials of novel analgesics designed to treat neuropathic pain have led to much speculation about the underlying reasons. One often discussed possibility is that the placebo response in these trials has increased in recent years, leading to lower separation between the drug and placebo arms. Whether this has indeed occurred has not yet been adequately addressed. Here, we extracted data from published randomized controlled trials (RCTs) of drugs for the treatment of chronic neuropathic pain over the years 1990 to 2013. We find that placebo responses have increased considerably over this period, but drug responses have remained stable, leading to diminished treatment advantage. This trend has been driven by studies conducted in the United States. Consideration of participant and study characteristics revealed that in the United States but not elsewhere, RCTs have increased in study size and length. These changes are associated with larger placebo response. Analysis of individual RCT time courses showed different kinetics for the treatment vs placebo responses, with the former evolving more quickly than the latter and plateauing, such that maximum treatment advantage was achieved within 4 weeks. PMID:26307858

  6. Increasing Daily Water Intake and Fluid Adherence in Children Receiving Treatment for Retentive Encopresis

    PubMed Central

    Hoodin, Flora; Rice, Jennifer; Felt, Barbara T.; Rausch, Joseph R.; Patton, Susana R.

    2010-01-01

    Objective?To examine the efficacy of an enhanced intervention (EI) compared to standard care (SC) in increasing daily water intake and fluid goal adherence in children seeking treatment for retentive encopresis.?Methods?Changes in beverage intake patterns and fluid adherence were examined by comparing 7-week diet diary data collected during participation in the EI to achieved data for families who had previously completed the SC.?Results?Compared to children in SC (n = 19), children in the EI (n = 18) demonstrated a significantly greater increase in daily water intake from baseline to the conclusion of treatment ( p ? .001), and were four and six times more likely to meet fluid targets in Phases 1 (Weeks 3–4) and 2 (Weeks 5–6) of fluid intervention, respectively (both p ? .001).?Conclusions?Enhanced education and behavioral strategies were efficacious in increasing children’s intake of water and improving fluid adherence. Future research should replicate the findings in a prospective randomized clinical trial to discern their effectiveness. PMID:20439348

  7. Excess selenium increases Ca sup ++ -induced clotting times in chicks and rats

    SciTech Connect

    Herz, W.C.; Combs, G.F. Jr. )

    1991-03-11

    Calcium (Ca{sup ++})-induced clotting times (i.e., prothrombin times, PT times) in young White Leghorn chickens and male weanling Sprague Dawley rats were shown to be elevated in animals fed diets for 20-30 days containing excess Se. Clotting times of chicks were prolonged from those of controls in animals fed either deficient or excess Se, although all dietary treatment groups showed comparable concentrations of total plasma protein. Rats showed significantly prolonged PT times when fed Se at either 5 ppm or 10 ppm. The plasma activities of certain enzymes of hepatic origin (alanine aminotransferase, aspartate aminotransferase, {gamma}-glutamyl transpeptidase) in rats fed excess Se were comparable to those of controls, despite the increase in the PT times. Body weights and liver weights were significantly depressed in those animals only at the 10 ppm Se level. These results demonstrate increased PT times in both chicks and rats. In each species, this effect is independent of feed intake and body weight, and is apparent at levels of Se intake that do not affect other indicators of hepatic damage. Therefore, prolonged PT time may be an early indicator of sub-acute selenosis.

  8. Olanzapine, but Not Fluoxetine, Treatment Increases Survival in Activity-Based Anorexia in Mice

    PubMed Central

    Klenotich, Stephanie J; Seiglie, Mariel P; McMurray, Matthew S; Roitman, Jamie D; Le Grange, Daniel; Dugad, Priya; Dulawa, Stephanie C

    2012-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by extreme hypophagia, hyperactivity, and fear of weight gain. No approved pharmacological treatments exist for AN despite high mortality rates. The activity-based anorexia (ABA) phenomenon models aspects of AN in rodents, including progressive weight loss, reduced food intake, and hyperactivity. First, we optimized the ABA paradigm for mice. We compared mouse strains (Balb/cJ, A/J) for susceptibility with ABA, and evaluated the effects of different food access durations (2, 4, 6, 8, and 10?h) on ABA parameters. Balb/cJ mice exhibited significantly shorter survival time (days until 25% bodyweight loss) in the ABA paradigm compared with A/J mice. Furthermore, 6?h of food access reduced survival in mice housed with wheels without reducing survival in mice housed without wheels. We then evaluated the effects of chronic treatment with fluoxetine (4 weeks) or subchronic treatment with olanzapine (OLZ) (1 week) on ABA in BALB/cJ mice. OLZ (12?mg/kg/day) significantly increased survival and reduced food anticipatory activity (FAA). However, OLZ did not alter food intake or running wheel activity during ad-lib feeding (baseline) or restriction conditions, or in mice housed without wheels. Fluoxetine (18?mg/kg/day) increased food intake and reduced FAA, but did not alter survival. Here, we report for the first time that OLZ, but not fluoxetine, reduces ABA in mice. Our findings indicate further need for clinical investigations into the effects of OLZ, but not selective serotonin reuptake inhibitors, on core features of AN. PMID:22395732

  9. Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice.

    PubMed

    Klenotich, Stephanie J; Seiglie, Mariel P; McMurray, Matthew S; Roitman, Jamie D; Le Grange, Daniel; Dugad, Priya; Dulawa, Stephanie C

    2012-06-01

    Anorexia nervosa (AN) is an eating disorder characterized by extreme hypophagia, hyperactivity, and fear of weight gain. No approved pharmacological treatments exist for AN despite high mortality rates. The activity-based anorexia (ABA) phenomenon models aspects of AN in rodents, including progressive weight loss, reduced food intake, and hyperactivity. First, we optimized the ABA paradigm for mice. We compared mouse strains (Balb/cJ, A/J) for susceptibility with ABA, and evaluated the effects of different food access durations (2, 4, 6, 8, and 10?h) on ABA parameters. Balb/cJ mice exhibited significantly shorter survival time (days until 25% bodyweight loss) in the ABA paradigm compared with A/J mice. Furthermore, 6?h of food access reduced survival in mice housed with wheels without reducing survival in mice housed without wheels. We then evaluated the effects of chronic treatment with fluoxetine (4 weeks) or subchronic treatment with olanzapine (OLZ) (1 week) on ABA in BALB/cJ mice. OLZ (12?mg/kg/day) significantly increased survival and reduced food anticipatory activity (FAA). However, OLZ did not alter food intake or running wheel activity during ad-lib feeding (baseline) or restriction conditions, or in mice housed without wheels. Fluoxetine (18?mg/kg/day) increased food intake and reduced FAA, but did not alter survival. Here, we report for the first time that OLZ, but not fluoxetine, reduces ABA in mice. Our findings indicate further need for clinical investigations into the effects of OLZ, but not selective serotonin reuptake inhibitors, on core features of AN. PMID:22395732

  10. Timing of cholecystectomy in biliary pancreatitis treatment

    PubMed Central

    Demir, Uygar; Yaz?c?, P?nar; Bostanc?, Özgür; Kaya, Cemal; Köksal, Hakan; I??l, Gürhan; Bozda?, Emre; Mihmanl?, Mehmet

    2014-01-01

    Objective: Gallstone pancreatitis constitutes 40% of all cases with pancreatitis while it constitutes up to 90% of cases with acute pancreatitis. The treatment modality in this patient population is still controversial. In this study, we aimed to compare the results of early and late cholecystectomy for patients with biliary pancreatitis. Material and Methods: Patients treated with a diagnosis of acute biliary pancreatitis in our clinics between January 2000 and December 2011 were retrospectively reviewed. Patients were divided into two groups: Group A, patients who underwent cholecystectomy during the first pancreatitis attack, Group B, patients who underwent an interval cholecystectomy at least 8 weeks after the first pancreatitis episode. The demographic characteristics, clinical symptoms, number of episodes, length of hospital stay, morbidity and mortality data were recorded. All data were evaluated with Statistical Package for the Social Sciences (SPSS) 13.0 for windows and p <0.05 was considered as statistically significant. Results: During the last 12 years, a total of 91 patients with surgical treatment for acute biliary pancreatitis were included into the study. There were 62 female and 29 male patients, with a mean age of 57.9±14.6 years (range: 21–89). A concomitant acute cholecystitis was present in 46.2% of the patients. Group A and B included 48 and 43 patients, respectively. The length of hospital stay was significantly higher in group B (9.4 vs. 6.8 days) (p<0,05). More than half of the patients in Group B were readmitted to the hospital for various reasons. No significant difference was observed between the two groups, one patient died due to heart failure in the postoperative period in group B. Conclusion: In-hospital cholecystectomy after remission of acute pancreatitis is feasible. It will not only result in lower recurrence and complication rates but also shorten length of hospital stay. We recommend performing cholecystectomy during the course of the first episode in patients with acute pancreatitis. PMID:25931883

  11. Intra-oral pre-treatment with capsaicin increases consumption of sweet solutions in rats.

    PubMed

    Gu, Xue Feng; Lee, Jong-Ho; Yoo, Sang Bae; Moon, Young Wha; Jahng, Jeong Won

    2009-08-01

    Sprague-Dawley rats received preference tests for sucrose or saccharin daily following oral treatment with 0.02% capsaicin. Consumed sweet solutions and preference scores increased in capsaicin-treated rats, compared to control rats on the second to fifth exposure period for sucrose and all exposure periods for saccharin. Chow intake was not affected by repeated treatment with capsaicin. Real-time RT-PCR analysis revealed decreased expression of sweet receptors T1R2 and T1R3 as well as capsaicin receptor VR1 in the circumvallate after this repeated oral exposure to capsaicin. VR1 immunoreactivities were also localized in the vallate taste cells by fluorescence immunohistochemistry. Results suggest that decreased expression of sweet receptors in the circumvallate may be related to increased sweet consumption in capsaicin-treated rats; any causal relationship should be further studied. Also, these data suggest that capsaicin may interact with a sweet transduction pathway in the mediation of its receptor VR1 that are located in the vallate taste cells. PMID:19622238

  12. Time-delay Cosmography: Increased Leverage with Angular Diameter Distances

    E-print Network

    Jee, Inh; Suyu, Sherry H; Huterer, Dragan

    2015-01-01

    Strong lensing time-delay systems constrain cosmological parameters via the so-called time-delay distance and the angular diameter distance to the lens. In previous studies, only the former information was used. In this paper, we show that the cosmological constraints improve significantly when the latter information is also included. Specifically, the angular diameter distance plays a crucial role in breaking the degeneracy between the curvature of the Universe and the time-varying equation of state of dark energy. Using a mock sample of 55 bright quadruple lens systems based on expectations for ongoing/future imaging surveys, we find that adding the angular diameter distance information to the time-delay distance information and the cosmic microwave background data of Planck improves the constraint on the constant equation of state by 30%, on the time variation in the equation of state by a factor of two, and on the Hubble constant in the flat $\\Lambda$CDM model by a factor of two. Therefore, previous forec...

  13. Response Time Analysis in Cognitive Tasks with Increasing Difficulty

    ERIC Educational Resources Information Center

    Dodonov, Yury S.; Dodonova, Yulia A.

    2012-01-01

    In the present study, speeded tasks with differing assumed difficulties of the trials are regarded as a special class of simple cognitive tasks. Exploratory latent growth modeling with data-driven shape of a growth curve and nonlinear structured latent curve modeling with predetermined monotonically increasing functions were used to analyze…

  14. Energy of Tycho's Supernova Remnant is increasing with time

    PubMed Central

    Barenblatt, Grigory Isaakovich

    2008-01-01

    It is shown, using the Zeldovich integral relations, that the energy of Tycho's Supernova Remnant is strongly growing with time, approximately as t1/3. This growth can be attributed to the exothermic reactions going inside the remnant. The use of the assumption of the adiabaticity of the motion inside of the shock front, and no losses or gain of energy at the front, seems therefore unjustified. PMID:18202174

  15. Increasing LARC utilization: any woman, any place, any time.

    PubMed

    Hathaway, Mark; Torres, Leah; Vollett-Krech, Jennifer; Wohltjen, Hannah

    2014-12-01

    Intrauterine contraceptive devices and the progestin implant are the most effective long-acting reversible contraception (LARC) methods available for preventing unintended pregnancy. LARC devices are safe, non-user-dependent methods that have the highest rates of continuation and satisfaction of all reversible contraceptives. Use of these contraceptives remains low in the United States due to several barriers including: misperceptions among both providers and patients; cost barriers; and patient access to the devices. Increasing the opportunities for women to access LARC methods in the primary care, postabortion, and postpartum setting can be achieved by addressing the system, provider, and patient barriers that exist. PMID:25314089

  16. Pancreatic cancer Increased organ sparing using shape-based treatment plan optimization for

    E-print Network

    Kazhdan, Michael

    Pancreatic cancer Increased organ sparing using shape-based treatment plan optimization for intensity modulated radiation therapy of pancreatic adenocarcinoma Steven F. Petit b,c,d, , Binbin Wu Available online 15 June 2011 Keywords: Pancreatic cancer Intensity modulated radiotherapy (IMRT) Treatment

  17. Automated Compile-Time and Run-Time Techniques to Increase Usable Memory in MMU-Less Embedded Systems

    E-print Network

    Dick, Robert

    Automated Compile-Time and Run-Time Techniques to Increase Usable Memory in MMU-Less Embedded propose the use of automated compile-time and run-time techniques to increase the amount of usable memory suited to this application, as well as run- time library routines and compiler transformations to control

  18. Chemotaxis Increases the Residence Time of Bacteria in Granular Media Containing Distributed Contaminant Sources.

    PubMed

    Adadevoh, Joanna S T; Triolo, Sarah; Ramsburg, C Andrew; Ford, Roseanne M

    2016-01-01

    The use of chemotactic bacteria in bioremediation has the potential to increase access to, and the biotransformation of, contaminant mass within the subsurface. This laboratory-scale study aimed to understand and quantify the influence of chemotaxis on the residence times of pollutant-degrading bacteria within homogeneous treatment zones. Focus was placed on a continuous-flow sand-packed column in which a uniform distribution of naphthalene crystals created distributed sources of dissolved-phase contaminant. A 10 mL pulse of Pseudomonas putida G7, which is chemotactic to naphthalene, and Pseudomonas putida G7 Y1, a nonchemotactic mutant strain, were simultaneously introduced into the sand-packed column at equal concentrations. Breakthrough curves obtained from experiments conducted with and without naphthalene were used to quantify the effect of chemotaxis on transport parameters. In the presence of the chemoattractant, longitudinal dispersion of PpG7 increased by a factor of 3, and percent recovery decreased by 43%. In contrast, PpG7 Y1 transport was not influenced by the presence of naphthalene. The results imply that pore-scale chemotaxis responses are evident at an interstitial velocity of 1.8 m/day, which is within the range of typical groundwater flow. Within the context of bioremediation, chemotaxis may work to enhance bacterial residence times in zones of contamination, thereby improving treatment. PMID:26605857

  19. Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength of Intact Bones in Adult Male Rats

    PubMed Central

    Suen, Pui Kit; Zhu, Tracy Y.; Chow, Dick Ho Kiu; Huang, Le; Zheng, Li-Zhen; Qin, Ling

    2015-01-01

    We investigated the systemic effect of sclerostin monoclonal antibody (Scl-Ab) treatment on intact non-operated bones in an open osteotomy male Sprague Dawley (SD) rat model. Six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were injected subcutaneously with vehicle or Scl-Ab (25?mg/kg, 2 times per week) treatment for 9 weeks. Compared with vehicle control, Scl-Ab treatment significantly improved trabecular and cortical bone mass and microarchitecture at L5 vertebrae and left femora by micro-CT at week 6 and 9. Mechanical testing showed that Scl-Ab treatment resulted in significantly higher stiffness, energy to failure and ultimate load at the femora at week 9. Mineral apposition rate, mineralizing surface and bone formation rate on the trabecular bone in the distal femora was significantly increased in Scl-Ab group at week 6 and 9. The administered Scl-Ab was localized in the osteocytes and beta-catenin was strongly expressed in osteoblasts. Scl-Ab treatment significantly increased serum P1NP level and there was no between-group difference in serum level of CTX-1. In conclusion, Scl-Ab treatment could induce rapid and sustained increase in bone formation, bone mass and bone strength in non-operated bones. Sclerostin inhibition might be advantageous to prevent secondary fracture(s). PMID:26494536

  20. Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength of Intact Bones in Adult Male Rats.

    PubMed

    Suen, Pui Kit; Zhu, Tracy Y; Chow, Dick Ho Kiu; Huang, Le; Zheng, Li-Zhen; Qin, Ling

    2015-01-01

    We investigated the systemic effect of sclerostin monoclonal antibody (Scl-Ab) treatment on intact non-operated bones in an open osteotomy male Sprague Dawley (SD) rat model. Six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were injected subcutaneously with vehicle or Scl-Ab (25?mg/kg, 2 times per week) treatment for 9 weeks. Compared with vehicle control, Scl-Ab treatment significantly improved trabecular and cortical bone mass and microarchitecture at L5 vertebrae and left femora by micro-CT at week 6 and 9. Mechanical testing showed that Scl-Ab treatment resulted in significantly higher stiffness, energy to failure and ultimate load at the femora at week 9. Mineral apposition rate, mineralizing surface and bone formation rate on the trabecular bone in the distal femora was significantly increased in Scl-Ab group at week 6 and 9. The administered Scl-Ab was localized in the osteocytes and beta-catenin was strongly expressed in osteoblasts. Scl-Ab treatment significantly increased serum P1NP level and there was no between-group difference in serum level of CTX-1. In conclusion, Scl-Ab treatment could induce rapid and sustained increase in bone formation, bone mass and bone strength in non-operated bones. Sclerostin inhibition might be advantageous to prevent secondary fracture(s). PMID:26494536

  1. High energy neutron treatment for pelvic cancers: study stopped because of increased mortality.

    PubMed Central

    Errington, R D; Ashby, D; Gore, S M; Abrams, K R; Myint, S; Bonnett, D E; Blake, S W; Saxton, T E

    1991-01-01

    OBJECTIVE--To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN--Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING--Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS--151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION--Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES--Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS--In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS--The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons. PMID:1903663

  2. On Optimal Treatment Regimes Selection for Mean Survival Time

    PubMed Central

    Geng, Yuan; Zhang, Hao Helen; Lu, Wenbin

    2014-01-01

    In clinical studies with time-to-event as a primary endpoint, one main interest is to find the best treatment strategy to maximize patients’ mean survival time. Due to patient’s heterogeneity in response to treatments, great efforts have been devoted to developing optimal treatment regimes by integrating individuals’ clinical and genetic information. A main challenge arises in the selection of important variables that can help to build reliable and interpretable optimal treatment regimes since the dimension of predictors may be high. In this paper, we propose a robust loss-based estimation framework that can be easily coupled with shrinkage penalties for both estimation of optimal treatment regimes and variable selection. The asymptotic properties of the proposed estimators are studied. Moreover, a model-free estimator of restricted mean survival time under the derived optimal treatment regime is developed and its asymptotic property is studied. Simulations are conducted to assess the empirical performance of the proposed method for parameter estimation, variable selection, and optimal treatment decision. An application to an AIDS clinical trial data set is given to illustrate the method. PMID:25515005

  3. Increased expression of renal TRPM6 compensates for Mg2+ wasting during furosemide treatment

    PubMed Central

    van Angelen, Annelies A.; van der Kemp, AnneMiete W.; Hoenderop, Joost G.; Bindels, René J.

    2012-01-01

    Background Furosemide is a loop diuretic, which blocks the Na+, K+, 2Cl? cotransporter (NKCC2) in the thick ascending limb of Henle (TAL). By diminishing sodium (Na+) reabsorption, loop diuretics reduce the lumen-positive transepithelial voltage and consequently diminish paracellular transport of magnesium (Mg2+) and calcium (Ca2+) in TAL. Indeed, furosemide promotes urinary Mg2+ excretion; however, it is unclear whether this leads, especially during prolonged treatment, to hypomagnesaemia. The aim of the present study was, therefore, to determine the effect of chronic furosemide application on renal Mg2+ handling in mice. Methods Two groups of 10 mice received an osmotic minipump subcutaneously for 7 days with vehicle or 30 mg/kg/day furosemide. Serum and urine electrolyte concentrations were determined. Next, renal mRNA levels of the epithelial Mg2+ channel (TRPM6), the Na+, Cl? cotransporter (NCC), the epithelial Ca2+ channel (TRPV5), the cytosolic Ca2+-binding protein calbindin-D28K, as well parvalbumin (PV), claudin-7 (CLDN7) and claudin-8 (CLDN8), the epithelial Na+ channel (ENaC) and the Na+–H+ exchanger 3 (NHE3) were determined by real-time quantitative polymerase chain reaction. Renal protein levels of NCC, TRPV5, calbindin-D28K and ENaC were also measured using semi-quantitative immunohistochemistry and immunoblotting. Results The mice chronically treated with 30 mg/kg/day furosemide displayed a significant polyuria (2.1 ± 0.3 and 1.3 ± 0.2 mL/24 h, furosemide versus control respectively, P < 0.05). Furosemide treatment resulted in increased serum concentrations of Na+ [158 ± 3 (treated) and 147 ± 1 mmol/L (control), P < 0.01], whereas serum K+, Ca2+ and Mg2+ values were not significantly altered in mice treated with furosemide. Urinary excretion of Na+, K+, Ca2+ and Mg2+ was not affected by chronic furosemide treatment. The present study shows specific renal upregulation of TRPM6, NCC, TRPV5 and calbindin-D28K. Conclusions During chronic furosemide treatment, enhanced active reabsorption of Mg2+ via the epithelial channel TRPM6 in DCT compensates for the reduced reabsorption of Mg2+ in TAL. PMID:26069797

  4. Phenelzine treatment increases transcription factor AP-2 levels in rat brain

    PubMed Central

    Damberg, Mattias; Berggård, Cecilia; Oreland, Lars

    2003-01-01

    Background The elevations of noradrenaline (NA) and serotonin (5-HT) levels in response to acute serotonin reuptake inhibitor (SSRI) or tricyclic antidepressant (TCA) exposure are not consistent with the time course for the therapeutic action of these antidepressants. Thus, neuronal adaptations are needed for the therapeutic effect to arise. Transcription factor Activating Protein –2 (AP-2) is critical for mammalian neural gene expression. Several genes involved in brainstem CNS transmitter systems, especially the monoamines, have AP-2 binding sites in their regulatory regions. We have previously shown that treatment with citalopram and imipramin resulted in a decrease in AP-2? and AP-2? levels in rat brain. We have also reported an association between a specific genotype of AP-2? to personality traits, binge-eating disorder and platelet monoamine oxidase (MAO) activity. Results Subchronic administration (10 days) of phenelzine (PLZ) increased the levels of AP-2?, AP-2? and the DNA binding activity of AP-2 in nuclear extracts prepared from rat whole brain when compared with sham treated animals. Conclusion These data suggest that AP-2 is not involved in the theraputic effect of antidepressants. Rather, the effects of antidepressants seen on the levels of AP-2 might be involved in the expression of side-effects during the lag-period. PMID:12943557

  5. Real-time monitoring of HIFU treatment using pulse inversion

    NASA Astrophysics Data System (ADS)

    Song, Jae Hee; Yoo, Yangmo; Song, Tai-Kyong; Chang, Jin Ho

    2013-08-01

    Ultrasound (US) imaging is widely used for the real-time guidance of high-intensity focused ultrasound (HIFU) treatment at a relatively low cost. However, ultrasound image guided HIFU (USgHIFU) is limited in the real-time monitoring of HIFU treatment due to the large amplitude HIFU signals received by the US imaging transducer. The amplitude of the HIFU scattered signal is generally much higher than the amplitude of the pulse-echo signal received by the imaging transducer. This creates an interference pattern obscuring the image of the tissue. As such, it is difficult to monitor lesion location. This paper proposes a real-time monitoring method to be performed concurrently with the HIFU insonation, but without HIFU interference, which allows for the improvement of treatment accuracy and safety in USgHIFU. The proposed method utilizes the physical properties of pulse inversion which is capable of removing the fundamental and odd harmonic components of the HIFU interference. Therefore, it is possible to secure the desired spectral bandwidth used to construct US images for HIFU treatment monitoring. The performance of the proposed method was evaluated through experiments with both a bovine serum albumin phantom and a chicken breast. The results demonstrated that the proposed method is capable of providing interference-free US images, thus successfully allowing for US imaging during HIFU treatment.

  6. Plating on aluminum: influence of varying zinc immersion treatment times

    SciTech Connect

    Overturf, G.E. III; Dini, J.W.

    1983-07-18

    Quantitative adhesion data are presented for copper electrodeposits applied to 1100, 6061 and 7075 aluminum alloys. The substrates were prepared for plating by the zinc immersion process. In all cases, a double zinc immersion treatment was used and the time of immersion for the first and second zincate steps was varied. Ring shear tests were used to measure adhesion.

  7. Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity

    PubMed Central

    Endara, P; Vaca, M; Chico, M E; Erazo, S; Oviedo, G; Quinzo, I; Rodriguez, A; Lovato, R; Moncayo, A-L; Barreto, M L; Rodrigues, L C; Cooper, P J

    2010-01-01

    Background The low prevalence of allergic disease in the rural tropics has been attributed to the protective effects of chronic helminth infections. There is concern that treatment-based control programmes for these parasites may lead to an increase in the prevalence of allergic diseases. Objective We measured the impact of 15–17 years of anthelmintic treatment with ivermectin on the prevalence of allergen skin test reactivity and allergic symptoms in school-age children. Methods The prevalence of allergen skin test reactivity, exercise-induced bronchospasm and allergic symptoms was compared between school-age children living in communities that had received community-based treatments with ivermectin (for onchocerciasis control) for a period of 15–17 years with those living in geographically adjacent communities that had received no ivermectin. Results The prevalence of allergen skin test reactivity was double in children living in treated communities compared with those in untreated communities (16.7% vs. 8.7%, adjusted OR 2.10, 95% CI 1.50–2.94, P<0.0001), and the effect was mediated partly by a reduced prevalence of Trichuris trichiura among treated children. Ivermectin treatments were associated with an increased prevalence of recent eczema symptoms (adjusted OR 2.24, 95% CI 1.05–4.78, P=0.04) but not symptoms of asthma or rhino-conjunctivitis. The effect on eczema symptoms was not associated with reductions in geohelminth infections. Conclusion Long-term periodic treatments with ivermectin were associated with an increased prevalence of allergen skin test reactivity. There was some evidence that treatment was associated with an increased prevalence of recent eczema symptoms but not those of asthma or rhino-conjunctivitis. Cite this as: P. Endara, M. Vaca, M. E. Chico, S. Erazo, G. Oviedo, I. Quinzo, A. Rodriguez R. Lovato, A.-L. Moncayo, M. L. Barreto, L. C. Rodrigues and P. J. Cooper, Clinical & Experimental Allergy, 2010 (40) 1669–1677. PMID:21039971

  8. Hot topic: Early postpartum treatment of commercial dairy cows with nonsteroidal antiinflammatory drugs increases whole-lactation milk yield.

    PubMed

    Carpenter, A J; Ylioja, C M; Vargas, C F; Mamedova, L K; Mendonça, L G; Coetzee, J F; Hollis, L C; Gehring, R; Bradford, B J

    2016-01-01

    Previous research has shown that postpartum administration of the nonsteroidal antiinflammatory drug (NSAID) sodium salicylate can increase 305-d milk yield in older dairy cattle (parity 3 and greater). However, in this prior work, sodium salicylate was delivered to cows via the drinking water, a method that does not align well with current grouping strategies on commercial dairy farms. The objective of the current study was to replicate these results on a commercial dairy farm with a simplified treatment protocol and to compare sodium salicylate with another NSAID, meloxicam. Dairy cattle in their second lactation and greater (n=51/treatment) were alternately assigned to 1 of 3 treatments at parturition, with treatments lasting for 3d. Experimental treatments began 12 to 36h after parturition and were (1) 1 placebo bolus on the first day and 3 consecutive daily drenches of sodium salicylate (125g/cow per day; SAL); (2) 1 bolus of meloxicam (675mg/cow) and 3 drenches of an equal volume of water (MEL); or (3) 1 placebo bolus and 3 drenches of water (CON). Blood samples were collected on the first day of treatment, immediately following the last day of treatment, and 7d after the last day of treatment; plasma was analyzed for glucose, ?-hydroxybutyrate (BHB), free fatty acids, haptoglobin, and paraoxonase. Milk production, body condition score, reproductive status, and retention in the herd were monitored for 365d posttreatment, and effects of treatment, parity, days in milk, and interactions were evaluated in mixed effects models. Significance was declared at P<0.05. Whole-lactation milk and protein yields were greater in NSAID-treated cows, although 305-d fat production was not affected. There was a significant interaction of treatment and parity for plasma glucose concentration; MEL increased plasma glucose concentrations compared with CON and SAL in older cows. Sodium salicylate decreased plasma BHB concentration compared with MEL at 7d posttreatment, although no difference was detected immediately following treatment. Haptoglobin concentrations were elevated in SAL cows compared with CON. There was a tendency for CON cows to be removed from the herd more quickly than MEL cows (42 vs. 26% at 365d posttreatment). Body condition score, concentrations of plasma free fatty acids and paraoxonase, and time to pregnancy were not affected by treatment. These results indicate that NSAID administration in postpartum cows has the potential to be a viable way to improve productivity and potentially longevity in commercial dairies, although further research is necessary to optimize recommendations for producers. PMID:26519977

  9. Increasing bioavailability of (R)-alpha-lipoic acid to boost antioxidant activity in the treatment of neuropathic pain.

    PubMed

    Maglione, Emilia; Marrese, Cinzia; Migliaro, Elisa; Marcuccio, Fortuna; Panico, Claudia; Salvati, Carmine; Citro, Giuseppe; Quercio, Marco; Roncagliolo, Federico; Torello, Carlo; Brufani, Mario

    2015-01-01

    a-lipoic acid (a-LA) is a potent natural antioxidant because it has a broad spectrum of action towards a great many free radical species and boosts the endogenous antioxidant systems.Although it is a multi-functional molecule, its pharmacokinetic characteristics pose restrictions to its use in the treatment of oxidative stress-dependent illnesses. Formulations that increase the bioavailability of a-LA have a better potential efficacy as adjuvants for the treatment of these conditions.This objective was achieved with a liquid formulation for oral use containing only R-aLA, the natural enantiomeric and most active form of a-lipoic acid.For the first time, the effects of this formulation were evaluated on neuropathic pain, a symptom caused by an increase in oxidative stress, regardless of the underlying cause. Neuropathic patients who have used this dietary supplement noticed an improvement in their quality of life and a significant reduction was observed in a number of certain descriptive pain parameters (intensity, burning, unpleasantness, superficial pain).Undoubtedly further, more in-depth, studies need to be conducted; however, this first investigation confirms the role of R-aLA as an anti-oxidant for the aetiological treatment of peripheral neuropathy. Increasing its plasma bioavailability even after a non-invasive administration through the oral route is a good starting point for proposing a valid adjuvant for the treatment of pain symptoms. PMID:26694149

  10. Effect of heat treatment time on microstructure and electrical conductivity in LATP glass ceramics

    SciTech Connect

    Sonigra, Dhiren E-mail: ajit.kulkarni@iitb.ac.in; Soman, Swati E-mail: ajit.kulkarni@iitb.ac.in; Kulkarni, Ajit R. E-mail: ajit.kulkarni@iitb.ac.in

    2014-04-24

    Glass-ceramic is prepared by heat treatment of melt quenched 14Li{sub 2}O?9Al{sub 2}O{sub 3}?38TiO{sub 2}?39P{sub 2}O{sub 5} glass in the vicinity of crystallization temperature. Growth of ceramic phase is controlled by tuning heat treatment time at fixed temperature. Ceramic phase was identified to be LiTi{sub 2}(PO{sub 4}){sub 3} from X Ray Diffraction analysis. Microstructural evolution of this phase with hold time was observed under high resolution Scanning Electron Microscope. DC conductivity is observed to increase by 4-5 orders of magnitude in this glass-ceramic compared to parent glass. However, formation of pores and cracks with very large heat treatment time seem to hinder further increase of conductivity.

  11. Glioblastoma Treatment: Bypassing the Toxicity of Platinum Compounds by Using Liposomal Formulation and Increasing Treatment Efficiency With Concomitant Radiotherapy

    SciTech Connect

    Charest, Gabriel; Sanche, Leon; Fortin, David; Mathieu, David; Paquette, Benoit

    2012-09-01

    Purpose: Treatments of glioblastoma with cisplatin or oxaliplatin only marginally improve the overall survival of patients and cause important side effects. To prevent adverse effects, improve delivery, and optimize the tumor response to treatment in combination with radiotherapy, a potential approach consists of incorporating the platinum agent in a liposome. Methods and Materials: In this study, cisplatin, oxaliplatin, carboplatin, Lipoplatin (the liposomal formulation of cisplatin), and Lipoxal (the liposomal formulation of oxaliplatin) were tested on F98 glioma orthotopically implanted in Fischer rats. The platinum compounds were administered by intracarotid infusion and were assessed for the ability to reduce toxicity, improve cancer cell uptake, and increase survival of animals when combined or not combined with radiotherapy. Results: The tumor uptake was 2.4-fold more important for Lipoxal than the liposome-free oxaliplatin. Lipoxal also improved the specificity of oxaliplatin as shown by a higher ratio of tumor to right hemisphere uptake. Surprisingly, Lipoplatin led to lower tumor uptake compared with cisplatin. However, Lipoplatin had the advantage of largely reducing the toxicity of cisplatin and allowed us to capitalize on the anticancer activity of this agent. Conclusion: Among the five platinum compounds tested, carboplatin showed the best increase in survival when combined with radiation for treatment of glioma implanted in Fischer rats.

  12. Effect of Price Increase of Adrenocorticotropic Hormone on Treatment Practices of Infantile Spasms

    PubMed Central

    Wray, Carter D.; Benke, Timothy A.

    2011-01-01

    Intramuscular adrenocorticotropic hormone putatively constitutes the most efficacious treatment for infantile spasms. Adrenocorticotropic hormone in the United States is an “orphan drug,” made by a single manufacturer. The price of adrenocorticotropic hormone increased almost 14-fold on August 27, 2007. We sought to evaluate the impact of this price increase on treatment practices at our institution, using a retrospective chart review of all children with infantile spasms treated during 2007-2009. We identified 97 patients whose spasms were treated using antiepileptic drugs, and we determined the length of stay for those hospitalized to initiate adrenocorticotropic hormone. Patients before the price increase were more likely to have been treated with adrenocorticotropic hormone as first medication, and were hospitalized 2.2 ± 0.5 S.D. days for initiation. Patients after the price increase were more likely to have been treated initially with oral antiepileptic drugs rather than adrenocorticotropic hormone (P < 0.002). Those commencing adrenocorticotropic hormone after the price increase were hospitalized significantly longer (5.1 ± 0.6 days S.D., P < 0.001). Treatment choices need to be evidence-based, but other factors often influence them. PMID:20691936

  13. Increasing dependency of older people in nursing homes is associated with need for dental treatments

    PubMed Central

    Zenthöfer, Andreas; Rammelsberg, Peter; Cabrera, Tomas; Hassel, Alexander Jochen

    2014-01-01

    To determine relationships between the need for dental treatments of institutionalized elderly people and cognitive impairment and the general level of care needed. Two hundred and sixty-eight residents of long-term care facilities in Germany were included in this study. Age, sex, diseases, number of frequently taken drugs, and location of the long-term care facility of the participants were recorded. For each participant, the need for care was assessed by use of the Barthel index (BI). Cognitive impairment was evaluated by use of the mini-mental state examination (MMSE). To assess dental treatment needs, the revised oral assessment guide (ROAG) was applied for different oral health conditions, which were rated “healthy” or “treatment needed”. Spearman correlations were performed to evaluate associations between BI and MMSE and dental treatment needs. Statistical analysis revealed significant associations of BI (P<0.001) and MMSE (P=0.015) with the ROAG score. Increasing dependency and decreasing cognitive ability worsen oral health and increase the need for dental treatment. PMID:25506220

  14. Use of complementary and alternative treatments for children with autistic spectrum disorders is increasing.

    PubMed

    Levy, Susan E; Hyman, Susan L

    2003-10-01

    Interventions considered to be CAM are in constant flux. New treatments emerge, older treatments become less popular, and the cycle recurs. Data supporting new treatments should be scrutinized for scientific study design, clinical safety, and scientific validity. Many families approach the clinician armed with brochures, handouts, and printouts from Web sites that are dedicated to the care and support of parents and children with ASD. A recent web search using "autism and detoxification" resulted in almost 8,000 sites. The Defeat Autism Now! (DAN!) Project arose in 1995 from collaboration of members of the Autism Research Institute. The DAN! Project advocates a specific and extensive protocol for diagnosis and treatment and can be viewed at http://www.autism.com/ari/#dan. The scientific validation and support for many interventions is incomplete and disparate from the recommendation in the American Academy of Pediatrics Policy Statement. Families should be encouraged to discuss all proposed investigations or treatments they wish to try with their primary care provider so the practitioner can serve as the medical home (Sidebar, page 688). The clinician should communicate and collaborate with the family and educational professionals to encourage objective identification of what works. With increasing access to health information and societal pressure for families to actively participate in their health management, continued growth of interest in CAM can be anticipated. Clinicians must remember that parents may have different beliefs regarding the effectiveness of treatment and different tolerance for treatment risks. Practitioners must keep avenues of communication open, remain open-minded, and not assume a "don't ask, don't tell" posture in the context of providing a medical home to the increasing number of children diagnosed with autism. PMID:14606219

  15. 20 CFR 404.996 - Increase in future benefits where time period for reopening expires.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Increase in future benefits where time period for reopening expires. 404.996 Section 404.996 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... § 404.996 Increase in future benefits where time period for reopening expires. If, after the time...

  16. 20 CFR 404.996 - Increase in future benefits where time period for reopening expires.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Increase in future benefits where time period for reopening expires. 404.996 Section 404.996 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... § 404.996 Increase in future benefits where time period for reopening expires. If, after the time...

  17. 20 CFR 404.996 - Increase in future benefits where time period for reopening expires.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Increase in future benefits where time period for reopening expires. 404.996 Section 404.996 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... § 404.996 Increase in future benefits where time period for reopening expires. If, after the time...

  18. 20 CFR 404.996 - Increase in future benefits where time period for reopening expires.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Increase in future benefits where time period for reopening expires. 404.996 Section 404.996 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... § 404.996 Increase in future benefits where time period for reopening expires. If, after the time...

  19. Attractiveness of periodic orbits in parametrically forced systems with time-increasing friction

    E-print Network

    Attractiveness of periodic orbits in parametrically forced systems with time-increasing friction-dimensional systems subject to a periodic force and study numer- ically how a time-varying friction affects oscillator in the presence of friction. We find that, if the damping coefficient increases in time up

  20. Attractiveness of periodic orbits in parametrically forced systems with time-increasing friction

    E-print Network

    Bartuccelli, Michele

    Attractiveness of periodic orbits in parametrically forced systems with time- increasing friction with time-increasing friction Michele Bartuccelli,1,a) Jonathan Deane,1,b) and Guido Gentile2,c) 1 oscillator in the presence of friction, and study numerically how time-varying friction affects the dynamics

  1. Lamivudine does not increase the efficacy of interferon in the treatment of mutant type chronic viral heaptitis B

    PubMed Central

    Yang, Sien-Sing; Hsu, Chao-Tien; Hu, Jui-Ting; Lai, Yung-Chih; Wu, Chi-Hwa

    2002-01-01

    AIM: To study the role of lamivudine in improving the efficiency of interferon for the treatment of mutant type chronic hepatitis B. METHODS: Fifteen patients with mutant type chronic hepatitis B were prospectively studied. All patients had liver histology and serology to prove the diagnosis of chronic hepatitis B. Each patient received 4.5 millionunits of interferon alpha-2a thrice weekly and 100 mg of oral lamivudine daily for 24 wk. Patients were observed and tested for blood chemistry every week for the initial 4 wk and every 2 wk thereafter during the treatment until 24 wk. After the end of treatment, patients were followed up at 4-week intervals for an additional 6 mo. Serum HBV DNA levels were tested using the liquid phase molecular hybridization assay. Those with non-detectable HBV DNA were also tested using the real-time polymerase chain reaction. One patient, who did not finish treatment due to depression, was excluded. RESULTS: At the end of treatment, 7 (50%) patients had serum ALT levels within normal limits; 12 (86%) patients had serum HBV DNA levels < 5 pg/mL using the liquid phase molecular hybridization assay, but only 8 (67%) were < 20 copies/dL using the real-time polymerase chain reaction. Six months after treatment, only two (14%) patients had a sustained complete response to the combination therapy with serum ALT level < 35 iu/L and undetectable serum HBV DNA levels. CONCLUSION: These pilot data showed that lamivudine did not increase the efficacy of interferon in the treatment of mutant type chronic hepatitis B. The liquid phase molecular hybridization assay was not sensitive enough to detect the low HBV DNA levels during combined interferon and lamivudine therapy. PMID:12378632

  2. Corticosteroid Treatments in Males With Duchenne Muscular Dystrophy: Treatment Duration and Time to Loss of Ambulation

    PubMed Central

    Kim, Sunkyung; Campbell, Kimberly A.; Fox, Deborah J.; Matthews, Dennis J.; Valdez, Rodolfo

    2015-01-01

    This population-based study examines the association between corticosteroid treatment and time to loss of ambulation, stratifying by treatment duration (short: 0.25–3 years, long: >3 years), among 477 Duchenne muscular dystrophy cases identified by the Muscular Dystrophy Surveillance Tracking and Research Network (MDSTARnet). Those cases who received short-term corticosteroid treatment had a time to loss of ambulation that was 0.8 years shorter (t test) and an annual risk of losing ambulation 77% higher than the untreated (Cox regression). Conversely, cases who received long-term corticosteroid treatment had a time to loss of ambulation that was 2 years longer and an annual risk of losing ambulation 82% lower than the untreated, up to age 11 years; after which the risks were not statistically different. The relationship of corticosteroids and time to loss of ambulation is more complex than depicted by previous studies limited to treatment responders or subjects who lost ambulation during study follow-up. PMID:25414237

  3. Corticosteroid Treatments in Males With Duchenne Muscular Dystrophy: Treatment Duration and Time to Loss of Ambulation.

    PubMed

    Kim, Sunkyung; Campbell, Kimberly A; Fox, Deborah J; Matthews, Dennis J; Valdez, Rodolfo

    2015-09-01

    This population-based study examines the association between corticosteroid treatment and time to loss of ambulation, stratifying by treatment duration (short: 0.25-3 years, long: >3 years), among 477 Duchenne muscular dystrophy cases identified by the Muscular Dystrophy Surveillance Tracking and Research Network (MDSTARnet). Those cases who received short-term corticosteroid treatment had a time to loss of ambulation that was 0.8 years shorter (t test) and an annual risk of losing ambulation 77% higher than the untreated (Cox regression). Conversely, cases who received long-term corticosteroid treatment had a time to loss of ambulation that was 2 years longer and an annual risk of losing ambulation 82% lower than the untreated, up to age 11 years; after which the risks were not statistically different. The relationship of corticosteroids and time to loss of ambulation is more complex than depicted by previous studies limited to treatment responders or subjects who lost ambulation during study follow-up. PMID:25414237

  4. EFFECTS OF MANURE AMENDMENTS AND DIET TREATMENTS ON SOIL TEST P WITH TIME

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent data indicate that dietary modification may increase potential phosphorus (P) losses when manure is applied to pastures. This study was conducted to determine the effects of feed and manure treatments on P in soil with time. Manure was collected from studies of swine and poultry fed modified ...

  5. Risk factors and timing of default from treatment for non-multidrug-resistant tuberculosis in Moldova

    E-print Network

    Cohen, Ted

    proportions of TB patients with multidrug-resistant tuberculosis (MDR-TB) worldwide. Objective--To assess risk factors and timing of default from treatment for non-MDR-TB. Default has been associated with increased mortality and amplification of drug resistance and may contribute to the high MDR-TB rates in Moldova

  6. Trigger finger appearing as gradually increasing digital nerve disorder after surgical treatment.

    PubMed

    Tsuchie, Hiroyuki; Nishi, Tomio; Abe, Hidekazu; Takeshima, Masaaki; Shimada, Yoichi

    2013-01-01

    Trigger finger is a common disease, and operative treatments are often applied for it. Digital nerve injury is one of the complications of this surgical treatment, and paresthesia and sensory disturbance occur early after the operation. This paper presents a case of trigger finger appearing gradually as increasing digital nerve disorder after surgical treatment. In the second surgery, scar tissue covered the palmar MP joint where the A1 pulley had existed before, and palmar digital neurovascular tissue of the ulnar side was found on the inside of the scar. The ulnar digital nerve showed swelling like a neuroma, and bilateral digital nerves existed nearer to the center of the flexor pollicis longus tendon than normal digital nerves. Even when we operate on trigger finger by open release, we should create an appropriate surgical space for observation and be careful of digital nerve injury. PMID:23634312

  7. Short report: Increasing access to treatment for Chagas disease: the case of Morelos, Mexico.

    PubMed

    Manne-Goehler, Jennifer; Ramsey, Janine M; Salgado, Marco Ocampo; Wirtz, Veronika J; Reich, Michael R

    2014-12-01

    Chagas disease is a neglected vector-borne disease with an estimated prevalence of 1.1 million cases in Mexico. Recent research showed that access to treatment of Chagas disease is limited in Mexico, with < 0.5% of infected cases treated. This brief report used quantitative data from the Morelos Program on Chagas disease and qualitative analysis of key informant interviews to examine strategies to increase treatment access for infected patients in Morelos, Mexico. From 2007 to 2011, 263 (9.2%) of the registered cases of Chagas disease in Mexico occurred in Morelos. Among these, 152 (57.8%) were treated and 97.3% of those treated received benznidazole. The assessment finds that state officials decided to directly purchase benznidazole from the distributor to increase access and improve clinical quality of treatment of patients in their state. They also faced significant barriers, especially in regulation and health system organization, which limited efforts to make high quality treatment available. PMID:25266353

  8. Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue

    PubMed Central

    Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r?=?0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone. PMID:25084454

  9. Optimal treatment allocation for placebo-treatment comparisons in trials with discrete-time survival endpoints.

    PubMed

    Moerbeek, Mirjam; Wong, Weng-Kee

    2015-11-30

    In many randomized controlled trials, treatment groups are of equal size, but this is not necessarily the best choice. This paper provides a methodology to calculate optimal treatment allocations for longitudinal trials when we wish to compare multiple treatment groups with a placebo group, and the comparisons may have unequal importance. The focus is on trials with a survival endpoint measured in discrete time. We assume the underlying survival process is Weibull and show that values for the parameters in the Weibull distribution have an impact on the optimal treatment allocation scheme in an interesting way. Additionally, we incorporate different cost considerations at the subject and measurement levels and determine the optimal number of time periods. We also show that when many events occur at the beginning of the trial, fewer time periods are more efficient. As an application, we revisit a risperidone maintenance treatment trial in schizophrenia and use our proposed methodology to redesign it and compare merits of our optimal design. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26119759

  10. Tick bites and Lyme disease: the need for timely treatment.

    PubMed

    Overstreet, Maria L

    2013-06-01

    In the United States, 30,158 people were reported as having contracted Lyme disease during 2010; 96% of the cases in 2011 were reported from 13 northeast and north-central states. Time of tick attachment is a critical factor. Prolonged attachment allows time for a bacterium to move from tick to human. Patient history and meticulous skin inspection are the most important elements used in diagnosis of Lyme disease. The most common drug for treatment is doxycycline. Ticks find their hosts by several senses: odor, moisture, heat, and vibration. Avoidance of tick-infested areas, such as wooded areas and leaf piles, is paramount in preventing Lyme disease. PMID:23692936

  11. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis.

    PubMed

    Xue, Hong-Xia; Fu, Wen-Yi; Cui, Hua-Dong; Yang, Li-Li; Zhang, Ning; Zhao, Li-Juan

    2015-05-01

    Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ? 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide. PMID:26109960

  12. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

    PubMed Central

    Xue, Hong-xia; Fu, Wen-yi; Cui, Hua-dong; Yang, Li-li; Zhang, Ning; Zhao, Li-juan

    2015-01-01

    Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ? 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide. PMID:26109960

  13. Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression

    PubMed Central

    Nugent, Allison C; Carlson, Paul J; Bain, Earle E; Eckelman, William; Herscovitch, Peter; Manji, Husseini; Zarate, Carlos A; Drevets, Wayne C

    2013-01-01

    Abnormal serotonin type 1A (5-HT1A) receptor function and binding have been implicated in the pathophysiology of mood disorders. Preclinical studies have consistently shown that stress decreases the gene expression of 5-HT1A receptors in experimental animals, and that the associated increase in hormone secretion plays a crucial role in mediating this effect. Chronic administration of the mood stabilizers lithium and divalproex (valproate semisodium) reduces glucocorticoid signaling and function in the hippocampus. Lithium has further been shown to enhance 5-HT1A receptor function. To assess whether these effects translate to human subject with bipolar disorder (BD), positron emission tomography (PET) and [18F]trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazino]-ethyl)-N-(2-pyridyl) cyclohexanecarboxamide ([18F]FCWAY) were used to acquire PET images of 5-HT1A receptor binding in 10 subjects with BD, before and after treatment with lithium or divalproex. Mean 5-HT1A binding potential (BPP) significantly increased following mood stabilizer treatment, most prominently in the mesiotemporal cortex (hippocampus plus amygdala). When mood state was also controlled for, treatment was associated with increases in BPP in widespread cortical areas. These preliminary findings are consistent with the hypothesis that these mood stabilizers enhance 5-HT1A receptor expression in BD, which may underscore an important component of these agents' mechanism of action. PMID:23926239

  14. Protracted treatment with diazepam increases the turnover of putative endogenous ligands for the benzodiazepine/. beta. -carboline recognition site

    SciTech Connect

    Miyata, M.; Mocchetti, I.; Ferrarese, C.; Guidotti, A.; Costa, E.

    1987-03-01

    DBI (diazepam-binding inhibitor) is a putative neuromodulatory peptide isolated from rat brain that acts on ..gamma..-aminobutyric acid-benzodiazepine-Cl/sup -/ ionosphore receptor complex inducing ..beta..-carboline-like effects. The authors used a cDNA probe complementary to DBI mRNA and a specific antibody for rat DBI to study in rat brain how the dynamic state of DBI can be affected after protected (three times a day for 10 days) treatment with diazepam and chlordiazepoxide by oral gavage. Both the content of DBI and DBI mRNA increased in the cerebellum and cerebral cortex but failed to change in the hippocampus and striatum of rats receiving this protracted benzodiazepine treatment. Acute treatment with diazepam did not affect the dynamic state of brain DBI. An antibody was raised against a biologically active octadecaneuropeptide derived from the tryptic digestion of DBI. The combined HPLC/RIA analysis of rat cerebellar extracts carried out with this antibody showed that multiple molecular forms of the octadecaneuropeptide-like reactivity are present and all of them are increased in rats receiving repeated daily injections of diazepam. It is inferred that tolerance to benzodiazepines in associated with an increase in the turnover rate of DBI, which may be responsible for the ..gamma..-aminobutyric acid receptor desensitization that occurs after protracted benzodiazepine administration.

  15. SU-E-T-610: Comparison of Treatment Times Between the MLCi and Agility Multileaf Collimators

    SciTech Connect

    Ramsey, C; Bowling, J

    2014-06-01

    Purpose: The Agility is a new 160-leaf MLC developed by Elekta for use in their Infinity and Versa HD linacs. As compared to the MLCi, the Agility increased the maximum leaf speed from 2 cm/s to 3.5 cm/s, and the maximum primary collimator speed from 1.5 cm/s to 9.0 cm/s. The purpose of this study was to determine if the Agility MLC resulted in improved plan quality and/or shorter treatment times. Methods: An Elekta Infinity that was originally equipped with a 80 leaf MLCi was upgraded to an 160 leaf Agility. Treatment plan quality was evaluated using the Pinnacle planning system with SmartArc. Optimization was performed once for the MLCi and once for the Agility beam models using the same optimization parameters and the same number of iterations. Patient treatment times were measured for all IMRT, VMAT, and SBRT patients treated on the Infinity with the MLCi and Agility MLCs. Treatment times were extracted from the EMR and measured from when the patient first walked into the treatment room until exiting the treatment room. Results: 11,380 delivery times were measured for patients treated with the MLCi, and 1,827 measurements have been made for the Agility MLC. The average treatment times were 19.1 minutes for the MLCi and 20.8 minutes for the Agility. Using a t-test analysis, there was no difference between the two groups (t = 0.22). The dose differences between patients planned with the MLCi and the Agility MLC were minimal. For example, the dose difference for the PTV, GTV, and cord for a head and neck patient planned using Pinnacle were effectively equivalent. However, the dose to the parotid glands was slightly worse with the Agility MLC. Conclusion: There was no statistical difference in treatment time, or any significant dosimetric difference between the Agility MLC and the MLCi.

  16. Investigation of parameters affecting treatment time in MRI-guided transurethral ultrasound therapy

    NASA Astrophysics Data System (ADS)

    N'Djin, W. A.; Burtnyk, M.; Chopra, R.; Bronskill, M. J.

    2010-03-01

    MRI-guided transurethral ultrasound therapy shows promise for minimally invasive treatment of localized prostate cancer. Real-time MR temperature feedback enables the 3D control of thermal therapy to define an accurate region within the prostate. Previous in-vivo canine studies showed the feasibility of this method using transurethral planar transducers. The aim of this simulation study was to reduce the procedure time, while maintaining treatment accuracy by investigating new combinations of treatment parameters. A numerical model was used to simulate a multi-element heating applicator rotating inside the urethra in 10 human prostates. Acoustic power and rotation rate were varied based on the feedback of the temperature in the prostate. Several parameters were investigated for improving the treatment time. Maximum acoustic power and rotation rate were optimized interdependently as a function of prostate radius and transducer operating frequency, while avoiding temperatures >90° C in the prostate. Other trials were performed on each parameter separately, with the other parameter fixed. The concept of using dual-frequency transducers was studied, using the fundamental frequency or the 3rd harmonic component depending on the prostate radius. The maximum acoustic power which could be used decreased as a function of the prostate radius and the frequency. Decreasing the frequency (9.7-3.0 MHz) or increasing the power (10-20 W.cm-2) led to treatment times shorter by up to 50% under appropriate conditions. Dual-frequency configurations, while helpful, tended to have less impact on treatment times. Treatment accuracy was maintained and critical adjacent tissues like the rectal wall remained protected. The interdependence between power and frequency may require integrating multi-parametric functions inside the controller for future optimizations. As a first approach, however, even slight modifications of key parameters can be sufficient to reduce treatment time.

  17. Gamma irradiation or hydrocortisone treatment of rats increases the proteinase activity associated with histones of thymus nuclei

    SciTech Connect

    Kutsyi, M.P.; Gaziev, A.I.

    1994-11-01

    An increase in the activity of histone-associated rat thymus nucleus proteinases specific for histones H2A, H2B and H1 was shown after {gamma} irradiation or hydrocortisone treatment of animals. Histone H1-specific proteinase activity is dependent on DNA and increases in the presence of denatured DNA, whereas proteinases specific for core histones are inhibited in the presence of denatured DNA. The increase in the activity of histone-associated proteinases depends on the radiation dose and the time after irradiation or hydrocortisone injection. In the presence of dithiothreitol and sodium dodecyl sulfate, these proteinases dissociate from histones. It was found by gel electrophoresis that several proteinases of various molecular masses are closely associated with histones obtained from thymus nuclei of irradiated or hydrocortisone-treated rats. 43 refs., 7 figs.

  18. Overestimation of the second time interval replaces time-shrinking when the difference between two adjacent time intervals increases

    PubMed Central

    Nakajima, Yoshitaka; Hasuo, Emi; Yamashita, Miki; Haraguchi, Yuki

    2014-01-01

    When the onsets of three successive sound bursts mark two adjacent time intervals, the second time interval can be underestimated when it is physically longer than the first time interval by up to 100 ms. This illusion, time-shrinking, is very stable when the first time interval is 200 ms or shorter (Nakajima et al., 2004, Perception, 33). Time-shrinking had been considered a kind of perceptual assimilation to make the first and the second time interval more similar to each other. Here we investigated whether the underestimation of the second time interval was replaced by an overestimation if the physical difference between the neighboring time intervals was too large for the assimilation to take place; this was a typical situation in which a perceptual contrast could be expected. Three experiments to measure the overestimation/underestimation of the second time interval by the method of adjustment were conducted. The first time interval was varied from 40 to 280 ms, and such overestimations indeed took place when the first time interval was 80–280 ms. The overestimations were robust when the second time interval was longer than the first time interval by 240 ms or more, and the magnitude of the overestimation was larger than 100 ms in some conditions. Thus, a perceptual contrast to replace time-shrinking was established. An additional experiment indicated that this contrast did not affect the perception of the first time interval substantially: The contrast in the present conditions seemed unilateral. PMID:24860471

  19. Increases in Perspective Embedding Increase Reading Time Even with Typical Text Presentation: Implications for the Reading of Literature

    PubMed Central

    Whalen, D. H.; Zunshine, Lisa; Holquist, Michael

    2015-01-01

    Reading fiction is a major component of intellectual life, yet it has proven difficult to study experimentally. One aspect of literature that has recently come to light is perspective embedding (“she thought I left” embedding her perspective on “I left”), which seems to be a defining feature of fiction. Previous work (Whalen et al., 2012) has shown that increasing levels of embedment affects the time that it takes readers to read and understand short vignettes in a moving window paradigm. With increasing levels of embedment from 1 to 5, reading times in a moving window paradigm rose almost linearly. However, level 0 was as slow as 3–4. Accuracy on probe questions was relatively constant until dropping at the fifth level. Here, we assessed this effect in a more ecologically valid (“typical”) reading paradigm, in which the entire vignette was visible at once, either for as long as desired (Experiment 1) or a fixed time (Experiment 2). In Experiment 1, reading times followed a pattern similar to that of the previous experiment, with some differences in absolute speed. Accuracy matched previous results: fairly consistent accuracy until a decline at level 5, indicating that both presentation methods allowed understanding. In Experiment 2, accuracy was somewhat reduced, perhaps because participants were less successful at allocating their attention than they were during the earlier experiment; however, the pattern was the same. It seems that literature does not, on average, use easiest reading level but rather uses a middle ground that challenges the reader, but not too much. PMID:26635684

  20. Increases in Perspective Embedding Increase Reading Time Even with Typical Text Presentation: Implications for the Reading of Literature.

    PubMed

    Whalen, D H; Zunshine, Lisa; Holquist, Michael

    2015-01-01

    Reading fiction is a major component of intellectual life, yet it has proven difficult to study experimentally. One aspect of literature that has recently come to light is perspective embedding ("she thought I left" embedding her perspective on "I left"), which seems to be a defining feature of fiction. Previous work (Whalen et al., 2012) has shown that increasing levels of embedment affects the time that it takes readers to read and understand short vignettes in a moving window paradigm. With increasing levels of embedment from 1 to 5, reading times in a moving window paradigm rose almost linearly. However, level 0 was as slow as 3-4. Accuracy on probe questions was relatively constant until dropping at the fifth level. Here, we assessed this effect in a more ecologically valid ("typical") reading paradigm, in which the entire vignette was visible at once, either for as long as desired (Experiment 1) or a fixed time (Experiment 2). In Experiment 1, reading times followed a pattern similar to that of the previous experiment, with some differences in absolute speed. Accuracy matched previous results: fairly consistent accuracy until a decline at level 5, indicating that both presentation methods allowed understanding. In Experiment 2, accuracy was somewhat reduced, perhaps because participants were less successful at allocating their attention than they were during the earlier experiment; however, the pattern was the same. It seems that literature does not, on average, use easiest reading level but rather uses a middle ground that challenges the reader, but not too much. PMID:26635684

  1. Post-Injury Treatment with Rolipram Increases Hemorrhage After Traumatic Brain Injury

    PubMed Central

    Atkins, C.M.; Kang, Y.; Furones, C.; Truettner, J.S.; Alonso, O.F.; Dietrich, W.D.

    2012-01-01

    The pathology caused by traumatic brain injury (TBI) is exacerbated by the inflammatory response of the injured brain. Two pro-inflammatory cytokines that contribute to inflammation after TBI are tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?). In previous studies using the parasagittal fluid-percussion brain injury model, we reported that the anti-inflammatory drug rolipram, a phosphodiesterase 4 inhibitor, reduced TNF-? and IL-1? levels and improved histopathological outcome when administered 30 min prior to injury. We now report that treatment with (±)-rolipram given 30 min after injury significantly reduced TNF-? levels in the cortex and hippocampus. However, post-injury administration of (±)-rolipram significantly increased cortical contusion volume and increased atrophy of the cortex as compared to vehicle-treated animals at 10 days post-injury. Thus, despite the reduction in pro-inflammatory cytokine levels, histopathological outcome was worsened with post-TBI (±)-rolipram treatment. Further histological analysis of (±)-rolipram-treated TBI animals revealed significant hemorrhage in the contused brain. Given the well known role of (±)-rolipram to increase vasodilation, it is likely that (±)-rolipram worsened outcome after fluid-percussion brain injury by causing increased bleeding. PMID:22535545

  2. FOXO1 Content Is Reduced in Cystic Fibrosis and Increases with IGF-I Treatment

    PubMed Central

    Smerieri, Arianna; Montanini, Luisa; Maiuri, Luigi; Bernasconi, Sergio; Street, Maria E.

    2014-01-01

    Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced ?2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes. PMID:25299696

  3. Increased Learning Time under Stimulus-Funded School Improvement Grants: High Hopes, Varied Implementation

    ERIC Educational Resources Information Center

    McMurrer, Jennifer

    2012-01-01

    Research has long suggested that significantly increasing quality time in school for teaching and learning can have a positive impact on student achievement. Recognizing this connection, federal guidance requires low-performing schools to increase student learning time if they are implementing two popular reform models using school improvement…

  4. Increase of bulk optical damage threshold fluences of KDP crystals by laser irradiation and heat treatment

    DOEpatents

    Swain, J.E.; Stokowski, S.E.; Milam, D.; Kennedy, G.C.; Rainer, F.

    1982-07-07

    The bulk optical damage threshold fluence of potassium dihydrogen phosphate (KDP) crystals is increased by irradiating the crystals with laser pulses of duration 1 to 20 nanoseconds of increasing fluence, below the optical damage threshold fluence for untreated crystals, or by baking the crystals for times of the order of 24 hours at temperatures of 110 to 165/sup 0/C, or by a combination of laser irradiation and baking.

  5. Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time

    PubMed Central

    Kaplan, Robert M.; Irvin, Veronica L.

    2015-01-01

    Background We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI) funded trials has increased over time. Methods We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease. Trials were included if direct costs >$500,000/year, participants were adult humans, and the primary outcome was cardiovascular risk, disease or death. The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000, whether they registered in clinicaltrials.gov prior to publication, used active or placebo comparator, and whether or not the trial had industry co-sponsorship. We tabulated whether the study reported a positive, negative, or null result on the primary outcome variable and for total mortality. Results 17 of 30 studies (57%) published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 (8%) trials published after 2000 (?2=12.2,df= 1, p=0.0005). There has been no change in the proportion of trials that compared treatment to placebo versus active comparator. Industry co-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward null findings. Conclusions The number NHLBI trials reporting positive results declined after the year 2000. Prospective declaration of outcomes in RCTs, and the adoption of transparent reporting standards, as required by clinicaltrials.gov, may have contributed to the trend toward null findings. PMID:26244868

  6. Increasing model complexity in simulating phosphorus dynamics in a large treatment wetland: does it matter?

    NASA Astrophysics Data System (ADS)

    Paudel, R.; Jawitz, J. W.

    2011-12-01

    As the structure of ecological models grows more complex, it becomes increasingly important to identify the appropriate level of complexity for reliable process description and prediction. Here, a suite of mechanistic biogeochemical models with increasing level of complexity for representing phosphorus cycling processes was developed and tested against observations from a large treatment wetland. The study site was the 147-ha Cell 4 of Stormwater Treatment Area 1 West, which was designed to help protect the greater Everglades, FL, USA from nutrient over-enrichment. The biogeochemical models were coupled with a pre-calibrated two-dimensional hydrodynamic model of Cell 4. We provide guidance for evaluating a set of models with varying level of process complexity using key model attributes that influence the suitability of a model or a set of models. Considerations of model accuracy, complexity, and explanatory depth are combined into a single indicator of model effectiveness. Results revealed that the most complex model structure may not necessarily the most effective in simulating the dynamics of total phosphorus concentrations in the wetland. The rate of improvement in the model performance decreased as model complexity increased. Although the most complex model reproduced the field observations best, the marginal improvement in model performance compared to simpler models was outweighed by the higher costs of increased complexity. Highly detailed representations of system structures may not be useful to simulate total phosphorus dynamics in treatment wetlands if comprehensive data sets are not available to constrain each pathway in the model. It is crucial for model developers and users to evaluate model structures of differing complexity to identify the optimal level of model complexity for given data and questions of interest.

  7. Increasing complexity: which drug class to choose for treatment of hypertension in the elderly?

    PubMed Central

    Kaiser, Edelgard Anna; Lotze, Ulrich; Schäfer, Hans Hendrik

    2014-01-01

    Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP) and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and direct renin inhibitors (DRIs) are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost savings due to high adherence. PMID:24711696

  8. Increased Clearance of Antipyrine and d-Propranolol after Phenobarbital Treatment in the Monkey

    PubMed Central

    Branch, Robert A.; Shand, David G.; Wilkinson, Grant R.; Nies, Alan S.

    1974-01-01

    The effects of phenobarbital treatment for 12 days on the regional distribution of blood flow and on the disposition of two model drugs, antipyrine and d-propranolol, have been determined in six unanesthetized rhesus monkeys. Phenobarbital significantly increased total hepatic blood flow from 179±15 to 239±27 ml/min. Liver weight was increased to a similar degree (34%) in phenobarbital-treated animals as compared to control monkeys. The clearance of both antipyrine and d-propranolol was increased and the half-life decreased significantly by phenobarbital. Analysis of the data by a perfusion-limited pharmacokinetic model showed that the changes in antipyrine clearance were due almost entirely to enzyme induction. On the other hand, with d-propranolol, the increase in liver blood flow contributed as much to the enhanced clearance as did the stimulation of drug metabolism. The mechanism by which phenobarbital produces the frequently observed increase in drug clearance, therefore, depends upon the initial clearance value of the drug. For low clearance drugs like antipyrine, clearance changes occur largely as a result of enzyme induction. With higher clearance drugs, the effects of increased hepatic blood flow become progressively more important the greater the initial clearance value. PMID:4205524

  9. Does Employment Growth Increase Travel Time to Work?: An Empirical Analysis using Military Troop Movements1

    E-print Network

    Lin, C.-Y. Cynthia

    1 Does Employment Growth Increase Travel Time to Work?: An Empirical Analysis using Military Troop. This paper examines the short-run impacts of rapid employment growth on travel time to work. We exploit Realignment and Closure (BRAC) in order to identify the effect of employment growth on travel time using

  10. An investigation on sol-gel treatment to aramid yarn to increase inter-yarn friction

    NASA Astrophysics Data System (ADS)

    Chu, Yanyan; Chen, Xiaogang; Wang, Qing; Cui, Shizhong

    2014-11-01

    Inter-yarn friction helps to increase energy absorption in ballistic fabrics. This paper reports on the results of sol-gel treatment on aramid yarns to increase the inter-yarn friction. Two types of TiO2/ZnO hydrosols (submicro-sized and nano-sized) prepared using hydrolysis and peptization methods were used to treat aramid yarns with and without curing. SEM was used to characterize the change in morphology. FTIR and EDX analyses were applied to identify the coating substance. The inter-yarn friction was tested using Capstan method. Images from SEM showed that the surface of the yarn treated with TiO2/ZnO submicro-sized hydrosol was covered with lump-like coating whilst in the case of TiO2/ZnO nano-sized sol treatment, the coating on the fibres was more film-like. The substance in the coating was confirmed as titanium dioxide and zinc oxide by FTIR and EDX analyses. The test results for coefficient of friction revealed that the coefficient of friction between the yarns treated by submicro-sized hydrosol was 54% higher than the non-treated, and the nano-sized hydrosol was associated to a 10% increase. However, the curing process had little effect on the coefficient of friction between yarns. The study also showed that the tensile properties of the treated yarns and the weight add-on were not significantly affected.

  11. Wnt2 Expression and Signaling is Increased by Different Classes of Antidepressant Treatments

    PubMed Central

    Okamoto, Hideki; Voleti, Bhavya; Banasr, Mounira; Sarhan, Maysa; Duric, Vanja; Girgenti, Matthew J.; DiLeone, Ralph J.; Newton, Samuel S.; Duman, Ronald S.

    2010-01-01

    Background Despite recent interest in glycogen synthase kinase-3b (GSK-3b) as a target for the treatment of mood disorders, there has been very little work related to these illnesses on the upstream signaling molecules that regulate this kinase, as well as downstream targets. Methods Using a focused microarray approach we examined the influence of different classes of antidepressants on Wnt signaling that controls GSK-3b activity as well as the transcription factors that contribute to the actions of GSK-3b. Results The results demonstrate that Wnt2 is a common target of different classes of antidepressants, and also show differential regulation of Wnt-GSK-3b signaling genes. Increased expression and function of Wnt2 was confirmed by secondary measures. Moreover, using a viral vector approach we demonstrate that increased expression of Wnt2 in the hippocampus is sufficient to produce antidepressant-like behavioral actions in well-established models of depression and treatment response. Conclusions These findings demonstrate that Wnt2 expression and signaling is a common target of antidepressants and that increased Wnt2 is sufficient to produce antidepressant effects. PMID:20570247

  12. Increasing Physicians' and Nurses' Compliance with Treatment Guidelines in Cancer Care Program.

    ERIC Educational Resources Information Center

    Slenker, Suzanne E.; And Others

    1985-01-01

    The effect of the use of guidelines on the care of patients with breast, colon, and non-small-cell lung cancers is reported. Audits of patient records revealed an increase over time in the percentage of recommended cancer care procedures that were complied with. (Author/MLW)

  13. Short treatment time and excellent treatment outcome in accelerated hyperfractionated radiotherapy for T1 glottic cancer

    PubMed Central

    Tamaki, Yukihisa; Hieda, Yoko; Yoshida, Rika; Yoshizako, Takeshi; Fuchiwaki, Takafumi; Aoi, Noriaki; Sekihara, Kazumasa; Kitajima, Kazuhiro; Kawauchi, Hideyuki; Kitagaki, Hajime; Sasaki, Ryohei; Inomata, Taisuke

    2015-01-01

    ABSTRACT Accelerated hyperfractionated radiotherapy was performed as treatment for patients with T1 glottic cancer, and its utility was evaluated based on treatment outcomes and adverse effects. Fifty-eight men who had undergone radiotherapy were retrospectively reviewed. Tumor classification was Tis in 4 patients, T1a in 38, and T1b in 16. Histological examination revealed squamous cell carcinoma in 55 patients. Travel time from home to hospital was 0–1 hour for 24 patients, 1–2 hours for 9, and >2 hours for 25. Laser vaporization was performed prior to radiotherapy in 38 patients, and 19 patients received concurrent chemotherapy with an agent such as S-1. Patients were irradiated twice daily using an irradiation container. Most patients received a dose of 1.5 Gy/fraction up to a total of 60 Gy. The median overall treatment time was 30 days, with a median observation period of 59.6 months. A complete response was observed in all patients. The 5-year overall survival, disease-free survival, and local control rates were 97.2%, 93.2%, and 97.8%, respectively. Although grade 3 pharyngeal mucositis was observed in 2 patients, there were no other grade 3 or higher acute adverse events. As late toxicity, grade 2 laryngeal edema and grade 1 laryngeal hemorrhage were observed in 1 patient each, but no serious events such as laryngeal necrosis or laryngeal stenosis were observed. In conclusion, this treatment method brings excellent outcome and will substantially reduce the treatment duration among patients who need to stay at nearby hotels while undergoing treatment at hospitals in rural areas. PMID:26663937

  14. Sarcomere length dependence of power output is increased after PKA treatment in rat cardiac myocytes

    PubMed Central

    Hanft, Laurin M.; McDonald, Kerry S.

    2009-01-01

    The Frank-Starling relationship of the heart yields increased stroke volume with greater end-diastolic volume, and this relationship is steeper after ?-adrenergic stimulation. The underlying basis for the Frank-Starling mechanism involves length-dependent changes in both Ca2+ sensitivity of myofibrillar force and power output. In this study, we tested the hypothesis that PKA-induced phosphorylation of myofibrillar proteins would increase the length dependence of myofibrillar power output, which would provide a myofibrillar basis to, in part, explain the steeper Frank-Starling relations after ?-adrenergic stimulation. For these experiments, adult rat left ventricles were mechanically disrupted, permeabilized cardiac myocyte preparations were attached between a force transducer and position motor, and the length dependence of loaded shortening and power output were measured before and after treatment with PKA. PKA increased the phosphorylation of myosin binding protein C and cardiac troponin I, as assessed by autoradiography. In terms of myocyte mechanics, PKA decreased the Ca2+ sensitivity of force and increased loaded shortening and power output at all relative loads when the myocyte preparations were at long sarcomere length (?2.30 ?m). PKA had less of an effect on loaded shortening and power output at short sarcomere length (?2.0 ?m). These changes resulted in a greater length dependence of myocyte power output after PKA treatment; peak normalized power output increased ?20% with length before PKA and ?40% after PKA. These results suggest that PKA-induced phosphorylation of myofibrillar proteins explains, in part, the steeper ventricular function curves (i.e., Frank-Starling relationship) after ?-adrenergic stimulation of the left ventricle. PMID:19252095

  15. Thoracic intramedullary epidermoid cyst-timely fashion diagnosis and treatment.

    PubMed

    Babayev, Rasim; Abbasov, Bahadur; Ek?i, Murat ?akir

    2015-05-01

    Epidermoid cysts are composed of stratified squamous epithelium, which develop from inclusion of ectodermal tissue remnants entrapped during primitive neural tube closure period between the 3rd and 5th weeks of gestation. Intramedullary epidermoid cysts (IEC) are very rare in childhood. Eleven cases have been reported previously. Even though it is a rare entity, early diagnosis with timely fashioned surgical treatment has a great influence on patients' symptoms, especially if there are myelopathic findings. In this case report, we demonstrate this fact with a demonstrative clinical case and review radiological, pathological, and surgical perspectives with literature review. PMID:25681950

  16. Chronic SIV and morphine treatment increases heat shock protein 5 expression at the synapse.

    PubMed

    Pendyala, Gurudutt; Periyasamy, Palsamy; Callen, Shannon; Fox, Howard S; Lisco, Steven J; Buch, Shilpa J

    2015-10-01

    The abuse of opiates such as morphine in synergy with HIV infection accelerates neurocognitive impairments and neuropathology in the CNS of HIV-infected subjects, collectively referred to as HAND. To identify potential pathogenic markers associated with HIV and morphine in perturbing the synaptic architecture, we performed quantitative mass spectrometry proteomics on purified synaptosomes isolated from the caudate of two groups of rhesus macaques chronically infected with SIV differing by one regimen-morphine treatment. The upregulation of heat shock 70-kDa protein 5 in the SIV?+?morphine group points to increased cellular stress during SIV/morphine interaction thus leading to CNS dysfunction. PMID:26037114

  17. Increasing the creation yield of shallow single defects in diamond by surface plasma treatment

    SciTech Connect

    Osterkamp, Christian; Scharpf, Jochen; Naydenov, Boris; Jelezko, Fedor; Pezzagna, Sebastien; Meijer, Jan; Diemant, Thomas; Jürgen Behm, Rolf

    2013-11-04

    Single Nitrogen-Vacancy (NV) centers in diamond close to the crystal surface are very promising magnetic field sensors with very high sensitivity. Here, we report the enhanced creation of very shallow (less than 3 nm below the diamond surface) NV centers by using fluorine and oxygen plasma treatment. We observe a four fold increase—from 0.11% to about 0.45% in the production yield when the sample surface is terminated with fluorine or oxygen atoms. This effect is explained by the stabilization of the NV's negative charge state which is influenced by the various defects present on the diamond surface.

  18. Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy

    PubMed Central

    2012-01-01

    Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315

  19. Short communication: Methamphetamine treatment increases in vitro and in vivo HIV replication.

    PubMed

    Toussi, Sima Shelly; Joseph, Aviva; Zheng, Jian Hua; Dutta, Monica; Santambrogio, Laura; Goldstein, Harris

    2009-11-01

    To delineate the mechanistic basis for the epidemiological association between methamphetamine use and accelerated progression to AIDS, we evaluated the direct in vitro and in vivo effects of methamphetamine on HIV-1 replication. Methamphetamine administration significantly increased HIV-1 production by both HIV-infected monocytes and CD4 T lymphocytes in vitro. In addition, in vivo methamphetamine treatment increased HIV production and viremia in mice transgenic for a replication-competent HIV provirus and human cyclin T1. Methamphetamine activated transcription of the HIV long terminal repeat (LTR) regulatory region, was associated with nuclear translocation of NF-kappaB. Our results provide further insights into the mechanisms by which methamphetamine accelerates disease course in HIV-infected individuals. PMID:19895343

  20. Restoration of CBX7 expression increases the susceptibility of human lung carcinoma cells to irinotecan treatment.

    PubMed

    Cacciola, Nunzio Antonio; Sepe, Romina; Forzati, Floriana; Federico, Antonella; Pellecchia, Simona; Malapelle, Umberto; De Stefano, Alfonso; Rocco, Danilo; Fusco, Alfredo; Pallante, Pierlorenzo

    2015-11-01

    Lung cancer is one of the most common causes of cancer-related death worldwide in men and women, and, despite the recent remarkable scientific advances, drug treatment is still unsatisfactory. Polycomb protein chromobox homolog 7 (CBX7) is involved in several biological processes, including development and cancer progression, indeed the lack of CBX7 protein correlates with a highly malignant phenotype and a poor prognosis. However, its role in lung cancer still remains unknown. Since CBX7 is drastically downregulated in human lung carcinomas, we investigated whether restoration of CBX7 expression could affect growth property of lung cancer cells and modulate their sensitivity to treatment with irinotecan and etoposide, two chemoterapy drugs most commonly used in lung cancer therapy. Here, we demonstrate that restoration of CBX7 in two human lung carcinoma cell lines (A549 and H1299), in which this protein is not detectable, leads to a decreased proliferation (at least in part through a downregulation of phosphorylated ERK and phosphorylated p38) and an increased apoptotic cell death after drug exposure (at least in part through the downregulation of Bcl-2, phosphorylated Akt, and phosphorylated JNK). Taken together, these results suggest that the retention of CBX7 expression may play a role in the modulation of chemosensitivity of lung cancer patients to the treatment with irinotecan and etoposide. PMID:26216446

  1. [Is there an increased risk for renal tumors during long-term treatment with lithium?].

    PubMed

    Conell, J; Lewitzka, U; Ritter, P; Severus, E; Pilhatsch, M; Pfennig, A; Berghöfer, M; Bauer, M

    2015-09-01

    Lithium salts are the recommended first-line treatment (gold standard) in national and international treatment guidelines for acute and maintenance treatment of affective disorders, such as bipolar disorders. Lithium has also been shown to have a unique protective effect against suicide in patients suffering from affective disorders. Despite the well-known acute and long-term adverse effects lithium therapy can be safely administered if patients are properly educated and carefully monitored. A recent study from France now shows that patients with severely impaired renal function who had been treated with lithium salts for more than 10 years could have an increased risk for kidney tumors (benign and malignant). This resulted in an adjustment concerning information within the package leaflet by European authorities. The authors of this article reflect the currently available data in order to better understand and handle this new finding and to warn about uncritical reactions including withdrawal of lithium in successfully treated patients. This article provides clinical recommendations to provide further insight relating to the risk of kidney cancer in long-term lithium therapy. PMID:26341836

  2. Treatment with oxytocin antagonists before embryo transfer may increase implantation rates after IVF.

    PubMed

    Moraloglu, Ozlem; Tonguc, Esra; Var, Turgut; Zeyrek, Tugba; Batioglu, Sertac

    2010-09-01

    This report aimed to examine the effects of atosiban on pregnancy outcome after IVF-embryo transfer. A prospective, randomized, placebo-controlled clinical study was performed. A total of 180 women undergoing intracytoplasmic sperm injection who had top-quality embryos were randomly allocated into treatment and control groups. All the patients had infertility due to tubal factor, hormonal-anovulatory disorders, male factor or unexplained reasons. The treatment group received intravenous administration of atosiban before embryo transfer with a total administered dose of 37.5 mg. In the control group, the same number of cycles was performed with placebo medication. The clinical pregnancy rate (PR) per cycle and implantation rate (IR) per transfer were 46.7% and 20.4% in the atosiban-treated group, which were significantly higher than in the control group (28.9% and 12.6%, respectively, P=0.01). The miscarriage rates of groups 1 and 2 were 16.7% and 24.4%, respectively (P=0.01). These results have indicated that atosiban increases the IR and PR after IVF-embryo transfer. These results suggest that atosiban treatment before embryo transfer is effective in priming of the uterus for implantation. This is the first study to investigate the possible contributions of atosiban for improving the PR after IVF-embryo transfer. PMID:20638340

  3. Modeling the Variability of Single-Cell Lag Times for Listeria innocua Populations after Sublethal and Lethal Heat Treatments?

    PubMed Central

    Métris, A.; George, S. M.; Mackey, B. M.; Baranyi, J.

    2008-01-01

    Optical density measurements were used to estimate the effect of heat treatments on the single-cell lag times of Listeria innocua fitted to a shifted gamma distribution. The single-cell lag time was subdivided into repair time (the shift of the distribution assumed to be uniform for all cells) and adjustment time (varying randomly from cell to cell). After heat treatments in which all of the cells recovered (sublethal), the repair time and the mean and the variance of the single-cell adjustment time increased with the severity of the treatment. When the heat treatments resulted in a loss of viability (lethal), the repair time of the survivors increased with the decimal reduction of the cell numbers independently of the temperature, while the mean and variance of the single-cell adjustment times remained the same irrespective of the heat treatment. Based on these observations and modeling of the effect of time and temperature of the heat treatment, we propose that the severity of a heat treatment can be characterized by the repair time of the cells whether the heat treatment is lethal or not, an extension of the F value concept for sublethal heat treatments. In addition, the repair time could be interpreted as the extent or degree of injury with a multiple-hit lethality model. Another implication of these results is that the distribution of the time for cells to reach unacceptable numbers in food is not affected by the time-temperature combination resulting in a given decimal reduction. PMID:18820061

  4. Exercise increases pyridinoline cross-linking and counters the mechanical effects of concurrent lathyrogenic treatment.

    PubMed

    McNerny, Erin M B; Gardinier, Joseph D; Kohn, David H

    2015-12-01

    The collagen cross-link profile of bone, associated with bone strength and fracture toughness, is tightly regulated (affecting cross-link quantity, type, lysine hydroxylation and maturity) and may contribute to the improvements in bone quality during exercise. We hypothesized that 1) exercise promotes mature cross-link formation, 2) increased mature cross-linking is accompanied by shifts in lysine hydroxylation, and 3) these changes in collagen cross-link profile have positive effects on mechanical properties. Growing male C57Bl6 mice were treated with 30min/day of running exercise, 350mg/kg/day ?-aminopropionitrile (BAPN) injected subcutaneously to inhibit enzymatic collagen cross-linking, or both exercise and BAPN, from 5 to 8weeks of age. Bone collagen cross-linking profile, mechanical properties, morphology, and mineralization were measured from the tibiae. Cross-link measures, including immature, pyridinoline, pyrrole and pentosidine cross-links, ratios reflecting cross-link maturity and hydroxylation, and mineralization were tested for their importance to mechanical properties across 8week groups through correlation analyses and step-wise linear regressions. BAPN treatment significantly reduced lysylpyridinoline, pyrrole, hydroxylysinorleucine, and total mature collagen cross-linking, resulting in decreased bone elastic modulus and increased yield strain despite a marginal increase in TMD. Exercise caused a shift toward pyridinoline cross-linking, with increased hydroxylysylpyridinoline and decreased pyrrole cross-linking resulting in total mature cross-linking and estimated tissue level mechanical properties matching sedentary control levels. Exercise superimposed on BAPN treatment increased total mature cross-linking from BAPN to control levels, but did so by increasing pyridinoline, not pyrrole, cross-links. Exercise also counteracted the BAPN effects on modulus and strain, without a change in TMD. Pyrrole cross-linking was the strongest correlate of modulus (r=0.470, p<0.01) and yield strain (r=-0.467, p<0.01). Cross-links with similar levels of telopeptide lysine hydroxylation to pyrrole (lysylpyridinoline and hydroxylysinorleucine) also correlated with modulus and strain to a lesser extent. In conclusion, exercise in growing mice promotes pyridinoline collagen cross-linking in bone, the resulting increase in total mature cross-linking is sufficient to counteract the mechanical effects of concurrent cross-link inhibition, and this responsiveness to loading is a potential means by which exercise might improve bone quality in diseased or otherwise compromised bone. PMID:26211995

  5. The increasing roles of epigenetics in breast cancer: Implications for pathogenicity, biomarkers, prevention and treatment.

    PubMed

    Basse, Clémence; Arock, Michel

    2015-12-15

    Nowadays, the mechanisms governing the occurrence of cancer are thought to be the consequence not only of genetic defects but also of epigenetic modifications. Therefore, epigenetic has become a very attractive and increasingly investigated field of research in order to find new ways of prevention and treatment of neoplasia, and this is particularly the case for breast cancer (BC). Thus, this review will first develop the main known epigenetic modifications that can occur in cancer and then expose the future role that control of epigenetic modifications might play in prevention, prognostication, follow-up and treatment of BC. Indeed, epigenetic biomarkers found in peripheral blood might become new tools to detect BC, to define its prognostic and to predict its outcome, whereas epi-drugs might have an increasing potential of development in the next future. However, if DNA methyltransferase inhibitors and histone desacetylase inhibitors have shown encouraging results in BC, their action remains nonspecific. Thus, additional clinical studies are needed to evaluate more precisely the effects of these molecules, even if they have provided encouraging results in cotreatment and combined therapies. This review will also deal with the potential of RNA interference (RNAi) as epi-drugs. Finally, we will focus on the potential prevention of BC through epigenetic based on diet and we will particularly develop the possible place of isothiocyanates from cruciferous vegetables or of Genistein from soybean in a dietary program that might potentially reduce the risk of BC in large populations. PMID:25410431

  6. Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia.

    PubMed

    Tropea, Kristen A; Leder, Eva; Aslam, Muhammad; Lau, Allison N; Raiser, David M; Lee, Joo-Hyeon; Balasubramaniam, Vivek; Fredenburgh, Laura E; Alex Mitsialis, S; Kourembanas, Stella; Kim, Carla F

    2012-05-01

    Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity resulting in significant morbidity and mortality. The pathology of BPD is multifactorial and leads to alveolar simplification and distal lung injury. Previous studies have shown a beneficial effect of systemic treatment with bone marrow-derived mesenchymal stromal cells (MSCs) and MSC-conditioned media (MSC-CM) leading to amelioration of the lung parenchymal and vascular injury in vivo in the hyperoxia murine model of BPD. It is possible that the beneficial response from the MSCs is at least in part due to activation of endogenous lung epithelial stem cells. Bronchioalveolar stem cells (BASCs) are an adult lung stem cell population capable of self-renewal and differentiation in culture, and BASCs proliferate in response to bronchiolar and alveolar lung injury in vivo. Systemic treatment of neonatal hyperoxia-exposed mice with MSCs or MSC-CM led to a significant increase in BASCs compared with untreated controls. Treatment of BASCs with MSC-CM in culture showed an increase in growth efficiency, indicating a direct effect of MSCs on BASCs. Lineage tracing data in bleomycin-treated adult mice showed that Clara cell secretory protein-expressing cells including BASCs are capable of contributing to alveolar repair after lung injury. MSCs and MSC-derived factors may stimulate BASCs to play a role in the repair of alveolar lung injury found in BPD and in the restoration of distal lung cell epithelia. This work highlights the potential important role of endogenous lung stem cells in the repair of chronic lung diseases. PMID:22328358

  7. The role of temperature increase rate in combinational hyperthermia chemotherapy treatment

    NASA Astrophysics Data System (ADS)

    Tang, Yuan; McGoron, Anthony J.

    2010-02-01

    Hyperthermia in combination with chemotherapy has been widely used in cancer treatment. Our previous study has shown that rapid rate hyperthermia in combination with chemotherapy can synergistically kill cancer cells whereas a sub-additive effect was found when a slow rate hyperthermia was applied. In this study, we explored the basis of this difference. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. P-glycoprotein (P-gp) expression, Caspase 3 activity, and heat shock protein 70 (HSP 70) expression following the two different modes of heating were measured. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. Slow rate hyperthermia was provided by a cell culture incubator. Two sets of thermal doses were delivered by either slow rate or rapid rate hyperthermia. HSP70 expression was highly elevated under low dose slow rate incubator hyperthermia while maintained at the baseline level under the other three treatments. Caspase3 level slightly increased after low dose slow rate incubator hyperthermia while necrotic cell death was found in the other three types of heat treatment. In conclusion, when given at the same thermal dose, slow rate hyperthermia is more likely to induce thermotolerance. Meanwhile, hyperthermia showed a dose dependent capability in reversing P-gp mediated MDR; when MDR is reversed, the combinational treatment induced extensive necrotic cell death. During this process, the rate of heating also played a very important role; necrosis was more dramatic in rapid rate hyperthermia than in slow rate hyperthermia even though they were given at the same dose.

  8. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.

    PubMed

    Hove, Michael J; Keller, Peter E

    2015-03-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  9. Quantifying the value of reduced lead time and increased delivery frequency

    E-print Network

    Walkenhorst, Joseph Sean

    2007-01-01

    A large consumer package goods company would like to know the answer to the following question. What is the value to its customers of increased delivery frequency or reduced lead time? To answer this question, we collected ...

  10. Use and abuse of clinical trials. Is the timing of treatment critical?

    PubMed

    Tognoni, G

    1994-01-01

    The timing of treatment for any condition is dependent on the underlying pathophysiology. One of the issues to consider is whether decreasing the time to intervention can be translated into recognisable benefits. Key data have been generated over the last 10 years which are relevant to the treatment of acute myocardial infarction (MI), including results of the large-scale 'mega-trials' in broad population groups. The therapeutic interventions which will be considered here are beta blockers, aspirin, thrombolytics and angiotensin-converting enzyme (ACE) inhibitors. Of these, aspirin seems to be the least time-dependent, provided it is administered within 12-24 h of symptom onset. Mortality benefits associated with beta blocker therapy increase as the time of administration from symptom onset is reduced and the extent to which thrombolytic therapy is beneficial is also clearly time dependent. The results from GISSI-3 and ISIS-4, which recruited a broader patient population than in previous trials, were concordant, showing a significant improvement in survival after five to six weeks' treatment. The message from GISSI-3 was that administration of ACE inhibitors within 24 h of symptom onset will improve survival and left ventricular function provided patients are hemodynamically stable, are not hypotensive and have no renal dysfunction; 76 lives were saved (representing an 11% risk reduction in mortality) after six weeks' lisinopril treatment, 54 of which were saved in the first five days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7743538

  11. Evaluating sedimentation problems in activated sludge treatment plants operating at complete sludge retention time.

    PubMed

    Amanatidou, Elisavet; Samiotis, Georgios; Trikoilidou, Eleni; Pekridis, George; Taousanidis, Nikolaos

    2015-02-01

    Zero net sludge growth can be achieved by complete retention of solids in activated sludge wastewater treatment, especially in high strength and biodegradable wastewaters. When increasing the solids retention time, MLSS and MLVSS concentrations reach a plateau phase and observed growth yields values tend to zero (Yobs ? 0). In this work, in order to evaluate sedimentation problems arised due to high MLSS concentrations and complete sludge retention operational conditions, two identical innovative slaughterhouse wastewater treatment plants were studied. Measurements of wastewaters' quality characteristics, treatment plant's operational conditions, sludge microscopic analysis and state point analysis were conducted. Results have shown that low COD/Nitrogen ratios increase sludge bulking and flotation phenomena due to accidental denitrification in clarifiers. High return activated sludge rate is essential in complete retention systems as it reduces sludge condensation and hydraulic retention time in the clarifiers. Under certain operational conditions sludge loading rates can greatly exceed literature limit values. The presented methodology is a useful tool for estimation of sedimentation problems encountered in activated sludge wastewater treatment plants with complete retention time. PMID:25463928

  12. 20 CFR 261.10 - Increase in future benefits where time period for reopening has expired.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Increase in future benefits where time period for reopening has expired. 261.10 Section 261.10 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ADMINISTRATIVE FINALITY § 261.10 Increase in future...

  13. 20 CFR 261.10 - Increase in future benefits where time period for reopening has expired.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Increase in future benefits where time period for reopening has expired. 261.10 Section 261.10 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ADMINISTRATIVE FINALITY § 261.10 Increase in future...

  14. 20 CFR 261.10 - Increase in future benefits where time period for reopening has expired.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Increase in future benefits where time period for reopening has expired. 261.10 Section 261.10 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ADMINISTRATIVE FINALITY § 261.10 Increase in future...

  15. Covariate Adjustment Strategy Increases Power in the Randomized Controlled Trial With Discrete-Time Survival Endpoints

    ERIC Educational Resources Information Center

    Safarkhani, Maryam; Moerbeek, Mirjam

    2013-01-01

    In a randomized controlled trial, a decision needs to be made about the total number of subjects for adequate statistical power. One way to increase the power of a trial is by including a predictive covariate in the model. In this article, the effects of various covariate adjustment strategies on increasing the power is studied for discrete-time

  16. Increasing On-Task Behavior Using Teacher Attention Delivered on a Fixed-Time Schedule

    ERIC Educational Resources Information Center

    Riley, Jessica L.; McKevitt, Brian C.; Shriver, Mark D.; Allen, Keith D.

    2011-01-01

    The effectiveness of fixed-time delivery of attention to increase the on-task behavior of 2 students in general education was examined. The teacher in this study provided attention to students on a 5-min fixed-time schedule and responded to students in her typical manner between cued intervals. An ABAB withdrawal design was used to test the…

  17. Time Delay Embedding Increases Estimation Precision of Models of Intraindividual Variability

    ERIC Educational Resources Information Center

    von Oertzen, Timo; Boker, Steven M.

    2010-01-01

    This paper investigates the precision of parameters estimated from local samples of time dependent functions. We find that "time delay embedding," i.e., structuring data prior to analysis by constructing a data matrix of overlapping samples, increases the precision of parameter estimates and in turn statistical power compared to standard…

  18. A system for EPID-based real-time treatment delivery verification during dynamic IMRT treatment

    SciTech Connect

    Fuangrod, Todsaporn; Woodruff, Henry C.; O’Connor, Daryl J.; Uytven, Eric van; McCurdy, Boyd M. C.; Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba R3T 2N2; Department of Radiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2 ; Kuncic, Zdenka; Greer, Peter B.

    2013-09-15

    Purpose: To design and develop a real-time electronic portal imaging device (EPID)-based delivery verification system for dynamic intensity modulated radiation therapy (IMRT) which enables detection of gross treatment delivery errors before delivery of substantial radiation to the patient.Methods: The system utilizes a comprehensive physics-based model to generate a series of predicted transit EPID image frames as a reference dataset and compares these to measured EPID frames acquired during treatment. The two datasets are using MLC aperture comparison and cumulative signal checking techniques. The system operation in real-time was simulated offline using previously acquired images for 19 IMRT patient deliveries with both frame-by-frame comparison and cumulative frame comparison. Simulated error case studies were used to demonstrate the system sensitivity and performance.Results: The accuracy of the synchronization method was shown to agree within two control points which corresponds to approximately ?1% of the total MU to be delivered for dynamic IMRT. The system achieved mean real-time gamma results for frame-by-frame analysis of 86.6% and 89.0% for 3%, 3 mm and 4%, 4 mm criteria, respectively, and 97.9% and 98.6% for cumulative gamma analysis. The system can detect a 10% MU error using 3%, 3 mm criteria within approximately 10 s. The EPID-based real-time delivery verification system successfully detected simulated gross errors introduced into patient plan deliveries in near real-time (within 0.1 s).Conclusions: A real-time radiation delivery verification system for dynamic IMRT has been demonstrated that is designed to prevent major mistreatments in modern radiation therapy.

  19. Effect of enzyme concentration, addition of water and incubation time on increase in yield of starch from potato.

    PubMed

    Sit, Nandan; Agrawal, U S; Deka, Sankar C

    2014-05-01

    Enzymatic treatment process for starch extraction from potato was investigated using cellulase enzyme and compared with conventional process. The effects of three parameters, cellulase enzyme concentration, incubation time and addition of water were evaluated for increase in starch yield as compared to the conventional process i.e., without using enzyme. A two-level full factorial design was used to study the process. The results indicated that all the main parameters and their interactions are statistically significant. Enzyme concentration and incubation time had a positive effect on the increase in starch yield while addition of water had a negative effect. The increase in starch yield ranged from 1.9% at low enzyme concentration and incubation time and high addition of water to a maximum of 70% increase from conventional process in starch yield was achieved when enzyme concentration and incubation time were high and addition of water was low suggesting water present in the ground potato meal is sufficient for access to the enzyme with in the slurry ensuring adequate contact with the substrate. PMID:24803713

  20. Economic evaluation of the photo-Fenton process. Mineralization level and reaction time: the keys for increasing plant efficiency.

    PubMed

    Santos-Juanes Jordá, L; Ballesteros Martín, M M; Ortega Gómez, E; Cabrera Reina, A; Román Sánchez, I M; Casas López, J L; Sánchez Pérez, J A

    2011-02-28

    The use of the solar photo-Fenton process is proposed to degrade Paracetamol in water in order to form biodegradable reaction intermediates which can be finally removed with a downstream biological treatment. Firstly, biodegradability enhancement with photo-Fenton treatment time has been evaluated; the minimum mineralization level should be at least 18.6% where Paracetamol has been degraded and biodegradability efficiency is higher than 40%. 20 mg L(-1) of Fe(2+) and 200 mg L(-1) of H(2)O(2) were selected in a lab-scale study looking at Paracetamol's degradation rate and organic carbon mineralization rate. As a result of scaling up the process at a pilot plant, 157.5 mg L(-1) of Paracetamol (?1 mM) was treated in 25 min of photo-Fenton treatment achieving the desired biodegradability. A further economic evaluation shows how the proposed treatment strategy markedly increases plant efficiency, resulting in an 83.33% reduction in reagent cost and a 79.11% reduction in costs associated with reaction time. Total cost is reduced from 3.4502 €/m(3) to 0.7392 €/m(3). PMID:21232848

  1. Mung Bean Nuclease Treatment Increases Capture Specificity of Microdroplet-PCR Based Targeted DNA Enrichment

    PubMed Central

    Yu, Zhenming; Cao, Kajia; Tischler, Tanya; Stolle, Catherine A.; Santani, Avni B.

    2014-01-01

    Targeted DNA enrichment coupled with next generation sequencing has been increasingly used for interrogation of select sub-genomic regions at high depth of coverage in a cost effective manner. Specificity measured by on-target efficiency is a key performance metric for target enrichment. Non-specific capture leads to off-target reads, resulting in waste of sequencing throughput on irrelevant regions. Microdroplet-PCR allows simultaneous amplification of up to thousands of regions in the genome and is among the most commonly used strategies for target enrichment. Here we show that carryover of single-stranded template genomic DNA from microdroplet-PCR constitutes a major contributing factor for off-target reads in the resultant libraries. Moreover, treatment of microdroplet-PCR enrichment products with a nuclease specific to single-stranded DNA alleviates off-target load and improves enrichment specificity. We propose that nuclease treatment of enrichment products should be incorporated in the workflow of targeted sequencing using microdroplet-PCR for target capture. These findings may have a broad impact on other PCR based applications for which removal of template DNA is beneficial. PMID:25058678

  2. Mung bean nuclease treatment increases capture specificity of microdroplet-PCR based targeted DNA enrichment.

    PubMed

    Yu, Zhenming; Cao, Kajia; Tischler, Tanya; Stolle, Catherine A; Santani, Avni B

    2014-01-01

    Targeted DNA enrichment coupled with next generation sequencing has been increasingly used for interrogation of select sub-genomic regions at high depth of coverage in a cost effective manner. Specificity measured by on-target efficiency is a key performance metric for target enrichment. Non-specific capture leads to off-target reads, resulting in waste of sequencing throughput on irrelevant regions. Microdroplet-PCR allows simultaneous amplification of up to thousands of regions in the genome and is among the most commonly used strategies for target enrichment. Here we show that carryover of single-stranded template genomic DNA from microdroplet-PCR constitutes a major contributing factor for off-target reads in the resultant libraries. Moreover, treatment of microdroplet-PCR enrichment products with a nuclease specific to single-stranded DNA alleviates off-target load and improves enrichment specificity. We propose that nuclease treatment of enrichment products should be incorporated in the workflow of targeted sequencing using microdroplet-PCR for target capture. These findings may have a broad impact on other PCR based applications for which removal of template DNA is beneficial. PMID:25058678

  3. SIMVASTATIN TREATMENT ATTENUATES INCREASED RESPIRATORY VARIABILITY AND APNEA/HYPOPNEA INDEX IN RATS WITH CHRONIC HEART FAILURE RR

    PubMed Central

    Haack, Karla K.V.; Marcus, Noah J.; Rio, Rodrigo Del; Zucker, Irving H.; Schultz, Harold D.

    2014-01-01

    Cheyne-Stokes respiration (CSR) and cardiac arrhythmias are associated with increased morbidity and mortality in patients with congestive heart failure (CHF). Enhanced carotid body chemoreflex (CBC) sensitivity is associated with these abnormalities in CHF. Reduced carotid body nitric oxide and nitric oxide synthase (NOS) levels play an important role in the enhanced CBC. In other disease models, Simvastatin (statin) treatment increases endothelial NOS (eNOS) in part by increasing Kruppel like Factor 2 (KLF2) expression. We hypothesized that statin treatment would ameliorate enhanced CBC sensitivity as well as increased respiratory variability (RV), apnea/hypopnea index (AHI), and arrhythmia index (AI), in a rodent model of CHF. Resting breathing pattern, cardiac rhythm, and the ventilatory and carotid body (CB) chemoreceptor afferent responses to hypoxia (CBC) were assessed in rats with CHF induced by coronary ligation. CHF was associated with enhanced ventilatory and CB afferent responses to hypoxia as well as increased RV, AHI, and AI. Statin treatment prevented the increases in CBC sensitivity and the concomitant increases in RV, AHI, and AI. KLF2 and eNOS protein were decreased in the CB and nucleus tractus solitarii (NTS) of CHF animals and statin treatment increased the expression of these proteins. Our findings demonstrate that the increased CBC sensitivity, respiratory instability and cardiac arrhythmias observed in CHF are ameliorated by statin treatment and suggest that statins may be an effective treatment for CSR and arrhythmias in patient populations with high chemoreflex sensitivity. PMID:24516105

  4. Obesity increases operating room times in patients undergoing primary hip arthroplasty: a retrospective cohort analysis

    PubMed Central

    Kadry, Bassam; Press, Christopher D.; Alosh, Hassan; Opper, Isaac M.; Orsini, Joe; Popov, Igor A.; Macario, Alex

    2014-01-01

    Background. Obesity impacts utilization of healthcare resources. The goal of this study was to measure the relationship between increasing body mass index (BMI) in patients undergoing total hip arthroplasty (THA) with different components of operating room (OR) time. Methods. The Stanford Translational Research Integrated Database Environment (STRIDE) was utilized to identify all ASA PS 2 or 3 patients who underwent primary THA at Stanford Medical Center from February 1, 2008 through January 1, 2013. Patients were divided into five groups based on the BMI weight classification. Regression analysis was used to quantify relationships between BMI and the different components of total OR time. Results. 1,332 patients were included in the study. There were no statistically significant differences in age, gender, height, and ASA PS classification between the BMI groups. Normal-weight patients had a total OR time of 138.9 min compared 167.9 min (P < 0.001) for morbidly obese patients. At a BMI > 35 kg/m2 each incremental BMI unit increase was associated with greater incremental total OR time increases. Conclusion. Morbidly obese patients required significantly more total OR time than normal-weight patients undergoing a THA procedure. This increase in time is relevant when scheduling obese patients for surgery and has an important impact on health resource utilization. PMID:25210656

  5. UV/H(2)O(2) treatment of drinking water increases post-chlorination DBP formation.

    PubMed

    Dotson, Aaron D; Keen, Volha Olya S; Metz, Debbie; Linden, Karl G

    2010-06-01

    Ultraviolet (UV) irradiation has become popular as a primary disinfectant because it is very effective against Cryptosporidium and does not directly form regulated disinfection by-products. Higher UV doses and UV advanced oxidation (UV/H2O2) processes are under consideration for the treatment of trace organic pollutants (e.g. pharmaceuticals, personal care products). Despite the disinfection effectiveness of UV light, a secondary disinfectant capable of maintaining a distribution system residual is required to meet current U.S. regulation. This study investigated changes in disinfection by-product (DBP) formation attributed to UV or UV/H2O2 followed by application of free chlorine to quench hydrogen peroxide and provide residual disinfectant. At a UV dose of 1000 mJ/cm(2), trihalomethane (THM) yield increased by up to 4 microg/mg-C and 13 microg/mg-C when treated with low and medium pressure UV, respectively. With the addition of hydrogen peroxide, THM yield increased by up to 25 microg/mg-C (5mg-H2O2/L) and 37 microg/mg-C (10 mg-H2O2/L). Although no changes in DBPs are expected during UV disinfection, application of UV advanced oxidation followed by chlorine addition was assessed with regard to impacts on DBP formation. PMID:20471054

  6. Increasing Whole Grain Intake as Part of Prevention and Treatment of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Ross, Alastair B.; Godin, Jean-Philippe; Minehira, Kaori; Kirwan, John P.

    2013-01-01

    In conjunction with the rise in rates of obesity, there has been an increase in the rate of nonalcoholic fatty liver disease (NAFLD). While NAFLD at least partially originates from poor diet, there is a lack of nutritional recommendations for patients with suspected or confirmed diagnosis of NAFLD, beyond eating a healthy diet, increasing physical activity, and emphasising weight loss. The limited current literature suggests that there may be opportunities to provide more tailored dietary advice for people diagnosed with or at risk of NAFLD. Epidemiological studies consistently find associations between whole grain intake and a reduced risk of obesity and related diseases, yet no work has been done on the potential of whole grains to prevent and/or be a part of the treatment for fatty liver diseases. In this review, we examine the potential and the current evidence for whole grains having an impact on NAFLD. Due to their nutrient and phytochemical composition, switching from consuming mainly refined grains to whole grains should be considered as part of the nutritional guidelines for patients diagnosed with or at risk for fatty liver disease. PMID:23762052

  7. Shortening treatment time in robotic radiosurgery using a novel node reduction technique

    SciTech Connect

    Water, Steven van de; Hoogeman, Mischa S.; Breedveld, Sebastiaan; Heijmen, Ben J. M.

    2011-03-15

    Purpose: The fraction duration of robotic radiosurgery treatments can be reduced by generating more time-efficient treatment plans with a reduced number of node positions, beams, and monitor units (MUs). Node positions are preprogramed locations where the robot can position the focal spot of the x-ray beam. As the time needed for the robot to travel between node positions takes up a large part of the treatment time, the aim of this study was to develop and evaluate a node reduction technique in order to reduce the treatment time per fraction for robotic radiosurgery. Methods: Node reduction was integrated into the inverse planning algorithm, developed in-house for the robotic radiosurgery modality. It involved repeated inverse optimization, each iteration excluding low-contribution node positions from the planning and resampling new candidate beams from the remaining node positions. Node reduction was performed until the exclusion of a single node position caused a constraint violation, after which the shortest treatment plan was selected retrospectively. Treatment plans were generated with and without node reduction for two lung cases of different complexity, one oropharyngeal case and one prostate case. Plan quality was assessed using the number of node positions, beams and MUs, and the estimated treatment time per fraction. All treatment plans had to fulfill all clinical dose constraints. Extra constraints were added to maintain the low-dose conformality and restrict skin doses during node reduction. Results: Node reduction resulted in 12 residual node positions, on average (reduction by 77%), at the cost of an increase in the number of beams and total MUs of 28% and 9%, respectively. Overall fraction durations (excluding patient setup) were shortened by 25% (range of 18%-40%), on average. Dose distributions changed only little and dose in low-dose regions was effectively restricted by the additional constraints. Conclusions: The fraction duration of robotic radiosurgery treatments can be reduced considerably by node reduction with minimal changes in dosimetrical plan quality. Additional constraints are required to guarantee low-dose conformality and to avoid unacceptable skin dose.

  8. Analysis of a High-Probability Instructional Sequence and Time-Out in the Treatment of Child Noncompliance.

    ERIC Educational Resources Information Center

    Rortvedt, Angela K.; Miltenberger, Raymond G.

    1994-01-01

    This study evaluated the effectiveness of high probability requests and time-out as treatments for noncompliance which appeared to be maintained by contingent attention in two developmentally normal children. The introduction of high-probability requests increased compliance for one child but not the other. Time-out was effective with both…

  9. DPP-4 inhibitor des-F-sitagliptin treatment increased insulin exocytosis from db/db mice {beta} cells

    SciTech Connect

    Nagamatsu, Shinya; Ohara-Imaizumi, Mica; Nakamichi, Yoko; Aoyagi, Kyota; Nishiwaki, Chiyono

    2011-09-09

    Highlights: {yields} Anti-diabetic new drug, DPP-4 inhibitor, can affect the insulin exocytosis. {yields} DPP-4 inhibitor treatment altered syntaxin 1 expression. {yields} Treatment of db/db mice with DPP-4 inhibitor increased insulin release. -- Abstract: Incretin promotes insulin secretion acutely. Recently, orally-administered DPP-4 inhibitors represent a new class of anti-hyperglycemic agents. Indeed, inhibitors of dipeptidyl peptidase-IV (DPP-4), sitagliptin, has just begun to be widely used as therapeutics for type 2 diabetes. However, the effects of sitagliptin-treatment on insulin exocytosis from single {beta}-cells are yet unknown. We therefore investigated how sitagliptin-treatment in db/db mice affects insulin exocytosis by treating db/db mice with des-F-sitagliptin for 2 weeks. Perfusion studies showed that 2 weeks-sitagliptin treatment potentiated insulin secretion. We then analyzed insulin granule motion and SNARE protein, syntaxin 1, by TIRF imaging system. TIRF imaging of insulin exocytosis showed the increased number of docked insulin granules and increased fusion events from them during first-phase release. In accord with insulin exocytosis data, des-F-sitagliptin-treatment increased the number of syntaxin 1 clusters on the plasma membrane. Thus, our data demonstrated that 2-weeks des-F-sitagliptin-treatment increased the fusion events of insulin granules, probably via increased number of docked insulin granules and that of syntaxin 1 clusters.

  10. E. E#ects On Time and Quality of Learning with Increasing the Number of Variables

    E-print Network

    Brown, Laura E.

    44 E. E#ects On Time and Quality of Learning with Increasing the Number of Variables E.1. Effect on Greedy Search of increasing the number of variables 0 100 200 300 400 500 600 10 -1 10 0 10 1 10 2 NumberFinder 0 100 200 300 400 500 600 0 1 2 3 4 5 6 7 Number of Variables in Network Norm. SHD of GS Norm. SHD

  11. Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia

    PubMed Central

    Schirmbeck, Frederike; Mier, Daniela; Esslinger, Christine; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias

    2015-01-01

    Background Patients with schizophrenia have an approximately 10-fold higher risk for obsessive–compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. Methods To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. Results We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. Limitations The main limitation of this study is its cross-sectional design. Conclusion To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations. PMID:25268790

  12. Pluronic modified leptin with increased systemic circulation, brain uptake and efficacy for treatment of obesity?

    PubMed Central

    Yi, Xiang; Yuan, Dongfen; Farr, Susan A.; Banks, William A.; Poon, Chi-Duen; Kabanov, Alexander V.

    2014-01-01

    Modification of hydrophilic proteins with amphiphilic block copolymers capable of crossing cell membranes is a new strategy to improve protein delivery to the brain. Leptin, a candidate for the treatment of epidemic obesity, has failed in part because of impairment in its transport across the blood–brain barrier (BBB) that develops with obesity. We posit that modification of leptin with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly (ethylene oxide), Pluronic P85 (P85) might permit this protein to penetrate the BBB independently of its transporter, thereby overcoming peripheral leptin resistance. Here we report that peripherally administered leptin–P85 conjugates exhibit biological activity by reducing food intake in mouse models of obesity (ob/ob, and diet-induced obese mouse). We further generated two new leptin–P85 conjugates: one, Lep(ss)–P85(L), containing one P85 chain and another, Lep(ss)–P85(H), containing multiple P85 chains. We report data on their purification, analytical characterization, peripheral and brain pharmacokinetics (PK). Lep(ss)–P85(L) crosses the BBB using the leptin transporter, and exhibits improved peripheral PK along with increased accumulation in the brain compared to unmodified leptin. Lep(ss)–P85(H) also has improved peripheral PK but in a striking difference to the first conjugate penetrates the BBB independently of the leptin transporter via a non-saturable mechanism. The results demonstrate that leptin analogs can be developed through chemical modification of the native leptin with P85 to overcome leptin resistance at the level of the BBB, thus improving the potential for the treatment of obesity. PMID:24881856

  13. Channel Design to Increase Wastewater Treatment Wetland Capacity and Connectivity in Stockton, CA

    E-print Network

    Cubbison, Erin O.

    2006-01-01

    daily monitoring of water levels and control structures,level of treatment, removal of “suspended solids, biochemical oxygen demand, and ammonia-nitrogen” (Frank, Treatment, 1), which faster moving water

  14. Federal Parity Law Associated With Increased Probability Of Using Out-Of-Network Substance Use Disorder Treatment Services

    PubMed Central

    McGinty, Emma E.; Busch, Susan H.; Stuart, Elizabeth A.; Huskamp, Haiden A.; Gibson, Teresa B.; Goldman, Howard H.; Barry, Colleen L.

    2015-01-01

    The Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 requires commercial insurers providing group coverage for substance use disorder services to offer benefits for those services at a level equal to those for medical or surgical benefits. Unlike previous parity policies instituted for federal employees and in individual states, the law extends parity to out-of-network services. We conducted an interrupted time-series analysis using insurance claims from large self-insured employers to evaluate whether federal parity was associated with changes in out-of-network treatment for 525,620 users of substance use disorder services. Federal parity was associated with an increased probability of using out-of-network services, an increased average number of out-of-network outpatient visits, and increased average total spending on out-of-network services among users of those services. Our findings were broadly consistent with the contention of federal parity proponents that extending parity to out-of-network services would broaden access to substance use disorder care obtained outside of plan networks. PMID:26240247

  15. Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma

    PubMed Central

    Ludwig, Heinz; Adam, Zdenek; Tóthová, Elena; Hajek, Roman; Labar, Boris; Egyed, Miklós; Spicka, Ivan; Gisslinger, Heinz; Drach, Johannes; Kuhn, Ingrid; Hinke, Axel; Zojer, Niklas

    2010-01-01

    Background Thalidomide maintenance therapy after stem cell transplantation resulted in increased progression-free survival and overall survival in a few trials, but its role in non-transplant eligible patients with multiple myeloma remains unclear. This study assessed the impact of thalidomide-interferon in comparison to interferon maintenance therapy in elderly patients with multiple myeloma. Design and Methods Of 289 elderly patients with multiple myeloma who were randomized to thalidomide-dexamethasone or melphalan-prednisolone induction therapy, 137 finally completed 9 cycles of induction therapy with stable disease or better and thereby qualified for maintenance treatment. Of these, 128 have been randomized to either thalidomide-interferon or interferon alone. Primary study endpoints were progression-free survival and response rates; secondary endpoints were overall survival, toxicity and quality of life. Results Thalidomide-interferon maintenance therapy led to a significantly longer progression-free survival compared to interferon (27.7 vs. 13.2 months, P=0.0068), but overall survival was similar in both groups (52.6 vs. 51.4 months, P=0.81) and did not differ between patients aged 75 years or older, or younger patients (P=0.39). Survival after disease progression tended to be shorter in patients on thalidomide-interferon maintenance therapy (P=0.056). Progression-free survival and overall survival tended to be shorter in patients with adverse cytogenetic (FISH) findings compared to the standard risk group but differences were not significant (P=0.084 and P=0.082, respectively). Patients on thalidomide-interferon presented with more neuropathy (P=0.0015), constipation (P=0.0004), skin toxicity (P=0.0041) and elevated creatinine (P=0.026). Conclusions Thalidomide plus interferon maintenance therapy increased progression-free survival but not overall survival and was associated with slightly more toxicity than maintenance with interferon alone. (ClinicalTrials.gov Identifier: NCT00205751). PMID:20418244

  16. Improving Reading Achievement Through Increased Motivation, Specific Skill Enhancement, and Practice Time for Elementary Students

    ERIC Educational Resources Information Center

    Ecklund, Britt K.; Lamon, Kathryn M.

    2008-01-01

    The action research project report began when the teacher researchers determined that students at Sites A and B struggled with reading achievement. The purpose of the project was to improve students' reading achievement through increased motivation, specific skill instruction, and additional practice time. The project involved 26 students: 17…

  17. Federal Rule Yields Hope for Science: Testing Mandate Is Expected to Increase Time for Subject

    ERIC Educational Resources Information Center

    Cavanagh, Sean

    2007-01-01

    Some proponents of science education say they have faced no greater foe over the past few years than federally mandated tests in reading and mathematics, which have forced teachers to devote increasingly bigger chunks of class time to building students' skills in those two subjects. But if testing has squeezed science out, can testing also bring…

  18. Increasing temperature forcing reduces the Greenland Ice Sheet's response time scale

    NASA Astrophysics Data System (ADS)

    Applegate, Patrick J.; Parizek, Byron R.; Nicholas, Robert E.; Alley, Richard B.; Keller, Klaus

    2015-10-01

    Damages from sea level rise, as well as strategies to manage the associated risk, hinge critically on the time scale and eventual magnitude of sea level rise. Satellite observations and paleo-data suggest that the Greenland Ice Sheet (GIS) loses mass in response to increased temperatures, and may thus contribute substantially to sea level rise as anthropogenic climate change progresses. The time scale of GIS mass loss and sea level rise are deeply uncertain, and are often assumed to be constant. However, previous ice sheet modeling studies have shown that the time scale of GIS response likely decreases strongly with increasing temperature anomaly. Here, we map the relationship between temperature anomaly and the time scale of GIS response, by perturbing a calibrated, three-dimensional model of GIS behavior. Additional simulations with a profile, higher-order, ice sheet model yield time scales that are broadly consistent with those obtained using the three-dimensional model, and shed light on the feedbacks in the ice sheet system that cause the time scale shortening. Semi-empirical modeling studies that assume a constant time scale of sea level adjustment, and are calibrated to small preanthropogenic temperature and sea level changes, may underestimate future sea level rise. Our analysis suggests that the benefits of reducing greenhouse gas emissions, in terms of avoided sea level rise from the GIS, may be greatest if emissions reductions begin before large temperature increases have been realized. Reducing anthropogenic climate change may also allow more time for design and deployment of risk management strategies by slowing sea level contributions from the GIS.

  19. Increased Physical Activity Not Decreased Energy Intake Is Associated with Inpatient Medical Treatment for Anorexia Nervosa in Adolescent Females

    PubMed Central

    Higgins, Janine; Hagman, Jennifer; Pan, Zhaoxing; MacLean, Paul

    2013-01-01

    There is a dearth of data regarding changes in dietary intake and physical activity over time that lead to inpatient medical treatment for anorexia nervosa (AN). Without such data, more effective nutritional therapies for patients cannot be devised. This study was undertaken to describe changes in diet and physical activity that precede inpatient medical hospitalization for AN in female adolescents. This data can be used to understand factors contributing to medical instability in AN, and may advance rodent models of AN to investigate novel weight restoration strategies. It was hypothesized that hospitalization for AN would be associated with progressive energy restriction and increased physical activity over time. 20 females, 11–19 years (14.3±1.8 years), with restricting type AN, completed retrospective, self-report questionnaires to assess dietary intake and physical activity over the 6 month period prior to inpatient admission (food frequency questionnaire, Pediatric physical activity recall) and 1 week prior (24 hour food recall, modifiable activity questionnaire). Physical activity increased acutely prior to inpatient admission without any change in energy or macronutrient intake. However, there were significant changes in reported micronutrient intake causing inadequate intake of Vitamin A, Vitamin D, and pantothenic acid at 1 week versus high, potentially harmful, intake of Vitamin A over 6 months prior to admission. Subject report of significantly increased physical activity, not decreased energy intake, were associated with medical hospitalization for AN. Physical activity and Vitamin A and D intake should be carefully monitored following initial AN diagnosis, as markers of disease progression as to potentially minimize the risk of medical instability. PMID:23637854

  20. Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Wang Li; Correa, Candace R.; Hayman, James A.; Zhao Lujun; Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P.; Kong, F.-M.

    2009-07-01

    Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived {>=} 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

  1. Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking.

    PubMed

    Levin, E D; Westman, E C; Stein, R M; Carnahan, E; Sanchez, M; Herman, S; Behm, F M; Rose, J E

    1994-02-01

    A variety of studies have shown that nicotine skin patches are effective in promoting smoking cessation. This study replicated this effect, in addition, nicotine skin patches were found to decrease a variety of withdrawal effects, including craving for cigarettes, negative affect, hypoarousal, and increased appetite. This study also assessed the depressive symptoms shown by smokers before and after they quit smoking. Control subjects showed a significant increase in depressive symptoms after smoking cessation, whereas the subjects given the nicotine skin patch were not as affected. If the subjects slipped and smoked a cigarette during the time they were wearing the patch, they were asked to rate the effects of that cigarette. These "slip" cigarettes were rated significantly lower in satisfaction and good taste by subjects in the nicotine patch group than by controls. The nicotine skin patch may improve smoking cessation rates both by reducing nicotine withdrawal effects and by reducing the reward of slips back to smoking. This latter effect may prove to be effective in preventing slips from turning into relapses. PMID:8151002

  2. Causal Effects of Time-Dependent Treatments in Older Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Akushevich, Igor; Arbeev, Konstantin; Kravchenko, Julia; Berry, Mark

    2015-01-01

    Background Treatment selection for elderly patients with lung cancer must balance the benefits of curative/life-prolonging therapy and the risks of increased mortality due to comorbidities. Lung cancer trials generally exclude patients with comorbidities and current treatment guidelines do not specifically consider comorbidities, so treatment decisions are usually made on subjective individual-case basis. Methods Impacts of surgery, radiation, and chemotherapy mono-treatment as well as combined chemo/radiation on one-year overall survival (compared to no-treatment) are studied for stage-specific lung cancer in 65+ y.o. patients. Methods of causal inference such as propensity score with inverse probability weighting (IPW) for time-independent and marginal structural model (MSM) for time-dependent treatments are applied to SEER-Medicare data considering the presence of comorbid diseases. Results 122,822 patients with stage I (26.8%), II (4.5%), IIIa (11.5%), IIIb (19.9%), and IV (37.4%) lung cancer were selected. Younger age, smaller tumor size, and fewer baseline comorbidities predict better survival. Impacts of radio- and chemotherapy increased and impact of surgery decreased with more advanced cancer stages. The effects of all therapies became weaker after adjustment for selection bias, however, the changes in the effects were minor likely due to the weak selection bias or incompleteness of the list of predictors that impacted treatment choice. MSM provides more realistic estimates of treatment effects than the IPW approach for time-independent treatment. Conclusions Causal inference methods provide substantive results on treatment choice and survival of older lung cancer patients with realistic expectations of potential benefits of specific treatments. Applications of these models to specific subsets of patients can aid in the development of practical guidelines that help optimize lung cancer treatment based on individual patient characteristics. PMID:25849715

  3. Reducing Adolescents' Perceived Barriers to Treatment and Increasing Help-Seeking Intentions: Effects of Classroom Presentations by General Practitioners

    ERIC Educational Resources Information Center

    Wilson, Coralie Joy; Deane, Frank P.; Marshall, Kellie L.; Dalley, Andrew

    2008-01-01

    The "Building Bridges to General Practice" (BBGP) program is an outreach initiative. It aims to reduce young peoples' perceived knowledge- and belief-based barriers to engaging in treatment and to increase their behavioral intentions to consult a general medical practitioner (GP) for physical and psychological problems. By increasing intentions,…

  4. The Timing of Exposure in Clinic-Based Treatment for Childhood Anxiety Disorders

    ERIC Educational Resources Information Center

    Gryczkowski, Michelle R.; Tiede, Michael S.; Dammann, Julie E.; Jacobsen, Amy Brown; Hale, Lisa R.; Whiteside, Stephen P. H.

    2013-01-01

    The present study examines treatment length and timing of exposure from two child anxiety disorders clinics. Data regarding symptoms and treatment characteristics for 28 youth were prospectively obtained through self, parent, and therapist report at each session. Information regarding length of treatment, timing of exposure initiation, and…

  5. A Semiquantitative Framework for Gene Regulatory Networks: Increasing the Time and Quantitative Resolution of Boolean Networks

    PubMed Central

    Kerkhofs, Johan; Geris, Liesbet

    2015-01-01

    Boolean models have been instrumental in predicting general features of gene networks and more recently also as explorative tools in specific biological applications. In this study we introduce a basic quantitative and a limited time resolution to a discrete (Boolean) framework. Quantitative resolution is improved through the employ of normalized variables in unison with an additive approach. Increased time resolution stems from the introduction of two distinct priority classes. Through the implementation of a previously published chondrocyte network and T helper cell network, we show that this addition of quantitative and time resolution broadens the scope of biological behaviour that can be captured by the models. Specifically, the quantitative resolution readily allows models to discern qualitative differences in dosage response to growth factors. The limited time resolution, in turn, can influence the reachability of attractors, delineating the likely long term system behaviour. Importantly, the information required for implementation of these features, such as the nature of an interaction, is typically obtainable from the literature. Nonetheless, a trade-off is always present between additional computational cost of this approach and the likelihood of extending the model’s scope. Indeed, in some cases the inclusion of these features does not yield additional insight. This framework, incorporating increased and readily available time and semi-quantitative resolution, can help in substantiating the litmus test of dynamics for gene networks, firstly by excluding unlikely dynamics and secondly by refining falsifiable predictions on qualitative behaviour. PMID:26067297

  6. Estimating safety performance trends over time for treatments at intersections in Florida.

    PubMed

    Wang, Jung-Han; Abdel-Aty, Mohamed A; Park, Juneyoung; Lee, Chris; Kuo, Pei-Fen

    2015-07-01

    Researchers have put great efforts in quantifying Crash Modification Factors (CMFs) for diversified treatment types. In the Highway Safety Manual (HSM), CMFs have been identified to predict safety effectiveness of converting a stop-controlled to a signal-controlled intersection (signalization) and installing Red Light Running Cameras (RLCs). Previous studies showed that both signalization and adding RLCs reduced angle crashes but increased rear-end crashes. However, some studies showed that CMFs varied over time after the treatment was implemented. Thus, the objective of this study is to investigate trends of CMFs for the signalization and adding RLCs over time. CMFs for the two treatments were measured in each month and 90-day moving windows respectively. The ARMA time series model was applied to predict trends of CMFs over time based on monthly variations in CMFs. The results of the signalization show that the CMFs for rear-end crashes were lower at the early phase after the signalization but gradually increased from the 9th month. On the other hand, the CMFs for angle crashes were higher at the early phase after adding RLCs but decreased after the 9th month and then became stable. It was also found that the CMFs for total and fatal/injury crashes after adding RLCs in the first 18 months were significantly greater than the CMFs in the following 18 months. This indicates that there was a lag effect of the treatments on safety performance. The results of the ARMA model show that the model can better predict trends of the CMFs for the signalization and adding RLCs when the CMFs are calculated in 90-day moving windows compared to the CMFs calculated in each month. In particular, the ARMA model predicted a significant safety effect of the signalization on reducing angle and left-turn crashes in the long term. Thus, it is recommended that the safety effects of the treatment be assessed using the ARMA model based on trends of CMFs in the long term after the implementation of the treatment. PMID:25866922

  7. Improving the Depth-Time Fit of Holocene Climate Proxy Measures by Increasing Coherence with a Reference Time-Series

    NASA Astrophysics Data System (ADS)

    Rahim, K. J.; Cumming, B. F.; Hallett, D. J.; Thomson, D. J.

    2007-12-01

    An accurate assessment of historical local Holocene data is important in making future climate predictions. Holocene climate is often obtained through proxy measures such as diatoms or pollen using radiocarbon dating. Wiggle Match Dating (WMD) uses an iterative least squares approach to tune a core with a large amount of 14C dates to the 14C calibration curve. This poster will present a new method of tuning a time series with when only a modest number of 14C dates are available. The method presented uses the multitaper spectral estimation, and it specifically makes use of a multitaper spectral coherence tuning technique. Holocene climate reconstructions are often based on a simple depth-time fit such as a linear interpolation, splines, or low order polynomials. Many of these models make use of only a small number of 14C dates, each of which is a point estimate with a significant variance. This technique attempts to tune the 14C dates to a reference series, such as tree rings, varves, or the radiocarbon calibration curve. The amount of 14C in the atmosphere is not constant, and a significant source of variance is solar activity. A decrease in solar activity coincides with an increase in cosmogenic isotope production, and an increase in cosmogenic isotope production coincides with a decrease in temperature. The method presented uses multitaper coherence estimates and adjusts the phase of the time series to line up significant line components with that of the reference series in attempt to obtain a better depth-time fit then the original model. Given recent concerns and demonstrations of the variation in estimated dates from radiocarbon labs, methods to confirm and tune the depth-time fit can aid climate reconstructions by improving and serving to confirm the accuracy of the underlying depth-time fit. Climate reconstructions can then be made on the improved depth-time fit. This poster presents a run though of this process using Chauvin Lake in the Canadian prairies and Mt. Barr Cirque Lake located in British Columbia as examples.

  8. Visualisation of blood and lymphatic vessels with increasing exposure time of the detector

    SciTech Connect

    Kalchenko, V V; Kuznetsov, Yu L; Meglinski, I V

    2013-07-31

    We describe the laser speckle contrast method for simultaneous noninvasive imaging of blood and lymphatic vessels of living organisms, based on increasing detector exposure time. In contrast to standard methods of fluorescent angiography, this technique of vascular bed imaging and lymphatic and blood vessel demarcation does not employ toxic fluorescent markers. The method is particularly promising with respect to the physiology of the cardiovascular system under in vivo conditions. (laser applications in biology and medicine)

  9. Visualisation of blood and lymphatic vessels with increasing exposure time of the detector

    NASA Astrophysics Data System (ADS)

    Kalchenko, V. V.; Kuznetsov, Yu L.; Meglinski, I. V.

    2013-07-01

    We describe the laser speckle contrast method for simultaneous noninvasive imaging of blood and lymphatic vessels of living organisms, based on increasing detector exposure time. In contrast to standard methods of fluorescent angiography, this technique of vascular bed imaging and lymphatic and blood vessel demarcation does not employ toxic fluorescent markers. The method is particularly promising with respect to the physiology of the cardiovascular system under in vivo conditions.

  10. 12 CFR 1024.34 - Timely escrow payments and treatment of escrow account balances.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...payments and treatment of escrow account balances. 1024.34 Section 1024.34 Banks...payments and treatment of escrow account balances. (a) Timely escrow disbursements...17(k). (b) Refund of escrow balance. (1) In general....

  11. Time intervals and associated factors of emergency treatment: first insight into Pakistani system.

    PubMed

    Noorani, Muhammad Muslim; Khaliq, Muhammad Farhan; Shoaib, Maria; Sheikh, Asfandyar; Moughal, Um-E-Roman; Moazzum, Wardah; Ali, Syed Arsalan

    2014-01-01

    The objective of this study is to determine the time interval from decision to seek medical help and arrival of the patients to the emergency department (ED). The duration of stay in ED was also calculated. This study also assesses factors responsible delayed presentation to hospital. This prospective study was conducted during day timings (9 am to 3 pm) from May 2012 to August 2012 in ED at Civil Hospital, Karachi. Patients older than 18 years and meeting the inclusion criteria were considered to be eligible for the study. Statistical analysis was done using SPSS version 17. The study sample consisted of 4,226 patients with a response rate of 96.5%. The median decision time was 146 minutes (IQR?=?74-339), median transit time was 84 minutes (IQR?=?42-188), median physician time was 58 minutes (IQR?=?47-103), median diagnostic time was 148 minutes (IQR?=?135-192), median transfer time was 155 minutes (IQR?=?118-274) and the median ED LOS was 327 minutes (IQR?=?209-488). Patient beliefs regarding spontaneous resolution of the symptoms was the most common reason (44.8%) cited for increased time spent in taking decision to seek medical help. Mode of transportation other than ambulance and traffic gridlock were the most common reasons found to be significantly associated with increased transit time (p?time intervals calculated from our study were found to be higher than studies reported from countries. This calls for urgent intervention for formulation of triage systems to improve patient treatment and satisfaction. PMID:25484915

  12. Chicory inulin does not increase stool weight or speed up intestinal transit time in healthy male subjects.

    PubMed

    Slavin, Joanne; Feirtag, Joellen

    2011-01-01

    Inulin is a non-digestible oligosaccharide classified as a prebiotic, a substrate that promotes the growth of certain beneficial microorganisms in the gut. We examined the effect of a 20 g day(-1) supplement of chicory inulin on stool weight, intestinal transit time, stool frequency and consistency, selected intestinal microorganisms and enzymes, fecal pH, short chain fatty acids and ammonia produced as by-products of bacterial fermentation. Twelve healthy male volunteers consumed a well-defined, controlled diet with and without a 20 g day(-1) supplement of chicory inulin (degree of polymerization (DP) ranging for 2-60), with each treatment lasting for 3 weeks in a randomized, double-blind crossover trial. Inulin was consumed in a low fat ice cream. No differences were found in flavor or appeal between the control and inulin-containing ice creams. Inulin consumption resulted in a significant increase in total anaerobes and Lactobacillus species and a significant decrease in ammonia levels and ?-glucuronidase activity. Flatulence increased significantly with the inulin treatment. No other significant differences were found in bowel function with the addition of inulin to the diet. Thus, inulin is easily incorporated into a food product and has no negative effects on food acceptability. Twenty grams of inulin was well tolerated, but had minimal effects on measures of laxation in healthy, human subjects. PMID:21773588

  13. Gonadotropin releasing hormone agonist treatment to increase final stature in children with precocious puberty: a meta-analysis.

    PubMed

    Li, Pin; Li, Yan; Yang, Chung-Lin

    2014-12-01

    In the setting of central precocious puberty (CPP), the motivation for hormonal intervention is to help the child to reach a taller adult stature than she would achieve otherwise. While gonadotropin-releasing hormone analogs (GnRHa) constitute an established treatment for improving adult stature in girls presenting with CPP up to age 6 (true precocious puberty), it is not yet clear whether or not the same is true in the setting of CPP presented in girls beyond age 6 (advance puberty). GnRHa may slow growth velocity, offsetting the anticipated improvement in final height that should have resulted from the increased time before growth plate fusion. Consequently, it's been suggested that growth hormone (GH) should be combined with GnRHa to improve the results.Few controlled prospective studies have been performed with GnRHa in children and many conclusions rely in part on collective expert opinion. Therefore, the literature was searched and relevant studies were selected using the search terms "gonadotropin releasing hormone agonist," "precocious puberty/early puberty," and "GnRH analogue." After selected articles were screened for relevance, the process yielded 8 studies, the results of which were then pooled in a meta-analysis aimed at evaluating the effects of GnRHa therapy both with and without added GH in the setting of early puberty. A significant difference was elucidated in final height and predicted adult height comparing GnRHa and combined GnRHa/GH groups. However, no significant difference was elucidated in final height standard deviation scores (SDS) and initial height SDS when comparing GnRHa and control groups. At the same time, the final analysis revealed no significant difference in final height SDS and initial height SDS when GnRHa and combined GnRHa/GH groups were compared.The results suggest GnRHa therapy may have a positive effect on final adult height in girls with early puberty, while adding GH to the treatment may suggest more advantage. Interpretation of the results requires extreme caution, given the complexity of the outcome analysis. Final height gain may prove to be a more appropriate measure of treatment efficacy in any case. PMID:25501098

  14. Long driving time is associated with haematological markers of increased cardiovascular risk in taxi drivers

    PubMed Central

    Chen, J; Chen, Y; Chang, W; Christiani, D

    2005-01-01

    Aims: To examine the association between driving time and changes in haematological markers of increased risks for cardiovascular diseases (CVD). Methods: The authors conducted a cross sectional analysis of baseline data from the Taxi Drivers' Health Study cohort in Taipei, Taiwan. They retrieved information on comorbidity, laboratory tests, age, and anthropometric measures from medical records of 1157 subjects (mean age 44.6 (SD 8.6) years). Whole blood cell (WBC) count was used as the primary haematological marker for increased CVD risk, and platelet count and haematocrit as the secondary markers. Standardised questionnaires were implemented to collect information on demographics, lifestyle, work related physical and psychosocial factors, and driving time profiles. Multiple regression was used to estimate the adjusted effects of driving time on three haematological markers. Results: The mean measured hematological marker was 6656 (SD 1656) cells x106/l for WBC, 47.2 (SD 3.5) % for hematocrit, and 243 (SD 52) cells x109/l for platelets. The driving time was 264 (SD 76) hours/month. Compared with drivers who drove ?208 hours/month (1st quartile cut off), drivers who drove >208 hours/month had a higher WBC count (by 317 x106/l; 95% CI 99 to 535), haematocrit (by 0.8%; 95% CI 0.3 to 1.2), and platelets (7.9 x109/l; 95% CI 1.0 to 14.8). After adjusting for conventional CVD risk factors (age, sex, smoking, hypertension, diabetes, and hypercholesterolaemia), obesity, alcohol drinking, regular exercise, and sociodemographics (education, marital status, income, and so on), long driving time was still associated with significant increases in WBC and platelets, whereas the effect on haematocrit was diminished and became statistically non-significant. Additional controls for physical workload, self-perceived job stress, and job dissatisfaction did not alter the associations with increased WBC and platelets. Conclusions: Longitudinal studies are needed to confirm the observed cross sectional association and to further examine the specific occupational exposures accountable for the association between driving time and haematological markers of systemic inflammation and haemostatic alteration. PMID:16299099

  15. Increased Oil Recovery from Mature Oil Fields Using Gelled Polymer Treatments

    SciTech Connect

    Willhite, G.P.; Green, D.W.; McCool, C.S.

    2001-01-22

    This report describes the progress of the first year of a three-year research program. This program is aimed at reducing barriers to the widespread use of gelled polymer treatments by (1) developing methods to predict gel behavior during placement in matrix rock and fractures, (2) determining the persistence of permeability reduction after gel placement, and (3) developing methods to design production well treatments to control water production.

  16. Radiotherapy beyond cancer: Target localization in real-time MRI and treatment planning for cardiac radiosurgery

    SciTech Connect

    Ipsen, S.; Blanck, O.; Rades, D.; Oborn, B.; Bode, F.; Liney, G.; Hunold, P.; Schweikard, A.; Keall, P. J.

    2014-12-15

    Purpose: Atrial fibrillation (AFib) is the most common cardiac arrhythmia that affects millions of patients world-wide. AFib is usually treated with minimally invasive, time consuming catheter ablation techniques. While recently noninvasive radiosurgery to the pulmonary vein antrum (PVA) in the left atrium has been proposed for AFib treatment, precise target location during treatment is challenging due to complex respiratory and cardiac motion. A MRI linear accelerator (MRI-Linac) could solve the problems of motion tracking and compensation using real-time image guidance. In this study, the authors quantified target motion ranges on cardiac magnetic resonance imaging (MRI) and analyzed the dosimetric benefits of margin reduction assuming real-time motion compensation was applied. Methods: For the imaging study, six human subjects underwent real-time cardiac MRI under free breathing. The target motion was analyzed retrospectively using a template matching algorithm. The planning study was conducted on a CT of an AFib patient with a centrally located esophagus undergoing catheter ablation, representing an ideal case for cardiac radiosurgery. The target definition was similar to the ablation lesions at the PVA created during catheter treatment. Safety margins of 0 mm (perfect tracking) to 8 mm (untracked respiratory motion) were added to the target, defining the planning target volume (PTV). For each margin, a 30 Gy single fraction IMRT plan was generated. Additionally, the influence of 1 and 3 T magnetic fields on the treatment beam delivery was simulated using Monte Carlo calculations to determine the dosimetric impact of MRI guidance for two different Linac positions. Results: Real-time cardiac MRI showed mean respiratory target motion of 10.2 mm (superior–inferior), 2.4 mm (anterior–posterior), and 2 mm (left–right). The planning study showed that increasing safety margins to encompass untracked respiratory motion leads to overlapping structures even in the ideal scenario, compromising either normal tissue dose constraints or PTV coverage. The magnetic field caused a slight increase in the PTV dose with the in-line MRI-Linac configuration. Conclusions: The authors’ results indicate that real-time tracking and motion compensation are mandatory for cardiac radiosurgery and MRI-guidance is feasible, opening the possibility of treating cardiac arrhythmia patients completely noninvasively.

  17. Effect of real-time teledermatology on diagnosis, treatment and clinical improvement.

    PubMed

    Al Quran, Hanadi A; Khader, Yousef Saleh; Ellauzi, Ziad Mohd; Shdaifat, Amjad

    2015-03-01

    We assessed the effect of real-time teledermatology consultations on diagnosis and disease management, patients' quality of life and time- and cost-savings. All consecutive patients with skin diseases attending teledermatology clinics at two rural hospitals in Jordan were included in the study. Patients were interviewed at their initial visit and again after eight weeks. Various questionnaires and forms, including quality of life questionnaires, were used to collect the data. Ninety teledermatology consultations were performed for 88 patients between September 2013 and January 2014. A diagnosis was established as part of the teledermatology consultation in 43% of patients and changed from that of the referring provider in 19% of patients. The treatment plan was established for 67% of patients and changed for 9% patients. The mean SF-8 score increased significantly (P?time (96%), shorter waiting time (83%) and less cost (96%) than a visit to the specialist clinic at the main hospital. The patients' mean satisfaction score was 90.5 (SD 8.5), indicating a high level of satisfaction. Teledermatology resulted in changes in the patients' diagnosis and treatment plan, and was associated with improved health state and quality of life. PMID:25589469

  18. A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification

    SciTech Connect

    Mourad, Waleed F.; Packianathan, Satyaseelan; Shourbaji, Rania A.; Zhang Zhen; Graves, Mathew; Khan, Majid A.; Baird, Michael C.; Russell, George; Vijayakumar, Srinivasan

    2012-03-01

    Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patients were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.

  19. Optimal timing of extracorporeal shock wave treatment to protect ischemic tissue.

    PubMed

    Reichenberger, Matthias A; Keil, Holger; Mueller, Wolf; Herold-Mende, Christel; Meirer, Romed; Gebhard, Martha Maria; Germann, Günter; Engel, Holger

    2011-11-01

    Enhancement of flap survival through extracorporeal shock wave treatment (ESWT) is a promising new technique; however, no attempt has been made to define the optimal time point and frequency of ESWT to optimize treatment with ESWT for ischemic indications. Twenty-eight male Wistar rats were randomized into 4 groups and an oversized, random-pattern flap was raised and reattached in place in each animal. ESWT was applied 7 days before (group E7) or immediately after the surgical intervention (group E0). The third group was treated with ESWT 7 days before and additionally immediately after the operation (group E7/0). The fourth group served as a control group and did not receive any ESWT (group C). Seven days after flap harvest the results of flap survival, perfusion, microvessel density, and vascular endothelial growth factor concentrations were assessed. Flap survival was significantly increased in all ESWT groups as compared with the control group. The groups (E7 and E0) that received ESWT pre- or postoperatively showed a significant increase in flap perfusion and microvessel density. Combined pre- and postoperative ESWT application (group E0/E7) did not demonstrate a cumulative effect in any evaluation. In this study, we were be able to prove the effectiveness of ESWT in the protection of ischemic tissue flaps. This study suggests that single postoperative application is the most efficacious protocol for clinical applications of ESWT in the treatment of ischemic tissue. PMID:21587053

  20. Just-in-Time Compound Pooling Increases Primary Screening Capacity without Compromising Screening Quality.

    PubMed

    Elkin, L L; Harden, D G; Saldanha, S; Ferguson, H; Cheney, D L; Pieniazek, S N; Maloney, D P; Zewinski, J; O'Connell, J; Banks, M

    2015-06-01

    Compound pooling, or multiplexing more than one compound per well during primary high-throughput screening (HTS), is a controversial approach with a long history of limited success. Many issues with this approach likely arise from long-term storage of library plates containing complex mixtures of compounds at high concentrations. Due to the historical difficulties with using multiplexed library plates, primary HTS often uses a one-compound-one-well approach. However, as compound collections grow, innovative strategies are required to increase the capacity of primary screening campaigns. Toward this goal, we have developed a novel compound pooling method that increases screening capacity without compromising data quality. This method circumvents issues related to the long-term storage of complex compound mixtures by using acoustic dispensing to enable "just-in-time" compound pooling directly in the assay well immediately prior to assay. Using this method, we can pool two compounds per well, effectively doubling the capacity of a primary screen. Here, we present data from pilot studies using just-in-time pooling, as well as data from a large >2-million-compound screen using this approach. These data suggest that, for many targets, this method can be used to vastly increase screening capacity without significant reduction in the ability to detect screening hits. PMID:25722344

  1. The timing of acid-induced increase in saliva secretion in transplanted submandibular glands.

    PubMed

    Liu, X J; Li, M; Su, J Z; Xie, Z; Yu, G Y

    2015-08-01

    The purpose of this study was to determine the timing of acid-induced increase in saliva secretion and to investigate the possibility of parasympathetic reinnervation of transplanted submandibular glands (SMGs). Citric acid stimulation-induced changes in secretion of transplanted SMGs were evaluated in 27 patients who underwent SMG transplantation for keratoconjunctivitis sicca (KCS); (99m)Tc scintigraphy and Schirmer tests were done at 1, 3, 6, and 9 months after transplantation. Acetylcholinesterase staining was conducted to confirm the presence of parasympathetic reinnervation in three SMGs at 6 and 9 months after transplantation. Schirmer tests showed significantly increased secretion of the transplanted SMGs after acid stimulation at 6 and 9 months, but not at 1 and 3 months. On (99m)Tc scintigraphy, no decline was detected on the dynamic time-activity curve after acid stimulation at 1 and 3 months, but a decline was detected in nine glands at 6 months and in 19 glands at 9 months. No decline was observed in the remaining eight glands at 9 months after transplantation. The histology findings were consistent with scintigraphy results. In conclusion, acid-induced increase in saliva secretion occurs at ?6 months after SMG transplantation, and parasympathetic reinnervation of the transplanted SMG might occur. PMID:25697065

  2. Temperature and Time Requirements for Controlling Bed Bugs (Cimex lectularius) under Commercial Heat Treatment Conditions

    PubMed Central

    Kells, Stephen A.; Goblirsch, Michael J.

    2011-01-01

    Developing effective alternative approaches for disinfesting bed bugs from residential spaces requires a balance between obtaining complete insect mortality, while minimizing costs and energy consumption. One method of disinfestation is the application of lethal high temperatures directly to rooms and contents within a structure (termed whole-room heat treatments). However, temperature and time parameters for efficacy in whole-room heat treatments are unknown given the slower rate of temperature increase and the probable variability of end-point temperatures within a treated room. The objective of these experiments was to explore requirements to produce maximum mortality from heat exposure using conditions that are more characteristic of whole-room heat treatments. Bed bugs were exposed in an acute lethal temperature (LTemp) trial, or time trials at sub-acute lethal temperatures (LTime). The lethal temperature (LTemp99) for adults was 48.3 °C, while LTemp99 for eggs was 54.8 °C. Adult bed bugs exposed to 45 °C had a LTime99 of 94.8 min, while eggs survived 7 h at 45 °C and only 71.5 min at 48 °C. We discuss differences in exposure methodologies, potential reasons why bed bugs can withstand higher temperatures and future directions for research. PMID:26467736

  3. Prostate and Patient Intrafraction Motion: Impact on Treatment Time-Dependent Planning Margins for Patients With Endorectal Balloon

    SciTech Connect

    Steiner, Elisabeth; Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna ; Georg, Dietmar; Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna ; Goldner, Gregor; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna ; Stock, Markus; Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna

    2013-07-15

    Purpose: To investigate intrafraction prostate and patient motion during different radiation therapy treatments as a function of treatment time; included were prostate patients with an endorectal balloon (ERB). Margins accounting for setup uncertainties and intrafraction motion were determined. Methods and Materials: The study included 17 patients undergoing prostate cancer radiation therapy. All patients received 3 fiducial gold markers implanted in the prostate and were then immobilized in the supine position with a knee support and treated with an ERB. Twelve patients with intermediate risk for pelvic lymph node metastases received intensity modulated radiation therapy (IMRT), and 5 patients at low risk received a 4-field box treatment. After setup based on skin marks, patients were imaged with a stereoscopic imaging system. If the marker displacement exceeded a 3-mm tolerance relative to planning computed tomography, patients were shifted and verification images were taken. All patients underwent additional imaging after treatment; IMRT patients also received additional imaging at halftime of treatment. Prostate and bone drifts were evaluated as a function of treatment time for more than 600 fractions, and margins were extracted. Results: Patient motion evaluated by bone match was strongly patient dependent but in general was smallest in the superior-inferior (SI) direction. Prostate drifts were less patient dependent, showing an increase with treatment time in the SI and anterior-posterior (AP) directions. In the lateral (LAT) direction, the prostate stayed rather stable. Mean treatment times were 5.5 minutes for 4-field box, 10 minutes for 5-field boost IMRT, and 15 minutes or more for 9-field boost and 9-field pelvic IMRT treatments. Margins resulted in 2.2 mm, 3.9 mm, and 4.3 mm for 4-field box; 3.7 mm, 2.6 mm, and 3.6 mm for 5-field boost IMRT; 2.3 mm, 3.9 mm, and 6.2 mm for 9-field boost IMRT; and 4.2 mm, 5.1 mm, and 6.6 mm for 9-field pelvic IMRT in the LAT, SI, and AP directions, respectively. Conclusion: Intrafraction prostate and patient displacement increased with treatment time, showing different behaviors for the single directions of movement. Repositioning of the patients during long treatments or shorter treatment times will be necessary to further reduce the treatment margin.

  4. Attractiveness of periodic orbits in parametrically forced systemswith time-increasing friction

    E-print Network

    Michele Bartuccelli; Jonathan Deane; Guido Gentile

    2012-07-18

    We consider dissipative one-dimensional systems subject to a periodic force and study numerically how a time-varying friction affects the dynamics. As a model system, particularly suited for numerical analysis, we investigate the driven cubic oscillator in the presence of friction. We find that, if the damping coefficient increases in time up to a final constant value, then the basins of attraction of the leading resonances are larger than they would have been if the coefficient had been fixed at that value since the beginning. From a quantitative point of view, the scenario depends both on the final value and the growth rate of the damping coefficient. The relevance of the results for the spin-orbit model are discussed in some detail.

  5. Time resolution deterioration with increasing crystal length in a TOF-PET system

    NASA Astrophysics Data System (ADS)

    Gundacker, S.; Knapitsch, A.; Auffray, E.; Jarron, P.; Meyer, T.; Lecoq, P.

    2014-02-01

    Highest time resolution in scintillator based detectors is becoming more and more important. In medical detector physics L(Y)SO scintillators are commonly used for time of flight positron emission tomography (TOF-PET). Coincidence time resolutions (CTRs) smaller than 100 ps FWHM are desirable in order to improve the image signal to noise ratio and thus give benefit to the patient by shorter scanning times. Also in high energy physics there is the demand to improve the timing capabilities of calorimeters down to 10 ps. To achieve these goals it is important to study the whole chain, i.e. the high energy particle interaction in the crystal, the scintillation process itself, the scintillation light transfer in the crystal, the photodetector and the electronics. Time resolution measurements for a PET like system are performed with the time-over-threshold method in a coincidence setup utilizing the ultra-fast amplifier-discriminator NINO. With 2×2×3 mm3 LSO:Ce codoped 0.4%Ca crystals coupled to commercially available SiPMs (Hamamatsu S10931-050P MPPC) we achieve a CTR of 108±5 ps FWHM at an energy of 511 keV. Under the same experimental conditions an increase in crystal length to 5 mm deteriorates the CTR to 123±7 ps FWHM, 10 mm to 143±7 ps FWHM and 20 mm to 176±7 ps FWHM. This degradation in CTR is caused by the light transfer efficiency (LTE) and light transfer time spread (LTTS) in the crystal. To quantitatively understand the measured values, we developed a Monte Carlo simulation tool in MATLAB incorporating the timing properties of the photodetector and electronics, the scintillation properties of the crystal and the light transfer within the crystal simulated by SLITRANI. In this work, we show that the predictions of the simulation are in good agreement with the experimental data. We conclude that for longer crystals the deterioration in CTR is mainly caused by the LTE, i.e. the ratio of photons reaching the photodetector to the total amount of photons generated by the scintillation whereas the LTTS influence is partly offset by the gamma absorption in the crystal.

  6. High-temperature strength of prealloyed-powder products increased by heat/pressure treatment

    NASA Technical Reports Server (NTRS)

    Ashbrook, R. L.; Freche, J. C.; Waters, W. J.

    1971-01-01

    Heat treatment process involves heating products to a temperature above the solidus, and subsequently applying pressure at a temperature below the solidus. Technique can be modified to one step process involving simultaneous application if both high pressure and heat. Process is not limited to cobalt-base alloys.

  7. Treatment Fidelity of Motivational Interviewing Delivered by a School Nurse to Increase Girls' Physical Activity

    ERIC Educational Resources Information Center

    Robbins, Lorraine B.; Pfeiffer, Karin A.; Maier, Kimberly S.; LaDrig, Stacey M.; Berg-Smith, Steven Malcolm

    2012-01-01

    Motivational interviewing, which involves the use of person-centered, directive counseling techniques, shows promise for changing adolescent behaviors. The purpose of this article was to describe the methodology and findings related to the treatment fidelity of three face-to-face motivational interviewing sessions involving middle school girls and…

  8. Beyond on/off: Increasing the benefits of patch spraying with multiple treatments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Site-specific weed management can encompass both limiting treatment to areas of the field where weed pressure is above the economic threshold (patch spraying) and varying the choice of herbicide for most cost-effective weed control of local populations. The potential benefits of patch spraying with ...

  9. Increasing Teacher Treatment Integrity through Performance Feedback Provided by School Personnel

    ERIC Educational Resources Information Center

    Hagermoser Sanetti, Lisa M.; Fallon, Lindsay M.; Collier-Meek, Melissa A.

    2013-01-01

    When implementing behavioral interventions in educational settings, some implementers need support to maintain high levels of treatment integrity. Performance feedback has a large body of research supporting it as a strategy for improving teachers' implementation of classroom interventions. However, in most prior studies, performance feedback has…

  10. The Social Marketing Approach: A Way to Increase Reporting and Treatment of Sexual Assault

    ERIC Educational Resources Information Center

    Boehm, Amnon; Itzhaky, Haya

    2004-01-01

    Objective: Too often communities remain silent in response to cases of sexual assault of children. Members of the community are afraid to report such incidents and victims are reluctant to seek and accept treatment. The purpose of the paper is to examine whether application of a social marketing approach may serve as an effective means for…

  11. Producer benefits using Terra Blue treatment technology: Increased pig productivity, expansion, and carbon credits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The State of North Carolina and USDA NRCS’s Environmental Quality Incentives Program started a statewide Lagoon Conversion Program (LCP) that provides financial support to livestock farmers installing Environmentally Superior Technology (EST) for manure management. A second generation treatment syst...

  12. Chronic fluoxetine treatment increases NO bioavailability and calcium-sensitive potassium channels activation in rat mesenteric resistance arteries.

    PubMed

    Pereira, Camila A; Ferreira, Nathanne S; Mestriner, Fabiola L; Antunes-Rodrigues, José; Evora, Paulo R B; Resstel, Leonardo B M; Carneiro, Fernando S; Tostes, Rita C

    2015-10-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K(+)) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine(1177) and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K(+) channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium-dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment. PMID:26362752

  13. Treatment timing and multidisciplinary approach in Apert syndrome.

    PubMed

    Fadda, Maria Teresa; Ierardo, Gaetano; Ladniak, Barbara; Di Giorgio, Gianni; Caporlingua, Alessandro; Raponi, Ingrid; Silvestri, Alessandro

    2015-01-01

    Apert syndrome is a rare congenital disorder characterized by craniosynostosis, midface hypoplasia and symmetric syndactyly of hands and feet. Abnormalities associated with Apert syndrome include premature fusion of coronal sutures system (coronal sutures and less frequently lambdoid suture) resulting in brachiturricephalic dismorphism and impaired skull base growth. After this brief explanation it is clear that these anatomical abnormalities may have a negative impact on the ability to perform essential functions. Due to the complexity of the syndrome a multidisciplinary (respiratory, cerebral, maxillo-mandibular, dental, ophthalmic and orthopaedic) approach is necessary in treating the psychological, aesthetic and functional issues. The aim of this paper is to analyse the different functional issues and surgical methods trying to enhance results through a treatment plan which includes different specialities involved in Apert syndrome treatment. Reduced intellectual capacity is associated to the high number of general anaesthesia the small patients are subject to. Therefore the diagnostic and therapeutic treatment plan in these patients has established integrated and tailored surgical procedures based on the patients' age in order to reduce the number of general anaesthesia, thus simplifying therapy for both Apert patients and their family members. PMID:26330906

  14. Treatment timing and multidisciplinary approach in Apert syndrome

    PubMed Central

    Fadda, Maria Teresa; Ierardo, Gaetano; Ladniak, Barbara; Di Giorgio, Gianni; Caporlingua, Alessandro; Raponi, Ingrid; Silvestri, Alessandro

    2015-01-01

    Summary Apert syndrome is a rare congenital disorder characterized by craniosynostosis, midface hypoplasia and symmetric syndactyly of hands and feet. Abnormalities associated with Apert syndrome include premature fusion of coronal sutures system (coronal sutures and less frequently lambdoid suture) resulting in brachiturricephalic dismorphism and impaired skull base growth. After this brief explanation it is clear that these anatomical abnormalities may have a negative impact on the ability to perform essential functions. Due to the complexity of the syndrome a multidisciplinary (respiratory, cerebral, maxillo-mandibular, dental, ophthalmic and orthopaedic) approach is necessary in treating the psychological, aesthetic and functional issues. The aim of this paper is to analyse the different functional issues and surgical methods trying to enhance results through a treatment plan which includes different specialities involved in Apert syndrome treatment. Reduced intellectual capacity is associated to the high number of general anaesthesia the small patients are subject to. Therefore the diagnostic and therapeutic treatment plan in these patients has established integrated and tailored surgical procedures based on the patients’ age in order to reduce the number of general anaesthesia, thus simplifying therapy for both Apert patients and their family members. PMID:26330906

  15. Can we explain increases in young people’s psychological distress over time?

    PubMed Central

    Sweeting, Helen; West, Patrick; Young, Robert; Der, Geoff

    2010-01-01

    This paper aims to explain previously described increases in self-reported psychological distress between 1987 and 2006 among samples identical in respect of age (15 years), school year and geographical location (West of Scotland). Such increases might be explained by changes in exposure (changes in levels of risk or protective factors) and/or by changes in vulnerability (changes in the relationship between risk/protective factors and psychological distress). Key areas of social change over this time period allow identification of potential explanatory factors, categorised as economic, family, educational, values and lifestyle and represented by variables common to each study. Psychological distress was measured via the 12-item General Health Questionnaire, Likert scored. Analyses were conducted on those with complete data on all variables (N = 3276 of 3929), and separately for males and females. Between 1987 and 2006, levels of almost every potential explanatory factor changed in line with general societal trends. Associations between explanatory factors and GHQ tended to be stronger among females, and at the later date. The strongest associations were with worries, arguments with parents, and, at the later date, school disengagement. The factors which best accounted for the increase in mean GHQ between 1987 and 2006 were arguments with parents, school disengagement, worry about school and, for females, worry about family relationships, reflecting both increasing exposure and vulnerability to these risk factors. A number of limitations to our analysis can be identified. However, our results reinforce the conclusions of others in highlighting the role of family and educational factors as plausible explanations for increases in young people’s psychological distress. PMID:20870334

  16. Ultraviolet-B light treatment increases antioxidant capacity of carrot products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abiotic stresses such as cutting and ultraviolet (UV) light exposure of plant cells triggers an increased activity response by phenylalanine ammonia-lyase (PAL) and chalcone synthase resulting in increased synthesis of phenolic compounds, mainly anthocyanins and flavonoids. This study investigated ...

  17. Older women with localized breast cancer: costs and survival rates increased across two time periods.

    PubMed

    Feinstein, Aaron J; Long, Jessica; Soulos, Pamela R; Ma, Xiaomei; Herrin, Jeph; Frick, Kevin D; Chagpar, Anees B; Krumholz, Harlan M; Yu, James B; Ross, Joseph S; Gross, Cary P

    2015-04-01

    Significant national attention has been paid to the rising costs of cancer care. However, few studies have evaluated the association between trends in costs and survival outcomes. We used the Surveillance, Epidemiology, and End Results (SEER) Program-Medicare linked database to compare changes in costs and survival rates over time, among women ages 67-94 who were diagnosed with stage II or III breast cancer in 1994-96 or 2004-06. We found that median cancer-related costs increased from $12,335 to $17,396 among women with stage II disease, and from $18,107 to $32,598 among women with stage III disease. Although the median cost of breast surgery declined between the two study periods, the median cost of chemo- and radiation therapy increased substantially, leading to an overall rise in cancer-related costs. Meanwhile, adjusted overall five-year survival improved, from 67.8 percent to 72.5 percent for women with stage II disease and from 38.5 percent to 51.9 percent for those with stage III disease. These findings suggest that increases in cancer care costs have been accompanied by improved outcomes. Future work should identify opportunities to optimize efficiency in cancer care. PMID:25847641

  18. Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis.

    PubMed

    Miller, Matthew S; Gardner, Thomas J; Krammer, Florian; Aguado, Lauren C; Tortorella, Domenico; Basler, Christopher F; Palese, Peter

    2013-08-14

    Antigenic diversity shapes immunity in distinct and unexpected ways. This is particularly true of the humoral response generated against influenza A viruses. Although it is known that immunological memory developed against previously encountered influenza A virus strains affects the outcome of subsequent infections, exactly how sequential exposures to antigenically variant viruses shape the humoral immune response in humans remains poorly understood. To address this important question, we performed a longitudinal analysis of antibody titers against various pandemic and seasonal strains of influenza virus spanning a 20-year period (1987 to 2008) with samples from 40 individuals (birth dates, 1917 to 1952) obtained from the Framingham Heart Study. Longitudinal increases in neutralizing antibody titers were observed against previously encountered pandemic H2N2, H3N2, and H1N1 influenza A virus strains. Antibody titers against seasonal strains encountered later in life also increased longitudinally at a rate similar to that against their pandemic predecessors. Titers of cross-reactive antibodies specific to the hemagglutinin stalk domain were also investigated because they are influenced by exposure to antigenically diverse influenza A viruses. These titers rose modestly over time, even in the absence of major antigenic shifts. No sustained increase in neutralizing antibody titers against an antigenically more stable virus (human cytomegalovirus) was observed. The results herein describe a role for antigenic variation in shaping the humoral immune compartment and provide a rational basis for the hierarchical nature of antibody titers against influenza A viruses in humans. PMID:23946196

  19. HIV treatment produces economic returns through increased work and education, and warrants continued US support.

    PubMed

    Thirumurthy, Harsha; Galárraga, Omar; Larson, Bruce; Rosen, Sydney

    2012-07-01

    Federal expenditures are under scrutiny in the United States, and the merits of continuing and expanding the President's Emergency Plan for AIDS Relief (PEPFAR) to support access to antiretroviral therapy have become a topic of debate. A growing body of research on the economic benefits of treatment with antiretroviral therapy has important implications for these discussions. For example, research conducted since the inception of PEPFAR shows that HIV-infected adults who receive antiretroviral therapy often begin or resume productive work, and that children living in households with infected adults who are on treatment are more likely to attend school than those in households with untreated adults. These benefits should be considered when weighing the overall benefits of providing antiretroviral therapy against its costs, particularly in the context of discussions about the future of PEPFAR. A modest case can also be made in favor of having private companies in HIV-affected countries provide antiretroviral therapy to their employees and dependents, thus sharing some of the burden of funding HIV treatment. PMID:22778336

  20. A new angle into time-resolved photoacoustic spectroscopy: A layered prism cell increases experimental flexibility

    SciTech Connect

    Autrey, T.; Foster, N.S.; Klepzig, K.; Amonette, J.E.; Daschbach, J.L.

    1998-06-01

    A new pulsed photoacoustic calorimetry cell that uses transmission of light through a pair of dovetail prisms is discussed. The layered prism cell (LPC) combines the enhanced time-resolution capabilities of the {open_quotes}layered{close_quotes} front-face irradiation geometry with the zero-background and broadband flexibility of the classical cuvette geometry. This work provides a phenomenological description of photoinduced pressure changes to yield an analytical expression to calculate the magnitude of the photoinduced acoustic pressure wave in a series of solvents. The mechanical to electrical conversion efficiency for an ultrasonic transducer coupled to the LPC is presented to provide a comparison of the experimentally observed photoinduced acoustic signal amplitudes to the empirically calculated acoustic signal amplitudes. An analysis of the background signals due to absorption and electrostriction of the media provides insight into the issues of sensitivity and limitations of pulsed photoacoustic experiments. The LPC provides several benefits to increase the flexibility of the photoacoustic spectroscopy: (1) greater sensitivity, (2) enhanced time resolution, and (3) the ability to obtain kinetic data in complex solvent mixtures. Under optically dilute conditions in the layered cell geometry, the acoustic transient time, {tau}a, approaches zero because the photoinduced acoustic wave homogeneously expands against the walls of the photoacoustic cell. To demonstrate the unique capabilities of the LPC, rates of hydrogen abstraction by {ital tert}-butoxyl radical from solvent mixtures containing ethyl and methyl alcohol are presented. {copyright} {ital 1998 American Institute of Physics.} thinsp

  1. Genotypic diversity effects on the performance of Taraxacum officinale populations increase with time and environmental favorability.

    PubMed

    Drummond, Emily B M; Vellend, Mark

    2012-01-01

    Within-population genetic diversity influences many ecological processes, but few studies have examined how environmental conditions may impact these short-term diversity effects. Over four growing seasons, we followed experimental populations of a clonal, ubiquitous weed, Taraxacum officinale, with different numbers of genotypes in relatively favorable fallow field and unfavorable mowed lawn environmental treatments. Population performance (measured as total leaf area, seed production or biomass) clearly and consistently increased with diversity, and this effect became stronger over the course of the experiment. Diversity effects were stronger, and with different underlying mechanisms, in the fallow field versus the mowed lawn. Large genotypes dominated in the fallow field driving overyielding (via positive selection effects), whereas in the mowed lawn, where performance was limited by regular disturbance, there was evidence for complementarity among genotypes (with one compact genotype in particular performing better in mixture than monoculture). Hence, we predict stronger genotypic diversity effects in environments where intense intraspecific competition enhances genotypic differences. Our four-year field experiment plus seedling establishment trials indicate that genotypic diversity effects have far-reaching and context-dependent consequences across generations. PMID:22348004

  2. Anti-tumour necrosis factor treatment increases circulating T helper type 17 cells similarly in different types of inflammatory arthritis.

    PubMed

    Hull, D N; Williams, R O; Pathan, E; Alzabin, S; Abraham, S; Taylor, P C

    2015-09-01

    We investigated changes in circulating T helper type 17 (Th17) cells following anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMC) were isolated from 25 RA, 15 AS and eight PsA patients at baseline 4 and 12 weeks after treatment, and Th17 cell frequencies were analysed using interleukin (IL)-17 enzyme-linked immunospot (ELISPOT) and flow cytometry. A significant increase in IL-17-producing cells was observed by ELISPOT in RA and AS patients at 12 weeks. Flow cytometry confirmed significant increases in CD4(+) IL-17(+) cells at 12 weeks in RA and AS and 4 weeks in PsA patients. Anti-TNF treatment increases circulating Th17 cells in three different diseases. PMID:25766640

  3. Development of a Multilevel Framework to Increase Use of Targeted Evidence-Based Practices in Addiction Treatment Clinics

    PubMed Central

    Molfenter, Todd; McCarty, Dennis; Capoccia, Victor; Gustafson, David

    2013-01-01

    Implementing specific evidence-based practices (EBPs) across a set of addiction treatment providers have been a persistent challenge. In the Advancing Recovery(AR) demonstration project, single state agencies, the entities that distribute federal funds for substance use disorder prevention and treatment services, worked in partnership with providers to increase the use of EBPs in the treatment of addiction. The project supported two cohorts of six 2-year awards. Field observations from the first year of implementation guided development of a multilevel framework (the Advancing Recovery Framework). Government entities and other payers can use the framework as a guide for implementing evidence-based clinical practices within treatment networks. The Advancing Recover Framework calls for a combination of policy and organizational changes at both the payer (government agency) and provider levels. Using the Advancing Recovery Framework, 11 of the 12 AR payer/provider partnerships increased use of clinical EPBs. This article identifies key payer policy changes applied during different phases of EBP program implementation. The public health benefit of the demonstration project was broader use of medication–assisted therapy and continuing care in addiction treatment services. PMID:24955331

  4. Low temperature, long time treatment of porcine M. longissimus thoracis et lumborum in a combi steamer under commercial conditions.

    PubMed

    Becker, André; Boulaaba, Annika; Pingen, Sylvia; Röhner, Anja; Klein, Günter

    2015-12-01

    As the interest in low temperature, long time (LTLT) treatment of meat, as well as the use of modern combi steamer technology is growing, this study characterized the effects of LTLT treatments on porcine Musculus longissimus thoracis et lumborum in a combi steamer. Upon heating for 10 and 20h at 53°C or 58°C, weight loss increased with both time and temperature, while no significant changes over time could be reached between 20 and 30h. Redness only varied with temperature, showing lower a* values at 53°C. Shear force values at 58°C remained at a stable level over time and were lower than values at 53°C after 10 and 20h. In contrast, at 53°C, shear force was reduced with increasing treatment time, until after 30h both temperatures showed similar shear force values. Inoculation experiments revealed that already the lowest LTLT condition (53°C, 10h) inactivated 5 log10 cfu/g of certain indicator pathogens confirming the safety of these treatments. PMID:26263040

  5. Calcitriol treatment increases serum levels of the soluble receptor of advanced glycation end products in hemodialysis patients with secondary hyperparathyroidism.

    PubMed

    Sung, Ji Yoon; Chung, Wookyung; Kim, Ae Jin; Kim, Hyung Soo; Ro, Han; Chang, Jae Hyun; Lee, Hyun Hee; Jung, Ji Yong

    2013-01-01

    Cardiovascular disease is common in the patients with end-stage renal disease, who often suffer from secondary hyperparathyroidism (SHP). Vitamin D is considered for the first-line therapy managing SHP in hemodialysis (HD) patients and has a beneficial effect in the chronic inflammation and development of cardiovascular disease. The soluble receptor for advanced glycation end products (sRAGE) may be protective by binding AGE in the pathogenesis of atherosclerotic vascular complications, whereas extracellular RAGE-binding protein (EN-RAGE) represents pro-inflammatory ligands for RAGE. We have hypothesized that vitamin D treatment may alter the levels of sRAGE and EN-RAGE in HD patients. Therefore, this prospective observational study was performed in 51 HD patients with SHP who had low serum 1,25 dihydroxyvitamin D3 (1,25D) levels and elevated intact parathyroid hormone (PTH) levels. We evaluated the changes in the values of sRAGE, EN-RAGE, and other inflammatory marker, interleukin-6 (IL-6), before and at the end of the 8-week calcitriol treatment. After calcitriol treatment, the serum levels of 1,25D were increased, whereas the serum intact PTH levels were decreased. In addition, the sRAGE levels were increased, whereas those of IL-6 were decreased after calcitriol treatment. A positive correlation between 1,25D and sRAGE levels (r = 0.609, P < 0.001) and a negative correlation between sRAGE and EN-RAGE levels (r = -0.368, P = 0.020) were detected after calcitriol treatment. This study suggests that calcitriol treatment could play an anti-inflammatory role through the increasing sRAGE in HD patients with SHP. PMID:23748365

  6. [Waiting time for treatment shall be calculated correctly].

    PubMed

    Pedersen, Jørgen Ejler

    2011-05-23

    Every system is perfectly designed to achieve the results it gets and in the Danish health care system there is a significant waiting time for the patients. If we want this result to change, we have to change something in the system, but before we do that, we need to understand the system. With queuing theory as a frame of reference, the anatomy and physiology of waiting time is illuminated in order to bring additional knowledge into the design of systems in health care. PMID:21627909

  7. Treatment of ovine oocytes with caffeine increases the accessibility of DNase I to the donor chromatin and reduces apoptosis in somatic cell nuclear transfer embryos.

    PubMed

    Choi, Inchul; Campbell, Keith H S

    2010-01-01

    Caffeine treatment of ovine oocytes increases the activity of maturation-promoting factor (MPF) and mitogen-activated protein kinases (MAPKs) and, in somatic cell nuclear transfer (SCNT) embryos, increases the frequency of nuclear envelope breakdown (NEBD) and premature chromosome condensation (PCC). At the blastocyst stage, caffeine-treated SCNT embryos have increased cell numbers. One explanation for this is that NEBD and PCC release chromatin-bound somatic factors, allowing greater access of oocyte factors involved in DNA synthesis and nuclear reprogramming to donor chromatin. This could advance DNA replication and cleavage in the first cell cycle, resulting in increased cell numbers. Alternatively, increased MAPK activity may affect localisation of heat shock proteins (HSPs) and reduce apoptosis. To investigate these possibilities, we investigated chromatin accessibility, the timing of DNA synthesis and first cleavage, the localisation of HSP27 during early development and the frequency of apoptotic nuclei at the blastocyst stage. Compared with control SCNT (non-caffeine treatment), caffeine treatment (10 mM caffeine for 6 h prior to activation) increased the accessibility of DNase I to donor chromatin (P < 0.05 at 1.5 h post activation (h.p.a.)), advanced DNA synthesis (43.5% v. 67.6%, respectively; P < 0.01 at 6 h.p.a.) and first cleavage (27.3% v. 40.5% at 20 h.p.a., respectively) and increased nuclear localisation of HSP27. Although development to the blastocyst stage was not affected, caffeine increased total cell numbers (98.5 v. 76.6; P < 0.05) and reduced the frequency of apoptotic nuclei (11.27% v. 20.3%; P < 0.05) compared with control SCNT group. PMID:20591334

  8. Real-time optical monitoring of the wastewater treatment process.

    PubMed

    Tomperi, Jani; Koivuranta, Elisa; Kuokkanen, Anna; Juuso, Esko; Leiviskä, Kauko

    2016-02-01

    One activated sludge process line was optically monitored in situ by a novel image analysis equipment. The results of the image analysis were studied to find out dependencies to the process variables of the wastewater treatment plant (WWTP) and to the quality of the treated wastewater. The quality parameter of the treated wastewater, suspended solids, was modelled using the image analysis results. The model can be used for evaluating the performance of the WWTP and for the better control for stable effluent quality. It was shown that the results of the online optical monitoring reveal useful information from the process and can be used in forecasting the quality of biologically treated wastewater. The optical monitoring method together with process measurements has an important role in keeping the process in stable operating conditions and avoiding environmental risks. PMID:26238162

  9. Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke.

    PubMed

    Li, Wen-Lei; Cai, Hui-Hui; Wang, Bin; Chen, Ling; Zhou, Qi-Gang; Luo, Chun-Xia; Liu, Na; Ding, Xin-Sheng; Zhu, Dong-Ya

    2009-01-01

    Cognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis in the hippocampus in physiological situations and some neurological diseases. However, whether it has effects on ischemia-induced spatial cognitive impairment and hippocampal neurogenesis has not been determined. Here we report that fluoxetine treatment (10 mg kg(-1), i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic hippocampus and, consequently, attenuated spatial memory impairment of mice after focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the beneficial effect of fluoxetine on ischemia-induced spatial cognitive impairment. These results suggest that chronic fluoxetine treatment benefits spatial cognitive function recovery following ischemic insult, and the improved cognitive function is associated with enhanced newborn cell survival in the hippocampus. Our results raise the possibility that fluoxetine can be used as a drug to treat poststroke spatial cognitive deficits. PMID:18711744

  10. Hydrothermal treatment coupled with mechanical expression at increased temperature for excess sludge dewatering: the dewatering performance and the characteristics of products.

    PubMed

    Wang, Liping; Li, Aimin

    2015-01-01

    Hydrothermal treatment coupled with mechanical expression at increased temperature in two separate cells respectively is effective for the dewatering of excess sludge with low energy consumption. The objectives of this study were to evaluate the dewatering performance and the characteristics of obtained products (hydrothermal sludge, hydrochar and filtrate). The results showed that harsher hydrothermal treatment (temperature from 120 to 210 °C and residence time from 10 to 90 min) led to greater water removal (from 7.44 to 96.64% reduction of total water) and mechanical pressure became less significant as it increased. The whole expression stage was completely described by the modified Terzaghi-Voigt rheological model. The role of tertiary consolidation stage in the water removal was reduced with hydrothermal treatment being stronger. The hydrothermal treatment is mainly a devolatilization process. The observed changes in H/C and O/C for hydrothermal sludge suggested dehydration was the major reaction mechanism and decarboxylation only occurred significantly at higher temperature. The higher heating value correlated well with carbon content of sludge, which was increased by 4.8% for hydrothermal sludge at 210 °C for 60 min and significantly decreased by 15.4% for hydrochar after 6.0 MPa for 20 min. The solubilization and decomposition of proteins, polysaccharides and DNA were determined to be temperature and residence time dependent. The improvement of dewaterability was closely correlated to the variation of these biopolymers. The filtrates collected above 150 °C were found to be acidic. The increase of humic substances and the melanoidins formed by Maillard reaction were largely responsible for the filtrate color. PMID:25462737

  11. Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

    SciTech Connect

    Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Doppelt, S.H.; Rosenthal, D.I.; Segre, G.V.; Crowley, W.F. Jr. )

    1989-10-01

    To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), while trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.

  12. Hygienic quality of artificial greywater subjected to aerobic treatment: a comparison of three filter media at increasing organic loading rates.

    PubMed

    Lalander, Cecilia; Dalahmeh, Sahar; Jönsson, Håkan; Vinnerås, Björn

    2013-01-01

    With a growing world population, the lack of reliable water sources is becoming an increasing problem. Reusing greywater could alleviate this problem. When reusing greywater for crop irrigation it is paramount to ensure the removal of pathogenic organisms. This study compared the pathogen removal efficiency of pine bark and activated charcoal filters with that of conventional sand filters at three organic loading rates. The removal efficiency of Escherichia coli O157:H7 decreased drastically when the organic loading rate increased fivefold in the charcoal and sand filters, but increased by 2 log10 in the bark filters. The reduction in the virus model organism coliphage phiX174 remained unchanged with increasing organic loading in the charcoal and sand filters, but increased by 2 log10 in the bark filters. Thus, bark was demonstrated to be the most promising material for greywater treatment in terms of pathogen removal. PMID:24527627

  13. Hygienic quality of artificial greywater subjected to aerobic treatment: a comparison of three filter media at increasing organic loading rates

    PubMed Central

    Lalander, Cecilia; Dalahmeh, Sahar; Jönsson, Håkan; Vinnerås, Björn

    2013-01-01

    With a growing world population, the lack of reliable water sources is becoming an increasing problem. Reusing greywater could alleviate this problem. When reusing greywater for crop irrigation it is paramount to ensure the removal of pathogenic organisms. This study compared the pathogen removal efficiency of pine bark and activated charcoal filters with that of conventional sand filters at three organic loading rates. The removal efficiency of Escherichia coli O157:H7 decreased drastically when the organic loading rate increased fivefold in the charcoal and sand filters, but increased by 2 log10 in the bark filters. The reduction in the virus model organism coliphage ?X174 remained unchanged with increasing organic loading in the charcoal and sand filters, but increased by 2 log10 in the bark filters. Thus, bark was demonstrated to be the most promising material for greywater treatment in terms of pathogen removal. PMID:24527627

  14. Rapid increases and time-lagged declines in amphibian occupancy after wildfire

    USGS Publications Warehouse

    Hossack, Blake R.; Lowe, Winsor H.; Corn, Paul Stephen

    2013-01-01

    Climate change is expected to increase the frequency and severity of drought and wildfire. Aquatic and moisture-sensitive species, such as amphibians, may be particularly vulnerable to these modified disturbance regimes because large wildfires often occur during extended droughts and thus may compound environmental threats. However, understanding of the effects of wildfires on amphibians in forests with long fire-return intervals is limited. Numerous stand-replacing wildfires have occurred since 1988 in Glacier National Park (Montana, U.S.A.), where we have conducted long-term monitoring of amphibians. We measured responses of 3 amphibian species to fires of different sizes, severity, and age in a small geographic area with uniform management. We used data from wetlands associated with 6 wildfires that burned between 1988 and 2003 to evaluate whether burn extent and severity and interactions between wildfire and wetland isolation affected the distribution of breeding populations. We measured responses with models that accounted for imperfect detection to estimate occupancy during prefire (0-4 years) and different postfire recovery periods. For the long-toed salamander (Ambystoma macrodactylum) and Columbia spotted frog (Rana luteiventris), occupancy was not affected for 6 years after wildfire. But 7-21 years after wildfire, occupancy for both species decreased ? 25% in areas where >50% of the forest within 500 m of wetlands burned. In contrast, occupancy of the boreal toad (Anaxyrus boreas) tripled in the 3 years after low-elevation forests burned. This increase in occupancy was followed by a gradual decline. Our results show that accounting for magnitude of change and time lags is critical to understanding population dynamics of amphibians after large disturbances. Our results also inform understanding of the potential threat of increases in wildfire frequency or severity to amphibians in the region.

  15. Rapid increases and time-lagged declines in amphibian occupancy after wildfire.

    PubMed

    Hossack, Blake R; Lowe, Winsor H; Corn, Paul Stephen

    2013-02-01

    Climate change is expected to increase the frequency and severity of drought and wildfire. Aquatic and moisture-sensitive species, such as amphibians, may be particularly vulnerable to these modified disturbance regimes because large wildfires often occur during extended droughts and thus may compound environmental threats. However, understanding of the effects of wildfires on amphibians in forests with long fire-return intervals is limited. Numerous stand-replacing wildfires have occurred since 1988 in Glacier National Park (Montana, U.S.A.), where we have conducted long-term monitoring of amphibians. We measured responses of 3 amphibian species to fires of different sizes, severity, and age in a small geographic area with uniform management. We used data from wetlands associated with 6 wildfires that burned between 1988 and 2003 to evaluate whether burn extent and severity and interactions between wildfire and wetland isolation affected the distribution of breeding populations. We measured responses with models that accounted for imperfect detection to estimate occupancy during prefire (0-4 years) and different postfire recovery periods. For the long-toed salamander (Ambystoma macrodactylum) and Columbia spotted frog (Rana luteiventris), occupancy was not affected for 6 years after wildfire. But 7-21 years after wildfire, occupancy for both species decreased ? 25% in areas where >50% of the forest within 500 m of wetlands burned. In contrast, occupancy of the boreal toad (Anaxyrus boreas) tripled in the 3 years after low-elevation forests burned. This increase in occupancy was followed by a gradual decline. Our results show that accounting for magnitude of change and time lags is critical to understanding population dynamics of amphibians after large disturbances. Our results also inform understanding of the potential threat of increases in wildfire frequency or severity to amphibians in the region. PMID:22978248

  16. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways

    PubMed Central

    Patel, A; Nouraei, S A R

    2015-01-01

    Emergency and difficult tracheal intubations are hazardous undertakings where successive laryngoscopy–hypoxaemia–re-oxygenation cycles can escalate to airway loss and the ‘can't intubate, can't ventilate’ scenario. Between 2013 and 2014, we extended the apnoea times of 25 patients with difficult airways who were undergoing general anaesthesia for hypopharyngeal or laryngotracheal surgery. This was achieved through continuous delivery of transnasal high-flow humidified oxygen, initially to provide pre-oxygenation, and continuing as post-oxygenation during intravenous induction of anaesthesia and neuromuscular blockade until a definitive airway was secured. Apnoea time commenced at administration of neuromuscular blockade and ended with commencement of jet ventilation, positive-pressure ventilation or recommencement of spontaneous ventilation. During this time, upper airway patency was maintained with jaw-thrust. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) was used in 15 males and 10 females. Mean (SD [range]) age at treatment was 49 (15 [25–81]) years. The median (IQR [range]) Mallampati grade was 3 (2–3 [2–4]) and direct laryngoscopy grade was 3 (3–3 [2–4]). There were 12 obese patients and nine patients were stridulous. The median (IQR [range]) apnoea time was 14 (9–19 [5–65]) min. No patient experienced arterial desaturation < 90%. Mean (SD [range]) post-apnoea end-tidal (and in four patients, arterial) carbon dioxide level was 7.8 (2.4 [4.9–15.3]) kPa. The rate of increase in end-tidal carbon dioxide was 0.15 kPa.min?1. We conclude that THRIVE combines the benefits of ‘classical’ apnoeic oxygenation with continuous positive airway pressure and gaseous exchange through flow-dependent deadspace flushing. It has the potential to transform the practice of anaesthesia by changing the nature of securing a definitive airway in emergency and difficult intubations from a pressured stop–start process to a smooth and unhurried undertaking. PMID:25388828

  17. Timing of testing and treatment for asymptomatic diseases

    SciTech Connect

    K?rk?zlar, Eser; Faissol, Daniel M.; Griffin, Paul M.; Swann, Julie L.

    2010-07-01

    Many papers in the medical literature analyze the cost-effectiveness of screening for diseases by comparing a limited number of a priori testing policies under estimated problem parameters. However, this may be insufficient to determine the best timing of the tests or incorporate changes over time. In this paper, we develop and solve a Markov Decision Process (MDP) model for a simple class of asymptomatic diseases in order to provide the building blocks for analysis of a more general class of diseases. We provide a computationally efficient method for determining a cost-effective dynamic intervention strategy that takes into account (i) the results of the previous test for each individual and (ii) the change in the individual’s behavior based on awareness of the disease. We demonstrate the usefulness of the approach by applying the results to screening decisions for Hepatitis C (HCV) using medical data, and compare our findings to current HCV screening recommendations.

  18. Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.

    PubMed

    Isgren, Anniella; Jakobsson, Joel; Pålsson, Erik; Ekman, Carl Johan; Johansson, Anette G M; Sellgren, Carl; Blennow, Kaj; Zetterberg, Henrik; Landén, Mikael

    2015-01-01

    Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication. PMID:25451615

  19. Short-term Intravenous Antibiotic Treatment in Uncomplicated Diverticulitis Does Not Increase the Risk of Recurrence Compared to Long-term Treatment

    PubMed Central

    Buchs, Nicolas Christian; Poncet, Antoine; Konrad-Mugnier, Béatrice; Gervaz, Pascal; Morel, Philippe; Ris, Frédéric

    2015-01-01

    Purpose This study included all patients treated at the University Hospital of Geneva for a first episode of uncomplicated diverticulitis. Risks of recurrence and treatment failure were evaluated by comparing the results between short-course and long-course intravenous (IV) antibiotic therapy groups. Methods The records of all patients hospitalized at our facility from January 2007 to February 2012 for a first episode of uncomplicated diverticulitis (Hinchey Ia), as confirmed by computed tomography, were prospectively collected. We published an auxiliary analysis from this registered study at Clinicaltrials.gov (identifier number: NCT01015378). Two groups of patients were considered: one received a short-course IV antibiotic arm (ceftriaxone and metronidazole) for up to 5 days (followed by 5 days of oral antibiotics); the other received a long-course IV arm between days 5 and 10. The primary outcome was the recurrence-free survival time. Results Follow-up was completed for 256 patients-50% men and 50% women, with a median age of 56 years (range, 24-85 years). The average follow-up was 50 months (range, 19-89 months). Of the 256 patients included in the study, 46 patients received a short-course IV antibiotic treatment and 210 received a long-course treatment. The recurrence-free survivals were very similar between the two groups, which was supported by a log rank test (P = 0.772). Four treatment failures, all in the long-course IV antibiotic treatment group, occurred. Conclusion Treatment of diverticulitis with a short IV antibiotic treatment is possible and does not modify the recurrence rate in patients with uncomplicated diverticulitis. PMID:25960972

  20. In vivo treatment by diallyl disulfide increases histone acetylation in rat colonocytes

    SciTech Connect

    Druesne-Pecollo, Nathalie . E-mail: Nathalie.Pecollo@jouy.inra.fr; Chaumontet, Catherine; Pagniez, Anthony; Vaugelade, Pierre; Bruneau, Aurelia; Thomas, Muriel; Cherbuy, Claire; Duee, Pierre-Henri; Martel, Paule

    2007-03-02

    Diallyl disulfide (DADS) is an organosulfur compound from garlic which exhibits various anticarcinogenic properties including inhibition of tumor cell proliferation. DADS antiproliferative effects were previously associated with an increase in histone acetylation in two human tumor colon cell lines, suggesting that DADS-induced histone hyperacetylation could be one of the mechanisms involved in its protective properties on colon carcinogenesis. The effects of DADS on histone H4 and H3 acetylation levels were investigated in vivo in colonocytes isolated from non-tumoral rat. Administrated by intracaecal perfusion or gavage, DADS increases histone H4 and H3 acetylation in colonocytes. Moreover, data generated using cDNA expression arrays suggest that DADS could modulate the expression of a subset of genes. These results suggest the involvement of histone acetylation in modulation of gene expression by DADS in normal rat colonocytes, which might play a role in its biological effects as well as in its anticarcinogenic properties in vivo.

  1. In vivo morphine treatment synergistically increases LPS-induced caspase activity in immune organs

    PubMed Central

    Olin, Michael; Lee, Brian; Roy, Sabita; Molitor, Thomas

    2013-01-01

    Apoptosis is an important mechanism for the elimination of infected cells, which would normally serve as hosts for further pathogen replication. Apoptosis is initiated through complex pathways involving a family of cysteine proteases known as caspases. The detection of apoptosis is essential for understanding the long-term health effects inflicted by the therapeutic use of opiate drugs such as morphine for pain treatment following major trauma or disease and abusive use of such drugs in addiction. Common practices of apoptosis detection involve the removal of tissues, which subsequently induce spontaneous apoptosis unrelated to the actual effects of the opioid drug exposure. The objective of this study was to develop an in vivo detection method for assessing morphine’s ability to directly induce apoptosis, and in the combination of morphine following an inflammatory response induced by lipopolysaccharide (LPS). Mice were administered saline, morphine, LPS, or a combination of morphine and LPS. Prior to sacrifice, mice were injected with a poly-caspase-specific apoptosis detection probe, to detect internal caspase activity in vivo. Administration of morphine alone did not directly induce apoptosis. However, morphine significantly enhanced the LPS induced apoptosis in splenocyte and bone marrow cells as well as in spleen, liver, and thymus tissues. The use of a poly-caspase detection probe methodology, to label apoptotic cells in vivo, provides a powerful quantitative tool for the in vivo analysis of caspase activity. PMID:20390371

  2. Soil Drench Treatment with ß-Aminobutyric Acid Increases Drought Tolerance of Potato

    PubMed Central

    Sós-Heged?s, Anita; Juhász, Zsófia; Poór, Péter; Kondrák, Mihály; Antal, Ferenc; Tari, Irma; Mauch-Mani, Brigitte; Bánfalvi, Zsófia

    2014-01-01

    The non-protein amino acid ?-aminobutyric acid (BABA) is known to be a priming agent for a more efficient activation of cellular defence responses and a potent inducer of resistance against biotic and abiotic stresses in plants. Nevertheless, most of the studies on priming have been carried out in Arabidopsis. In potato, the effect of BABA was demonstrated only on biotic stress tolerance. We investigated the effect of BABA on the drought tolerance of potato and found that soil drenched with BABA at a final concentration of 0.3 mM improves the drought tolerance of potato. Water loss from the leaves of the primed plants is attenuated and the yield is increased compared to the unprimed drought-stressed plants. The metabolite composition of the tubers of the BABA-treated plants is less affected by drought than the tuber composition of the non-treated plants. Nitric oxide and ROS (reactive oxygen species) production is increased in the BABA-treated roots but not in the leaves. In the leaves of the BABA-treated plants, the expression of the drought-inducible gene StDS2 is delayed, but the expression of ETR1, encoding an ethylene receptor, is maintained for a longer period under the drought conditions than in the leaves of the non-treated, drought-stressed control plants. This result suggests that the ethylene-inducible gene expression remains suppressed in primed plants leading to a longer leaf life and increased tuber yield compared to the non-treated, drought-stressed plants. The priming effect of BABA in potato, however, is transient and reverts to an unprimed state within a few weeks. PMID:25489951

  3. Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota

    PubMed Central

    Munyaka, Peris Mumbi; Eissa, N.; Bernstein, Charles Noah; Khafipour, Ehsan; Ghia, Jean-Eric

    2015-01-01

    Background and aims Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. Methods Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1? and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. Results ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. Conclusions The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers. PMID:26605545

  4. Sodium salicylate treatment in early lactation increases whole-lactation milk and milk fat yield in mature dairy cows.

    PubMed

    Farney, J K; Mamedova, L K; Coetzee, J F; Minton, J E; Hollis, L C; Bradford, B J

    2013-01-01

    Multiple lines of inquiry have suggested that a high degree of inflammation in early lactation cows is associated with low productivity and increased disease incidence. In addition, some small studies have suggested that milk production increases in response to antiinflammatory treatment in the first week of lactation. Our objective was to determine if administration of sodium salicylate (SS), a nonsteroidal antiinflammatory drug (NSAID), in the first week of lactation changes whole-lactation productivity and retention in the herd. At calving, 78 cows [n=39 primiparous (1P); n=24 second parity (2P); n=15 third parity or greater (3P)] were alternately assigned to either control (CON) or SS treatments for 7 d postpartum. Sodium salicylate treatment was administered via individual water bowls at a concentration of 1.95 g/L, delivering a mean of 123.3±5.5 g of salicylate/d during the 7-d treatment. For the first 21 d of lactation, dry matter intake, water intake, milk yield, and health were monitored daily, and milk samples were collected twice weekly for milk component analysis. Monthly milk yield and component testing through the rest of the lactation provided data to assess long-term responses, and the effects of treatment on the risk of leaving the herd and on 305-d milk, fat, and protein yields were assessed. During the first 21 d of lactation, we observed no differences in morbidity, except for increased risk of metritis in 3P SS cows. Treatment interacted with parity to influence both 305-d milk and milk fat yields, and a tendency for an interaction was detected for 305-d milk protein yield. Milk yield was 2,469±646 kg greater over the lactation in 3P SS cows compared with 3P CON cows (21% increase) and tended to decrease by 8% in 1P cows treated with SS; no effects were detected in 2P cows. Furthermore, 3P SS cows produced 130±23 kg more milk fat over the lactation (30% increase), with no effects detected for 1P or 2P. Treatment with SS tended to increase 305-d milk protein yield in 3P cows by 14%, with no effects in 1P or 2P cows. A tendency for a treatment × parity interaction was also observed for the risk of leaving the herd. First-parity cows treated with SS tended to have greater risk of leaving the herd than controls (30 vs. 6% risk); however, treatment did not alter herd retention in 2P or 3P groups, and SS had no effect on the risk of leaving the herd overall. Results indicate that SS has long-term effects on lactation of mature dairy cows, particularly on fat yield, but may have negative effects for primiparous cows. PMID:24140330

  5. Acute and repeated ECS treatment increases CRF, POMC and PENK gene expression in selected regions of the rat hypothalamus.

    PubMed

    Garcia-Garcia, L; Llewellyn-Jones, V; Fernandez Fernandez, I; Fuentes, J A; Manzanares, J

    1998-01-01

    The purpose of this study was to investigate the effects of acute and repeated electroconvulsive shock (ECS) on corticotropin releasing factor (CRF), proopiomelanocortin (POMC) and proenkephalin (PENK) gene expression in selected regions of the brain and pituitary of the rat. Acute ECS increased CRF gene expression in the paraventricular nucleus (PVN) by 20%, an effect that was further enhanced to 38% when rats received repeated ECS treatment. Acute and repeated ECS increased POMC gene expression in the arcuate nucleus (ARC) by 49-59% but failed to alter these mRNA levels in the anterior lobe (AL) of the pituitary gland. PENK gene expression was increased by 35% in the nucleus accumbens (NA) and by 180% the ventromedial nucleus (VMN) after acute or repeated ECS treatment but no significant changes were found in the PVN or striatum (ST). Taken together, these results indicate a differential CRF and opioid gene expression regulation after acute or repeated ECS treatment that may be relevant to their therapeutic or side effects in depression. PMID:9592051

  6. SLUDGE BATCH SUPPLEMENTAL SRAT RUNS EFFECTS OF YIELD STRESS AND CYCLE TIME INCREASE

    SciTech Connect

    Fernandez, A.

    2010-08-10

    The Defense Waste Processing Facility (DWPF) has transitioned from Sludge Batch 5 (SB5) processing to Sludge Batch 6 (SB6) processing. Phase III-Tank 40 Chemical Process Cell (CPC) flowsheet simulations have been completed to determine the initial processing conditions for the DWPF transition. The impact of higher yield stress (SB-25) and cycle time extension (SB6-26) on the physical and chemical effects of SB6 processing during the SRAT (Sludge Receipt and Adjustment Tank) cycle were evaluated. No significant impacts on the SRAT chemistry were noted during the higher yield stress run. In particular, no impact on mercury stripping was noted, indicating that settling of elemental mercury was not the primary factor in the low mercury recovery noted in the flowsheet testing. The SRAT product from this run retained the higher yield stress of the starting sludge. The run indicated that ultrasonication is an effective tool to increase the yield stress of simulants to targeted values and the chemistry of downstream processing is not impacted. Significant differences were noted in the cycle time extension test compared to the Phase III flowsheet baseline runs. Large decreases in the ammonia and hydrogen generation rates were noted along with reduced mercury stripping efficiency. The latter effect is similar to that of operating under a high acid stoichiometry. It is conceivable that, under the distinctly different conditions of high formic acid concentration (high acid run) or slow formic acid addition (extended run), that mercury could form amalgams with noble metals, possibly rendering both inert. Thus, the removal of free mercury and noble metals could decrease the rate of catalytic formic acid reactions which would decrease generation of ammonium and hydrogen. The potential underlying reasons for the behavior noted during this run would require additional testing.

  7. Antioxidant treatment during preservation of bovine ovaries increased the development potential of embryos.

    PubMed

    Nagao, Yoshikazu; Harada, Yumiko; Yamaguchi, Mari; Igarashi, Akane; Ooshima, Yuki; Kato, Yoku

    2010-11-01

    The overnight preservation of bovine ovaries would be highly useful in the subsequent harvest of viable oocytes for reproductive study. The present study aimed to optimize conditions for overnight preservation of bovine ovaries by examining the effects of temperature, solution and supplementation. In Experiment 1, the rate of development to the blastocyst stage of oocytes derived from ovaries preserved at 15°C was higher than that at either 5 or 25°C (p < 0.05). In Experiment 2, the rate of development to the blastocyst stage of oocytes derived from ovaries preserved in University of Wisconsin solution was higher than when PBS or saline was used (p < 0.05). In Experiment 3, oocytes preserved in saline supplemented with 0.3 mM glutathione (GSH) exhibited an increase in the rate of blastocyst formation compared with oocytes supplemented with 0 or 3 mM GSH (p < 0.05). In Experiment 4, supplementation with 10 ?M epigallocatechin gallate during ovary preservation increased the rate of blastocyst formation (p < 0.05). The blastocysts derived from ovaries stored in saline supplemented with GSH at 15°C for 24 h were shown to develop into normal offsprings following transfer to recipient heifers. Our studies indicate that bovine IVM/IVF embryos derived from ovaries preserved in saline supplemented with an antioxidant at 15°C for 24 h can successfully develop to the blastocyst stage and result in offspring. PMID:20444311

  8. Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus.

    PubMed

    Nomura, Toshihiro; Oyamada, Yoshihiro; Fernandes, Herman B; Remmers, Christine L; Xu, Jian; Meltzer, Herbert Y; Contractor, Anis

    2016-01-01

    Repeated administration of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) to rodents causes long-lasting deficits in cognition and memory, and has effects on behaviors that have been suggested to be models of the cognitive impairment associated with schizophrenia (CIAS). Despite this being a widely studied animal model, little is known about the long lasting changes in synapses and circuits that underlie the altered behaviors. Here we examined synaptic transmission ex-vivo in the hippocampus of mice after a subchronic PCP (scPCP) administration regime. We found that after at least one week of drug free washout period when mice have impaired cognitive function, the threshold for long-term potentiation (LTP) of CA1 excitatory synapses was elevated. This elevated LTP threshold was directly related to increased inhibitory input to CA1 pyramidal cells through increased activity of GABAergic neurons. These results suggest repeated PCP administration causes a long-lasting metaplastic change in the inhibitory circuits in the hippocampus that results in impaired LTP, and could contribute to the deficits in hippocampal-dependent memory in PCP-treated mice. Changes in GABA signaling have been described in patients with schizophrenia, therefore our results support using scPCP as a model of CIAS. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. PMID:25937215

  9. Increased saccharification yields from aspen biomass upon treatment with enzymatically generated peracetic acid.

    PubMed

    Duncan, Shona; Jing, Qing; Katona, Adrian; Kazlauskas, Romas J; Schilling, Jonathan; Tschirner, Ulrike; Aldajani, Waleed Wafa

    2010-03-01

    The recalcitrance of lignocellulosic biomass to enzymatic release of sugars (saccharification) currently limits its use as feedstock for biofuels. Enzymatic hydrolysis of untreated aspen wood releases only 21.8% of the available sugars due primarily to the lignin barrier. Nature uses oxidative enzymes to selectively degrade lignin in lignocellulosic biomass, but thus far, natural enzymes have been too slow for industrial use. In this study, oxidative pretreatment with commercial peracetic acid (470 mM) removed 40% of the lignin (from 19.9 to 12.0 wt.% lignin) from aspen and enhanced the sugar yields in subsequent enzymatic hydrolysis to about 90%. Increasing the amount of lignin removed correlated with increasing yields of sugar release. Unfortunately, peracetic acid is expensive, and concentrated forms can be hazardous. To reduce costs and hazards associated with using commercial peracetic acid, we used a hydrolase to catalyze the perhydrolysis of ethyl acetate generating 60-70 mM peracetic acid in situ as a pretreatment to remove lignin from aspen wood. A single pretreatment was insufficient, but multiple cycles (up to eight) removed up to 61.7% of the lignin enabling release of >90% of the sugars during saccharification. This value corresponds to a predicted 581 g of fermentable sugars from 1 kg of aspen wood. Improvements in the enzyme stability are needed before the enzymatically generated peracetic acid is a commercially viable alternative. PMID:19484411

  10. Neonatal (+)-methamphetamine increases brain derived neurotrophic factor, but not nerve growth factor, during treatment and results in long-term spatial learning deficits

    PubMed Central

    Skelton, Matthew R.; Williams, Michael T.; Schaefer, Tori L.; Vorhees, Charles V.

    2009-01-01

    Summary In this study, brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were examined at five time points [postnatal day (P)11, 15, 20, 21, and 68 (the latter with or without behavioral testing)] during and after P11–20 (+)-methamphetamine (MA) (10 mg/ kg 4 × day) treatment. BDNF in MA-treated animals was elevated on P15 and P20 in the hippocampus but not in the hypothalamus and was unchanged on P11 and P21. On P68 (1 h after Morris water maze testing) MA-treated offspring showed a trend toward higher levels of BDNF in the hippocampus than saline-treated animals. MA treatment increased NGF levels in the hippocampus but only on P20. No effect of MA treatment was observed in the elevated zero maze. MA-treated offspring had increased latencies, cumulative distances, path lengths, and first bearings in the Morris water maze. The findings indicate that early MA exposure induces hippocampal BDNF increases that precede the later emergence of spatial learning deficits. PMID:17606327

  11. Improving Cycling Performance: Transcranial Direct Current Stimulation Increases Time to Exhaustion in Cycling

    PubMed Central

    Bertollo, Maurizio; Boggio, Paulo Sergio; Fregni, Felipe

    2015-01-01

    The central nervous system seems to have an important role in fatigue and exercise tolerance. Novel noninvasive techniques of neuromodulation can provide insights on the relationship between brain function and exercise performance. The purpose of this study was to determine the effects of transcranial direct current stimulation (tDCS) on physical performance and physiological and perceptual variables with regard to fatigue and exercise tolerance. Eleven physically active subjects participated in an incremental test on a cycle simulator to define peak power output. During 3 visits, the subjects experienced 3 stimulation conditions (anodal, cathodal, or sham tDCS—with an interval of at least 48 h between conditions) in a randomized, counterbalanced order to measure the effects of tDCS on time to exhaustion at 80% of peak power. Stimulation was administered before each test over 13 min at a current intensity of 2.0 mA. In each session, the Brunel Mood State questionnaire was given twice: after stimulation and after the time-to-exhaustion test. Further, during the tests, the electromyographic activity of the vastus lateralis and rectus femoris muscles, perceived exertion, and heart rate were recorded. RM-ANOVA showed that the subjects performed better during anodal primary motor cortex stimulation (491 ± 100 s) compared with cathodal stimulation (443 ± 11 s) and sham (407 ± 69 s). No significant difference was observed between the cathodal and sham conditions. The effect sizes confirmed the greater effect of anodal M1 tDCS (anodal x cathodal = 0.47; anodal x sham = 0.77; and cathodal x sham = 0.29). Magnitude-based inference suggested the anodal condition to be positive versus the cathodal and sham conditions. There were no differences among the three stimulation conditions in RPE (p = 0.07) or heart rate (p = 0.73). However, as hypothesized, RM- ANOVA revealed a main effect of time for the two variables (RPE and HR: p < 0.001). EMG activity also did not differ during the test accross the different conditions. We conclude that anodal tDCS increases exercise tolerance in a cycling-based, constant-load exercise test, performed at 80% of peak power. Performance was enhanced in the absence of changes in physiological and perceptual variables. PMID:26674200

  12. Increasing Age and Treatment Modality Are Predictors for Subsequent Diagnosis of Bladder Cancer Following Prostate Cancer Diagnosis

    SciTech Connect

    Singh, Anurag K.; Mashtare, Terry L.; McCloskey, Susan A.; Seixas-Mikelus, Stefanie A.; Kim, Hyung L.; May, Kilian Salerno

    2010-11-15

    Purpose: To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer. Methods and Materials: The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded. Results: In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p < 0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. Conclusions: Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted.

  13. Dissolved Organic Nitrogen Inputs from Wastewater Treatment Plant Effluents Increase Responses of Planktonic Metabolic Rates to Warming.

    PubMed

    Vaquer-Sunyer, Raquel; Conley, Daniel J; Muthusamy, Saraladevi; Lindh, Markus V; Pinhassi, Jarone; Kritzberg, Emma S

    2015-10-01

    Increased anthropogenic pressures on coastal marine ecosystems in the last century are threatening their biodiversity and functioning. Global warming and increases in nutrient loadings are two major stressors affecting these systems. Global warming is expected to increase both atmospheric and water temperatures and increase precipitation and terrestrial runoff, further increasing organic matter and nutrient inputs to coastal areas. Dissolved organic nitrogen (DON) concentrations frequently exceed those of dissolved inorganic nitrogen in aquatic systems. Many components of the DON pool have been shown to supply nitrogen nutrition to phytoplankton and bacteria. Predictions of how global warming and eutrophication will affect metabolic rates and dissolved oxygen dynamics in the future are needed to elucidate their impacts on biodiversity and ecosystem functioning. Here, we experimentally determine the effects of simultaneous DON additions and warming on planktonic community metabolism in the Baltic Sea, the largest coastal area suffering from eutrophication-driven hypoxia. Both bacterioplankton community composition and metabolic rates changed in relation to temperature. DON additions from wastewater treatment plant effluents significantly increased the activation energies for community respiration and gross primary production. Activation energies for community respiration were higher than those for gross primary production. Results support the prediction that warming of the Baltic Sea will enhance planktonic respiration rates faster than it will for planktonic primary production. Higher increases in respiration rates than in production may lead to the depletion of the oxygen pool, further aggravating hypoxia in the Baltic Sea. PMID:26356812

  14. Head Injury in Children: Has a Change in Circumstances Caused an Increase in Treatment Numbers?

    PubMed

    Pal'a, Andrej; Kapapa, Melanie; Posovszky, Carsten; Röderer, Götz; König, Ralph; Woischneck, Dieter; Wirtz, Christian Rainer; Kapapa, Thomas

    2015-08-01

    The number of hospitalizations for head injuries in children is rising. The exact causes remain unclear. We analyzed data of children aged between 0 and 18 years who sustained a head injury between 2010 and 2011. The analysis focused on data related to demographics, trauma mechanism, clinical course, results of imaging scans, concomitant injuries, and outcome. A total of 794 inpatient cases of head injury were treated. The leading mechanism of injury was a fall (at home) primarily at the age of 1 to 4 years (46.5%), with the majority of the children sustaining a mild brain injury (764, 96.2%). Neurosurgery was performed in 21 (2.64%) cases; average hospital stay was 2.9 days (range: 0-68 days). This study is not able to confirm that children are increasingly being brought to the hospital by their parents because of new trauma mechanisms or parents' uncertainty, nor can we confirm that the number of nonaccidental injuries is rising. PMID:25370862

  15. Mechanism-Based Combination Treatment Dramatically Increases Therapeutic Efficacy in Murine Globoid Cell Leukodystrophy

    PubMed Central

    Hawkins-Salsbury, Jacqueline A.; Shea, Lauren; Jiang, Xuntian; Hunter, Daniel A.; Guzman, A. Miguel; Reddy, Adarsh S.; Qin, Elizabeth Y.; Li, Yedda; Gray, Steven J.; Ory, Daniel S.

    2015-01-01

    Globoid cell leukodystrophy (GLD, Krabbe disease) is a lysosomal storage disease (LSD) caused by a deficiency in galactocerebrosidase (GALC) activity. In the absence of GALC activity, the cytotoxic lipid, galactosylsphingosine (psychosine), accumulates in the CNS and peripheral nervous system. Oligodendrocytes and Schwann cells are particularly sensitive to psychosine, thus leading to a demyelinating phenotype. Although hematopoietic stem-cell transplantation provides modest benefit in both presymptomatic children and the murine model (Twitcher), there is no cure for GLD. In addition, GLD has been relatively refractory to virtually every experimental therapy attempted. Here, Twitcher mice were simultaneously treated with CNS-directed gene therapy, substrate reduction therapy, and bone marrow transplantation to target the primary pathogenic mechanism (GALC deficiency) and two secondary consequences of GALC deficiency (psychosine accumulation and neuroinflammation). Simultaneously treating multiple pathogenic targets resulted in an unprecedented increase in life span with improved motor function, persistent GALC expression, nearly normal psychosine levels, and decreased neuroinflammation. Treating the primary pathogenic mechanism and secondary targets will likely improve therapeutic efficacy for other LSDs with complex pathological and clinical presentations. PMID:25904800

  16. Increase in cone biomass and terpenophenolics in hops ( Humulus lupulus L.) by treatment with prohexadione-calcium.

    PubMed

    Kavalier, Adam R; Pitra, Nicholi J; Koelling, Jared M; Coles, Mark C; Kennelly, Edward J; Matthews, Paul D

    2011-06-22

    Humulus lupulus L. (hop), a specialty crop bred for flavor characteristics of the inflorescence, is an essential ingredient in beer. Hop inflorescences, commonly known as hop cones, contain terpenophenolic compounds, which are important for beer flavoring and of interest in biomedical research. Hop breeders focus their efforts on increasing cone biomass and terpenophenolic content. As an alternative to traditional breeding, hops were treated with prohexadione-calcium (Pro-Ca), a growth inhibitor previously shown to have positive agronomic effects in several crops. Application of Pro-Ca to hop plants during cone maturation induced increases in cone biomass production by 1.5-19.6% and increased terpenophenolic content by 9.1-87.3%; however, some treatments also induced significant decreases in terpenophenolic content. Induced changes in cone biomass production and terpenophenolic accumulation were most dependent on cultivar and the developmental stage at which plants were treated. PMID:21598976

  17. Investigation of Pitch and Jaw Width to Decrease Delivery Time of Helical Tomotherapy Treatments for Head and Neck Cancer

    SciTech Connect

    Moldovan, Monica; Fontenot, Jonas D.; Gibbons, John P.; Lee, Tae Kyu; Rosen, Isaac I.; Fields, Robert S.; Hogstrom, Kenneth R.

    2011-01-01

    Helical tomotherapy plans using a combination of pitch and jaw width settings were developed for 3 patients previously treated for head and neck cancer. Three jaw widths (5, 2.5, and 1 cm) and 4 pitches (0.86, 0.43, 0.287, and 0.215) were used with a (maximum) modulation factor setting of 4. Twelve plans were generated for each patient using an identical optimization procedure (e.g., number of iterations, objective weights, and penalties, etc.), based on recommendations from TomoTherapy (Madison, WI). The plans were compared using isodose plots, dose volume histograms, dose homogeneity indexes, conformity indexes, radiobiological models, and treatment times. Smaller pitches and jaw widths showed better target dose homogeneity and sparing of normal tissue, as expected. However, the treatment time increased inversely proportional to the jaw width, resulting in delivery times of 24 {+-} 1.9 min for the 1-cm jaw width. Although treatment plans produced with the 2.5-cm jaw were dosimetrically superior to plans produced with the 5-cm jaw, subsequent calculations of tumor control probabilities and normal tissue complication probabilities suggest that these differences may not be radiobiologically meaningful. Because treatment plans produced with the 5-cm jaw can be delivered in approximately half the time of plans produced with the 2.5-cm jaw (5.1 {+-} 0.6 min vs. 9.5 {+-} 1.1 min), use of the 5-cm jaw in routine treatment planning may be a viable approach to decreasing treatment delivery times from helical tomotherapy units.

  18. Increasing Time and Enriching Learning for Greater Equity in Schools: Perspective from Two Community Funders

    ERIC Educational Resources Information Center

    Lopez, Janet; Rivera, Peter

    2015-01-01

    Foundations across the country engage in grantmaking to eliminate the opportunity and achievement gaps in K-12 public schools. Many of the strategies and investments that funders have supported in recent years focus not only on "more time" but also on "better use of time" in schools. This better use of time centers on outcomes…

  19. Effect of medical comorbidity on response to fluoxetine augmentation or dose increase in outpatients with treatment-resistant depression.

    PubMed

    Perlis, Roy H; Iosifescu, Dan V; Alpert, Jonathan; Nierenberg, Andrew A; Rosenbaum, Jerrold F; Fava, Maurizio

    2004-01-01

    This study assessed the effect of general medical comorbidity on response to next-step antidepressant treatments among subjects with major depressive disorder whose depression failed to respond to an 8-week open trial of 20 mg/day of fluoxetine. Of the 386 outpatients in the open trial, 101 who remained depressed were randomly assigned to double-blind treatment with either an increased dose of fluoxetine or lithium or desipramine augmentation for 4 weeks. The Cumulative Illness Rating Scale (CIRS) was used to assess baseline general medical comorbidity, and the Hamilton Depression Rating Scale was used to assess depressive symptoms. Logistic regression analysis showed that CIRS score was not associated with likelihood of remission or premature study discontinuation. Medical comorbidity thus does not appear to be associated with significantly poorer outcome among patients whose major depressive disorder failed initially to respond to an initial trial of 20 mg/day of fluoxetine. PMID:15123848

  20. Increase in pyrolytic carbon optical anisotropy and density during processing of coated particle fuel due to heat treatment

    NASA Astrophysics Data System (ADS)

    Hunn, J. D.; Jellison, G. E., Jr.; Lowden, R. A.

    2008-03-01

    Measurements of pyrolytic carbon optical anisotropy and density have been made on a series of tri-isotropic (TRISO) coated particles prepared for the United States Department of Energy's Advanced Gas Reactor Fuel Development and Qualification (AGR) program. These measurements show the effect of varying the deposition conditions, especially the deposition temperature, on the density and optical anisotropy of the carbon layers. Additional heat treatment studies of the coated particles at various stages illustrate the strong effect of post-deposition thermal processing on these two pyrolytic carbon properties. Such post-deposition heat treatment occurs during SiC deposition and fuel compact firing, resulting in increased anisotropy and density of the pyrolytic carbon layers.

  1. The clock is ticking: the rate and timeliness of antiretroviral therapy initiation from the time of treatment eligibility in Kenya

    PubMed Central

    Odeny, Thomas A; DeCenso, Brendan; Dansereau, Emily; Gasasira, Anne; Kisia, Caroline; Njuguna, Pamela; Haakenstad, Annie; Gakidou, Emmanuela; Duber, Herbert C

    2015-01-01

    Introduction Understanding the determinants of timely antiretroviral therapy (ART) initiation is useful for HIV programmes intent on developing models of care that reduce delays in treatment initiation while maintaining a high quality of care. We analysed patient- and facility-level determinants of time to ART initiation among patients who initiated ART in Kenya. Methods We collected facility-level information and conducted a retrospective chart review of adults initiating ART between 2007 and 2012 at 51 health facilities in Kenya. We evaluated the association between patient- and facility-level covariates at the time of ART eligibility and time to ART initiation. We also explored the determinants associated with timeliness of ART initiation. Results The analysis included 11,942 patients. The median age at the time eligibility was first determined was 37 years (interquartile range [IQR] 31–45). Overall, 75% of patients initiated ART within two months of eligibility. The median CD4 cell count at the time eligibility was first determined rose from 132 (IQR 51–217) in 2007 to 195 (IQR 91–286) in 2011 to 2012 (p<0.001). The cumulative probability of ART initiation among treatment-eligible patients increased over time: 87.1% (95% confidence interval [CI] 85.1–89.0%) in 2007; 96.8% (96.0–97.5%) in 2008; 97.1% (96.3–97.7%) in 2009; 98.5% (98.0 ?98.9%) in 2010; and 99.7% (95% CI 99.4 ?99.8%) in 2011 to 2012 (p<0.0001). In multivariate analyses, attending a health facility with high ART patient volumes within two months of eligibility was considered the key facility-level determinant of ART initiation (adjusted odds ratio 0.57, 95% CI 0.45–0.72, p<0.001). Patient-level determinants included being eligible for ART in the years subsequent to 2007, advanced World Health Organization clinical stage and low CD4 cell count at the time eligibility was first determined. Conclusions Overall, the time between treatment eligibility and ART initiation decreased substantially in Kenya between 2007 and 2012, with uniform gains across different types of health facilities. Our findings highlight the slow increase in CD4 cell counts at the time of ART eligibility over time, indicating that a large number of patients are still beginning ART with advanced HIV disease. Our findings also support the decentralisation of ART services at all health facilities that have the capacity to initiate treatment. Continued evaluation of programme- and country-level data is needed to monitor timeliness of ART initiation as countries continue to expand treatment access. PMID:26507824

  2. Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model

    PubMed Central

    Wikramanayake, Tongyu Cao; Alvarez-Connelly, Elizabeth; Simon, Jessica; Mauro, Lucia M.; Guzman, Javier; Elgart, George; Schachner, Lawrence A.; Chen, Juan; Plano, Lisa R.

    2010-01-01

    Alopecia areata (AA) is a common autoimmune disease characterized by non-scarring hair loss. Previous studies have demonstrated an association between AA and physiological/psychological stress. In this study, we investigated the effects of heat treatment, a physiological stress, on AA development in C3H/HeJ mice. Whereas this strain of mice are predisposed to AA at low incidence by 18 months of age, we observed a significant increase in the incidence of hair loss in heat-treated 8-month-old C3H/HeJ mice compared with sham-treated mice. Histological analysis detected mononuclear cell infiltration in anagen hair follicles, a characteristic of AA, in heat-treated mouse skin. As expected, increased expression of induced HSPA1A/B (formerly called HSP70i) was detected in skin samples from heat-treated mice. Importantly, increased HSPA1A/B expression was also detected in skin samples from C3H/HeJ mice that developed AA spontaneously. Our results suggest that induction of HSPA1A/B may precipitate the development of AA in C3H/HeJ mice. For future studies, the C3H/HeJ mice with heat treatment may prove a useful model to investigate stress response in AA. PMID:20582641

  3. Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model.

    PubMed

    Wikramanayake, Tongyu Cao; Alvarez-Connelly, Elizabeth; Simon, Jessica; Mauro, Lucia M; Guzman, Javier; Elgart, George; Schachner, Lawrence A; Chen, Juan; Plano, Lisa R; Jimenez, Joaquin J

    2010-11-01

    Alopecia areata (AA) is a common autoimmune disease characterized by non-scarring hair loss. Previous studies have demonstrated an association between AA and physiological/psychological stress. In this study, we investigated the effects of heat treatment, a physiological stress, on AA development in C3H/HeJ mice. Whereas this strain of mice are predisposed to AA at low incidence by 18 months of age, we observed a significant increase in the incidence of hair loss in heat-treated 8-month-old C3H/HeJ mice compared with sham-treated mice. Histological analysis detected mononuclear cell infiltration in anagen hair follicles, a characteristic of AA, in heat-treated mouse skin. As expected, increased expression of induced HSPA1A/B (formerly called HSP70i) was detected in skin samples from heat-treated mice. Importantly, increased HSPA1A/B expression was also detected in skin samples from C3H/HeJ mice that developed AA spontaneously. Our results suggest that induction of HSPA1A/B may precipitate the development of AA in C3H/HeJ mice. For future studies, the C3H/HeJ mice with heat treatment may prove a useful model to investigate stress response in AA. PMID:20582641

  4. Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys

    PubMed Central

    Miller, R T; Miksys, S; Hoffmann, E; Tyndale, R F

    2014-01-01

    BACKGROUND AND PURPOSE CYP2D6 metabolizes many centrally acting drugs, neurotoxins and endogenous neurochemicals, and differences in brain levels of CYP2D have been associated with brain function and drug response. Alcohol consumers and smokers have higher levels of CYP2D6 in brain, but not liver, suggesting ethanol and/or nicotine may induce human brain CYP2D6. We investigated the independent and combined effects of chronic ethanol self-administration and nicotine treatment on CYP2D expression in African green monkeys. EXPERIMENTAL APPROACH Forty monkeys were randomized into control, ethanol-only, nicotine-only and ethanol + nicotine groups. Two groups voluntarily self-administered 10% ethanol in sucrose solution for 4 h·day?1, whereas two groups consumed sucrose solution on the same schedule. Two groups received daily s.c. injections of 0.5 mg·kg?1 nicotine in saline bid, whereas two groups were injected with saline on the same schedule. KEY RESULTS Both nicotine and ethanol dose-dependently increased CYP2D in brain; brain mRNA was unaffected, and neither drug altered hepatic CYP2D protein or mRNA. The combination of ethanol and nicotine increased brain CYP2D protein levels to a greater extent than either drug alone (1.2–2.2-fold, P < 0.05 among the eight brain regions assessed). Immunohistochemistry revealed the induction of brain CYP2D protein within specific cell types and regions in the treatment groups. CONCLUSIONS AND IMPLICATIONS Ethanol and nicotine increase brain CYP2D protein levels in monkeys, in a region and treatment-specific manner, suggesting that CNS drug responses, neurodegeneration and personality may be affected among people who consume alcohol and/or nicotine. PMID:24611668

  5. Timing of treatment initiation for mild gestational diabetes and perinatal outcomes

    PubMed Central

    Palatnik, Anna; Mele, Lisa; Landon, Mark B.; Reddy, Uma M.; Ramin, Susan M.; Carpenter, Marshall W.; Wapner, Ronald J.; Varner, Michael W.; Rouse, Dwight J.; Thorp, John M.; Sciscione, Anthony; Catalano, Patrick; Saade, George R.; Caritis, Steve N.; Sorokin, Yoram

    2015-01-01

    Objective To examine the association between gestational age (GA) at the time of treatment initiation for gestational diabetes (GDM) and maternal and perinatal outcomes. Study Design A secondary analysis of a multicenter randomized treatment trial of mild GDM in which women with mild GDM were randomized to treatment versus usual care. The primary outcome of the original trial, as well as this analysis, was a composite perinatal adverse outcome that included neonatal hypoglycemia, hyperbilirubinemia, hyperinsulinemia, and perinatal mortality. Other outcomes examined included the frequency of large for gestational age (LGA), birth weight, neonatal intensive care unit admission (NICU), gestational hypertension / preeclampsia and cesarean delivery. The interaction between GA at treatment initiation (stratified as 24-26 weeks, 27 weeks, 28 weeks, 29 weeks, ?30 weeks) and treatment group (treated vs. routine care), with the outcomes of interest, was used to determine whether GA at treatment initiation was associated with outcome differences. Results Of 958 women analyzed, those who initiated treatment at an earlier GA did not gain an additional treatment benefit compared to those who initiated treatment at a later GA (p-value for interaction with the primary outcome is 0.44). Similarly, there was no evidence that other outcomes were significantly improved by earlier initiation of GDM treatment (LGA p=0.76; NICU admission p=0.8; cesarean delivery p=0.82). The only outcome that had a significant interaction between GA and treatment was gestational hypertension/preeclampsia (p=0.04), although there was not a clear cut GA trend where this outcome improved with treatment. Conclusion Earlier initiation of treatment of mild GDM was not associated with stronger effect of treatment on perinatal outcomes. PMID:26071920

  6. It's about Time! Increasing the Length of Student Classroom Writing without Setting Length Constraints.

    ERIC Educational Resources Information Center

    Passman, Roger

    This paper grew out of the collaborative relationship that emerged from in-class modeling of student-centered writing approaches as participating teachers and a consultant/researcher began to explore ways to increase the length of fourth-grade writing. The paper reports on a small study in fourth-grade writing aimed at increasing the length of…

  7. On reducing the post-heat-treatment time of the weldment

    NASA Astrophysics Data System (ADS)

    Jahanian, S.; Kunde, R. R.; Kuppa, P. V.

    2000-02-01

    Post heat treatment of weldments is one of the most extensively used techniques by the industrial community for relieving welding residual stresses. Such practice not only delays the manufacturing process, but also increases the cost of manufacturing. In this article, an idea of a new welding technique, which is a promising tool for relieving welding residual stresses, is presented. This method is anticipated to reduce the time and cost of the manufacturing process. The first part of the investigation focuses on simulation of an idea by using an auxiliary heat source for creating a weldment with a more uniform temperature distribution both spatially and temporally. A subroutine has been developed for optimizing the size of an auxiliary heat input (AHI). The details of the subroutine and the parameters considered for optimizing the AHI are presented. The results show that by increasing the stabilizing temperature and size of the AHI, the speed of cooling and spatial temperature gradient decreases. This may result in reducing the level of residual stresses.

  8. Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: Preliminary findings.

    PubMed

    Haroon, Ebrahim; Felger, Jennifer C; Woolwine, Bobbi J; Chen, Xiangchuan; Parekh, Samir; Spivey, James R; Hu, Xiaoping P; Miller, Andrew H

    2015-05-01

    Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate turnover by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been found in depression, a disorder associated with increased inflammation. Data by our group have shown increased glutamate as measured by magnetic resonance spectroscopy (MRS) in basal ganglia and dorsal anterior cingulate cortex of patients administered the inflammatory cytokine interferon (IFN)-alpha. Given data that increasing age is associated with an exaggerated CNS inflammatory response, we examined whether older age (>55years) would be associated with a greater IFN-alpha-induced increase in CNS glutamate. Using a longitudinal design, 31 patients with hepatitis C virus (HCV) underwent MRS, blood sampling for inflammatory markers, and behavioral assessments before (Visit 1) and after 4weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly greater increase in glutamate from Visit 1 to Visit 2 as reflected by the glutamate/creatine ratio (Glu/Cr) in left basal ganglia compared to older controls and younger IFN-alpha-treated and untreated subjects. In addition, increased Glu/Cr in older but not younger IFN-alpha-treated and untreated patients was associated with increased tumor necrosis factor, reduced motivation as measured by the Multidimensional Fatigue Inventory and increased choice movement time on the Cambridge Neuropsychological Test Automated Battery. Taken together, these preliminary data support the notion that older age may interact with inflammation to exaggerate the effects of inflammatory stimuli on CNS glutamate and behavior. PMID:25500218

  9. Sleep Restriction Therapy for Insomnia is Associated with Reduced Objective Total Sleep Time, Increased Daytime Somnolence, and Objectively Impaired Vigilance: Implications for the Clinical Management of Insomnia Disorder

    PubMed Central

    Kyle, Simon D.; Miller, Christopher B.; Rogers, Zoe; Siriwardena, A. Niroshan; MacMahon, Kenneth M.; Espie, Colin A.

    2014-01-01

    Study Objectives: To investigate whether sleep restriction therapy (SRT) is associated with reduced objective total sleep time (TST), increased daytime somnolence, and impaired vigilance. Design: Within-subject, noncontrolled treatment investigation. Setting: Sleep research laboratory. Participants: Sixteen patients [10 female, mean age = 47.1 (10.8) y] with well-defined psychophysiological insomnia (PI), reporting TST ? 6 h. Interventions: Patients were treated with single-component SRT over a 4-w protocol, sleeping in the laboratory for 2 nights prior to treatment initiation and for 3 nights (SRT night 1, 8, 22) during the acute interventional phase. The psychomotor vigilance task (PVT) was completed at seven defined time points [day 0 (baseline), day 1,7,8,21,22 (acute treatment) and day 84 (3 mo)]. The Epworth Sleepiness Scale (ESS) was completed at baseline, w 1-4, and 3 mo. Measurement and results: Subjective sleep outcomes and global insomnia severity significantly improved before and after SRT. There was, however, a robust decrease in PSG-defined TST during acute implementation of SRT, by an average of 91 min on night 1, 78 min on night 8, and 69 min on night 22, relative to baseline (P < 0.001; effect size range = 1.60-1.80). During SRT, PVT lapses were significantly increased from baseline (at three of five assessment points, all P < 0.05; effect size range = 0.69-0.78), returning to baseline levels by 3 mo (P = 0.43). A similar pattern was observed for RT, with RTs slowing during acute treatment (at four of five assessment points, all P < 0.05; effect size range = 0.57-0.89) and returning to pretreatment levels at 3 mo (P = 0.78). ESS scores were increased at w 1, 2, and 3 (relative to baseline; all P < 0.05); by 3 mo, sleepiness had returned to baseline (normative) levels (P = 0.65). Conclusion: For the first time we show that acute sleep restriction therapy is associated with reduced objective total sleep time, increased daytime sleepiness, and objective performance impairment. Our data have important implications for implementation guidelines around the safe and effective delivery of cognitive behavioral therapy for insomnia. Citation: Kyle SD; Miller CB; Rogers Z; Siriwardena AN; MacMahon KM; Espie CA. Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder. SLEEP 2014;37(2):229-237. PMID:24497651

  10. Increased Learning Time and Targeted Instruction Improve Academic Skills for At-Risk ESL Learners

    ERIC Educational Resources Information Center

    Nelson, April, Comp.

    2005-01-01

    Students with English as a Second Language (ESL) face two critical challenges: they need to develop English literacy while, at the same time, acquire content knowledge across subject areas. These students need a targeted ESL curriculum from elementary to high school that will allow an extended learning time and opportunities to practice as they…

  11. Examples of Decisions That Increased Risk At Macondo While Potentially Saving Time

    E-print Network

    Boynton, Walter R.

    /or redesigning slurry Yes Saved Time Halliburton (and perhaps BP) on shore Not running cement evaluation log Yes issues Yes Saved Time BP on shore Displacing mud from riser before setting surface cement plug Yes Unclear BP on shore Setting surface cement plug 3000 feet below mud line in seawater Yes Unclear BP

  12. Effects of Feedback Timing on Second Language Vocabulary Learning: Does Delaying Feedback Increase Learning?

    ERIC Educational Resources Information Center

    Nakata, Tatsuya

    2015-01-01

    Feedback, or information given to learners regarding their performance, is found to facilitate second language (L2) learning. Research also suggests that the timing of feedback (whether it is provided immediately or after a delay) may affect learning. The purpose of the present study was to identify the optimal feedback timing for L2 vocabulary…

  13. Increased Nek1 expression in Renal Cell Carcinoma cells is associated with decreased sensitivity to DNA-damaging treatment

    PubMed Central

    Chen, Yumay; Chen, Chi-Fen; Polci, Rosaria; Wei, Randy; Riley, Daniel J.; Chen, Phang-Lang

    2014-01-01

    Renal cell carcinoma (RCC) is a heterogeneous disease with resistance to systemic chemotherapy. Elevated expression of multiple drug resistance (MDR) has been suggested to be one of the mechanisms for this resistance. Here, we provide an alternative mechanism to explain RCC's resistance to chemotherapy-induced apoptosis. Never-in mitosis A-related protein kinase 1 (Nek1) plays an important role in DNA damage response and proper checkpoint activation. The association of Nek1 with the voltage-dependent anion channel (VDAC1) is a critical determinant of cell survival following DNA-damaging treatment. We report here that Nek1 is highly expressed in RCC tumor and cultured RCC cells compared to that of normal renal tubular epithelial cells (RTE). The association between Nek1 and VDAC1 is genotoxic dependent: prolonged Nek1/VDAC1 dissociation will lead to VDAC1 dephosphorylation and initiate apoptosis. Down-regulation of Nek1 expression in RCC cells enhanced their sensitivity to DNA-damaging treatment. Collectively, these results suggest that the increased Nek1 expression in RCC cells maintain persistent VDAC1 phosphorylation, closing its channel and preventing the onset of apoptosis under genotoxic insults. Based on these results, we believe that Nek1 can serve as a potential therapeutic target for drug development in the treatment of RCC. PMID:24970796

  14. Impact of electrode configurations on retention time and domestic wastewater treatment efficiency using microbial fuel cells

    E-print Network

    Impact of electrode configurations on retention time and domestic wastewater treatment efficiency wastewater under continuous flow conditions using microbial fuel cells (MFCs) requires hydraulic retention times (HRTs) that are similar to or less than those of conventional methods such as activated sludge

  15. Capillary Suction Time. Operational Control Tests for Wastewater Treatment Facilities. Instructor's Manual [and] Student Workbook.

    ERIC Educational Resources Information Center

    Wooley, John F.

    Capillary suction time is time required for the liquid phase of a treated sludge to travel through 1 centimeter of media (blotter or filter paper). Designed for individuals who have completed National Pollutant Discharge Elimination System (NPDES) level 1 laboratory training skills, this module provides waste water treatment plant operators with…

  16. Treatment time, outcome, and patient satisfaction comparisons of Damon and conventional brackets.

    PubMed

    Eberting, J J; Straja, S R; Tuncay, O C

    2001-11-01

    Efficiency of treatment mechanics has been a major focus throughout the history of orthodontics. Self-ligating brackets were developed on the premise that elimination of ligature ties creates a friction-free environment and allows for better sliding mechanics. It is expected that the self-ligating bracket will reduce the treatment time. This study was designed to compare the effectiveness and efficiency of Damon self-ligating (SL) brackets to those brackets ligated with either steel ligatures or elastomeric 'O' rings. Not only treatment time and the number of appointments needed were addressed, but the quality of the treatment outcome was also assessed. American Board of Orthodontics (ABO) grading criteria for models and panoramic radiographs were employed. Additionally, a nine-question survey was sent to the 215-patients in this study (108 Damon, 107 conventionally-ligated) to elicit their perceptions of how their orthodontic treatment progressed and finished. The results showed that patients treated with Damon SL brackets had significantly lower treatment times, required significantly fewer appointments, and had significantly higher ABO scores than those treated with conventionally-ligated edgewise brackets. There were no significant differences in Damon or non-Damon ABO scores with respect to gender. Damon patients over the age of 21 had significantly higher ABO scores. Conversely, the non-Damon patients under the age of 21 had significantly higher ABO scores. For pre-treatment Angle classification, no significant differences were noted. Patient responses showed that Damon patients perceived their treatment time as being shorter than expected. It appears that faster orthodontic treatment can be better as measured by the ABO criteria. PMID:11683812

  17. Changing to daylight saving time cuts into sleep and increases workplace injuries.

    PubMed

    Barnes, Christopher M; Wagner, David T

    2009-09-01

    The authors examine the differential influence of time changes associated with Daylight Saving Time on sleep quantity and associated workplace injuries. In Study 1, the authors used a National Institute for Occupational Safety and Health database of mining injuries for the years 1983-2006, and they found that in comparison with other days, on Mondays directly following the switch to Daylight Saving Time-in which 1 hr is lost-workers sustain more workplace injuries and injuries of greater severity. In Study 2, the authors used a Bureau of Labor Statistics database of time use for the years 2003-2006, and they found indirect evidence for the mediating role of sleep in the Daylight Saving Time-injuries relationship, showing that on Mondays directly following the switch to Daylight Saving Time, workers sleep on average 40 min less than on other days. On Mondays directly following the switch to Standard Time-in which 1 hr is gained-there are no significant differences in sleep, injury quantity, or injury severity. PMID:19702372

  18. Acute nicotine treatment attenuates lipopolysaccharide-induced cognitive dysfunction by increasing BDNF expression and inhibiting neuroinflammation in the rat hippocampus.

    PubMed

    Wei, Penghui; Liu, Qingshen; Li, Dong; Zheng, Qiang; Zhou, Jinfeng; Li, Jianjun

    2015-09-14

    Although nicotine has been shown to improve cognitive function in various studies, the mechanisms underlying acute nicotine treatment-induced neuroprotection remain incompletely understood. In this study, we evaluated the effect of acute nicotine treatment on the cognitive impairment induced by lipopolysaccharide (LPS) and explored the underlying mechanism. We found that acute nicotine injection markedly attenuated LPS-elicited cognitive deficits and suppressed the strong LPS-induced release of IL-1?, IL-6, and TNF-? into serum and the dorsal hippocampus at 4 and 24h after LPS injection. Western blot analysis indicated a clear increase in the levels of cleaved caspase-3 in LPS-treated animals but not in nicotine- or saline-treated animals. Furthermore, nicotine administration led to a significant increase in BDNF mRNA expression at 4 and 24h and in BDNF protein expression at 24h after LPS injection in the dorsal hippocampus. Taken together, acute nicotine administration attenuated LPS-induced cognitive dysfunction, and this neuroprotective effect may be related to the up-regulation of BDNF and the inhibition of neuroinflammation and apoptosis-related proteins in the dorsal hippocampus. PMID:26259694

  19. Increased viability but decreased culturability of Mycobacterium avium subsp. paratuberculosis in macrophages from inflammatory bowel disease patients under Infliximab treatment.

    PubMed

    Nazareth, Nair; Magro, Fernando; Appelberg, Rui; Silva, Jani; Gracio, Daniela; Coelho, Rosa; Cabral, José Miguel; Abreu, Candida; Macedo, Guilherme; Bull, Tim J; Sarmento, Amélia

    2015-12-01

    Mycobacterium avium subsp. paratuberculosis (MAP) has long been implicated as a triggering agent in Crohn's disease (CD). In this study, we investigated the growth/persistence of both M. avium subsp. hominissuis (MAH) and MAP, in macrophages from healthy controls (HC), CD and ulcerative colitis patients. For viability assessment, both CFU counts and a pre16SrRNA RNA/DNA ratio assay (for MAP) were used. Phagolysosome fusion was evaluated by immunofluorescence, through analysis of LAMP-1 colocalization with MAP. IBD macrophages were more permissive to MAP survival than HC macrophages (a finding not evident with MAH), but did not support MAP active growth. The lower MAP CFU counts in macrophage cultures associated with Infliximab treatment were not due to increased killing, but possibly to elevation in the proportion of intracellular dormant non-culturable MAP forms, as MAP showed higher viability in those macrophages. Increased MAP viability was not related to lack of phagolysosome maturation. The predominant induction of MAP dormant forms by Infliximab treatment may explain the lack of MAP reactivation during anti-TNF therapy of CD but does not exclude the possibility of MAP recrudescence after termination of therapy. PMID:25702170

  20. Wait times for publicly funded addiction and problem gambling treatment agencies in Ontario, Canada

    PubMed Central

    2013-01-01

    Background This study describes the definitions of wait times and intake processes used by drug and problem gambling treatment agencies in Ontario, Canada, as well as the various strategies employed to ameliorate client backlog. Methods An online survey was developed and distributed to 203 publicly-funded, provincial substance use and problem gambling treatment agencies from June to August, 2011. All aspects of the intake process were covered in the survey. Results Based on 139 responses, six different wait time periods were identified. Additional analyses were completed by type of service offered. Suggestions for effective interventions to shorten wait times and recommendations for future research are provided. Conclusion The results of this study highlight a need for standardized definitions of wait times across substance use and problem gambling treatment services. PMID:24252217

  1. Chronic treatment with olanzapine increases adiposity by changing fuel substrate and causes desensitization of the acute metabolic side effects.

    PubMed

    Girault, Elodie M; Guigas, Bruno; Alkemade, Anneke; Foppen, Ewout; Ackermans, Mariëtte T; la Fleur, Susanne E; Fliers, Eric; Kalsbeek, Andries

    2014-02-01

    Atypical antipsychotic drugs such as olanzapine induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these metabolic side-effects are unknown at the moment. In this study, we investigated the metabolic changes induced by a chronic treatment, as well as the influence of a preceding chronic treatment on the acute effects of olanzapine on glucose metabolism. The effect of chronic olanzapine treatment (±6.5 mg/kg/day, administered via drinking water) on body weight, locomotor activity, body temperature, fat distribution and energy expenditure was investigated in male rats. After 5 weeks, the animals received an acute olanzapine challenge (intragastric, IG) at 3 mg/kg/h during 160 min to investigate the acute effects of olanzapine on glucose metabolism. Chronic olanzapine-treated animals showed a slight decrease in nocturnal body temperature, and increased perirenal fat pad weights as well as plasma leptin. In addition, chronic olanzapine-treated animals showed hyperinsulinaemia with unchanged blood glucose concentrations. The acute challenge with IG olanzapine elevated blood glucose levels and endogenous glucose production in control animals, but not in chronic olanzapine-pre-treated rats. Chronic olanzapine-treated animals also showed reduced locomotor activity and a higher respiratory exchange ratio. Thus, chronic treatment with olanzapine in rats causes desensitization to its acute effects on glucose metabolism but promotes adiposity probably due to a shift from lipids to carbohydrates as an energy source. Chronic exposure to olanzapine changes body fat distribution and insulin sensitivity in an unfavourable direction, but it is still unclear what the primary mechanism is. PMID:24190543

  2. Increasing Pyruvate Dehydrogenase Flux as a Treatment for Diabetic Cardiomyopathy: A Combined 13C Hyperpolarized Magnetic Resonance and Echocardiography Study

    PubMed Central

    Le Page, Lydia M.; Rider, Oliver J.; Lewis, Andrew J.; Ball, Vicky; Clarke, Kieran; Johansson, Edvin; Carr, Carolyn A.; Heather, Lisa C.; Tyler, Damian J.

    2015-01-01

    Although diabetic cardiomyopathy is widely recognised, there are no specific treatments available. Altered myocardial substrate selection has emerged as a candidate mechanism behind the development of cardiac dysfunction in diabetes. As pyruvate dehydrogenase (PDH) activity appears central to the balance of substrate utilisation, we aimed to investigate the relationship between PDH flux and myocardial function in a rodent model of type-II diabetes and to explore whether or not increasing PDH flux, with dichloroacetate, would restore the balance of substrate utilisation and improve cardiac function. All animals underwent in vivo hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy and echocardiography to assess cardiac PDH flux and function respectively. Diabetic animals showed significantly higher blood glucose (10.8±0.7mM vs 8.4±0.5mM), lower PDH flux (0.005±0.001s?1 vs 0.017±0.002s?1) and significantly impaired diastolic function (E/E’ 12.2±0.8 vs 20±2) in keeping with early diabetic cardiomyopathy. Twenty-eight days treatment with dichloroacetate restored PDH flux to normal levels (0.018±0.002s?1), reversed diastolic dysfunction (E/E’ 14±1) and normalized blood glucose (7.5±0.7mM). Treatment of diabetes with dichloroacetate therefore restored the balance of myocardial substrate selection, reversed diastolic dysfunction and normalised blood glucose levels. This suggests that PDH modulation could be a novel therapy for the treatment and/or prevention of diabetic cardiomyopathy. PMID:25795215

  3. A Proton Beam Therapy System Dedicated to Spot-Scanning Increases Accuracy with Moving Tumors by Real-Time Imaging and Gating and Reduces Equipment Size

    PubMed Central

    Shimizu, Shinichi; Miyamoto, Naoki; Matsuura, Taeko; Fujii, Yusuke; Umezawa, Masumi; Umegaki, Kikuo; Hiramoto, Kazuo; Shirato, Hiroki

    2014-01-01

    Purpose A proton beam therapy (PBT) system has been designed which dedicates to spot-scanning and has a gating function employing the fluoroscopy-based real-time-imaging of internal fiducial markers near tumors. The dose distribution and treatment time of the newly designed real-time-image gated, spot-scanning proton beam therapy (RGPT) were compared with free-breathing spot-scanning proton beam therapy (FBPT) in a simulation. Materials and Methods In-house simulation tools and treatment planning system VQA (Hitachi, Ltd., Japan) were used for estimating the dose distribution and treatment time. Simulations were performed for 48 motion parameters (including 8 respiratory patterns and 6 initial breathing timings) on CT data from two patients, A and B, with hepatocellular carcinoma and with clinical target volumes 14.6 cc and 63.1 cc. The respiratory patterns were derived from the actual trajectory of internal fiducial markers taken in X-ray real-time tumor-tracking radiotherapy (RTRT). Results With FBPT, 9/48 motion parameters achieved the criteria of successful delivery for patient A and 0/48 for B. With RGPT 48/48 and 42/48 achieved the criteria. Compared with FBPT, the mean liver dose was smaller with RGPT with statistical significance (p<0.001); it decreased from 27% to 13% and 28% to 23% of the prescribed doses for patients A and B, respectively. The relative lengthening of treatment time to administer 3 Gy (RBE) was estimated to be 1.22 (RGPT/FBPT: 138 s/113 s) and 1.72 (207 s/120 s) for patients A and B, respectively. Conclusions This simulation study demonstrated that the RGPT was able to improve the dose distribution markedly for moving tumors without very large treatment time extension. The proton beam therapy system dedicated to spot-scanning with a gating function for real-time imaging increases accuracy with moving tumors and reduces the physical size, and subsequently the cost of the equipment as well as of the building housing the equipment. PMID:24747601

  4. Time dependent pre-treatment EPID dosimetry for standard and FFF VMAT.

    PubMed

    Podesta, Mark; Nijsten, Sebastiaan M J J G; Persoon, Lucas C G G; Scheib, Stefan G; Baltes, Christof; Verhaegen, Frank

    2014-08-21

    Methods to calibrate Megavoltage electronic portal imaging devices (EPIDs) for dosimetry have been previously documented for dynamic treatments such as intensity modulated radiotherapy (IMRT) using flattened beams and typically using integrated fields. While these methods verify the accumulated field shape and dose, the dose rate and differential fields remain unverified. The aim of this work is to provide an accurate calibration model for time dependent pre-treatment dose verification using amorphous silicon (a-Si) EPIDs in volumetric modulated arc therapy (VMAT) for both flattened and flattening filter free (FFF) beams. A general calibration model was created using a Varian TrueBeam accelerator, equipped with an aS1000 EPID, for each photon spectrum 6?MV, 10?MV, 6?MV-FFF, 10?MV-FFF. As planned VMAT treatments use control points (CPs) for optimization, measured images are separated into corresponding time intervals for direct comparison with predictions. The accuracy of the calibration model was determined for a range of treatment conditions. Measured and predicted CP dose images were compared using a time dependent gamma evaluation using criteria (3%, 3?mm, 0.5?sec). Time dependent pre-treatment dose verification is possible without an additional measurement device or phantom, using the on-board EPID. Sufficient data is present in trajectory log files and EPID frame headers to reliably synchronize and resample portal images. For the VMAT plans tested, significantly more deviation is observed when analysed in a time dependent manner for FFF and non-FFF plans than when analysed using only the integrated field. We show EPID-based pre-treatment dose verification can be performed on a CP basis for VMAT plans. This model can measure pre-treatment doses for both flattened and unflattened beams in a time dependent manner which highlights deviations that are missed in integrated field verifications. PMID:25088064

  5. Treatment and technical intervention time analysis of a robotic stereotactic radiotherapy system.

    PubMed

    Crop, F; Lacornerie, T; Szymczak, H; Felin, A; Bailleux, C; Mirabel, X; Lartigau, E

    2014-02-01

    The purpose of this study is to obtain a better operational knowledge of Stereotactic Body Radiotherapy (SBRT) treatments with CyberKnife(r). An analysis of both In-room Times (IRT) and technical interventions of 5 years of treatments was performed, during which more than 1600 patients were treated for various indications, including liver (21%), lung (29%), intracranial (13%), head and neck (11%) and prostate (7%). Technical interventions were recorded along with the time of the failure, time to the intervention, and the complexity and duration of the repair. Analyses of Time Between Failures (TBF) and Service Disrupting TBF(disr) were performed. Treatment time data and variability per indication and following different system upgrades were evaluated. Large variations of IRTs were found between indications, but also large variations for each indication. The combination of the time reduction Tool (using Iris(r)) and Improved Stop Handling was of major impact to shortening of treatment times. The first implementation of the Iris collimator alone did not lead to significantly shorter IRTs for us except during prostate treatments. This was mostly due to the addition at the same time of larger rotational compensation for prostate treatments (58 instead of 1.58). Significant differences of duration between the first fraction and following fractions of a treatment, representing the necessity of defining imaging parameters and explanation to patients, were found for liver (12 min) and lung treatments using Xsight(r) Spine (5 min). Liver and lung treatments represent the longest IRT's and involve the largest variability's in IRT. The malfunction rate of the system followed a Weibull distribution with the shape and scale parameters of 0.8 and 39.7. Mean TBF(disr) was 68 work hours. 60 to 80% of the service disrupting interventions were resolved within 30-60 min, 5% required external intervention and 30% occurred in the morning. The presented results can be applied in the evaluation of the required machine time in order to implement robotic radiosurgery for different indications. The analytical distributions of IRTs and technical interruptions can be used for simulations. PMID:23862744

  6. Video-Assisted Thoracoscopic Surgery for the Treatment of First-Time Spontaneous Pneumothorax versus Conservative Treatment

    PubMed Central

    Al-Mourgi, Majed; Alshehri, Fahad

    2015-01-01

    Background and aim of the work Recent studies have shown that video-assisted thoracoscopy (VATS) is safe and beneficial as first time treatment for patients presenting with primary spontaneous pneumothorax (PSP). In this study we will compare the outcome of patients presenting with first time PSP treated by VATS with those treated conservatively. Material and methods This was a prospective double-blind, randomized clinical trial conducted at our hospital, Forty one patients, presented to the hospital with first attack PSP from January 2010 to January 2013, were randomized to be treated by chest tube drainage (conservative group, group 1) or by primary video-assisted thoracoscopy (VATS group, group 2). Outcomes were; duration of intercostal tube drainage, mean hospital stay, and recurrence rates of pneumothorax during the period of follow up. Results There was no significant difference in both groups regarding demographic data. The mean durations of removal of intercostal tube and hospital stay were significantly higher in conservative group than in VATS group. The recurrence rate in conservative group was 40.9% versus 0% in VATS group (highly significant). Conclusions Initial VATS is considered an efficient treatment modality for PSP as it has a shorter hospital stay and lower recurrence than conservative treatment, which if occurs, requires re-hospitalization with needs for VATS or surgery. PMID:26715922

  7. GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment.

    PubMed

    Wilson, Gabriel J; Lennox, Brittany A; She, Pengxiang; Mirek, Emily T; Al Baghdadi, Rana J T; Fusakio, Michael E; Dixon, Joseph L; Henderson, Gregory C; Wek, Ronald C; Anthony, Tracy G

    2015-02-15

    The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis. PMID:25491724

  8. Method and computer product to increase accuracy of time-based software verification for sensor networks

    DOEpatents

    Foo Kune, Denis (Saint Paul, MN); Mahadevan, Karthikeyan (Mountain View, CA)

    2011-01-25

    A recursive verification protocol to reduce the time variance due to delays in the network by putting the subject node at most one hop from the verifier node provides for an efficient manner to test wireless sensor nodes. Since the software signatures are time based, recursive testing will give a much cleaner signal for positive verification of the software running on any one node in the sensor network. In this protocol, the main verifier checks its neighbor, who in turn checks its neighbor, and continuing this process until all nodes have been verified. This ensures minimum time delays for the software verification. Should a node fail the test, the software verification downstream is halted until an alternative path (one not including the failed node) is found. Utilizing techniques well known in the art, having a node tested twice, or not at all, can be avoided.

  9. Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy

    SciTech Connect

    Suzuki, Kazumichi; Gillin, Michael T.; Sahoo, Narayan; Zhu, X. Ronald; Lee, Andrew K.; Lippy, Denise

    2011-07-15

    Purpose: To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. Methods: The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. Results: The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 {+-} 35 patients. Conclusions: This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.

  10. Save Time and Increase Social Media Reach by Using IFTTT--If This, Then That

    ERIC Educational Resources Information Center

    Skrabut, Stan

    2014-01-01

    Extension educators, staff, and specialists are finding that social media tools such as Facebook, Twitter, YouTube, and blogs are powerful ways to disseminate educational content, announce events, and promote Extension services. The challenge to using all of these various tools is the lack of time. Tools such as IFTTT (If This, Then That) can help…

  11. INCREASING THE HOLDING TIME AT 15 C OF BOAR SPERMATOZOA BEFORE FREEZING DECREASES FERTILITY AFTER THAWING.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An experiment was conducted to determine the effect of pre-freeze holding time and commercial extender type on boar spermatozoa viability and fertility. One ejaculate from each of six boars was held in two commercial boar semen extenders, Beltsville Thawing Solution and Androhep Plus, for either 3 o...

  12. The Struggle for Identity in Today's Schools: Cultural Recognition in a Time of Increasing Diversity

    ERIC Educational Resources Information Center

    Jenlink, Patrick M., Ed; Townes, Faye Hicks, Ed

    2009-01-01

    The "Struggle for Identity in Today's Schools" examines cultural recognition and the struggle for identity in America's schools. In particular, the contributing authors focus on the recognition and misrecognition as antagonistic cultural forces that work to shape, and at times distort identity. What surfaces throughout the chapters are two lessons…

  13. Using multiple timescale models for the evaluation of a time-dependent treatment.

    PubMed

    Rebora, Paola; Galimberti, Stefania; Valsecchi, Maria Grazia

    2015-12-10

    In survival analysis, the absolute measure of cumulative risk provided by the Kaplan-Meier estimator is still the most used quantity for its easy calculation and direct interpretability. However, for describing the survival after an intervention that may occur at different times from baseline observation, the Kaplan-Meier estimator generally yields to biased results if intervention is considered as fixed at baseline. The main focus of the present paper is to extend the use of a multiple timescale model in the presence of a time dependent intervention. The aim is to obtain 1) an estimate of treatment effect in terms of hazard ratios by flexible modeling, 2) a valid prediction tool, i.e. estimate of prognosis for a patient who changes treatment later in time, and 3) an appropriate graphical representation of survival in the presence of a time dependent treatment change, accounting for different timescales. We will show the advantages of this approach on the comparison of chemotherapy versus transplant in children with high-risk acute lymphoblastic leukemia in first remission. We considered a model with two timescales that accounts for the change in treatment at different times in the disease course. An alternative approach to survival estimates is also proposed which has some advantages over the traditional landmark approach: it uses all the data available to plot survival from the date of remission, it avoids the arbitrary choice of a landmark time and explicitly models the change in hazard due to transplant. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26215851

  14. Environmental enrichment preceding early adulthood methylphenidate treatment leads to long term increase of corticosterone and testosterone in the rat.

    PubMed

    Avital, Avi; Dolev, Talya; Aga-Mizrachi, Shlomit; Zubedat, Salman

    2011-01-01

    Attention-deficit/hyperactivity disorder (ADD/ADHD) has been emerging as a world-wide psychiatric disorder. There appears to be an increasing rate of stimulant drug abuse, specifically methylphenidate (MPH) which is the most common treatment for ADHD, among individuals who do not meet the criteria for ADHD and particularly for cognitive enhancement among university students. However, the long term effects of exposure to MPH are unknown. Thus, in light of a developmental approach in humans, we aimed to test the effects of adolescence exposure to enriched environment (EE) followed by MPH administration during early adulthood, on reactions to stress in adulthood. Specifically, at approximate adolescence [post natal days (PND) 30-60] rats were reared in EE and were treated with MPH during early adulthood (PND 60-90). Adult (PND 90-92) rats were exposed to mild stress and starting at PND 110, the behavioral and endocrine effects of the combined drug and environmental conditions were assessed. Following adolescence EE, long term exposure to MPH led to decreased locomotor activity and increased sucrose preference. EE had a beneficial effect on PPI (attentive abilities), which was impaired by long term exposure to MPH. Finally, the interaction between EE and, exposure to MPH led to long-term elevated corticosterone and testosterone levels. In view of the marked increase in MPH consumption over the past decade, vigilance is crucial in order to prevent potential drug abuse and its long term detrimental consequences. PMID:21789212

  15. Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.

    PubMed

    Taylor, Adam; Sheng, Kuo-Ching; Herrero, Lara J; Chen, Weiqiang; Rulli, Nestor E; Mahalingam, Suresh

    2013-01-01

    Part of the Togaviridae family, alphaviruses, including chikungunya virus (CHIKV), Sindbis virus (SINV) and Ross River virus (RRV), are able to cause significant inflammatory pathologies ranging from arthritis to encephalitis. Following symptomatic infection with arthritis-associated alphaviruses, patients often experience severe joint pain, affecting distal and small joints, which can last six months or longer. Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug (DMARD), was used to treat patients experiencing chronic rheumatic symptoms following infection with CHIKV. Here, the effect of MTX on Ross River virus disease (RRVD) in mice was examined to better understand its therapeutic potential for alphaviral-induced musculoskeletal disease and to further our knowledge of the development of alphaviral pathologies. Using a mouse model, we analyzed the effect of MTX on RRVD. RRV disease pathogenesis in response to MTX treatment was determined by measuring levels of proinflammatory factors, cellular infiltrates, viral titer and histological analysis of infected tissues. RRV-infected mice receiving MTX treatment rapidly developed musculoskeletal disease, which correlated with a significant influx of inflammatory cell infiltrates into the skeletal muscle tissue. Although no difference was observed in the level of proinflammatory cytokines and chemokines, the viral load increased at early time points post infection in the serum and quadriceps of MTX treated mice, possibly contributing to disease pathogenesis. Results suggest that MTX treatment of acute RRVD in mice provides no therapeutic benefit and underline the importance of inflammatory monocytes in alphaviral induced arthritides. PMID:23951095

  16. Increased lymphocyte apoptosis in mouse models of colitis upon ABT-737 treatment is dependent upon BIM expression.

    PubMed

    Lutz, C; Mozaffari, M; Tosevski, V; Caj, M; Cippà, P; McRae, B L; Graff, C L; Rogler, G; Fried, M; Hausmann, M

    2015-08-01

    Exaggerated activation of lymphocytes contributes to the pathogenesis of inflammatory bowel disease (IBD). Medical therapies are linked to the BCL-2 family-mediated apoptosis. Imbalance in BCL-2 family proteins may cause failure in therapeutic responses. We investigated the role of BCL-2 inhibitor ABT-737 for lymphocyte apoptosis in mice under inflammatory conditions. B.6129P2-interleukin (IL)-10(tm1Cgn) /J (IL-10(-/-) ) weighing 25-30 g with ongoing colitis were used. Fifty mg/kg/day ABT-737 was injected intraperitoneally (i.p.). Haematological analyses were performed with an ADVIA 2120 flow cytometer and mass cytometry with a CyTOF 2. Following i.p. administration, ABT-737 was detected in both spontaneous and acute colitis in peripheral blood (PBL) and colon tissue. Treatment led to lymphopenia. CD4(+) CD44(+) CD62L(+) central memory and CD8(+) , CD44(+) CD62L(-) central memory T cells were decreased in PBL upon ABT-737 compared to vehicle-receiving controls. Increased apoptosis upon ABT-737 was determined in blood lymphocytes, splenocytes and Peyer's patches and was accompanied by a decrease in TNF and IL-1B. ABT-737 positively altered the colonic mucosa and ameliorated inflammation, as shown by colonoscopy, histology and colon length. A decreased BIM/BCL-2 ratio or absence of BIM in both Bim(-) (/) (-) and Il10(-) (/) (-) × Bim(-) (/) (-) impeded the protective effect of ABT-737. The BIM/BCL-2 ratio decreased with age and during the course of treatment. Thus, long-term treatment resulted in adapted TNF levels and macroscopic mucosal damage. ABT-737 was efficacious in diminishing lymphocytes and ameliorating colitis in a BIM-dependent manner. Regulation of inappropriate survival of lymphocytes by ABT-737 may provide a therapeutic strategy in IBD. PMID:25845418

  17. [Corrigendum] Naotaifang extract treatment results in increased ferroportin expression in the hippocampus of rats subjected to cerebral ischemia.

    PubMed

    Liao, Jun; Xia, Xing; Wang, Guo-Zuo; Shi, Yong-Mei; Ge, Jin-Wen

    2016-01-01

    Following the publication of this article, an interested reader drew to our attention anomalies associated with the presentation of Figs. 1 and 4. The image selected for Fig. 1A, the data pertaining to '2 h', was inadvertently selected for Fig. 4A, the image labeled 'Sham'. Additionally, in Fig. 4, the same source image had inadvertently been used to provide the images for the 'Low dose group' and 'Model' panels (although the view presented differed in these panels). On re?examining our data, we realized that these errors had occurred during the compilation of Fig. 4, and that the images were correctly selected for Fig. 1. An amended version of Fig. 4 is presented below, featuring images which correctly show the data for the 'Low dose', 'Sham' and 'Model' groups. The immunohistochemical results suggested that, following treatment with 27 g/kg naotaifang extract, the expression of Fpn increased significantly compared with the other treatment doses (P<0.05), whereas significant changes were not observed among the other groups (P>0.05). The errors made in the selection of certain images for Fig. 4A did not affect the overall conclusions reported in the present study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused. [the original article was published in the Molecular Medicine Reports 11: 4047-4052, 2015; DOI: 10.3892/mmr.2015.3309]. PMID:26648551

  18. E. Effects On Time and Quality of Learning with Increasing the Number of Variables

    E-print Network

    Brown, Laura E.

    on the Child, Insurance, Alarm, Hailfinder tiled networks. SuppAppendices.tex; 5/08/2005; 16:18; p.44 #12;45 0 of Variables in Network LogNorm.TimeofGS Norm. Time Results Greedy Search SS=500 Child Insurance Alarm Hail Results Greedy Search SS=500 Child Insurance Alarm HailFinder 0 100 200 300 400 500 600 10 -1 10 0 10 1 10

  19. A Course-Based Research Experience: How Benefits Change with Increased Investment in Instructional Time

    PubMed Central

    Shaffer, Christopher D.; Alvarez, Consuelo J.; Bednarski, April E.; Dunbar, David; Goodman, Anya L.; Reinke, Catherine; Rosenwald, Anne G.; Wolyniak, Michael J.; Bailey, Cheryl; Barnard, Daron; Bazinet, Christopher; Beach, Dale L.; Bedard, James E. J.; Bhalla, Satish; Braverman, John; Burg, Martin; Chandrasekaran, Vidya; Chung, Hui-Min; Clase, Kari; DeJong, Randall J.; DiAngelo, Justin R.; Du, Chunguang; Eckdahl, Todd T.; Eisler, Heather; Emerson, Julia A.; Frary, Amy; Frohlich, Donald; Gosser, Yuying; Govind, Shubha; Haberman, Adam; Hark, Amy T.; Hauser, Charles; Hoogewerf, Arlene; Hoopes, Laura L. M.; Howell, Carina E.; Johnson, Diana; Jones, Christopher J.; Kadlec, Lisa; Kaehler, Marian; Silver Key, S. Catherine; Kleinschmit, Adam; Kokan, Nighat P.; Kopp, Olga; Kuleck, Gary; Leatherman, Judith; Lopilato, Jane; MacKinnon, Christy; Martinez-Cruzado, Juan Carlos; McNeil, Gerard; Mel, Stephanie; Mistry, Hemlata; Nagengast, Alexis; Overvoorde, Paul; Paetkau, Don W.; Parrish, Susan; Peterson, Celeste N.; Preuss, Mary; Reed, Laura K.; Revie, Dennis; Robic, Srebrenka; Roecklein-Canfield, Jennifer; Rubin, Michael R.; Saville, Kenneth; Schroeder, Stephanie; Sharif, Karim; Shaw, Mary; Skuse, Gary; Smith, Christopher D.; Smith, Mary A.; Smith, Sheryl T.; Spana, Eric; Spratt, Mary; Sreenivasan, Aparna; Stamm, Joyce; Szauter, Paul; Thompson, Jeffrey S.; Wawersik, Matthew; Youngblom, James; Zhou, Leming; Mardis, Elaine R.; Buhler, Jeremy; Leung, Wilson; Lopatto, David; Elgin, Sarah C. R.

    2014-01-01

    There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. An alumni survey revealed that time spent on a research project is also a significant factor in the value former students assign to the experience one or more years later. We conclude: 1) implementation of a bioinformatics project within the biology curriculum provides a mechanism for successfully engaging large numbers of students in undergraduate research; 2) benefits to students are achievable at a wide variety of academic institutions; and 3) successful implementation of course-based research experiences requires significant investment of instructional time for students to gain full benefit. PMID:24591510

  20. Semi-aerobic fermentation as a novel pre-treatment to obtain VFA and increase methane yield from primary sludge.

    PubMed

    Peces, M; Astals, S; Clarke, W P; Jensen, P D

    2016-01-01

    There is a growing trend to consider organic wastes as potential sources of renewable energy and value-add products. Fermentation products have emerged as attractive value-add option due to relative easy production and broad application range. However, pre-fermentation and extraction of soluble products may impact down-stream treatment processes, particularly energy recovery by anaerobic digestion. This paper investigates primary sludge pre-fermentation at different temperatures (20, 37, 55, and 70°C), treatment times (12, 24, 48, and 72h), and oxygen availability (semi-aerobic, anaerobic); and its impact on anaerobic digestion. Pre-fermentation at 20 and 37°C succeeded for VFA production with acetate and propionate being major products. Pre-fermentation at 37, 55, and 70°C resulted in higher solubilisation yield but it reduced sludge methane potential by 20%. Under semi-aerobic conditions, pre-fermentation allowed both VFA recovery (43gCODVFAkg(-1)VS) and improved methane potential. The latter phenomenon was linked to fungi that colonised the sludge top layer during pre-fermentation. PMID:26551651

  1. Impact of Treatment Time on the Survival of Patients Suffering From Invasive Fungal Rhinosinusitis

    PubMed Central

    Piromchai, Patorn; Thanaviratananich, Sanguansak

    2014-01-01

    BACKGROUND Invasive fungal rhinosinusitis is an uncommon disease with high mortality rates. There is currently no consensus on the best treatment timing. We studied the impact of the treatment timing on the survival of patients experiencing invasive fungal rhinosinusitis. METHODS We conducted a retrospective study of patients suffering from invasive fungal rhinosinusitis. The duration of symptoms, clinical presentations, clinical signs, diagnoses, treatments, and outcomes were collected. RESULTS It was observed that more than 70% of the mortalities occurred within the subgroup of patients who exhibited symptoms of the disease within 14 days before admission. After adjusting for the confounders, the time taken to treat the patients was the most statistically significant predictor for mortality (P = 0.045). We found no significant relationships between mortality and its significant covariates, which included the underlying diseases (P = 0.91) or complications (P = 0.55). CONCLUSIONS Our study demonstrates that the time taken to treat the patients is an important determinant for the survival of patients who are afflicted with invasive fungal rhinosinusitis. The appropriate treatments should be administered within 14 days from the time the symptoms begin to manifest. PMID:25288891

  2. Disruption of IGF-1R signaling increases TRAIL-induced apoptosis: A new potential therapy for the treatment of melanoma

    SciTech Connect

    Karasic, Thomas B.; Hei, Tom K.; Ivanov, Vladimir N.

    2010-07-15

    Resistance of cancer cells to apoptosis is dependent on a balance of multiple genetic and epigenetic mechanisms, which up-regulate efficacy of the surviving growth factor-receptor signaling pathways and suppress death-receptor signaling pathways. The Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling pathway is highly active in metastatic melanoma cells by mediating downstream activation of PI3K-AKT and MAPK pathways and controlling general cell survival and proliferation. In the present study, we used human melanoma lines with established genotypes that represented different phases of cancer development: radial-growth-phase WM35, vertical-growth-phase WM793, metastatic LU1205 and WM9 [1]. All these lines have normal NRAS. WM35, WM793, LU1205 and WM9 cells have mutated BRAF (V600E). WM35 and WM9 cells express normal PTEN, while in WM793 cells PTEN expression is down-regulated; finally, in LU1205 cells PTEN is inactivated by mutation. Cyclolignan picropodophyllin (PPP), a specific inhibitor of IGF-1R kinase activity, strongly down-regulated the basal levels of AKT activity in WM9 and in WM793 cells, modestly does so in LU1205, but has no effect on AKT activity in the early stage WM35 cells that are deficient in IGF-1R. In addition, PPP partially down-regulated the basal levels of active ERK1/2 in all lines used, highlighting the role of an alternative, non-BRAF pathway in MAPK activation. The final result of PPP treatment was an induction of apoptosis in WM793, WM9 and LU1205 melanoma cells. On the other hand, dose-dependent inhibition of IGF-1R kinase activity by PPP at a relatively narrow dose range (near 500 nM) has different effects on melanoma cells versus normal cells, inducing apoptosis in cancer cells and G2/M arrest of fibroblasts. To further enhance the pro-apoptotic effects of PPP on melanoma cells, we used a combined treatment of TNF-Related Apoptosis-Inducing Ligand (TRAIL) and PPP. This combination substantially increased death by apoptosis for WM793 and WM9 cells, but did so only modestly for LU1205 cells with very high basal activity of AKT. The ultimate goal of this direction of research is the discovery of a new treatment method for highly resistant human metastatic melanomas. Our findings provide the rationale for further preclinical evaluation of this novel treatment.

  3. Observation of increases in emission from modern vehicles over time in Hong Kong using remote sensing.

    PubMed

    Lau, Jason; Hung, W T; Cheung, C S

    2012-04-01

    In this study on-road gaseous emissions of vehicles are investigated using remote sensing measurements collected over three different periods. The results show that a high percentage of gaseous pollutants were emitted from a small percentage of vehicles. Liquified Petroleum Gas (LPG) vehicles generally have higher gaseous emissions compared to other vehicles, particularly among higher-emitting vehicles. Vehicles with high vehicle specific power (VSP) tend to have lower CO and HC emissions while petrol and LPG vehicles tend to have higher NO emissions when engine load is high. It can be observed that gaseous emission factors of petrol and LPG vehicles increase greatly within 2 years of being introduced to the vehicle fleet, suggesting that engine and catalyst performance deteriorate rapidly. It can be observed that LPG vehicles have higher levels of gaseous emissions than petrol vehicles, suggesting that proper maintenance of LPG vehicles is essential in reducing gaseous emissions from vehicles. PMID:22325426

  4. Time variation of adipose tissue refractive index under photodynamic treatment: in vitro study using OCT

    NASA Astrophysics Data System (ADS)

    Yanina, Irina Yu.; Trunina, Natalia A.; Tuchin, Valery V.

    2012-03-01

    Time variation of the adipose tissue refractive index under photodynamic treatment was studied using OCT. Fat tissue slices 200-500 ?m thick were used in in vitro experiments. To stain the fat tissue we used water-ethanol solutions of indocyanine green (ICG) and brilliant green (BG) with the concentration 1 mg/ml and 6 mg/ml, respectively. The CW laser diode (VD-VII DPSS, 808 nm) and the dental diode irradiator Ultra Lume Led 5 (442 and 597 nm) were used for irradiation of tissue slices. The irradiation time was 5 min for the laser and 15 min for the diode lamp. The experiments were carried out at room temperature. It was discovered the immersion optical clearing of fat tissue slices due to fat cell lipolysis under photodynamic treatment. Released cell content works as an immersion agent, thus the relative refractive index of tissue scatterers decreasing with the time elapsed after the treatment. These data support the hypothesis that photodynamic treatment induces fat cell lipolysis for some period after treatment.

  5. A passive acoustic device for real-time monitoring of the efficacy of shockwave lithotripsy treatment.

    PubMed

    Leighton, T G; Fedele, F; Coleman, A J; McCarthy, C; Ryves, S; Hurrell, A M; De Stefano, A; White, P R

    2008-10-01

    Extracorporeal shockwave lithotripsy (ESWL) is the preferred modality for the treatment of renal and ureteric stone disease. Currently X-ray or ultrasound B-scan imaging are used to locate the stone and to check that it remains targeted at the focus of the lithotripter during treatment. Neither imaging modality is particularly effective in allowing the efficacy of treatment to be judged during the treatment session. A new device is described that, when placed on the patient's skin, can passively monitor the acoustic signals that propagate through the body after each lithotripter shock, and which can provide useful information on the effectiveness of targeting. These acoustic time histories are analyzed in real time to extract the two main characteristic peak amplitudes (m(1) and m(2)) and the time between these peaks (t(c)). A set of rules based on the acoustic parameters was developed during a clinical study in which a complete set of acoustic and clinical data was obtained for 30 of the 118 subjects recruited. The rules, which complied with earlier computational fluid dynamics (CFD) modeling and in vitro tests, allow each shock to be classified as "effective" or "ineffective." These clinically-derived rules were then applied in a second clinical study in which complete datasets were obtained for 49 of the 85 subjects recruited. This second clinical study demonstrated almost perfect agreement (kappa = 0.94) between the number of successful treatments, defined as >50% fragmentation as determined by X-ray at the follow-up appointment, and a device-derived global treatment score, TS(0), a figure derived from the total number of effective shocks in any treatment. The acoustic system is shown to provide a test of the success of the treatment that has a sensitivity of 91.7% and a specificity of 100%. In addition to the predictive capability, the device provides valuable real-time feedback to the lithotripter operator by indicating the effectiveness of each shock, plus an indication TS(t) of the cumulative effectiveness of the shocks given so far in any treatment, and trends in key parameters. This feedback would allow targeting adjustments to be made during treatment. An example is given of its application to mistargeting because of respiration. PMID:18562085

  6. Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

    PubMed Central

    Rahmani, Anahita; Kheradmand, Danial; Keyhanvar, Peyman; Darbandi-Azar, Amir

    2013-01-01

    Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI). Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase) plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC) fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and ?-tubulin were detected after neurogenesis as neural markers. Ten ?M of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology. PMID:24024202

  7. The first clinical treatment with kilovoltage intrafraction monitoring (KIM): A real-time image guidance method

    SciTech Connect

    Keall, Paul J. O’Brien, Ricky; Huang, Chen-Yu; Aun Ng, Jin; Colvill, Emma; Rugaard Poulsen, Per; Fledelius, Walther; Juneja, Prabhjot; Booth, Jeremy T.; Simpson, Emma; Bell, Linda; Alfieri, Florencia; Eade, Thomas; Kneebone, Andrew

    2015-01-15

    Purpose: Kilovoltage intrafraction monitoring (KIM) is a real-time image guidance method that uses widely available radiotherapy technology, i.e., a gantry-mounted x-ray imager. The authors report on the geometric and dosimetric results of the first patient treatment using KIM which occurred on September 16, 2014. Methods: KIM uses current and prior 2D x-ray images to estimate the 3D target position during cancer radiotherapy treatment delivery. KIM software was written to process kilovoltage (kV) images streamed from a standard C-arm linear accelerator with a gantry-mounted kV x-ray imaging system. A 120° pretreatment kV imaging arc was acquired to build the patient-specific 2D to 3D motion correlation. The kV imager was activated during the megavoltage (MV) treatment, a dual arc VMAT prostate treatment, to estimate the 3D prostate position in real-time. All necessary ethics, legal, and regulatory requirements were met for this clinical study. The quality assurance processes were completed and peer reviewed. Results: During treatment, a prostate position offset of nearly 3 mm in the posterior direction was observed with KIM. This position offset did not trigger a gating event. After the treatment, the prostate motion was independently measured using kV/MV triangulation, resulting in a mean difference of less than 0.6 mm and standard deviation of less than 0.6 mm in each direction. The accuracy of the marker segmentation was visually assessed during and after treatment and found to be performing well. During treatment, there were no interruptions due to performance of the KIM software. Conclusions: For the first time, KIM has been used for real-time image guidance during cancer radiotherapy. The measured accuracy and precision were both submillimeter for the first treatment fraction. This clinical translational research milestone paves the way for the broad implementation of real-time image guidance to facilitate the detection and correction of geometric and dosimetric errors, and resultant improved clinical outcomes, in cancer radiotherapy.

  8. 'Mind the Gap'-The Impact of Variations in the Duration of the Treatment Gap and Overall Treatment Time in the First UK Anal Cancer Trial (ACT I)

    SciTech Connect

    Glynne-Jones, Rob; Sebag-Montefiore, David; Adams, Richard; McDonald, Alec; Gollins, Simon; James, Roger; Northover, John M.A.; Meadows, Helen M.; Jitlal, Mark

    2011-12-01

    Purpose: The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. Methods and Materials: A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone or CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Results: Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35-1.12; p = 0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48-1.68; p = 0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p = 0.51). OTT was longer by 6.1 days for EBRT (p = 0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p = 0.03). Conclusions: These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control.

  9. Post-infarct treatment with [Pyr(1)]apelin-13 improves myocardial function by increasing neovascularization and overexpression of angiogenic growth factors in rats.

    PubMed

    Azizi, Yaser; Faghihi, Mahdieh; Imani, Alireza; Roghani, Mehrdad; Zekri, Ali; Mobasheri, Maryam Beigom; Rastgar, Tayebeh; Moghimian, Maryam

    2015-08-15

    Ischemic heart disease is the leading cause of mortality in the world. Angiogenesis is important for cardiac repair after myocardial infarction (MI) as restores blood supply to the ischemic myocardium and preserves cardiac function. Apelin is a peptide that has been recently shown to potentiate angiogenesis. The aim of this study was to investigate angiogenic effects of [Pyr(1)]apelin-13 in the rat model of post-MI. Male Wistar rats (n=36) were randomly divided into three groups: (1) sham (2) MI and (3) MI treated with [Pyr(1)]apelin-13 (MI+Apel). MI animals were subjected to 30min left anterior descending coronary artery (LAD) ligation and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr(1)]apelin-13 (10nmol/kg/day) was administered i.p. for 5 days. Hemodynamic functions by catheter introduced into the left ventricle (LV), myocardial fibrosis by Masson?s trichrome staining, gene expression of vascular endothelial growth factor-A (VEGFA), VEGF receptor-2 (Kdr), Ang-1 (angiopoietin-1), Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2) and eNOS by Real-time polymerase chain reaction (Real-Time PCR) and myocardial angiogenesis by CD31 imunostaining were assessed at day 14 post-MI. Post-infarct treatment with [Pyr(1)]apelin-13 improved LV function and decreased myocardial fibrosis. [Pyr(1)]apelin-13 treatment led to a significant increase in the expression of VEGFA, Kdr, Ang-1, Tie2 and eNOS. Further, treatment with [Pyr(1)]apelin-13 promoted capillary density. [Pyr(1)]apelin-13 has angiogenic and anti-fibrotic activity via formation of new blood vessels and overexpression of VEGFA, Kdr, Ang-1, Tie2 and eNOS in the infarcted myocardium which could in turn repair myocardium and improve LV function. PMID:25936512

  10. Protein denaturation and water-protein interactions as affected by low temperature long time treatment of porcine longissimus dorsi.

    PubMed

    Christensen, Line; Bertram, Hanne C; Aaslyng, Margit D; Christensen, Mette

    2011-08-01

    The relationship between water-protein interactions and heat-induced protein denaturation in low temperature long time (LTLT) treated pork Longissimus dorsi was investigated by combining low-field NMR T? relaxometry with DSC measurements and measures of shrinkage of porcine Longissimus dorsi heated to 53 °C, 55 °C, 57 °C and 59 °C for either 3 or 20 h. Water within the myofibrils, measured by NMR T?? relaxation times, was affected by both temperature and holding time during LTLT treatment between 53 °C and 59 °C. The changes in NMR T?? relaxation times were associated with decreased fiber diameter and increased cooking loss, revealing a relationship between transverse shrinkage, water-protein interactions and cooking loss. DSC measurements revealed a concomitant decrease in ?H(68 °C), which suggests impact of collagen denaturation on the retention of water within the meat during LTLT treatment. Furthermore, a decrease in ?H(75 °C) suggested that prolonged cooking (20 h) resulted in actin denaturation leading to decreased T?? relaxation times and higher cooking loss. PMID:21450413

  11. The Right Treatment for the Right Patient (at the Right Time)

    E-print Network

    Davidian, Marie

    The Right Treatment for the Right Patient (at the Right Time): Personalized Medicine and Statistics.ncsu.edu/~davidian 1/47 Personalized Medicine and Statistics #12;2/47 Personalized Medicine and Statistics #12;"Personalized Medicine " Source of graphic: http://www.personalizedmedicine.com/ 2/47 Personalized Medicine

  12. Acute Time to Response in the Treatment for Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    Kratochvil, Christopher; Emslie, Graham; Silva, Susan; McNulty, Steve; Walkup, John; Curry, John; Reinecke, Mark; Vitiello, Benedetto; Rohde, Paul; Feeny, Nora; Casat, Charles; Pathak, Sanjeev; Weller, Elizabeth; May, Diane; Mayes, Taryn; Robins, Michele; March, John

    2006-01-01

    Objective: To examine the time to response for both pharmacotherapy and psychotherapy in the Treatment for Adolescents with Depression Study (TADS). Method: Adolescents (N = 439, ages 12 to 17 years) with major depressive disorder were randomized to fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or pill placebo…

  13. 12 CFR 1024.34 - Timely escrow payments and treatment of escrow account balances.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... account balances. 1024.34 Section 1024.34 Banks and Banking BUREAU OF CONSUMER FINANCIAL PROTECTION REAL... treatment of escrow account balances. (a) Timely escrow disbursements required. If the terms of a mortgage... to avoid a penalty, as governed by the requirements in § 1024.17(k). (b) Refund of escrow balance....

  14. Quantum Mechanical Treatment of Transit-Time Optical Stochastic Cooling of Muons A. E. Charman1

    E-print Network

    Wurtele, Jonathan

    Quantum Mechanical Treatment of Transit-Time Optical Stochastic Cooling of Muons A. E. Charman1 quantum mechanically, and raising doubts as to whether this weak signal even contains sufficient phase are treated quantum mechanically, indicates that fast cooling is in principle possible, with cooling rates

  15. Time Course of Treatment Effect of OROS[R] Methylphenidate in Children with ADHD

    ERIC Educational Resources Information Center

    Armstrong, Robert B.; Damaraju, C. V.; Ascher, Steve; Schwarzman, Lesley; O'Neill, James; Starr, H. Lynn

    2012-01-01

    Objective: The authors evaluated the time course of the treatment effect of Osmotic-Release Oral System methylphenidate (OROS[R] MPH) HCl (Concerta[R], Raritan, NJ) CII in children with ADHD. Method: Data were combined from two double-blind, randomized, placebo-controlled, cross-over, analog classroom studies in children (9-12 years) with ADHD.…

  16. Protein synthesis yield increased 72 times in the cell-free PURE system.

    PubMed

    Jackson, Kirsten; Kanamori, Takashi; Ueda, Takuya; Fan, Z Hugh

    2014-08-01

    Compared to cell-based protein expression, cell-free protein synthesis (CFPS) offers several advantages including a greater control over system additives. This control is further enhanced with a CFPS system called the Protein synthesis Using Recombinant Elements (PURE) system, which consists of 108 purified transcriptional and translational elements. With the PURE system, all elements are known, nuclease and protease activities are reduced, and the concentration of each element can be optimized for maximal protein expression. However, protein expression yield with this system is relatively low due to the consumption of nutrients and energy molecules as well as the accumulation of inhibitory byproducts in the batch format. To enhance protein expression with the PURE system, we developed a feeding solution that was optimized using a miniaturized fluid array device (?FAD) in a continuous-exchange cell-free (CECF) format. The device enabled (1) continuous supply of energy/nutrient molecules from the feeding solution to the reaction solution where protein synthesis occurred, and (2) simultaneous removal of inhibitory expression byproducts from the reaction solution to the feeding solution. Consequently, the synthesis yield of green fluorescent protein (GFP) increased 72.5-fold in comparison with the same reaction in the conventional batch format. PMID:25008400

  17. Time series modelling of increased soil temperature anomalies during long period

    NASA Astrophysics Data System (ADS)

    Shirvani, Amin; Moradi, Farzad; Moosavi, Ali Akbar

    2015-10-01

    Soil temperature just beneath the soil surface is highly dynamic and has a direct impact on plant seed germination and is probably the most distinct and recognisable factor governing emergence. Autoregressive integrated moving average as a stochastic model was developed to predict the weekly soil temperature anomalies at 10 cm depth, one of the most important soil parameters. The weekly soil temperature anomalies for the periods of January1986-December 2011 and January 2012-December 2013 were taken into consideration to construct and test autoregressive integrated moving average models. The proposed model autoregressive integrated moving average (2,1,1) had a minimum value of Akaike information criterion and its estimated coefficients were different from zero at 5% significance level. The prediction of the weekly soil temperature anomalies during the test period using this proposed model indicated a high correlation coefficient between the observed and predicted data - that was 0.99 for lead time 1 week. Linear trend analysis indicated that the soil temperature anomalies warmed up significantly by 1.8°C during the period of 1986-2011.

  18. Timing Rhythms: Perceived Duration Increases with a Predictable Temporal Structure of Short Interval Fillers

    PubMed Central

    Horr, Ninja K.; Di Luca, Massimiliano

    2015-01-01

    Variations in the temporal structure of an interval can lead to remarkable differences in perceived duration. For example, it has previously been shown that isochronous intervals, that is, intervals filled with temporally regular stimuli, are perceived to last longer than intervals left empty or filled with randomly timed stimuli. Characterizing the extent of such distortions is crucial to understanding how duration perception works. One account to explain effects of temporal structure is a non-linear accumulator-counter mechanism reset at the beginning of every subinterval. An alternative explanation based on entrainment to regular stimulation posits that the neural response to each filler stimulus in an isochronous sequence is amplified and a higher neural response may lead to an overestimation of duration. If entrainment is the key that generates response amplification and the distortions in perceived duration, then any form of predictability in the temporal structure of interval fillers should lead to the perception of an interval that lasts longer than a randomly filled one. The present experiments confirm that intervals filled with fully predictable rhythmically grouped stimuli lead to longer perceived duration than anisochronous intervals. No general over- or underestimation is registered for rhythmically grouped compared to isochronous intervals. However, we find that the number of stimuli in each group composing the rhythm also influences perceived duration. Implications of these findings for a non-linear clock model as well as a neural response magnitude account of perceived duration are discussed. PMID:26474047

  19. Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?

    PubMed Central

    Fuentes, Sílvia; Daviu, Núria; Gagliano, Humberto; Garrido, Pedro; Zelena, Dóra; Monasterio, Nela; Armario, Antonio; Nadal, Roser

    2014-01-01

    Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces “detrimental” effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first post-natal days and exposure to a “substitute” mother. The maternal care of biological and “substitute” mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM), acoustic startle response (ASR) and forced swim test (FST). In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects). Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behavior by a five choice serial reaction time task (5CSRTT). ELS decreased pup body weight and increased the care of the biological mother; however, the “substitute” mother did not exhibit overt maltreatment. A mixture of “detrimental” and “beneficial” effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behavior. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR) and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may “buffer” the effects of ELS in a context-dependent manner. PMID:24616673

  20. Tiam1 Transgenic Mice Display Increased Tumor Invasive and Metastatic Potential of Colorectal Cancer after 1,2-Dimethylhydrazine Treatment

    PubMed Central

    Yu, Li-Na; Zhang, Qing-Ling; Li, Xin; Hua, Xing; Cui, Yan-Mei; Zhang, Nian-Jie; Liao, Wen-Ting; Ding, Yan-Qing

    2013-01-01

    Background T lymphoma invasion and metastasis 1 (Tiam1) is a potential modifier of tumor development and progression. Our previous study in vitro and in nude mice suggested a promotion role of Tiam1 on invasion and metastasis of colorectal cancer (CRC). In the present study, we generated Tiam1/C1199-CopGFP transgenic mice to investigate the tumorigenetic, invasive and metastatic alterations in the colon and rectum of wild-type and Tiam1 transgenic mice under 1,2-dimethylhydrazine (DMH) treatment. Methods Transgenic mice were produced by the method of pronuclear microinlectlon. Whole-body fluorescence imaging (Lighttools, Edmonton, Alberta, Canada), PCR, and immunohistochemical techniques (IHC) were applied sequentially to identify the transgenic mice. The carcinogen DMH (20 mg/kg) was used to induce colorectal tumors though intraperitoneal (i.p.) injections once a week for 24 weeks from the age of 4 weeks on Tiam1 transgenic or non-transgenic mice. Results We successfully generated Tiam1/C1199-CopGFP transgenic mice and induced primary tumors in the intestine of both wild type and Tiam1 transgenic mice by DMH treatment. In addition, Tiam1 transgenic mice developed larger and more aggressive neoplasm than wild-type mice. Moreover, immunohistochemical staining revealed that upregulation of Tiam1 was correlated with increased expression of ?-Catenin and Vimentin, and downregulation of E-Cadherin in these mice. Conclusions Our study has provided in vivo evidence supporting that Tiam1 promotes invasion and metastasis of CRC, most probably through activation of Wnt/?-catenin signaling pathway, in a Tiam1 transgenic mouse model. PMID:24069171

  1. Dramatic increase in cortical thickness induced by femoral marrow ablation followed by a 3-month treatment with PTH in rats.

    PubMed

    Zhang, Qing; Carlson, Jodi; Ke, Hua Zhu; Li, Jiliang; Kim, Michael; Murphy, Kieran; Mehta, Nozer; Gilligan, James; Vignery, Agnès

    2010-06-01

    We previously reported that following mechanical ablation of the marrow from the midshaft of rat femurs, there is a rapid and abundant but transient growth of bone, and this growth is enhanced and maintained over a 3-week period by the bone anabolic hormone parathyroid hormone (PTH). Here, we asked whether further treatment with PTH or bisphosphonates can extend the half-life of the new bone formed in lieu of marrow. We subjected the left femur of rats to mechanical marrow ablation and treated the animals 5 days a week with PTH for 3 weeks (or with vehicle as a control) to replace the marrow by bone. Some rats were euthanized and used as positive controls or treated with vehicle, PTH, or the bisphosphonate alendronate for a further 9 weeks. We subjected both femurs from each rat to soft X-ray, peripheral quantitative computed tomography (pQCT), micro-computed tomography (microCT), dynamic histomorphometry analysis, and biomechanical testing. We also determined the concentrations of serum osteocalcin to confirm the efficacy of PTH. Treatment with PTH for 3 months dramatically enhanced endosteal and periosteal bone formation, leading to a 30% increase in cortical thickness. In contrast, alendronate protected the bone that had formed in the femoral marrow cavity after marrow ablation and 3 weeks of treatment with PTH but failed to promote endosteal bone growth or to improve the biomechanical properties of ablated femurs. We further asked whether calcium-phosphate cements could potentiate the formation of bone after marrow ablation. Marrow cavities from ablated femurs were filled with one of two calcium-phosphate cements, and rats were treated with PTH or PBS for 84 days. Both cements helped to protect the new bone formed after ablation. To some extent, they promoted the formation of bone after ablation, even in the absence of any anabolic hormone. Our data therefore expand the role of PTH in bone engineering and open new avenues of investigation to the field of regenerative medicine and tissue engineering. Local bone marrow aspiration in conjunction with an anabolic agent, a bisphosphonate, or a calcium-phosphate cement might provide a new platform for rapid preferential site-directed bone growth in areas of high bone loss. PMID:20200940

  2. Effects of selective breeding for increased wheel-running behavior on circadian timing of substrate oxidation and ingestive behavior

    E-print Network

    Saltzman, Wendy

    with an approximately 24 h rotation, most animal species have a circadian rhythm in activity and resting, with specificEffects of selective breeding for increased wheel-running behavior on circadian timing of substrate in substrate preference and utilization across the circadian cycle may be influenced by the degree of physical

  3. Increased Levels of Multiresistant Bacteria and Resistance Genes after Wastewater Treatment and Their Dissemination into Lake Geneva, Switzerland

    PubMed Central

    Czekalski, Nadine; Berthold, Tom; Caucci, Serena; Egli, Andrea; Bürgmann, Helmut

    2012-01-01

    At present, very little is known about the fate and persistence of multiresistant bacteria (MRB) and their resistance genes in natural aquatic environments. Treated, but partly also untreated sewage of the city of Lausanne, Switzerland is discharged into Vidy Bay (Lake Geneva) resulting in high levels of contamination in this part of the lake. In the present work we have studied the prevalence of MRB and resistance genes in the wastewater stream of Lausanne. Samples from hospital and municipal raw sewage, treated effluent from Lausanne’s wastewater treatment plant (WTP) as well as lake water and sediment samples obtained close to the WTP outlet pipe and a remote site close to a drinking water pump were evaluated for the prevalence of MRB. Selected isolates were identified (16S rRNA gene fragment sequencing) and characterized with regards to further resistances, resistance genes, and plasmids. Mostly, studies investigating this issue have relied on cultivation-based approaches. However, the limitations of these tools are well known, in particular for environmental microbial communities, and cultivation-independent molecular tools should be applied in parallel in order to take non-culturable organisms into account. Here we directly quantified the sulfonamide resistance genes sul1 and sul2 from environmental DNA extracts using TaqMan real-time quantitative PCR. Hospital sewage contained the highest load of MRB and antibiotic resistance genes (ARGs). Wastewater treatment reduced the total bacterial load up to 78% but evidence for selection of extremely multiresistant strains and accumulation of resistance genes was observed. Our data clearly indicated pollution of sediments with ARGs in the vicinity of the WTP outlet. The potential of lakes as reservoirs of MRB and potential risks are discussed. PMID:22461783

  4. Glycated Albumin Levels in Patients with Type 2 Diabetes Increase Relative to HbA1c with Time

    PubMed Central

    Yoon, Hye-jin; Lee, Yong-ho; Kim, Kwang Joon; Kim, So Ra; Kang, Eun Seok; Cha, Bong-Soo; Lee, Hyun Chul; Lee, Byung-Wan

    2015-01-01

    We recently reported that glycated albumin (GA) is increased in subjects with longer duration of diabetes and with decreased insulin secretory function. Based on this, we investigated whether GA increases with time relative to glycated hemoglobin (HbA1c) and the association between GA and beta-cell function. We analyzed 340 type 2 diabetes patients whose serum GA and HbA1c levels had been repeatedly measured over 4 years. We assessed the pattern of changes with time in glycemic indices (GA, HbA1c, and GA/HbA1c ratio) and their relationship with beta-cell function. In all patients, glycemic indices decreased and maintained low levels around 15 and 27 months. However, from 39 months to 51 months, GA significantly increased but HbA1c tended to increase without statistical significance. We defined ?GA/HbA1c as the difference between the nadir point (at 15 to 27 months) and the end point (at 39 to 51 months) and found that ?GA/HbA1c was positively correlated with diabetes duration and negatively related to beta-cell function. In multivariable linear regression analyses, ?GA/HbA1c was independently associated with diabetes duration. In conclusion, this study demonstrated that serum GA levels increase relative to HbA1c levels with time. PMID:26484352

  5. Hydrothermal treatment coupled with mechanical expression at increased temperature for excess sludge dewatering: influence of operating conditions and the process energetics.

    PubMed

    Wang, Liping; Zhang, Lei; Li, Aimin

    2014-11-15

    Dewatering is very important for excess sludge treatment and disposal. Hydrothermal treatment coupled with mechanical expression is a novel technology, in which a conventional pressure dewatering is combined with hydrothermal effect to realize an improved liquid/solids separation with low energy consumption. In this study, the process was performed by way of that the excess sludge was hydrothermally treated first and then the mechanical expression was employed immediately at increased temperature in two separate cells respectively. The results demonstrated that the mechanical expression employed at increased temperature showed a significant advantage than that at room temperature, given a further reduction of 19-47% of the moisture content. The dewatering process at room temperature was mostly depended on the effect of mechanical expression. Hydrothermal process, more importantly than mechanical effect at increased temperatures, seemed to govern the extent to which the dewatering process occurred. The dewatering began to show a positive effect when the temperature was exceeded the threshold temperature (between 120 and 150 °C). The residence time of 30 min promoted a substantial conversion in the sludge surface properties. After dewatering at temperatures of 180-210 °C, the moisture content decreased from 52 to 20% and the corresponding total water removal as filtrate was between 81 and 93%. It was observed that the moisture content of filter cake correlated with surface charge (Rp = -0.93, p < 0.05) and relative hydrophobicity (Rp = -0.99, p < 0.05). The calculated energy balance suggested that no additional external energy input is needed to support the dewatering process for excess sludge. The dewatering process needs an obviously lower energy input compared to thermal drying and electro-dewatering to produce a higher solids content cake. PMID:25090626

  6. Social crowding in the night-time reduces an anxiety-like behavior and increases social interaction in adolescent mice.

    PubMed

    Ago, Yukio; Tanaka, Tatsunori; Ota, Yuki; Kitamoto, Mari; Imoto, Emina; Takuma, Kazuhiro; Matsuda, Toshio

    2014-08-15

    Rearing in crowded conditions is a psychosocial stressor that affects biological functions. The effects of continuous crowding for many days have been studied, but those of crowding over a limited time have not. In this study, we examined the effects of night-time or daytime crowding over 2 weeks on behavior in adolescent and adult mice. Crowding (20 mice/cage) in either the night-time or daytime did not affect locomotor activity in the open field test or cognitive function in the fear conditioning test. In contrast, night-time crowding, but not daytime crowding, had an anxiolytic effect in the elevated plus-maze test and increased social interaction in adolescent mice, but not in adult mice. The first night-time, but not daytime, crowding increased plasma corticosterone levels in adolescent mice, although night-time crowding over 2 weeks did not affect the corticosterone levels. Furthermore, no significant effects of the first crowding were observed in adult mice. In a second crowding condition (six mice/small cage), the anxiolytic-like effects of night-time crowding and the change in plasma corticosterone levels were not observed, suggesting that the density of mice is not important for the behavioral consequences of crowding. Night-time crowding did not affect neurotrophic/growth factor levels and hippocampal neurogenesis in adolescent mice. These findings suggest that night-time crowding leads to anxiolytic-like behaviors in adolescent mice, and imply that night-time crowding stress in adolescence may be beneficial to brain functions. PMID:24803212

  7. Characterization of a Therapeutic Model of Inhalational Anthrax Using an Increase in Body Temperature in New Zealand White Rabbits as a Trigger for Treatment

    PubMed Central

    Ray, Bryan D.; Henning, Lisa N.; Stark, Gregory V.; Barnewall, Roy E.; Mott, Jason M.; Meister, Gabriel T.

    2012-01-01

    The development of an appropriate animal therapeutic model is essential to assess the potential efficacy of therapeutics for use in the event of a Bacillus anthracis exposure. We conducted a natural history study that showed New Zealand White rabbits exhibited a significant increase in body temperature (SIBT), changes in hematologic parameters, and increases in C-reactive protein and succumbed to disease with an average time to death of approximately 73 h following aerosol challenge with B. anthracis Ames spores. The SIBT was used as a trigger to treat with a fully human monoclonal antibody directed at protective antigen (PA). Ninety percent (9/10) of the treated rabbits survived the lethal inhalational challenge of B. anthracis. Further characterization investigated the protective window of opportunity for anti-PA antibody administration up to 12 h post-onset of SIBT. Eighty-three percent (5/6) of the rabbits treated at SIBT and 100% (6/6) of those treated at 6 h after SIBT survived challenge. Only 67% (4/6) of the rabbits treated at 12 h after SIBT survived. The increase in body temperature corresponded with both bacteremia and antigenemia (PA in the blood), indicating that SIBT is a suitable trigger to initiate treatment in a therapeutic model of inhalational anthrax. PMID:22837095

  8. Modeling time variant distributions of cellular lifespans: increases in circulating reticulocyte lifespans following double phlebotomies in sheep

    PubMed Central

    Freise, Kevin J.; Widness, John A.; Schmidt, Robert L.

    2009-01-01

    Many pharmacodynamic (PD) models of cellular response assume a single and time invariant lifespan of all cells, despite the existence of a true underlying distribution of cellular lifespans and known changes in the lifespan distributions with time. To account for these features of cellular populations, a time variant cellular lifespan distribution PD model was formulated and theoretical aspects of modeling cellular populations presented. The model extends prior work assuming time variant “point distributions” of cellular lifespans (Freise et al. J Pharmacokinet Pharmacodyn 34:519–547, 2007) and models assuming a time invariant lifespan distribution (Krzyzanski et al. J Pharmacokinet Pharmacodyn 33:125–166, 2006). The formulated time variant lifespan distribution model was fitted to endogenous plasma erythropoietin (EPO), reticulocyte, and red blood cell (RBC) concentrations in sheep phlebotomized on two occasions, 8 days apart. The time variant circulating reticulocyte lifespan was modeled as a truncated and scaled Weibull distribution, with the location parameter of the distribution non-parametrically represented by an end constrained quadratic spline function. The formulated time variant lifespan distribution model was compared to the identical time invariant distribution, time variant “point distribution”, and time invariant “point distribution” cellular lifespan models. Parameters of the time variant lifespan distribution model were well estimated with low standard errors. The mean circulating reticulocyte lifespan was estimated at 0.304 days, which rapidly increased over 3-fold following the first phlebotomy to a maximum of 1.03 days (P = 0.009). On average, the percentage of erythrocytes being released as reticulocytes maximally increased an estimated two-fold following the phlebotomies. The primary features of immature RBC physiology were captured by the model and gave results consistent with other estimates in sheep and humans. The comparison of the four lifespan models gave similar parameter estimates of the stimulation function and fits to the RBC data. However, the time invariant models fit the reticulocyte data poorly, while the time variant “point distribution” cellular lifespan model gave physiologically unrealistic estimates of the changes in the circulating reticulocyte lifespan under stress erythropoiesis. Thus the underlying physiology must be considered when selecting the most appropriate cellular lifespan model and not just the goodness-of-fit criteria. The proposed PD model and the numerical implementation allows for a flexible framework to incorporate time variant lifespan distributions when modeling populations of cells whose production or stimulation depends on endogenous growth factors and/or exogenous drugs. PMID:18553126

  9. Modeling time variant distributions of cellular lifespans: increases in circulating reticulocyte lifespans following double phlebotomies in sheep.

    PubMed

    Freise, Kevin J; Widness, John A; Schmidt, Robert L; Veng-Pedersen, Peter

    2008-06-01

    Many pharmacodynamic (PD) models of cellular response assume a single and time invariant lifespan of all cells, despite the existence of a true underlying distribution of cellular lifespans and known changes in the lifespan distributions with time. To account for these features of cellular populations, a time variant cellular lifespan distribution PD model was formulated and theoretical aspects of modeling cellular populations presented. The model extends prior work assuming time variant "point distributions" of cellular lifespans (Freise et al. J Pharmacokinet Pharmacodyn 34:519-547, 2007) and models assuming a time invariant lifespan distribution (Krzyzanski et al. J Pharmacokinet Pharmacodyn 33:125-166, 2006). The formulated time variant lifespan distribution model was fitted to endogenous plasma erythropoietin (EPO), reticulocyte, and red blood cell (RBC) concentrations in sheep phlebotomized on two occasions, 8 days apart. The time variant circulating reticulocyte lifespan was modeled as a truncated and scaled Weibull distribution, with the location parameter of the distribution non-parametrically represented by an end constrained quadratic spline function. The formulated time variant lifespan distribution model was compared to the identical time invariant distribution, time variant "point distribution", and time invariant "point distribution" cellular lifespan models. Parameters of the time variant lifespan distribution model were well estimated with low standard errors. The mean circulating reticulocyte lifespan was estimated at 0.304 days, which rapidly increased over 3-fold following the first phlebotomy to a maximum of 1.03 days (P = 0.009). On average, the percentage of erythrocytes being released as reticulocytes maximally increased an estimated two-fold following the phlebotomies. The primary features of immature RBC physiology were captured by the model and gave results consistent with other estimates in sheep and humans. The comparison of the four lifespan models gave similar parameter estimates of the stimulation function and fits to the RBC data. However, the time invariant models fit the reticulocyte data poorly, while the time variant "point distribution" cellular lifespan model gave physiologically unrealistic estimates of the changes in the circulating reticulocyte lifespan under stress erythropoiesis. Thus the underlying physiology must be considered when selecting the most appropriate cellular lifespan model and not just the goodness-of-fit criteria. The proposed PD model and the numerical implementation allows for a flexible framework to incorporate time variant lifespan distributions when modeling populations of cells whose production or stimulation depends on endogenous growth factors and/or exogenous drugs. PMID:18553126

  10. A simple method of independent treatment time verification in gamma knife radiosurgery using integral dose

    SciTech Connect

    Jin Jianyue; Drzymala, Robert; Li Zuofeng

    2004-12-01

    The purpose of this study is to develop a simple independent dose calculation method to verify treatment plans for Leksell Gamma Knife radiosurgery. Our approach uses the total integral dose within the skull as an end point for comparison. The total integral dose is computed using a spreadsheet and is compared to that obtained from Leksell GammaPlan registered . It is calculated as the sum of the integral doses of 201 beams, each passing through a cylindrical volume. The average length of the cylinders is estimated from the Skull-Scaler measurement data taken before treatment. Correction factors are applied to the length of the cylinder depending on the location of a shot in the skull. The radius of the cylinder corresponds to the collimator aperture of the helmet, with a correction factor for the beam penumbra and scattering. We have tested our simple spreadsheet program using treatment plans of 40 patients treated with Gamma Knife registered in our center. These patients differ in geometry, size, lesion locations, collimator helmet, and treatment complexities. Results show that differences between our calculations and treatment planning results are typically within {+-}3%, with a maximum difference of {+-}3.8%. We demonstrate that our spreadsheet program is a convenient and effective independent method to verify treatment planning irradiation times prior to implementation of Gamma Knife radiosurgery.

  11. Significance of Timing on Effect of Metaphylactic Toltrazuril Treatment against Eimeriosis in Calves.

    PubMed

    Enemark, Heidi Larsen; Dahl, Jan; Enemark, Jörg Matthias Dehn

    2015-08-01

    In this multicentric, randomised, blinded and placebo-controlled field study, the effect of treatment with toltrazuril (Baycox(®) Bovis, Bayer) on oocyst excretion, diarrhoea score and weight gain was studied in Danish dairy herds with confirmed history of eimeriosis (coccidiosis) and prevalence of Eimeria bovis and Eimeria zuernii. Three commercial herds and a total of 71 calves, aged 48 - 135 days, were included. Treatment with a single oral dose of toltrazuril (15 mg/kg) was given after relocation to common pens and one week before expected outbreak of eimeriosis. The effect of treatment was followed by weekly faecal sampling and weighing initially and at the end of a study period of 8 weeks. In Herd 2 and 3 toltrazuril treated calves gained on average 7.95 kg more than placebo treated calves (p = 0.007), and both oocyst excretion and prevalence of Eimeria spp. were significantly reduced the first weeks post treatment. In Herd 1, by contrast, the farmer made some unforeseen changes in the management which entailed relocation to large deep-litter pens 3 - 6 weeks post treatment. In addition, many calves were not treated metaphylactically while few calves excreted oocysts when the trial was initiated. Thus, no significant difference in weight gain was found between toltrazuril and placebo treated calves (p = 0.523), and the oocyst excretion of toltrazuril treated calves was significantly higher during week 7 and 8. Significant differences in faecal scores were observed between the herds (p<0.002) but not between treatment groups in any of the herds. In conclusion, timing of treatment is crucial for optimal effect of metaphylactic toltrazuril treatment on weight gain and oocyst excretion. PMID:26152421

  12. Temporal trends of time to antiretroviral treatment initiation, interruption and modification: examination of patients diagnosed with advanced HIV in Australia

    PubMed Central

    Wright, Stephen T; Law, Matthew G; Cooper, David A; Keen, Phillip; McDonald, Ann; Middleton, Melanie; Woolley, Ian; Kelly, Mark; Petoumenos, Kathy

    2015-01-01

    Introduction HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. Methods We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification. Results Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural–regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007–2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007–2012 versus 1996–2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. Conclusions Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods. PMID:25865372

  13. Multimedia trade off: Material substitution results in reduced VOC emissions and increased organic loading to liquid phase treatment processes

    SciTech Connect

    Yonge, D.R.; Trussler, S.; Claiborn, C.; Watts, R.

    1996-12-31

    Environmental concern regarding VOC emissions has resulted in efforts directed toward defining reliable and cost effective methods of emission reduction. One method that has attracted considerable interest is material substitution; the replacement of a hazardous material used in an industrial process or operation with one that is of less concern. A specific example of material replacement is the use of glycol ethers in place of more volatile surface cleaning agents. Such replacement significantly reduces VOC emissions, but often at the expense of increases in liquid phase contaminant loading. A comprehensive study was undertaken to define the fate of glycol ethers during metal surface cleaning operations. Information was also obtained regarding their impact of pretreatment operations and biodegradability. It was determined that the glycol ethers studied were amenable to catalyzed peroxide oxidation but that treatment process modification would be necessary to maintain desired effluent quality. Oxidation process optimization yielded evidence of the formation of an oxidation by-product that is interfering with OH{circ} formation or acting as an OH{circ} quenching agent. Preliminary biodegradation studies indicated that diethylene glycol monobutyl ether is biodegradable under aerobic conditions with no observed detrimental effects on sludge settling.

  14. The Immediate Effect of Neuromuscular Joint Facilitation (NJF) Treatment on Electromechanical Reaction Times of Hip Flexion.

    PubMed

    Huo, Ming; Wang, Hongzhao; Ge, Meng; Huang, Qiuchen; Li, Desheng; Maruyama, Hitoshi

    2013-11-01

    [Purpose] The aim of this study was to investigate the change in electromechanical reaction times (EMG-RT) of hip flexion of younger persons after neuromuscular joint facilitation (NJF) treatment. [Subjects] The subjects were 39 healthy young people, who were divided into two groups: a NJF group and a proprioceptive neuromuscular facilitation (PNF) group. The NJF group consisted of 16 subjects (7 males, 9 females), and the PNF group consisted of 23 subjects (10 males, 13 females). [Methods] Participants in the NJF group received NJF treatment. We measured the EMG-RT, the premotor time (PMT) and the motor time (MT) during hip flexion movement before and after the intervention in both groups. [Results] There were no significant differences among the results of the PNF group. For the NJF group, there were significant differences in PMT and EMG-RT after NJF treatment. [Conclusion] These results suggest that there is an immediate effect of NJF intervention on electromechanical reaction times of hip flexion. PMID:24396211

  15. Time to failure after definitive therapy for prostate cancer: implications for importance of aggressive local treatment

    PubMed Central

    Taira, Al V.; Butler, Wayne M.; Galbreath, Robert W.; Fiano, Ryan; Wallner, Kent E.; Adamovich, Edward

    2013-01-01

    Purpose To explore patterns of time to failure in men receiving high doses of permanent seed brachytherapy with or without external beam radiation therapy as a function of risk status. Material and methods Two thousand two hundred and thirty four patients were treated with prostate brachytherapy with median follow up of 8.0 years. The population was 35% low risk, 49% intermediate risk, and 16% high risk (NCCN). Median day 0 implant D90 was 119% and V100 was 98%. Treatment failure was defined as PSA > 0.40 ng/mL after nadir. Rates of biochemical failure, distant metastases, and prostate cancer death were determined with non-prostate death as a competing risk. Results For all patients, the 10-year biochemical failure, distant metastases, and cause-specific mortality were 4.4%, 1.4%, and 1.3%, respectively. The biochemical failure rates were 1.3%, 4.8%, and 10.0% for men with low, intermediate, and high risk disease, respectively. Median time to failure was 2.8 years. In men who died from prostate cancer, the median time from treatment failure to death was 4.2 years. Overall, 83% of biochemical failures and 97% of metastases occurred within the first 4 years after treatment. Conclusions With the dose escalation achieved by high quality brachytherapy dosimetry, even high-risk prostate cancer patients have excellent long term biochemical outcomes. Treatment failures occur early, and one third become metastatic and progress rapidly to prostate cancer death. The low frequency and pattern of failures suggest the presence of micrometastatic disease prior to treatment is rare, even in high risk patients. PMID:24474970

  16. Time Course of Mild Arm Lymphedema After Breast Conservation Treatment for Early-Stage Breast Cancer

    SciTech Connect

    Bar Ad, Voichita; Cheville, Andrea; Solin, Lawrence J.; Dutta, Pinaki; Both, Stefan; Harris, Eleanor

    2010-01-15

    Purpose: Arm lymphedema is a potential consequence of the treatment for breast carcinoma. The objective of this retrospective study was to characterize the progression of mild arm lymphedema after breast conservation treatment for breast cancer. Methods and Materials: The study cohort was drawn from 1,713 consecutive Stage I or II breast cancer patients who underwent breast conservation therapy, including axillary staging followed by radiation. Arm lymphedema was documented in 266 (16%) of 1,713 patients. One hundred nine patients, 6% of the overall group and 40% of the patients with arm lymphedema, presented with mild arm lymphedema, defined as a difference of 2 cm or less between the measured circumferences of the affected and unaffected arms. Results: Among the 109 patients with mild arm lymphedema at the time of arm lymphedema diagnosis, the rate of freedom from progression to more severe lymphedema was 79% at 1 year, 66% at 3 years, and 52% at 5 years. The patients who were morbidly obese, had positive axillary lymph nodes, or received supraclavicular irradiation at the time of breast cancer treatment were at higher risk of progression from mild arm lymphedema to more severe edema. Conclusions: Mild arm lymphedema, generally considered to be a minor complication after breast conservation treatment for breast cancer, was associated with a risk of progression to a more severe grade of arm lymphedema in a substantial fraction of patients.

  17. Extended field-of-view and increased-signal 3D holographic illumination with time-division multiplexing.

    PubMed

    Yang, Samuel J; Allen, William E; Kauvar, Isaac; Andalman, Aaron S; Young, Noah P; Kim, Christina K; Marshel, James H; Wetzstein, Gordon; Deisseroth, Karl

    2015-12-14

    Phase spatial light modulators (SLMs) are widely used for generating multifocal three-dimensional (3D) illumination patterns, but these are limited to a field of view constrained by the pixel count or size of the SLM. Further, with two-photon SLM-based excitation, increasing the number of focal spots penalizes the total signal linearly-requiring more laser power than is available or can be tolerated by the sample. Here we analyze and demonstrate a method of using galvanometer mirrors to time-sequentially reposition multiple 3D holograms, both extending the field of view and increasing the total time-averaged two-photon signal. We apply our approach to 3D two-photon in vivo neuronal calcium imaging. PMID:26699047

  18. Gentamicin-induced ototoxicity and nephrotoxicity vary with circadian time of treatment and entail separate mechanisms.

    PubMed

    Blunston, Mary A; Yonovitz, Al; Woodahl, Erica L; Smolensky, Michael H

    2015-11-01

    The aminoglycoside antibiotic gentamicin can cause both ototoxicity and nephrotoxicity, the severity of which varies with circadian time of daily treatment. However, it is not yet resolved if such drug-induced adverse effects are independent or interdependent phenomena. Two groups of 9 female Sprague-Dawley rats (200-250?g), each housed separately and entrained to a 12?h light (06:00-18:00?h) - 12?h dark cycle, received a daily subcutaneous injection of 100?mg/kg gentamicin. One group was treated at the beginning of the activity span, 2 Hours After Lights On (HALO), and the other at the beginning of the rest span, 14 HALO. Global toxicity was gauged by both body weight loss relative to the pre-treatment baseline and number of deaths. Ototoxicity, i.e., hearing loss, was assessed by changes in auditory brainstem response (ABR) for pure tone stimuli of 8, 16, 24, and 32?kHz before and after 2 and 4 weeks of gentamicin treatment. Renal toxicity was evaluated by changes in urinary N-acetyl-?-glucosaminidase (NAG)/creatinine (CR) concentration ratio before and after each week of treatment. In a complementary substudy of separate but comparable 2 and 14 HALO groups of rats, blood samples were obtained before and 30, 60, 120, and 240?min post-subcutaneous injection of 100?mg/kg gentamicin. Number of animal deaths was greater in the 2 (4 deaths) than 14 HALO (1 death) group, mirroring more severe initial (first two weeks of treatment) body weight losses from baseline, being more than 2-fold greater in animals of the 2 than 14 HALO group. Ototoxicity progressively worsened during the treatment; although, the extent of hearing loss varied according to circadian time of treatment across all frequencies (p?time course of nephrotoxicity differed from that of ototoxicity. The mean urinary NAG/CR ratio peaked after the first week of treatment, averaging 13.64-fold greater than baseline for the 2 HALO-treated animals compared to 7.38-fold greater than baseline for the 14 HALO-treated ones. Ratio values declined thereafter; although, even after the second week of dosing, they remained greater in the 2 than 14 HALO group (averaging 8.15-fold greater and 2.23-fold greater than baseline, respectively). Pharmacokinetic analysis of the blood gentamicin values revealed slower clearance, on average by ?25% (p?time course in rats of both treatment groups of gentamicin-induced ototoxicity and nephrotoxicity, supporting the hypothesis these organ toxicities are independent of one another, and further suggest the observed treatment-time differences in gentamicin adverse effects may be more dependent on local cell, tissue, or organ circadian (chrono) pharmacodynamic than (chrono) pharmacokinetic mechanisms. PMID:26506922

  19. Further treatment of decolorization liquid of azo dye coupled with increased power production using microbial fuel cell equipped with an aerobic biocathode.

    PubMed

    Sun, Jian; Bi, Zhe; Hou, Bin; Cao, Yun-qing; Hu, Yong-you

    2011-01-01

    A microbial fuel cell (MFC) incorporating a recently developed aerobic biocathode is designed and demonstrated. The aerobic biocathode MFC is able to further treat the liquid containing decolorization products of active brilliant red X-3B (ABRX3), a respective azo dye, and also provides increased power production. Batch test results showed that 24.8% of COD was removed from the decolorization liquid of ABRX3 (DL) by the biocathode within 12 h. Metabolism-dependent biodegradation of aniline-like compound might be mainly responsible for the decrease of overall COD. Glucose is not necessary in this process and contributes little to the COD removal of the DL. The similar COD removal rate observed under closed circuit condition (500 ?) and opened circuit condition indicated that the current had an insignificant effect on the degradation of the DL. Addition of the DL to the biocathode resulted in an almost 150% increase in open cycle potential (OCP) of the cathode accompanied by a 73% increase in stable voltage output from 0.33 V to 0.57 V and a 300% increase in maximum power density from 50.74 mW/m(2) to 213.93 mW/m(2). Cyclic voltammetry indicated that the decolorization products of the ABRX3 contained in the DL play a role as redox mediator for facilitating electron transfer from the cathode to the oxygen. This study demonstrated for the first time that MFC equipped with an aerobic biocathode can be successfully applied to further treatment of effluent from an anaerobic system used to decolorize azo dye, providing both cost savings and high power output. PMID:20727567

  20. Enhancement in dentin collagen’s biological stability after proanthocyanidins treatment in clinically relevant time periods

    PubMed Central

    Liu, Yi; Chen, Mingsheng; Yao, Xiaomei; Xu, Changqi; Zhang, Ying; Wang, Yong

    2013-01-01

    Objective To investigate whether proanthocyanidins (PA) is capable of improving dentin collagen’s biological stability through cross-linking within time periods that are clinically relevant. Materials and methods Demineralized dentin collagen slabs were treated with 3.75 wt% PA solution for 10 s, 1 min, 30 min, 60 min, 120 min, 360 min, and 720 min, respectively. The resultant cross-linked collagen samples were subject to digestion with 0.1% collagenase at 37 °C for 2 h, 6 h, 12 h, 24 h, 36 h, and 48 h. The percentage of weight loss after digestion was calculated to evaluate PA-treated collagen’s resistance toward enzymatic degradation. Fourier-Transformed Infrared (FTIR) spectroscopy was used to probe evidences of PA-collagen interactions after various periods of PA treatment. Results The collagenase digestion assay suggests that PA treatment as short as 10 s can enhance collagen’s resistance toward enzymatic challenge. The FTIR spectroscopy further verifies that PA is indeed incorporated into collagen regardless of treatment time, possibly via a mechanism involving the chemical interactions between PA and collagen. Significance This study confirmed that PA can effectively cross-link collagen and improve its biological stability in time periods as short as 10 s. The use of PA as a priming agent is therefore clinically feasible and is a promising approach to improving the durability of current dentin bonding systems. PMID:23434233

  1. Increased Oil Recovery from Mature Oil Fields Using Gelled Polymer Treatments, Annual Report, June 16,2000-June 15, 2001

    SciTech Connect

    Willhite, G.P.; Green, D.W.; McCool, C.S.

    2002-05-22

    This program was aimed at reducing barriers to the widespread use of gelled polymer treatments by (1) developing methods to predict gel behavior during placement in matrix rock and fractures, (2) determining the persistence of permeability reduction after gel placement, and (3) developing methods to design production well treatments to control water production.

  2. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study

    PubMed Central

    Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

    2015-01-01

    Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions. PMID:26158464

  3. Early timing of endovascular treatment for aneurysmal subarachnoid hemorrhage achieves improved outcomes.

    PubMed

    Qian, Zenghui; Peng, Tangming; Liu, Aihua; Li, Youxiang; Jiang, Chuhan; Yang, Hongchao; Wu, Jing; Kang, Huibin; Wu, Zhongxue

    2014-02-01

    Timing of treatment of aneurysmal subarachnoid hemorrhage has been controversial. This retrospective study was designed to access the safety and efficacy among cohorts of different timing of endovascular treatment patients with aneurysmal subarachnoid hemorrhage. A database of patients with aneurysmal subarachnoid hemorrhage was analyzed who were confirmed by CT, and underwent endovascular treatment between January 2005 and January 2012,. The patients were grouped into four cohorts according to the timing of treatment: ultra-early cohort (within 24 hours of onset which was confirmed by CT), early cohort (between 24 and 72 hours of onset which was confirmed by CT), intermediate cohort (between 4 and 10 days of onset which was confirmed by CT) and delayed cohort (after 11 days of onset which was confirmed by CT). Patient demographics, aneurysms features and clinical outcomes were analyzed to evaluate safety and efficacy for timing of endovascular treatment among four cohorts. In our series of 664 patients, 269 patients were grouped into ultra-early cohort, 62 patients in early cohort, 218 patients in intermediate cohort, and 115 patients in delayed cohort. The patient demographics, aneurysm characteristics and neurological conditions on admission among groups showed no statistical significance. As a result of the 9-month follow-up with 513 patients, good outcome (mRS<2) was achieved in 78% patients in "ultra-early" cohort compared with that of 57% in the "intermediate" group(p=0.000), whereas other comparisons showed no statistical significance(p<0.05) among the four groups. Dividing the patients with dichotomized mRS into "good outcome" group and "poor outcome" group (mRS<2) at the 9-month follow-up, the results showed lower Hunt-Hess scores (p=0.000) and smaller size of aneurysms (p=.001) which were correlated with the good outcome. Hypertension (p=0.776), age (p=0.327), sex (p=0.551) and location (p=0.901) showed no statistical significance between groups. Endovascular treatment of aneurysmal subarachnoid hemorrhage which was confirmed by CT within 72 hours achieved better outcomes than that confirmed after 72 hours, especially in those patients treated within 24 hours of onset in comparison with patients treated between 4 and 10 days. PMID:24320010

  4. A phantom study to determine the optimum size of a single collimator for shortening the treatment time in CyberKnife stereotactic radiosurgery of spherical targets.

    PubMed

    Harikrishnaperumal, Sudahar; Kurup, Gopalakrishna; Venkatraman, Murali; Jagadeesan, Velmurugan

    2012-01-01

    Prolonged treatment execution time is a concern in CyberKnife robotic radiosurgery. Beam reduction and node reduction technique, and monitor unit optimization methods are adopted to reduce the treatment time. Usage of single collimator in the CyberKnife treatment plan can potentially reduce collimator exchange time. An optimal single collimator, which yields an acceptable dose distribution along with minimum number of nodes, beams, and monitor units, can be a versatile alternative for shortening treatment time. The aim of the present study is to find the optimal single collimator in CyberKnife treatment planning to shorten the treatment time with the acceptable dose distribution. A spherical planning target volume PTV1 was drawn in an anthropomorphic head and neck phantom. Plans with same treatment goals were generated for all the 12 collimators independently. D(95%) was selected as the prescribing isodose and the prescribed dose was 10 Gy. The plan of the optimal collimator size was evaluated for conformity, homogeneity, and dose spillage outside the target. The optimum collimator size and the target dimensions were correlated. The study was repeated with two other target volumes PTV2 and PTV3 for generalizing the results. Collimator sizes just above the diameter of the spherical PTVs were yielding least number of nodes and beams with acceptable dose distributions. The collimator size of 35 mm is optimum for the PTV1, whose diameter is 31.4 mm. Similarly, 50 mm collimator is optimum for PTV2 (diameter= 45.2 mm) and 20 mm collimator is optimum for PTV3 (Diameter = 17.3 mm). The total number of monitor units is found to reduce with increasing collimator size. Optimal single collimator is found to be useful for shortening the treatment time in spherical targets. Studies on two clinical targets, (a brain metastasis and a liver metastasis cases) show comparable results with the phantom study. PMID:22955653

  5. Modeling and optimization of a time-resolved proton radiographic imaging system for proton cancer treatment

    NASA Astrophysics Data System (ADS)

    Han, Bin

    This dissertation describes a research project to test the clinical utility of a time-resolved proton radiographic (TRPR) imaging system by performing comprehensive Monte Carlo simulations of a physical device coupled with realistic lung cancer patient anatomy defined by 4DCT for proton therapy. A time-resolved proton radiographic imaging system was modeled through Monte Carlo simulations. A particle-tracking feature was employed to evaluate the performance of the proton imaging system, especially in its ability to visualize and quantify proton range variations during respiration. The Most Likely Path (MLP) algorithm was developed to approximate the multiple Coulomb scattering paths of protons for the purpose of image reconstruction. Spatial resolution of ˜ 1 mm and range resolution of 1.3% of the total range were achieved using the MLP algorithm. Time-resolved proton radiographs of five patient cases were reconstructed to track tumor motion and to calculate water equivalent length variations. By comparing with direct 4DCT measurement, the accuracy of tumor tracking was found to be better than 2 mm in five patient cases. Utilizing tumor tracking information to reduce margins to the planning target volume, a gated treatment plan was compared with un-gated treatment plan. The equivalent uniform dose (EUD) and the normal tissue complication probability (NTCP) were used to quantify the gain in the quality of treatments. The EUD of the OARs was found to be reduced up to 11% and the corresponding NTCP of organs at risk (OARs) was found to be reduced up to 16.5%. These results suggest that, with image guidance by proton radiography, dose to OARs can be reduced and the corresponding NTCPs can be significantly reduced. The study concludes that the proton imaging system can accurately track the motion of the tumor and detect the WEL variations, leading to potential gains in using image-guided proton radiography for lung cancer treatments.

  6. Peritumoral Neuropilin-1 and VEGF receptor-2 expression increases time to recurrence in hepatocellular carcinoma patients undergoing curative hepatectomy

    PubMed Central

    Zhuang, Peng-Yuan; Wang, Jian-Dong; Tang, Zhao-Hui; Zhou, Xue-Ping; Yang, Yong; Quan, Zhi-Wei; Liu, Ying-Bin; Shen, Jun

    2014-01-01

    Purpose To determined Neuropilin-1 (NRP-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) expression in the tumoral and peritumoral tissues of 214 treatment-naïve HCC patients and its correlation with overall survival (OS) and time to recurrence (TTR). Experimental Design NRP-1 and VEGFR-2 expression were examined by tissue microarray and peritumoral hypoxia by pimonidazole staining and angiogenesis by microvessel density (MVD). OS and TTR were evaluated by Kaplan-Meier analysis and log-rank test. Results Peritumoral NRP-1 and VEGFR-2 expression were significantly higher than that of the tumoral tissue (p < 0.001 for both), and high peritumoral expression of both factors was negatively associated with tumor size (p < 0.001 for both). Patients with high peritumoral expression of both proteins had the longest median OS (>94.0 months) and TTR (>84.0 months). The multivariate Cox proportional hazards analysis revealed that patients with high peritumoral expression of both NRP-1 and VEGFR-2 were more than 4 times less likely to have recurrence (p = 0.004) and more than 10 times likely to survive (p < 0.001). Conclusions Peritumoral NRP-1 and VEGFR-2 expression is associated with prolonged TTR and extended OS of HCC patients and both may be useful as predictors of surgical outcome of HCC patients and explored as potential therapeutic targets. PMID:25333267

  7. Extension of brain tolerance to hyperbaric O2 by intermittent air breaks is related to the time of CBF increase.

    PubMed

    Chavko, Mikulas; McCarron, Richard M

    2006-04-21

    Intermittent air breaks during hyperbaric oxygen (HBO2) exposures protect against pulmonary and central nervous system (CNS) toxicity. The mechanisms of this beneficial effect from intermittency are not known. In this study, we examined if release of vasoconstriction during HBO2 exposure indicates a threshold for toxic dose of HBO2 and how it may be related to tolerance by intermittency. Awake rats instrumented for EEG and cerebral blood flow (CBF) measurement were exposed to 100% O2 at 6 ATA (absolute pressure). Air breaks of 3 or 10 min were given at different times after CBF increase. Following the air break, animals were exposed to 100% O2 until seizure and total O2 time was used to calculate benefit/toxicity. The most beneficial schedule was then used to assess the role of the multiple air breaks in extension of HBO2 tolerance. A significant increase in seizure latency was observed in animals with a single 3- or 10 min air break given 5-10 min after CBF increase. No change in seizure latency was observed when air breaks were given beyond (>10 and <5 min) this window. The duration of total O2 time to seizures was doubled with multiple 3 min air breaks, and quadrupled with 10 min air breaks compared with continuous HBO2 exposures. With more time spent on O2, the duration of air breaks was not sufficient for recovery from O2 toxicity and for CBF to return to baseline. Results show that an "optimal window" of HBO2 exposure is required for benefits by intermittent exposure to air. PMID:16546146

  8. Climate Response to the Increase in Tropospheric Ozone since Preindustrial Times: A Comparison between Ozone and Equivalent CO2 Forcings

    NASA Technical Reports Server (NTRS)

    Mickley L. J.; Jacob, D. J.; Field, B. D.; Rind, D.

    2004-01-01

    We examine the characteristics of the climate response to anthropogenic changes in tropospheric ozone. Using a general circulation model, we have carried out a pair of equilibrium climate simulations with realistic present-day and preindustrial ozone distributions. We find that the instantaneous radiative forcing of 0.49 W m(sup -2) due to the increase in tropospheric ozone since preindustrial times results in an increase in global mean surface temperature of 0.28 C. The increase is nearly 0.4 C in the Northern Hemisphere and about 0.2 C in the Southern Hemisphere. The largest increases (greater than 0.8 C) are downwind of Europe and Asia and over the North American interior in summer. In the lower stratosphere, global mean temperatures decrease by about 0.2 C due to the diminished upward flux of radiation at 9.6 micrometers. The largest stratospheric cooling, up to 1.0 C, occurs over high northern latitudes in winter, with possibly important implications for the formation of polar stratospheric clouds. To identify the characteristics of climate forcing unique to tropospheric ozone, we have conducted two additional climate equilibrium simulations: one in which preindustrial tropospheric ozone concentrations were increased everywhere by 18 ppb, producing the same global radiative forcing as present-day ozone but without the heterogeneity; and one in which CO2 was decreased by 25 ppm relative to present day, with ozone at present-day values, to again produce the same global radiative forcing but with the spectral signature of CO2 rather than ozone. In the first simulation (uniform increase of ozone), the global mean surface temperature increases by 0.25 C, with an interhemispheric difference of only 0.03 C, as compared with nearly 0.2 C for the heterogeneous ozone increase. In the second simulation (equivalent CO2), the global mean surface temperature increases by 0.36 C, 30% higher than the increase from tropospheric ozone. The stronger surface warming from CO2 is in part because CO2 forcing (obscured by water vapor) is shifted relatively poleward where the positive ice-albedo feedback amplifies the climate response and in part because the magnitude of the CO2 forcing in the mid-troposphere is double that of ozone. However, we find that CO2 is far less effective than tropospheric ozone in driving lower stratospheric cooling at high northern latitudes in winter.

  9. Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

    PubMed Central

    Wibom, C; Pettersson, F; Sjöström, M; Henriksson, R; Johansson, M; Bergenheim, A T

    2006-01-01

    Radiotherapy is one of the mainstays of glioblastoma (GBM) treatment. This study aims to investigate and characterise differences in protein expression patterns in brain tumour tissue following radiotherapy, in order to gain a more detailed understanding of the biological effects. Rat BT4C glioma cells were implanted into the brain of two groups of 12 BDIX-rats. One group received radiotherapy (12?Gy single fraction). Protein expression in normal and tumour brain tissue, collected at four different time points after irradiation, were analysed using surface enhanced laser desorption/ionisation – time of flight – mass spectrometry (SELDI-TOF-MS). Mass spectrometric data were analysed by principal component analysis (PCA) and partial least squares (PLS). Using these multivariate projection methods we detected differences between tumours and normal tissue, radiation treatment-induced changes and temporal effects. 77 peaks whose intensity significantly changed after radiotherapy were discovered. The prompt changes in the protein expression following irradiation might help elucidate biological events induced by radiation. The combination of SELDI-TOF-MS with PCA and PLS seems to be well suited for studying these changes. In a further perspective these findings may prove to be useful in the development of new GBM treatment approaches. PMID:16736004

  10. Increased resistance to proteasome inhibitors in multiple myeloma mediated by cIAP2 - implications for a combinatorial treatment

    PubMed Central

    Agarwal, Prasoon; Arngården, Linda; Hammarberg, Anna; Maes, Ken; Van Valckenborgh, Els; Vanderkerken, Karin; Wiklund, Helena Jernberg

    2015-01-01

    Despite the introduction of new treatment options for multiple myeloma (MM), a majority of patients relapse due to the development of resistance. Unraveling new mechanisms underlying resistance could lead to identification of possible targets for combinatorial treatment. Using TRAF3 deleted/mutated MM cell lines, we evaluated the role of the cellular inhibitor of apoptosis 2 (cIAP2) in drug resistance and uncovered the plausible mechanisms underlying this resistance and possible strategies to overcome this by combinatorial treatment. In MM, cIAP2 is part of the gene signature of aberrant NF-?B signaling and is heterogeneously expressed amongst MM patients. In cIAP2 overexpressing cells a decreased sensitivity to the proteasome inhibitors bortezomib, MG132 and carfilzomib was observed. Gene expression analysis revealed that 440 genes were differentially expressed due to cIAP2 overexpression. Importantly, the data imply that cIAPs are rational targets for combinatorial treatment in the population of MM with deleted/mutated TRAF3. Indeed, we found that treatment with the IAP inhibitor AT-406 enhanced the anti-MM effect of bortezomib in the investigated cell lines. Taken together, our results show that cIAP2 is an important factor mediating bortezomib resistance in MM cells harboring TRAF3 deletion/mutation and therefore should be considered as a target for combinatorial treatment. PMID:26036313

  11. Increased resistance to proteasome inhibitors in multiple myeloma mediated by cIAP2--implications for a combinatorial treatment.

    PubMed

    Fristedt Duvefelt, Charlotte; Lub, Susanne; Agarwal, Prasoon; Arngården, Linda; Hammarberg, Anna; Maes, Ken; Van Valckenborgh, Els; Vanderkerken, Karin; Jernberg Wiklund, Helena

    2015-08-21

    Despite the introduction of new treatment options for multiple myeloma (MM), a majority of patients relapse due to the development of resistance. Unraveling new mechanisms underlying resistance could lead to identification of possible targets for combinatorial treatment. Using TRAF3 deleted/mutated MM cell lines, we evaluated the role of the cellular inhibitor of apoptosis 2 (cIAP2) in drug resistance and uncovered the plausible mechanisms underlying this resistance and possible strategies to overcome this by combinatorial treatment. In MM, cIAP2 is part of the gene signature of aberrant NF-?B signaling and is heterogeneously expressed amongst MM patients. In cIAP2 overexpressing cells a decreased sensitivity to the proteasome inhibitors bortezomib, MG132 and carfilzomib was observed. Gene expression analysis revealed that 440 genes were differentially expressed due to cIAP2 overexpression. Importantly, the data imply that cIAPs are rational targets for combinatorial treatment in the population of MM with deleted/mutated TRAF3. Indeed, we found that treatment with the IAP inhibitor AT-406 enhanced the anti-MM effect of bortezomib in the investigated cell lines. Taken together, our results show that cIAP2 is an important factor mediating bortezomib resistance in MM cells harboring TRAF3 deletion/mutation and therefore should be considered as a target for combinatorial treatment. PMID:26036313

  12. U18666A Treatment Results in Cholesterol Accumulation, Reduced Na(+), K(+)-ATPase Activity, and Increased Oxidative Stress in Rat Cortical Astrocytes.

    PubMed

    Copetti-Santos, Daniela; Moraes, Vitoria; Weiler, Dácio Franco; de Mello, Alexandre Silva; Machado, Fernanda de Souza; Marinho, Jéssica Pereira; Siebert, Cassiana; Kolling, Janaina; Funchal, Cláudia; Wyse, Angela T S; Coelho, Janice Carneiro

    2015-10-01

    The objective of this study was to determine the effect of U18666A, an inhibitor of cholesterol synthesis and its intracellular transport, on oxidative stress parameters in cortical astrocytes cultured from Wistar rats (0-3 days old). The cultures were incubated with U18666A (0.25 µg/mL) for 48 h, conditions that are considered ideal to mimic Niemann-Pick type C disease. A variety of indicators of oxidative stress were measured. U18666A treatment increased cholesterol 2-fold in treated compared to control astrocytes. Oxidative stress was significantly elevated in treated cells as demonstrated by a 1.7-fold increase in thiobarbituric acid reactive substances, a 60% decrease is sulfhydral groups, and a 3.7-fold increase in carbonyl groups, indicative of increased lipid and protein oxidation following U18666A treatment. Consistent with these changes, both catalase and superoxide dismutase activities were significantly reduced nearly 50% in treated compared to control astrocytes. Collectively, these change resulted in a 50% reduction in Na(+), K(+)-ATPase specific activity following U18666A treatment, suggesting a significant alteration in its plasma membrane environment. Overall, these changes indicate that U18666A treatment results in increased cholesterol levels and an increased level of oxidative stress in cortical astrocytes, consistent with what is observed in Niemann-Pick type C disease. PMID:26344921

  13. Process Improvement to Enhance Existing Stroke Team Activity Toward More Timely Thrombolytic Treatment

    PubMed Central

    Cho, Han-Jin; Lee, Kyung Yul; Nam, Hyo Suk; Kim, Young Dae; Song, Tae-Jin; Jung, Yo Han; Choi, Hye-Yeon

    2014-01-01

    Background and Purpose Process improvement (PI) is an approach for enhancing the existing quality improvement process by making changes while keeping the existing process. We have shown that implementation of a stroke code program using a computerized physician order entry system is effective in reducing the in-hospital time delay to thrombolysis in acute stroke patients. We investigated whether implementation of this PI could further reduce the time delays by continuous improvement of the existing process. Methods After determining a key indicator [time interval from emergency department (ED) arrival to intravenous (IV) thrombolysis] and conducting data analysis, the target time from ED arrival to IV thrombolysis in acute stroke patients was set at 40 min. The key indicator was monitored continuously at a weekly stroke conference. The possible reasons for the delay were determined in cases for which IV thrombolysis was not administered within the target time and, where possible, the problems were corrected. The time intervals from ED arrival to the various evaluation steps and treatment before and after implementation of the PI were compared. Results The median time interval from ED arrival to IV thrombolysis in acute stroke patients was significantly reduced after implementation of the PI (from 63.5 to 45 min, p=0.001). The variation in the time interval was also reduced. A reduction in the evaluation time intervals was achieved after the PI [from 23 to 17 min for computed tomography scanning (p=0.003) and from 35 to 29 min for complete blood counts (p=0.006)]. Conclusions PI is effective for continuous improvement of the existing process by reducing the time delays between ED arrival and IV thrombolysis in acute stroke patients. PMID:25324882

  14. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

    PubMed Central

    Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd; Gordin, Fred M; Grund, Birgit; Lundgren, Jens D; Neaton, James D; Pett, Sarah L; Phillips, Andrew; Touloumi, Giota; Vjecha, Michael J

    2012-01-01

    Background Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. Purpose In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. Methods A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/?L are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is <350 cells/ ?L (deferred ART) and followed for a minimum of 3 years. The primary outcome is time to AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Results Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot phase was well underway, and the complexities of conducting the trial in a geographically wide population with diverse regulatory requirements. With the successful completion of the pilot phase, more than 1000 participants from 100 sites in 23 countries have been enrolled. The study will expand to include 237 sites in 36 countries to reach the target accrual of 4000 participants. Conclusions START is addressing one of the most important questions in the clinical management of ART. The randomization provided a platform for the conduct of several substudies aimed at increasing our understanding of HIV disease and the effects of antiretroviral therapy beyond the primary question of the trial. The lessons learned from its design and implementation will hopefully be of use to future publicly funded international trials. PMID:22547421

  15. Weekly Intra-Amniotic IGF-1 Treatment Increases Growth of Growth-Restricted Ovine Fetuses and Up-Regulates Placental Amino Acid Transporters

    PubMed Central

    Wali, Jibran A.; de Boo, Hendrina A.; Derraik, José G. B.; Phua, Hui Hui; Oliver, Mark H.; Bloomfield, Frank H.; Harding, Jane E.

    2012-01-01

    Frequent treatment of the growth-restricted (IUGR) ovine fetus with intra-amniotic IGF-1 increases fetal growth. We aimed to determine whether increased growth was maintained with an extended dosing interval and to examine possible mechanisms. Pregnant ewes were allocated to three groups: Control, and two IUGR groups (induced by placental embolization) treated with weekly intra-amniotic injections of either saline (IUGR) or 360 µg IGF-1 (IGF1). IUGR fetuses were hypoxic, hyperuremic, hypoglycemic, and grew more slowly than controls. Placental glucose uptake and SLC2A1 (GLUT2) mRNA levels decreased in IUGR fetuses, but SLC2A3 (GLUT3) and SLC2A4 (GLUT4) levels were unaffected. IGF-1 treatment increased fetal growth rate, did not alter uterine blood flow or placental glucose uptake, and increased placental SLC2A1 and SLC2A4 (but not SLC2A3) mRNA levels compared with saline-treated IUGR animals. Following IGF-1 treatment, placental mRNA levels of isoforms of the system A, y+, and L amino acid transporters increased 1.3 to 5.0 fold, while the ratio of phosphorylated-mTOR to total mTOR also tended to increase. Weekly intra-amniotic IGF-1 treatment provides a promising avenue for intra-uterine treatment of IUGR babies, and may act via increased fetal substrate supply, up-regulating placental transporters for neutral, cationic, and branched-chain amino acids, possibly via increased activation of the mTOR pathway. PMID:22629469

  16. Adding Immediate Feedback to Explicit Timing: An Option for Enhancing Treatment Intensity to Improve Mathematics Fluency

    ERIC Educational Resources Information Center

    Duhon, Gary J.; House, Sara; Hastings, Kim; Poncy, Brian; Solomon, Benjamin

    2015-01-01

    The primary purpose of intensifying interventions is to increase the effect of the intervention currently being delivered. However, there has been little empirical work completed that can provide guidance on selecting intensification methods. Because intensity can be modified in a number of ways that may differentially impact the time, effort, or…

  17. Real-time increase in depth of field of an uncooled thermal camera using several phase-mask technologies.

    PubMed

    Diaz, Frédéric; Lee, Mane-Si Laure; Rejeaunier, Xavier; Lehoucq, Gaelle; Goudail, François; Loiseaux, Brigitte; Bansropun, Shailendra; Rollin, Joel; Debes, Eric; Mils, Philippe

    2011-02-01

    Imaging systems that combine a phase mask in the pupil and digital postprocessing may have better performance than conventional ones. We have built such a system to enhance the depth of field of an uncooled thermal camera. The phase masks are binary, their structures are optimized thanks to an image quality criterion, and they have been realized with three different technologies that give equivalent results. The deconvolution postprocessing is performed in real time with a graphics processing unit. A significant increase of the depth of field of a factor 3 has been obtained. PMID:21283209

  18. Development of equations to determine the increase in pavement condition due to treatment and the rate of decrease in condition after treatment for a local agency pavement network. 

    E-print Network

    Deshmukh, Maithilee Mukund.

    2010-07-14

    ........................................................................ 18? 2.3.1 Hypothesis .............................................................................. 19? 2.3.2 Regression Analysis ............................................................... 20? 2.3.3 Calculation of PCI Projected..., inspection or performance data, parametric data for performance equations, and unit cost for different treatments. Various analysis tools like performance prediction 4 models that are required to analyze a pavement also form an important part of the PMS...

  19. Artificial Neural Network classification of operator workload with an assessment of time variation and noise-enhancement to increase performance

    PubMed Central

    Casson, Alexander J.

    2014-01-01

    Workload classification—the determination of whether a human operator is in a high or low workload state to allow their working environment to be optimized—is an emerging application of passive Brain-Computer Interface (BCI) systems. Practical systems must not only accurately detect the current workload state, but also have good temporal performance: requiring little time to set up and train the classifier, and ensuring that the reported performance level is consistent and predictable over time. This paper investigates the temporal performance of an Artificial Neural Network based classification system. For networks trained on little EEG data good classification accuracies (86%) are achieved over very short time frames, but substantial decreases in accuracy are found as the time gap between the network training and the actual use is increased. Noise-enhanced processing, where artificially generated noise is deliberately added to the testing signals, is investigated as a potential technique to mitigate this degradation without requiring the network to be re-trained using more data. Small stochastic resonance effects are demonstrated whereby the classification process gets better in the presence of more noise. The effect is small and does not eliminate the need for re-training, but it is consistent, and this is the first demonstration of such effects for non-evoked/free-running EEG signals suitable for passive BCI. PMID:25520608

  20. Time-Dependent Predictors of Loss to Follow-Up in a Large HIV Treatment Cohort in Nigeria

    PubMed Central

    Meloni, Seema Thakore; Chang, Charlotte; Chaplin, Beth; Rawizza, Holly; Jolayemi, Oluwatoyin; Banigbe, Bolanle; Okonkwo, Prosper; Kanki, Phyllis

    2014-01-01

    Background ?Most evaluations of loss to follow-up (LTFU) in human immunodeficiency virus (HIV) treatment programs focus on baseline predictors, prior to antiretroviral therapy (ART) initiation. As risk of LTFU is a continuous issue, the aim of this evaluation was to augment existing information with further examination of time-dependent predictors of loss. Methods ?This was a retrospective evaluation of data collected between 2004 and 2012 by the Harvard School of Public Health and the AIDS Prevention Initiative in Nigeria as part of PEPFAR-funded program in Nigeria. We used multivariate modeling methods to examine associations between CD4+ cell counts, viral load, and early adherence patterns with LTFU, defined as no refills collected for at least 2 months since the last scheduled appointment. Results ?Of 51 953 patients initiated on ART between 2004 and 2011, 14 626 (28%) were LTFU by 2012. Factors associated with increased risk for LTFU were young age, having nonincome-generating occupations or no education, being unmarried, World Health Organization (WHO) stage, having a detectable viral load, and lower CD4+ cell counts. In a subset analysis, adherence patterns during the first 3 months of ART were associated with risk of LTFU by month 12. Conclusions ?In settings with limited resources, early adherence patterns, as well as CD4+ cell counts and unsuppressed viral load, at any time point in treatment are predictive of loss and serve as effective markers for developing targeted interventions to reduce rates of attrition. PMID:25734125

  1. Breast cancer mortality patterns and time trends in 10 new EU member states: mortality declining in young women, but still increasing in the elderly.

    PubMed

    Tyczynski, Jerzy E; Plesko, Ivan; Aareleid, Tiiu; Primic-Zakelj, Maja; Dalmas, Miriam; Kurtinaitis, Juozas; Stengrevics, Aivars; Parkin, D Maxwell

    2004-12-20

    Breast cancer is the cancer diagnosed most frequently in women worldwide. In Europe it is the most common cancer in the female population, with approximately 350,000 new cases diagnosed each year including 130,000 deaths. Incidence rates are increasing in the majority of European countries, whereas a decline in mortality rates has been observed in many West European countries since the late 1980s and early 1990s. Our study examines breast cancer mortality patterns and time trends in the new European Union (EU) member states and compares them with the situation in current EU member states. A Joinpoint regression analysis was used to assess temporal changes in mortality rates and the trends examined in the light of known risk factors, screening programs and advances in treatment. In the majority of the countries analyzed, a deceleration in the increase of mortality rates appeared, followed by a decrease of mortality in many of them in the second half of the 1990s. The declining tendency was visible primarily in young women, and to a lesser extent in middle-aged women, whereas in elderly women a continuing increase of mortality was observed. Analysis of mortality data, information from previous publications, as well as analysis of known factors influencing breast cancer risk suggest that changes observed are due mainly to recent advances in treatment rather than changes in lifestyle risk factors or the result of screening programs. Early detection and a shift toward more favorable stage distribution could have played the leading role for mortality decline in younger patients. PMID:15386350

  2. Improving substance abuse data systems to measure `waiting time to treatment': Lessons learned from a quality improvement initiative

    PubMed Central

    Hoffman, Kim A; Quanbeck, Andrew; Ford, James H; Wrede, Fritz; Wright, Dagan; Lambert-Wacey, Dawn; Chvojka, Phil; Hanchett, Andrew; McCarty, Dennis

    2012-01-01

    Robust data measurement systems assess health care performance and monitor population-level treatment trends. A key challenge in the assessment of substance abuse treatment is the development of systems to accurately monitor service delivery indicators. Wait time to treatment, as defined by the days between first request for service and first treatment, is an important measure of organizational process and delivery of care. The Network for the Improvement of Addiction Treatment emphasizes wait time as a primary outcome in their study of 201 addiction treatment agencies in the USA. This article describes the changes made in five state data systems to monitor wait times and outlines lessons learned that could be applied to other health data tracking systems. PMID:22193826

  3. Increased Survivorship and Altered Cytokine Profile from Treatment of Influenza A H1N1-Infected Mice with Ekybion: A Drug Complex of Natural Extracts and Inorganic Compounds

    PubMed Central

    Lupfer, Christopher; Besnouin, Didier; Tepper, Samuel E.; Maselko, Maciej; Patton, Kristin M.; Pastey, Manoj

    2011-01-01

    Ekybion is a drug complex of 16 natural extracts and inorganic compounds designed to treat a variety of respiratory pathogens of bacterial and viral origin. It is licensed throughout Europe for the treatment of respiratory tract infections from equine parainfluenza type 3 and equine herpes virus type 1 in equine stables. The purpose of this paper was to test the efficacy of Ekybion on a well-developed animal model of influenza A infection and determine a mode of action. Experiments were performed with Balb/c mice infected with a lethal dose of influenza A/PR/8/34 H1N1 virus and treated with nebulized Ekybion every 8?h in a time-dependant or dose-dependant fashion. These experiments showed that mice treated prior to infection with Ekybion had a higher survival rates (~46%) compared with untreated animals (~0%). Paradoxically, these mice showed no significant difference in lung virus titer or weight loss. There was, however, a decrease in the level of GM-CSF, IL-6, and G-CSF cytokines in the lungs of Ekybion-treated, infected mice. It is possible that decreases in proinflammatory cytokines may have contributed to increased survivorship in Ekybion-treated influenza-infected mice. PMID:20981272

  4. Treatment

    MedlinePLUS

    ... States, smallpox vaccine, antivirals, and vaccinia immune globulin (VIG) can be used. Learn more about smallpox vaccine, antivirals, and VIG treatments . Resource CDC's Smallpox Vaccine Information for the ...

  5. Hybridization and genome size evolution: timing and magnitude of nuclear DNA content increases in Helianthus homoploid hybrid species

    PubMed Central

    Baack, Eric J.; Whitney, Kenneth D.; Rieseberg, Loren H.

    2008-01-01

    Summary Hybridization and polyploidy can induce rapid genomic changes, including the gain or loss of DNA, but the magnitude and timing of such changes are not well understood. The homoploid hybrid system in Helianthus (three hybrid-derived species and their two parents) provides an opportunity to examine the link between hybridization and genome size changes in a replicated fashion. Flow cytometry was used to estimate the nuclear DNA content in multiple populations of three homoploid hybrid Helianthus species (Helianthus anomalus, Helianthus deserticola, and Helianthus paradoxus), the parental species (Helianthus annuus and Helianthus petiolaris), synthetic hybrids, and natural hybrid-zone populations. Results confirm that hybrid-derived species have 50% more nuclear DNA than the parental species. Despite multiple origins, hybrid species were largely consistent in their DNA content across populations, although H. deserticola showed significant interpopulation differences. First- and sixth-generation synthetic hybrids and hybrid-zone plants did not show an increase from parental DNA content. First-generation hybrids differed in DNA content according to the maternal parent. In summary, hybridization by itself does not lead to increased nuclear DNA content in Helianthus, and the evolutionary forces responsible for the repeated increases in DNA content seen in the hybrid-derived species remain mysterious. PMID:15998412

  6. Distributed network actions by nicotine increase the threshold for spike-timing-dependent plasticity in prefrontal cortex.

    PubMed

    Couey, Jonathan J; Meredith, Rhiannon M; Spijker, Sabine; Poorthuis, Rogier B; Smit, August B; Brussaard, Arjen B; Mansvelder, Huibert D

    2007-04-01

    Nicotine enhances attention and working memory by activating nicotinic acetylcholine receptors (nAChRs). The prefrontal cortex (PFC) is critical for these cognitive functions and is also rich in nAChR expression. Specific cellular and synaptic mechanisms underlying nicotine's effects on cognition remain elusive. Here we show that nicotine exposure increases the threshold for synaptic spike-timing-dependent potentiation (STDP) in layer V pyramidal neurons of the mouse PFC. During coincident presynaptic and postsynaptic activity, nicotine reduces dendritic calcium signals associated with action potential propagation by enhancing GABAergic transmission. This results from a series of presynaptic actions involving different PFC interneurons and multiple nAChR subtypes. Pharmacological block of nAChRs or GABA(A) receptors prevented nicotine's actions and restored STDP, as did increasing dendritic calcium signals with stronger postsynaptic activity. Thus, by activating nAChRs distributed throughout the PFC neuronal network, nicotine affects PFC information processing and storage by increasing the amount of postsynaptic activity necessary to induce STDP. PMID:17408579

  7. Interference of strength training can obviously increase the effect of moxibustion treatment on patients with knee joints injuries

    PubMed Central

    Yuan, Yan-Dong; Zhao, Xin-Ping; Deng, Zheng-Long; Song, Qing-Hua; Zhang, Li-Yan; Zhang, Hong-Yu

    2015-01-01

    Objective: Observe the effects of Acupoint moxibustion combined with muscle training in treating the patients with knee joints strain. Methods: The 36 patients with knee joint strains were divided into the experimental group and control group with the method of random number table, each group including 18 cases. The control group was treated with Acupoint moxibustion, while the experimental groups were treated with Acupoint moxibustion combined with muscle training. Before the treatment and after the treatment lasting 12 weeks, the therapy effects and improvement of the knee-joint muscle force for the 2 groups of patients were respectively evaluated. Results: Through the treatment of 12 weeks, the clinical symptoms of control group were evidently improved than prior-treatment , but the improvement effects of the knee-joint muscle force (the peak torques of bend and stretch respectively were (32.8 ± 8.8) N·m and (35.0 ± 11.2) N·m were not significant (P > 0.05); while the clinical symptoms and knee-joint muscle force of experimental group (the peak torques of bend and stretch respectively were (40.3 ± 9.3) N·m and (42.3 ± 10.6) N·m were evidently improved than prior-treatment, and the improvement range was also evidently better than the control group (P < 0.05). Conclusion: The Acupoint moxibustion combined with muscle force training had synergistic effects in treating the patients with elderly knee-joint strain, could further relieve the pain on knee joints, and improve the joint’ s movement, such therapy was worthy to promote and apply in clinic. PMID:26550321

  8. Medicare, Ethics, and Reflexive Longevity: Governing Time and Treatment in an Aging Society

    PubMed Central

    Kaufman, Sharon R.; Fjord, Lakshmi

    2013-01-01

    The clinical activities that constitute longevity making in the United States are perhaps the quintessential example of a dynamic modern temporality, characterized by the quest for risk reduction, the powerful progress narratives of science and medicine, and the personal responsibility of calculating the worth of more time in relation to medical options and age. This article explores how medicine materializes and problematizes time through a discussion of ethicality—in this case, the form of governance in which scientific evidence, Medicare policy and clinical knowledge and practice organize first, what becomes “thinkable” as the best medicine, and second, how that kind of understanding shapes a telos of living. Using liver disease and liver transplantation in the United States as my example, I explore the influence of Medicare coverage decisions on treatments, clinical standards, and ethical necessity. Reflexive longevity—a relentless future-thinking about life itself—is one feature of this ethicality. PMID:21834359

  9. Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer

    PubMed Central

    Andersson, Marianne; Arvidsson, Annette; Nordgren, Svante; Brevinge, Hans; Lagerstedt, Kristina; Lundholm, Kent

    2008-01-01

    This study evaluates HLA gene expression and tumor infiltration by B-cells, macrophages, dendritic cells, T-helper and cytotoxic T-lymphocytes in response to short-term preoperative treatment with cyclooxygenase inhibitors. Patients with colorectal carcinoma were randomized to receive oral NSAID (indomethacin or celebrex) for three days preoperatively; controls received esomeprazol. Peroperative tumor biopsies and normal colon tissue were analyzed by microarray, quantitative PCR and immunohistochemistry. Efficacy of short-term systemic NSAID treatment was confirmed by measurement of PGE2 production in blood monocytes from healthy volunteers. NSAID treatment upregulated genes at the MHC locus on chromosome 6p21 in tumor tissue, but not in normal colon tissue, from the same patient. 23 of the 100 most upregulated genes belonged to MHC class II. HLA-DM, -DO (peptide loading), HLA-DP, -DQ, -DR (antigen presentation), granzyme B, H, perforin and FCGR3A (CD16) (cytotoxicity) displayed increased expression, as did CD8, a marker of cytotoxic T-lymphocytes, while HLA-A and -C expression were not increased by NSAID treatment. MHC II protein (HLA-DP, -DQ, -DR) levels and infiltration by CD4+ T-helper cells of tumor stroma increased upon NSAID treatment, while CD8+ cytotoxic T-lymphocytes increased in both tumor stroma and epithelium. Molecules associated with immunosuppressive T regulatory cells (FOXP3, IL-10) were significantly decreased in indomethacin-exposed tumors. Standard oral administration of NSAID three days preoperatively was enough to increase tumor infiltration by seemingly activated immune cells. These findings agree with previous information that high prostanoid activities in colorectal cancer increase the risk for reduced disease-specific survival following tumor resection. PMID:18307280

  10. Dissolved organic carbon lability increases with water residence time in the alluvial aquifer of a river floodplain ecosystem

    NASA Astrophysics Data System (ADS)

    Helton, Ashley M.; Wright, Meredith S.; Bernhardt, Emily S.; Poole, Geoffrey C.; Cory, Rose M.; Stanford, Jack A.

    2015-04-01

    We assessed spatial and temporal patterns of dissolved organic carbon (DOC) lability and composition throughout the alluvial aquifer of the 16 km2 Nyack Floodplain in northwest Montana, USA. Water influx to the aquifer derives almost exclusively from the Middle Fork of the Flathead River, and water residence times within the aquifer range from days to months. Across seasons and channel discharge conditions, we measured DOC concentration, lability, and optical properties of aquifer water sampled from 12 wells, both near and ~3 m below the water table. Concentrations of DOC were typically low (542 ± 22.7 µg L-1; mean ± se), and the percentage of labile DOC averaged 18 ± 12% during 3 day laboratory assays. Parallel factor analysis of fluorescence excitation-emission matrices revealed two humic-like and two amino acid-like fluorescence groups. Total DOC, humic-like components, and specific UV absorbance decreased with water residence time, consistent with sorption to aquifer sediments. However, labile DOC (both concentration and fraction) increased with water residence time, suggesting a concurrent influx or production of labile DOC. Thus, although the carbon-poor, oxygen-rich aquifer is a net sink for DOC, recalcitrant DOC appears to be replaced with more labile DOC along aquifer flow paths. Our observation of DOC production in long flow paths contrasts with studies of hyporheic DOC consumption along short (centimeters to meters) flow paths and highlights the importance of understanding the role of labile organic matter production and/or influx in alluvial aquifer carbon cycling.

  11. The impact of time to thrombolytic treatment on outcome in patients with acute myocardial infarction

    PubMed Central

    Chareonthaitawee, P; Gibbons, R; Roberts, R; Christian, T; Burns, R

    2000-01-01

    OBJECTIVES—To examine the impact of time to thrombolytic treatment on multiple acute outcome variables in a single trial of thrombolysis in acute myocardial infarction.?DESIGN AND PATIENTS—Mortality and reinfarction rate were measured in 2770 patients with acute myocardial infarction who received thrombolysis within 12 hours in CORE, an international, dose ranging trial of poloxamer 188. Tc-99m sestamibi infarct size and radionuclide angiographic ejection fraction substudies included 1099 and 1074 patients, respectively.?RESULTS—Time to thrombolysis, subgrouped by intervals (< 2, 2-4, ? 4-6, and ? 6 hours), was significantly associated with infarct size (median 15.0%, 18.5%, 22.0%, 18.5% of left ventricle; p = 0.033), mean (SD) ejection fraction (51.5 (12.0)%, 48.3 (13.9)%, 48.2 (13.3)%, 48.2 (15.0)%; p = 0.006), 35 day mortality (5.7%, 7.1%, 7.9%, 12.5%; p = 0.0004), six month mortality (7.3%, 8.6%, 10.4%, 15.5%; p < 0.0001), and 35 day reinfarction rate (6.1%, 3.2%, 4.0%, 0.9%; p = 0.0001).?CONCLUSIONS—In this single large trial, the beneficial effect of time to thrombolysis on infarct size and ejection fraction was restricted to treatment given within two hours of symptom onset, while the effect on mortality was evident over all time intervals. Reinfarction rate was higher in patients treated with earlier thrombolysis.???Keywords: myocardial infarction; thrombolysis; infarct size PMID:10908248

  12. NOTE: Tradeoffs of integrating real-time tracking into IGRT for prostate cancer treatment

    NASA Astrophysics Data System (ADS)

    Zhu, X.; Bourland, J. D.; Yuan, Y.; Zhuang, T.; O'Daniel, J.; Thongphiew, D.; Wu, Q. J.; Das, S. K.; Yoo, S.; Yin, F. F.

    2009-09-01

    This study investigated the integration of the Calypso real-time tracking system, based on implanted ferromagnetic transponders and a detector array, into the current process for image-guided radiation treatment (IGRT) of prostate cancer at our institution. The current IGRT process includes magnetic resonance imaging (MRI) for prostate delineation, CT simulation for treatment planning, daily on-board kV and CBCT imaging for target alignment, and MRI/MRS for post-treatment assessment. This study assesses (1) magnetic-field-induced displacement and radio-frequency (RF)-induced heating of transponders during MRI at 1.5 T and 3 T, and (2) image artifacts caused by transponders and the detector array in phantom and patient cases with the different imaging systems. A tissue-equivalent phantom mimicking prostate tissue stiffness was constructed and implanted with three operational transponders prior to phantom solidification. The measurements show that the Calypso system is safe with all the imaging systems. Transponder position displacements due to the MR field are minimal (<1.0 mm) for both 1.5 T and 3 T MRI scanners, and the temperature variation due to MRI RF heating is <0.2 °C. The visibility of transponders and bony anatomy was not affected on the OBI kV and CT images. Image quality degradation caused by the detector antenna array is observed in the CBCT image. Image artifacts are most significant with the gradient echo sequence in the MR images, producing null signals surrounding the transponders with radii ~1.5 cm and length ~4 cm. Thus, Calypso transponders can preclude the use of MRI/MRS in post-treatment assessment. Modifications of the clinical flow are required to accommodate and minimize the substantial MRI artifacts induced by the Calypso transponders.

  13. Time-to-treatment of diffuse large B-cell lymphoma in São Paulo

    PubMed Central

    Xavier, Flávia Dias; Levy, Debora; Pereira, Juliana

    2014-01-01

    OBJECTIVE: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, accounting for nearly 50% of the cases in the Hematology Department of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo. The treatment outcome is influenced by age, abnormal lactate dehydrogenase levels, extranodal infiltration, the disease stage and the patient's performance status. In this study, we sought to report the time-to-treatment of diffuse large B-cell lymphoma in São Paulo's public health system network and its impact on patient outcomes. METHODS: We prospectively followed a cohort of 42 consecutive patients with de novo diffuse large B-cell lymphoma between 2008 and 2012. RESULTS: Our patients had more advanced disease than that reported in the literature (61.9% vs. 46%). In São Paulo's public health system network, it took an average of 7.4 months for a diagnosis to be made and an additional 1.4 months to obtain an appointment with a specialist. Once at our Hematology Department, it took less than 20 days for staging, confirmation of the diagnosis and treatment initiation. An interval from signs or symptoms to treatment of more than 6 months was associated with inferior progression-free survival in 3 years (p?=?0.049). CONCLUSION: A delay in the diagnosis of diffuse large B-cell lymphoma is a public health problem and may be associated with worse progression-free survival. PMID:24838904

  14. Treatment of flaxseed to reduce biohydrogenation of a-linolenic acid by ruminal microbes in sheep and cattle and increase n-3 fatty acid concentrations in red meat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our study determined if flaxseed treated with a formaldehyde-free process increased n-3 fatty acid (FA) levels in ruminant muscle. Twenty-four lambs (initial BW 43.8 ± 4.4 kg) were randomly divided into 4 groups for a 90-d trial. One treatment group (FLX) was fed 136 g/d of non-treated ground flaxse...

  15. Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S

    PubMed Central

    Heemskerk, Mattijs M.; Dharuri, Harish K.; van den Berg, Sjoerd A. A.; Jónasdóttir, Hulda S.; Kloos, Dick-Paul; Giera, Martin; van Dijk, Ko Willems; van Harmelen, Vanessa

    2014-01-01

    Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the “biosynthesis of unsaturated fatty acids” pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment. PMID:25320342

  16. Importance of increased intraosseous pressure in the development of osteonecrosis of the femoral head: implications for treatment

    SciTech Connect

    Hungerford, D.S.; Lennox, D.W.

    1985-10-01

    Early diagnosis of osteonecrosis by radiograph, bone scan, CT scan, magnetic resonance imaging (MRI), intraosseous pressure measurement, or intraosseous venogram can lead to early successful treatment. For early (Ficat stages I and II) osteonecrosis of the hip, core decompression can provide diagnostic confirmation and pain relief and may prevent progression of disease. For more advanced disease (Ficat stages II and IV), osteotomy, endoprosthetic or bipolar prosthetic replacement, total hip arthroplasty, and arthrodesis are surgical options.86 references.

  17. 4D dosimetry and its applications to pre-treatment quality control and real-time in vivo dosimetry of VMAT treatments

    NASA Astrophysics Data System (ADS)

    Nordström, F.; Wetterstedt, S. af; Bäck, S. Å. J.

    2013-06-01

    In this study, a 4D dosimetry concept was developed. This concept included a method for calculation of 3D reference absorbed dose matrices at every control point of the delivery using a clinical treatment planning system (TPS). Further, the gamma evaluation method was extended to incorporate the 4th dimension of the TPS calculated dose distributions. The applications of the 4D dosimetry concept on pre-treatment quality control and real-time in vivo dosimetry were investigated.

  18. A novel method for real-time skin impedance measurement during radiofrequency skin tightening treatments.

    PubMed

    Harth, Yoram; Lischinsky, Daniel

    2011-03-01

    The thermal effects of monopolar and bipolar radiofrequency (RF) have been proven to be beneficial in skin tightening. Nevertheless, these effects were frequently partial or unpredictable because of the uncontrolled nature of monopolar or unipolar RF and the superficial nature of energy flow for bipolar or tripolar configurations. One of the hypotheses for lack or predictability of efficacy of the first-generation RF therapy skin tightening systems is lack of adaptation of delivered power to differences in individual skin impedance. A novel multisource phase-controlled system was used (1 MHz, power range 0-65 W) for treatment and real-time skin impedance measurements in 24 patients (EndyMed PRO™; EndyMed, Cesarea, Israel). This system allows continuous real-time measurement of skin impedance delivering constant energy to the patient skin independent of changes in its impedance. More than 6000 unique skin impedance measurements on 22 patients showed an average session impedance range was 215-584 Ohm with an average of 369 Ohm (standard deviation of 49 Ohm). Analyzing individual pulses (total of 600 readings) showed a significant decrease in impedance during the pulse. These findings validate the expected differences in skin impedance between individual patients and in the same patients during the treatment pulse. Clinical study on 30 patients with facial skin aging using the device has shown high predictability of efficacy (86.7% of patients had good results or better at 3 months' follow-up [decrease of 2 or more grades in Fitzpatrick's wrinkle scale]). The real-time customization of energy according to skin impedance allows a significantly more accurate and safe method of nonablative skin tightening with more consistent and predictable results. PMID:21332912

  19. Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.

    PubMed

    Salari, Ali-Akbar; Bakhtiari, Amir; Homberg, Judith R

    2015-08-01

    Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500?g/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders. PMID:25983020

  20. The better the story, the bigger the serving: narrative transportation increases snacking during screen time in a randomized trial

    PubMed Central

    2013-01-01

    Background Watching television and playing video games increase energy intake, likely due to distraction from satiety cues. A study comparing one hour of watching TV, playing typical video games, or playing motion-controlled video games found a difference across groups in energy intake, but the reasons for this difference are not clear. As a secondary analysis, we investigated several types of distraction to determine potential psychosocial mechanisms which may account for greater energy intake observed during sedentary screen time as compared to motion-controlled video gaming. Methods Feelings of enjoyment, engagement (mental immersion), spatial presence (the feeling of being in the game), and transportation (immersion in a narrative) were investigated in 120 young adults aged 18 – 35 (60 female). Results Only narrative transportation was associated with total caloric intake (? = .205, P = .025). Transportation was also higher in the TV group than in the gaming groups (P = .002) and higher in males than in females (P = .003). Transportation mediated the relationship between motion-controlled gaming (as compared to TV watching) and square root transformed energy intake (indirect effect = ?1.34, 95% confidence interval ?3.57, ?0.13). No other distraction-related variables were associated with intake. Conclusions These results suggest that different forms of distraction may differentially affect eating behavior during screen time, and that narrative appears to be a particularly strong distractor. Future studies should further investigate the effects of narrative on eating behavior. PMID:23680389

  1. Increasing functional modularity with residence time in the co-distribution of native and introduced vascular plants

    PubMed Central

    Hui, Cang; Richardson, David M.; Pyšek, Petr; Le Roux, Johannes J.; Ku?era, Tomáš; Jarošík, Vojt?ch

    2013-01-01

    Species gain membership of regional assemblages by passing through multiple ecological and environmental filters. To capture the potential trajectory of structural changes in regional meta-communities driven by biological invasions, one can categorize species pools into assemblages of different residence times. Older assemblages, having passed through more environmental filters, should become more functionally ordered and structured. Here we calculate the level of compartmentalization (modularity) for three different-aged assemblages (neophytes, introduced after 1500 AD; archaeophytes, introduced before 1500 AD, and natives), including 2,054 species of vascular plants in 302 reserves in central Europe. Older assemblages are more compartmentalized than younger ones, with species composition, phylogenetic structure and habitat characteristics of the modules becoming increasingly distinctive. This sheds light on two mechanisms of how alien species are functionally incorporated into regional species pools: the settling-down hypothesis of diminishing stochasticity with residence time, and the niche-mosaic hypothesis of inlaid neutral modules in regional meta-communities. PMID:24045305

  2. Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients.

    PubMed

    Talib, L L; Hototian, S R; Joaquim, H P G; Forlenza, O V; Gattaz, W F

    2015-12-01

    Reduced phospholipase A2 (PLA2) activity and increased phosphorylation of glycogen synthase kinase 3B (GSK3B) participate in the production of beta-amyloid plaques and of neurofibrillary tangles, which are two neuropathological hallmarks of Alzheimer's disease (AD). Experimental evidences suggest a neuroprotective effect of the cholinesterase inhibitor donepezil in the treatment the disease. The aims of the present study were to evaluate in AD patients the effects of treatment with donepezil on PLA2 activity and GSK3B level. Thirty patients with AD were treated during 6 months with 10 mg daily of donepezil. Radio-enzymatic assays were used to measure PLA2 activity and Elisa assays for GSK3B level, both in platelets. Before treatment and after 3 and 6 months on donepezil, AD patients underwent a cognitive assessment and platelet samples were collected. Values were compared to a healthy control group of 42 sex- and age-matched elderly individuals. Before treatment, iPLA2 activity was lower in patients with AD as compared to controls (p < 0.001). At baseline, no differences were found in GSK3B level between both groups. After 3 and 6 months of treatment, we found a significant increase in iPLA2 activity (p = 0.015 and p < 0.001, respectively). iPLA2 increment was related to the cognitive improvement during treatment (p = 0.037). After 6 months, we found an increase in phosphorylated GSK3B (p = 0.02). The present findings suggest two possible mechanisms by which donepezil delays the progression of AD. The increment of iPLA2 activity may reduce the production of beta-amyloid plaques, whereas the phosphorylation of GSK3B inactivates the enzyme, reducing thus the phosphorylation of tau protein. PMID:25920742

  3. Acute atorvastatin treatment exerts antidepressant-like effect in mice via the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway and increases BDNF levels.

    PubMed

    Ludka, Fabiana K; Zomkowski, Andréa D E; Cunha, Mauricio P; Dal-Cim, Tharine; Zeni, Ana Lúcia B; Rodrigues, Ana Lúcia S; Tasca, Carla I

    2013-05-01

    Atorvastatin is a synthetic and lipophilic statin that presents a good effect in decreasing cholesterol levels and is safe and well tolerated. Population-based studies have suggested a positive role of statins in reducing depression risk. This study aimed at investigating the atorvastatin effect in the tail suspension test (TST) and in the forced swimming test (FST). The participation of NMDA receptors and L-arginine-NO-cGMP in an atorvastatin antidepressant-like effect in the TST was evaluated. Acute atorvastatin administration (0.1-30 mg/kg) reduced the immobility time both in TST and FST. A similar effect was observed by using imipramine as a positive control in the TST and FST (1 and 0.1-1 mg/kg, p.o., respectively). An atorvastatin (0.1 mg/kg) antidepressant-like effect was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), L-arginine (750 mg/kg, i.p.) or sildenafil (5 mg/kg, i.p.). The administration of MK-801 (0.001 mg/kg, i.p.), ketamine (0.1 mg/kg, i.p.), 7-nitroindazole (50 mg/kg, i.p.), methylene blue (20 mg/kg, i.p.), or ODQ (30 pmol/site i.c.v.) in combination with a subeffective dose of atorvastatin (0.01 mg/kg, p.o.) reduced the immobility time in the TST compared to drugs alone, showing the participation of the pathway L-arginine-NO-cGMP. The administration of drugs did not produce any significant alteration in locomotor activity in the open-field test. Acute atorvastatin treatment (0.1-10.0 mg/kg, v.o.) increased the hippocampal BDNF levels, which is an effect that has not been observed in imipramine-treated mice. These results demonstrate that atorvastatin exerts an antidepressant-like effect and point to dependence on the inhibition of NMDA receptors and NO-cGMP synthesis, and on the increase of hippocampal BDNF levels. PMID:22682406

  4. First-time admissions for opioid treatment: cross-sectional and descriptive study of new opioid users seeking treatment

    PubMed Central

    Flórez, Gerardo; López-Durán, Ana; Triñanes, Yolanda; Osorio, Jesús; Fraga, Jaime; Fernández, José Manuel; Becoña, Elisardo; Arrojo, Manuel

    2015-01-01

    Background The purpose of this study was to gain an understanding of the profiles of the new treatment demands posed by opioid addicts between 2005 and 2010 at the addictive disorders assistance units in Galicia, Spain. Methods A cluster analysis was performed using data from 1,655 treatment entrants. Clusters were constructed using sociodemographic and medicolegal variables. A cluster analysis was also conducted according to age. Once clusters were defined, their association with the following variables was analyzed: age at first use of opioids, years of use, frequency of opioid use in the previous month, psychiatric treatment, cocaine use, existence of a drug-dependent partner, and source of referral. Results Four clusters were obtained in the main analysis. Cluster 1 (34.01%) consisted of young males, cluster 2 (16.19%) consisted of not-so-young males, cluster 3 (32.62%) consisted mainly of older males and a small group of females, and cluster 4 (17.18%) was made up entirely of women. With regard to age-related clusters, two clusters were obtained in those under the age of 30 years: cluster 1 (73%) without medicolegal complications and cluster 2 (27%) with medicolegal complications. For those over the age of 30 years, two clusters were obtained: cluster 1 (53.92%) with hardly any medicolegal complications and cluster 2 (46.08%) with medicolegal complications. Conclusion Cluster analysis suggests that there have been no substantial changes in variables indicating greater severity in this new group of patients. Women are likely to seek help earlier, which reduces their duration of opioid use. The younger the patient, the shorter the duration of opioid use and the greater the likelihood of cessation of intravenous use. Public health systems should use a two-pronged treatment strategy of short but intense cessation therapies for women and younger treatment entrants and longer maintenance and replacement therapies for older treatment entrants with more psychosocial and medical complications. PMID:26445539

  5. Just-in-time production systems reduce the amount of inventory available at distribution centers or retailers and increase the need for

    E-print Network

    Bertini, Robert L.

    26 Just-in-time production systems reduce the amount of inventory available at distribution centers or retailers and increase the need for products or parts to arrive at the scheduled time. For example, a late a departure time that will ensure an on-time arrival at the destination. Although this research is specific

  6. Sci—Thur PM: Planning and Delivery — 06: Real-Time Interactive Treatment Planning

    SciTech Connect

    Matthews, Q; Mestrovic, A; Otto, K

    2014-08-15

    Purpose: To describe and evaluate a novel system for generalized Real-Time Interactive Planning (RTIP) applied to head and neck (H and N) VMAT. Methods: The clinician interactively manipulates dose distributions using DVHs, isodoses, or rate of dose fall-off, which may be subjected to user-defined constraints. Dose is calculated using a fast Achievable Dose Estimate (ADE) algorithm, which simulates the limits of what can be achieved during treatment. After each manipulation contributing fluence elements are modified and the dose distribution updates in effectively real-time. For H and N VMAT planning, structure sets for 11 patients were imported into RTIP. Each dose distribution was interactively modified to minimize OAR dose while constraining target DVHs. The resulting RTIP DVHs were transferred to the Eclipse™ VMAT optimizer, and conventional VMAT optimization was performed. Results: Dose calculation and update times for the ADE algorithm ranged from 2.4 to 22.6 milliseconds, thus facilitating effectively real-time manipulation of dose distributions. For each of the 11 H and N VMAT cases, the RTIP process took ?2–10 minutes. All RTIP plans exhibited acceptable PTV coverage, mean dose, and max dose. 10 of 11 RTIP plans achieved substantially improved sparing of one or more OARs without compromising dose to targets or other OARs. Importantly, 10 of the 11 RTIP plans required only one or two post-RTIP optimizations. Conclusions: RTIP is a novel system for manipulating and updating achievable dose distributions in real-time. H and N VMAT plans generated using RTIP demonstrate improved OAR sparing and planning efficiency. Disclosures: One author has a commercial interest in the presented materials.

  7. Natural history and treatment of HCV/HIV coinfection: Is it time to change paradigms?

    PubMed

    Arends, Joop E; Lieveld, Faydra I; Boeijen, Lauke L; de Kanter, Clara T M M; van Erpecum, Karel J; Salmon, Dominique; Hoepelman, Andy I M; Asselah, Tarik; Ustianowski, Andrew

    2015-11-01

    Evidence over the past decades have shown that HIV/HCV coinfected patients did not respond as well to HCV therapy as HCV mono-infected patients. However, these paradigms are being recently reassessed with the improvements of care for HIV and HCV patients. This article reviews these original paradigms and how the new data is impacting upon them. Treatment efficacy now appears comparable for HIV/HCV coinfected and HCV mono-infected patients, while liver fibrosis progression is increasingly similar in optimally managed patients. Additional importance of therapy is directed to drug-drug interactions and the impact of HCV reinfection, as well as the possibility of transmitted drug resistance. PMID:26186987

  8. Predictors of Staff Turnover and Turnover Intentions within Addiction Treatment Settings: Change Over Time Matters.

    PubMed

    Garner, Bryan R; Hunter, Brooke D

    2014-01-01

    This study examined the extent to which changes over time in clinicians' responses to measures of work attitude (eg, job satisfaction) and psychological climate (eg, supervisor support) could predict actual turnover and turnover intentions above and beyond absolute levels of these respective measures. Longitudinal data for this study were collected from a sample of clinicians (N = 96) being trained to implement an evidence-based treatment for adolescent substance use disorders. Supporting findings from a recent staff turnover study, we found job satisfaction change was able to predict actual turnover above and beyond average levels of job satisfaction. Representing new contributions to the staff turnover literature, we also found that change over time in several other key measures (eg, job satisfaction, role manageability, role clarity) explained a significant amount of variance in turnover intentions above and beyond the absolute level of each respective measure. A key implication of the current study is that organizations seeking to improve their ability to assess risk for staff turnover may want to consider assessing staff at multiple points in time in order to identify systematic changes in key employee attitudes like turnover intentions and job satisfaction. PMID:25336960

  9. Predictors of Staff Turnover and Turnover Intentions within Addiction Treatment Settings: Change Over Time Matters

    PubMed Central

    Garner, Bryan R; Hunter, Brooke D

    2014-01-01

    This study examined the extent to which changes over time in clinicians’ responses to measures of work attitude (eg, job satisfaction) and psychological climate (eg, supervisor support) could predict actual turnover and turnover intentions above and beyond absolute levels of these respective measures. Longitudinal data for this study were collected from a sample of clinicians (N = 96) being trained to implement an evidence-based treatment for adolescent substance use disorders. Supporting findings from a recent staff turnover study, we found job satisfaction change was able to predict actual turnover above and beyond average levels of job satisfaction. Representing new contributions to the staff turnover literature, we also found that change over time in several other key measures (eg, job satisfaction, role manageability, role clarity) explained a significant amount of variance in turnover intentions above and beyond the absolute level of each respective measure. A key implication of the current study is that organizations seeking to improve their ability to assess risk for staff turnover may want to consider assessing staff at multiple points in time in order to identify systematic changes in key employee attitudes like turnover intentions and job satisfaction. PMID:25336960

  10. Infective Endocarditis: Diagnosis, Treatment, and Mortality, as Related to Surgical Timing and Infectious Organism

    PubMed Central

    Attum, Abdulla A.; Masri, Zahi; Yared, Sam F.; Johnson, G. Stephan; Girardet, Roland; Lansing, Allan M.

    1987-01-01

    To evaluate the timing of surgical treatment in infective endocarditis and to determine the relationship between the risk of mortality and the species of infectious organism, we reviewed a consecutive series of 65 cases involving patients with infective endocarditis who had been treated over a 17-year period. The patients included 41 males and 24 females, who ranged in age from 6 to 85 years (mean, 39.3 years). Forty-five had native valve endocarditis, 14 had prosthetic valve endocarditis, and six had endocarditis associated with congenital heart defects. Fifty-two patients underwent valve replacement, which was associated with an overall operative mortality of 19%. Those who underwent valve replacement during the early active stage (first 3 weeks) of infection had a higher mortality rate than those who had surgery either during the late active stage (second 3 weeks) of infection or after 6 weeks of antibiotic therapy. S. aureus and Pseudomonas organisms were responsible for the most deaths. On the basis of this study, we recommend that, when cardiovascular function permits, patients who are hemodynamically stable and free of emboli should receive 4 to 6 weeks of antibiotic therapy before undergoing surgical treatment. In contrast, patients with high-risk organisms are more likely to survive if subjected to early surgical intervention. (Texas Heart Institute Journal 1987; 14:401-410) Images PMID:15227297

  11. The effect of time-since-treatment and other factors on the perceived scenic beauty of southern pine-oak forest plots 

    E-print Network

    Gritter, Molly Kay

    1997-01-01

    This study investigated the effects of silvicultural treatment, season, and time-since-treatment on the perceived scenic beauty of 20 pine-oak plots on the Ouachita National Forest, Arkansas. Treatments consisted of reproduction cuts in which...

  12. Waiting for treatment for chronic pain – a survey of existing benchmarks: Toward establishing evidence-based benchmarks for medically acceptable waiting times

    PubMed Central

    Lynch, Mary E; Campbell, Fiona A; Clark, Alexander J; Dunbar, Michael J; Goldstein, David; Peng, Philip; Stinson, Jennifer; Tupper, Helen

    2007-01-01

    As medical costs escalate, health care resources must be prioritized. In this context, there is an increasing need for benchmarks and best practices in wait time management. In December 2005, the Canadian Pain Society struck a Task Force to identify benchmarks for acceptable wait times for treatment of chronic pain. The task force mandate included a systematic review and survey to identify national or international wait time benchmarks for chronic pain, proposed or in use, along with a review of the evidence upon which they are based. An extensive systematic review of the literature and a survey of International Association for the Study of Pain Chapter Presidents and key informants has identified that there are no established benchmarks or guidelines for acceptable wait times for the treatment of chronic pain in use in the world. In countries with generic guidelines or wait time standards that apply to all outpatient clinics, there have been significant challenges faced by pain clinics in meeting the established targets. Important next steps are to ensure appropriate additional research and the establishment of international benchmarks or guidelines for acceptable wait times for the treatment of chronic pain. This will facilitate advocacy for improved access to appropriate care for people suffering from chronic pain around the world. PMID:18080042

  13. Camera selection for real-time in vivo radiation treatment verification systems using Cherenkov imaging

    SciTech Connect

    Andreozzi, Jacqueline M. Glaser, Adam K.; Zhang, Rongxiao; Jarvis, Lesley A.; Gladstone, David J.; Pogue, Brian W.

    2015-02-15

    Purpose: To identify achievable camera performance and hardware needs in a clinical Cherenkov imaging system for real-time, in vivo monitoring of the surface beam profile on patients, as novel visual information, documentation, and possible treatment verification for clinicians. Methods: Complementary metal-oxide-semiconductor (CMOS), charge-coupled device (CCD), intensified charge-coupled device (ICCD), and electron multiplying-intensified charge coupled device (EM-ICCD) cameras were investigated to determine Cherenkov imaging performance in a clinical radiotherapy setting, with one emphasis on the maximum supportable frame rate. Where possible, the image intensifier was synchronized using a pulse signal from the Linac in order to image with room lighting conditions comparable to patient treatment scenarios. A solid water phantom irradiated with a 6 MV photon beam was imaged by the cameras to evaluate the maximum frame rate for adequate Cherenkov detection. Adequate detection was defined as an average electron count in the background-subtracted Cherenkov image region of interest in excess of 0.5% (327 counts) of the 16-bit maximum electron count value. Additionally, an ICCD and an EM-ICCD were each used clinically to image two patients undergoing whole-breast radiotherapy to compare clinical advantages and limitations of each system. Results: Intensifier-coupled cameras were required for imaging Cherenkov emission on the phantom surface with ambient room lighting; standalone CMOS and CCD cameras were not viable. The EM-ICCD was able to collect images from a single Linac pulse delivering less than 0.05 cGy of dose at 30 frames/s (fps) and pixel resolution of 512 × 512, compared to an ICCD which was limited to 4.7 fps at 1024 × 1024 resolution. An intensifier with higher quantum efficiency at the entrance photocathode in the red wavelengths [30% quantum efficiency (QE) vs previous 19%] promises at least 8.6 fps at a resolution of 1024 × 1024 and lower monetary cost than the EM-ICCD. Conclusions: The ICCD with an intensifier better optimized for red wavelengths was found to provide the best potential for real-time display (at least 8.6 fps) of radiation dose on the skin during treatment at a resolution of 1024 × 1024.

  14. Metabolic syndrome increases oxidative stress but does not influence disability and short-time outcome in acute ischemic stroke patients.

    PubMed

    Simão, Andrea Name Colado; Lehmann, Marcio Francisco; Alfieri, Daniela Frizon; Meloni, Milena Zardetto; Flauzino, Tamires; Scavuzzi, Bruna Miglioranza; de Oliveira, Sayonara Rangel; Lozovoy, Marcell Alysson Batisti; Dichi, Isaias; Reiche, Edna Maria Vissoci

    2015-12-01

    Oxidative stress has been implicated in the pathophysiology of cardiovascular disease and MetS and it may be one of molecular mechanisms involved in stroke. The aims of the present study were to verify differences in oxidative stress markers in acute ischemic stroke patients with and without MetS and to verify whether MetS influences disability and short time outcome of the patients. 148 patients with acute ischemic stroke were divided in two groups: with MetS (n?=?92) and without MetS (n?=?56). The modified Rankin Scale (mRS) was used for measuring the functional disability after 3-month follow-up. The study assessed the metabolic profile and oxidative stress markers. Stroke patients with MetS had higher levels of lipid hydroperoxides (p?increase in oxidative stress markers was shown in acute ischemic stroke patients with MetS and this elevation seems to be involved mainly with changes in lipid profile, but the presence of MetS did not influence short-time disability and survival of the acute ischemic stroke patients. PMID:26342606

  15. Treatment of ?-Thalassemia/Hemoglobin E with Antioxidant Cocktails Results in Decreased Oxidative Stress, Increased Hemoglobin Concentration, and Improvement of the Hypercoagulable State

    PubMed Central

    Yanpanitch, Orn-uma; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Fucharoen, Suthat; Siritanaratkul, Noppadol; Kalpravidh, Ruchaneekorn W.

    2015-01-01

    Studies on the antioxidant treatment for thalassemia have reported variable outcomes. However, treatment of thalassemia with a combination of hydrophobic and hydrophilic antioxidants and an iron chelator has not been studied. This study investigated the effects of antioxidant cocktails for the treatment of ?-thalassemia/hemoglobin E (HbE), which is the most common form of ?-thalassemia in Southeast Asia. Sixty patients were divided into two groups receiving N-acetylcysteine, deferiprone, and either curcuminoids (CUR) or vitamin E (Vit-E), and their hematological parameters, iron load, oxidative stress, and blood coagulation potential were evaluated. Patients were classified as responders if they showed the improvements of the markers of iron load and oxidative stress, otherwise as nonresponders. During treatment, the responders in both groups had significantly decreased iron load, oxidative stress, and coagulation potential and significantly increased antioxidant capacity and hemoglobin concentration. The significantly maximum increase (P < 0.01) in hemoglobin concentration was 11% at month 4 in CUR group responders and 10% at month 10 in Vit-E group responders. In conclusion, the two antioxidant cocktails can improve anemia, iron overload, oxidative stress, and hypercoagulable state in ?-thalassemia/HbE. PMID:26078808

  16. Dwell time modulation restrictions do not necessarily improve treatment plan quality for prostate HDR brachytherapy

    NASA Astrophysics Data System (ADS)

    Balvert, Marleen; Gorissen, Bram L.; den Hertog, Dick; Hoffmann, Aswin L.

    2015-01-01

    Inverse planning algorithms for dwell time optimisation in interstitial high-dose-rate (HDR) brachytherapy may produce solutions with large dwell time variations within catheters, which may result in undesirable selective high-dose subvolumes. Extending the dwell time optimisation model with a dwell time modulation restriction (DTMR) that limits dwell time differences between neighboring dwell positions has been suggested to eliminate this problem. DTMRs may additionally reduce the sensitivity for uncertainties in dwell positions that inevitably result from catheter reconstruction errors and afterloader source positioning inaccuracies. This study quantifies the reduction of high-dose subvolumes and the robustness against these uncertainties by applying a DTMR to template-based prostate HDR brachytherapy implants. Three different DTMRs were consecutively applied to a linear dose-based penalty model (LD) and a dose-volume based model (LDV), both obtained from literature. The models were solved with DTMR levels ranging from no restriction to uniform dwell times within catheters in discrete steps. Uncertainties were simulated on clinical cases using in-house developed software, and dose-volume metrics were calculated in each simulation. For the assessment of high-dose subvolumes, the dose homogeneity index (DHI) and the contiguous dose volume histogram were analysed. Robustness was measured by the improvement of the lowest D90% of the planning target volume (PTV) observed in the simulations. For (LD), a DTMR yields an increase in DHI of approximately 30% and reduces the size of the largest high-dose volume by 2-5 cc. However, this comes at a cost of a reduction in D90% of the PTV of 10%, which often implies that it drops below the desired minimum of 100%. For (LDV), none of the DTMRs were able to improve high-dose volume measures. DTMRs were not capable of improving robustness of PTV D90% against uncertainty in dwell positions for both models.

  17. Evidence of increased anthropogenic emissions of platinum: time-series analysis of mussels (1991-2011) of an urban beach.

    PubMed

    Neira, Patricia; Cobelo-García, Antonio; Besada, Victoria; Santos-Echeandía, Juan; Bellas, Juan

    2015-05-01

    The anthropogenic emissions of Pt to the environment have increased significantly over the past decades, especially after the introduction of the catalytic converters in motor vehicles. In order to check whether this is affecting the levels of this trace metal on living organisms, time-series analysis of freeze-dried soft tissue material of wild mussels (Mytilus galloprovincialis) covering the period from 1991 to 2001 and collected at an urban beach in the city of Vigo (NW Iberian Peninsula) was conducted. Concentrations ranged from 0.30 to 0.68 ng g(-1) with an average concentration of 0.47 ± 0.10 ng g(-1) (n=21); these concentrations were higher than those obtained for samples collected at a control location away from anthropogenic pressure (0.31 ± 0.10 ng g(-1); n=5). Platinum concentrations followed a statistically significant temporal trend (at the 0.020 level), and the excess of Pt in mussels over the 1991-2011 period compared to the control location were correlated with the European Pt autocatalyst demand (p=0.0006) and, especially, the car sales in Spain (p=0.0001). A bioaccumulation factor of ~5·10(3) was derived, which is greater than those previously calculated for Pt from exposure experiments, but 1-2 orders of magnitude lower than other trace elements (e.g. Zn, Cu, Pb, Cd). PMID:25679817

  18. Conservative and timely treatment in retained products of conception: a case report of placenta accreta ritention

    PubMed Central

    Antonella, Guarino; Luisa, Di Benedetto; Chiara, Assorgi; Alessandra, Rocca; Caserta, Donatella

    2015-01-01

    The term retained products of conception (RPOC) refers to intrauterine tissue that develops after conception and persists after medical and surgical pregnancy termination, miscarriage, and vaginal or cesarean delivery. One of the most important factor risk for RPOC is placenta accreta, defined as “the abnormal adherence, either in whole or in part, of the afterbirth to the underlying uterine wall”. We report a case of a 37 years old woman referred to our gynecologic department with irregular vaginal bleeding. On her medical history, she had a cesarean occurred 3 months before. Ultrasonography revealed in the uterine cavity hyperechoic mass, treated with curettage. Two weeks later the curettage, patient complained still vaginal bleeding. On the transvaginal ultrasound, the uterine cavity was occupied again by a hyperechoic mass. She underwent to hysteroscopic resection and histological diagnosis was compatible with placenta accreta residual. In the follow up she had not complications. Early diagnosis, prompt evaluation of bleeding is important for timely treatment and for preventing immediate complications and demolitive approach. A careful follow up is necessary to prevent late consequences. The purpose of this study is to report our experience in timely diagnosis and conservative management. PMID:26722586

  19. Patient-Clinician Information Engagement Increases Treatment Decision Satisfaction Among Cancer Patients Through Feeling of Being Informed

    PubMed Central

    Martinez, Lourdes S.; Schwartz, J. Sanford; Freres, Derek; Fraze, Taressa; Hornik, Robert C.

    2009-01-01

    Objective: Examine how patient-clinician information engagement (PCIE) may operate through feeling informed to influence patients' treatment decision satisfaction (TDS). Methods: Randomly drawn sample (N=2013) from Pennsylvania Cancer Registry, comprised of breast, prostate and colon cancer patients completed mail surveys in Fall of 2006 (response rate = 64%) and Fall of 2007. Of 2013 baseline respondents, 85% agreed to participate in follow-up survey (N=1703). Of those who agreed, 76% (N=1293) completed follow-up surveys. The sample was split between males and females. The majority of participants were White, over the age of 50, married, and with a high school degree. Most reported having been diagnosed with in situ and local cancer. Results: PCIE was related to concurrent TDS (?=.06) and feeling informed (?=.15), after confounder adjustments. A mediation analysis was consistent with PCIE affecting TDS through feeling informed. Baseline PCIE predicted feeling informed (?=.04) measured one year later, after adjustments for baseline feeling informed and other confounders. Feeling informed was related to concurrent TDS (?=.35) after confounder adjustment and follow-up TDS (?=.13) after baseline TDS and confounder adjustment. Conclusion: Results suggest PCIE affects TDS in part through patients' feeling informed. Practice Implications: PCIE may be important in determining patients' level of feeling informed and TDS. PMID:19815365

  20. 18q deletion in a cystic fibrosis infant, increased morbidity and challenge for correct treatment choices: a case report

    PubMed Central

    2011-01-01

    Cystic Fibrosis (CF) is the most frequent recessive disease of Caucasian patients. Association with other diseases or syndromes has previously been reported. Co-morbidity may be a challenge for clinicians, who have to face more severe problems. We have described a CF infant, F508del homozygote, diagnosed by neonatal screening, who also had a chromosome 18q terminal deletion [del (18)(q22-qter)]. Some clinical features of the 18q deletion: e.g., cardiopathy, gastro-oesophageal reflux and severe muscular hypotonia, worsened the CF clinical picture and his quality of life, with repeated pulmonary exacerbations and failure to thrive in the first six months of life. The treatment strategy was chosen following an accurate multi-disciplinary team study of overlapping chromosome syndrome and CF symptoms. The use of a gastrostomy device for enteral nutrition together with a new device (Ez-PAP) for chest physiotherapy led to normal growth, a notably reduced hospitalization rate and improved quality of life. This case shows how co-morbidities worsening the clinical course of a "complicated patient" can be faced thanks to unconventional therapies that represent a challenge for clinicians. PMID:21586141

  1. A Novel Recruitment Message to Increase Enrollment into a Smoking Cessation Treatment Program: Preliminary Results from a Randomized Triala

    PubMed Central

    Schnoll, Robert A.; Cappella, Joseph; Lerman, Caryn; Pinto, Angela; Patterson, Freda; Wileyto, E. Paul; Leone, Frank

    2014-01-01

    Most smokers do not utilize approved interventions for nicotine dependence, reducing the probability of cessation. Smoking cessation programs typically use recruitment messages emphasizing the health threats of smoking. Augmenting this threat message by describing the genetic aspects of nicotine addiction may enhance enrollment into a cessation program. During telephone recruitment, 125 treatment-seeking smokers were randomized to receive by phone either a standard threat message or a threat plus genetic prime message and were offered open-label varenicline and counseling. There was a greater rate of enrollment into the cessation program for the threat plus genetic prime participants (51.7%) vs. the threat-only participants (37.7%; p = .03). Smokers who self-identified from racial/ethnic minority groups were less likely to enroll in the cessation program (p = .01) vs. smokers who self-identified as Caucasian. These preliminary data suggest that a simple, affordable, and transportable communication approach enhances enrollment of smokers into a smoking cessation program. A larger clinical trial to evaluate a genetic prime message for improving recruitment into smoking cessation programs is warranted. PMID:21667366

  2. Inhibition of Lysyl Oxidases Improves Drug Diffusion and Increases Efficacy of Cytotoxic Treatment in 3D Tumor Models

    PubMed Central

    Schütze, Friedrich; Röhrig, Florian; Vorlová, Sandra; Gätzner, Sabine; Kuhn, Anja; Ergün, Süleyman; Henke, Erik

    2015-01-01

    Tumors are characterized by a rigid, highly cross-linked extracellular matrix (ECM), which impedes homogeneous drug distribution and potentially protects malignant cells from exposure to therapeutics. Lysyl oxidases are major contributors to tissue stiffness and the elevated expression of these enzymes observed in most cancers might influence drug distribution and efficacy. We examined the effect of lysyl oxidases on drug distribution and efficacy in 3D in vitro assay systems. In our experiments elevated lysyl oxidase activity was responsible for reduced drug diffusion under hypoxic conditions and consequently impaired cytotoxicity of various chemotherapeutics. This effect was only observed in 3D settings but not in 2D-cell culture, confirming that lysyl oxidases affect drug efficacy by modification of the ECM and do not confer a direct desensitizing effect. Both drug diffusion and efficacy were strongly enhanced by inhibition of lysyl oxidases. The results from the in vitro experiments correlated with tumor drug distribution in vivo, and predicted response to therapeutics in murine tumor models. Our results demonstrate that lysyl oxidase activity modulates the physical barrier function of ECM for small molecule drugs influencing their therapeutic efficacy. Targeting this process has the potential to significantly enhance therapeutic efficacy in the treatment of malignant diseases. PMID:26620400

  3. Increased fertility in lactating dairy cows resynchronized with Double-Ovsynch compared with Ovsynch initiated 32 d after timed artificial insemination.

    PubMed

    Giordano, J O; Wiltbank, M C; Guenther, J N; Pawlisch, R; Bas, S; Cunha, A P; Fricke, P M

    2012-02-01

    The objective was to determine if using a Double-Ovsynch protocol [DO; Pre-Resynch: GnRH-7 d-PGF(2?)-3 d-GnRH, 7 d later Breeding-Resynch: GnRH-7 d-PGF(2?)-56 h-GnRH-16 h-timed artificial insemination (TAI)] to resynchronize ovulation after a previous TAI would increase synchrony and pregnancies per AI (P/AI) compared with an Ovsynch protocol initiated 32 d after TAI (D32; GnRH-7 d-PGF(2?)-56 h-GnRH-16 h-TAI). Lactating Holstein cows at various days in milk and prior AI services were blocked by parity and randomly assigned to resynchronization treatments. All DO cows received the first GnRH injection of Pre-Resynch 22 d after TAI, and cows (n=981) diagnosed not pregnant using transrectal ultrasonography 29 d after TAI continued the protocol. Pregnancy status for all D32 cows was evaluated 29 d after TAI so fertility and pregnancy loss could be compared with that of DO cows. All D32 cows received the first GnRH injection of Ovsynch 32 d after TAI, and cows (n=956) diagnosed not pregnant using transrectal palpation 39 d after TAI continued the protocol. In a subgroup of cows from each treatment, ultrasonography (n=751) and serum progesterone (P4) concentrations (n=743) were used to determine the presence of a functional corpus luteum (CL) and ovulation to the first GnRH injection of D32 and Breeding-Resynch of DO (GnRH1), luteal regression after PGF before TAI, and ovulation to the GnRH injection before TAI (GnRH2). Overall, P/AI 29 d after TAI was not affected by parity and was greater for DO compared with D32 cows (39 vs. 30%). Pregnancy loss from 29 to 74 d after TAI was not affected by parity or treatment. The percentage of cows with a functional CL (P4 ?1.0 ng/mL) at GnRH1 was greater for DO than D32 cows (81 vs. 58%), with most DO cows having medium P4 (60%; 1.0 to 3.49 ng/ml), whereas most D32 cows had either low (42%; <1.0 ng/mL) or high (36%; ?3.5 ng/mL) P4 at GnRH1. Ovulation to GnRH1 was similar between treatments but was affected by serum P4 at GnRH. Cows with low P4 (<1.0 ng/mL) had the greatest ovulatory response (59%), followed by cows with medium (?1.0 to 3.49 ng/mL; 38%) and then high (?3.50 ng/mL; 16%) P4 at GnRH1. A greater percentage of DO cows were synchronized compared with D32 cows (72 vs. 51%) primarily due to a greater percentage of D32 than DO cows without a functional CL at the PGF injection before TAI (35 vs. 17%) or without complete CL regression before GnRH2 (17 vs. 7%). We conclude that DO increased fertility of lactating dairy cows during a resynchronization program primarily by increasing synchronization of cows during the Ovsynch protocol before TAI. PMID:22281329

  4. Cost-effectiveness of Bariatric Surgery: Increasing the Economic Viability of the Most Effective Treatment for Type II Diabetes Mellitus.

    PubMed

    Warren, Jeremy A; Ewing, Joseph A; Hale, Allyson L; Blackhurst, Dawn W; Bour, Eric S; Scott, John D

    2015-08-01

    There has been considerable debate on the cost-effectiveness of bariatric surgery within larger population groups. Despite the recognition that morbid obesity and its comorbidities are best treated surgically, insurance coverage is not universally available. One of the more costly comorbidities of obesity is Type II diabetes mellitus (T2DM). We propose a model that demonstrates the cost-effectiveness of increasing the number of bariatric surgical operations performed on patients with T2DM in the United States. We applied published population cost estimates (2012) for medical care of T2DM to a retrospective cohort of morbidly obese patients in South Carolina. We compared differences in 10-year medical costs between those having bariatric surgery and controls. Resolution of T2DM in the bariatric cohort was assumed to be 40 per cent. Considering only the direct medical costs of T2DM, the 10-year aggregate cost savings compared with a control group is $2.7 million/1000 patients; the total (direct and indirect) cost savings is $5.4 million/1000 patients. When considering resolution of T2DM alone, increasing the number of bariatric operations for a given population leads to a substantial cost savings over a 10-year period. This study adds to the growing body of evidence suggesting that bariatric surgery is a cost-effective means of caring for the obese patient. PMID:26215244

  5. ZnO Nanoparticles Treatment Induces Apoptosis by Increasing Intracellular ROS Levels in LTEP-a-2 Cells.

    PubMed

    Wang, Caixia; Hu, Xiaoke; Gao, Yan; Ji, Yinglu

    2015-01-01

    Owing to the wide use of novel nanoparticles (NPs) such as zinc oxide (ZnO) in all aspects of life, toxicological research on ZnO NPs is receiving increasing attention in these days. In this study, the toxicity of ZnO NPs in a human pulmonary adenocarcinoma cell line LTEP-a-2 was tested in vitro. Log-phase cells were exposed to different levels of ZnO NPs for hours, followed by colorimetric cell viability assay using tetrazolium salt and cell survival rate assay using trypan blue dye. Cell morphological changes were observed by Giemsa staining and light microscopy. Apoptosis was detected by using fluorescence microscopy and caspase-3 activity assay. Both intracellular reactive oxygen species (ROS) and reduced glutathione (GSH) were examined by a microplate-reader method. Results showed that ZnO NPs (? 0.01 ?g/mL) significantly inhibited proliferation (P < 0.05) and induced substantial apoptosis in LTEP-a-2 cells after 4 h of exposure. The intracellular ROS level rose up to 30-40% corresponding to significant depletion (approximately 70-80%) in GSH content in LTEP-a-2 cells (P < 0.05), suggesting that ZnO NPs induced apoptosis mainly through increased ROS production. This study elucidates the toxicological mechanism of ZnO NPs in human pulmonary adenocarcinoma cells and provides reference data for application of nanomaterials in the environment. PMID:26339612

  6. ZnO Nanoparticles Treatment Induces Apoptosis by Increasing Intracellular ROS Levels in LTEP-a-2 Cells

    PubMed Central

    Wang, Caixia; Hu, Xiaoke; Gao, Yan; Ji, Yinglu

    2015-01-01

    Owing to the wide use of novel nanoparticles (NPs) such as zinc oxide (ZnO) in all aspects of life, toxicological research on ZnO NPs is receiving increasing attention in these days. In this study, the toxicity of ZnO NPs in a human pulmonary adenocarcinoma cell line LTEP-a-2 was tested in vitro. Log-phase cells were exposed to different levels of ZnO NPs for hours, followed by colorimetric cell viability assay using tetrazolium salt and cell survival rate assay using trypan blue dye. Cell morphological changes were observed by Giemsa staining and light microscopy. Apoptosis was detected by using fluorescence microscopy and caspase-3 activity assay. Both intracellular reactive oxygen species (ROS) and reduced glutathione (GSH) were examined by a microplate-reader method. Results showed that ZnO NPs (?0.01??g/mL) significantly inhibited proliferation (P < 0.05) and induced substantial apoptosis in LTEP-a-2 cells after 4?h of exposure. The intracellular ROS level rose up to 30–40% corresponding to significant depletion (approximately 70–80%) in GSH content in LTEP-a-2 cells (P < 0.05), suggesting that ZnO NPs induced apoptosis mainly through increased ROS production. This study elucidates the toxicological mechanism of ZnO NPs in human pulmonary adenocarcinoma cells and provides reference data for application of nanomaterials in the environment. PMID:26339612

  7. Wait times for prostate cancer treatment and patient perceptions of care in Canada: a mixed-methods report

    PubMed Central

    Tran, K.; Sandoval, C.; Rahal, R.; Porter, G.; Siemens, R.; Hernandez, J.; Fung, S.; Louzado, C.; Liu, J; Bryant, H.

    2015-01-01

    Background Access to cancer care is a significant concern for Canadians. Prolonged delays between cancer diagnosis and treatment have been associated with anxiety, stress, and perceived powerlessness for patients and their family members. Longer wait times can also be associated with poorer prognosis, although the evidence is inconclusive. Here, we report national wait times for radiation therapy and surgery for localized prostate cancer (pca) and the effect of wait time on patient perceptions of their care. Results Treatment wait times showed substantial interprovincial variation. The longest 90th percentile wait times for radiation therapy and surgery were, respectively, 40 days and 105 days. In all provinces, waits for radiation therapy were longer for pca patients than for patients with breast, colorectal, or lung cancer. In the focus groups and interviews conducted with 47 men treated for pca, many participants did not perceive that wait times for treatment were prolonged. Those who experienced delays between diagnosis and treatment voiced issues with a lack of communication about when they would receive treatment and a lack of support or information to make an informed decision about treatment. Minimizing treatment delays was an aspect of the cancer journey that participants would like to change because of the stress it caused. Conclusions Although wait time statistics are useful, a review of cancer control in Canada cannot be considered complete unless an effort is made to give voice to the experiences of individuals with cancer. The findings presented here are intended to provide a snapshot of national care delivery for localized pca and to identify opportunities for improvement in clinical practice. PMID:26628869

  8. Prolongation of Total Treatment Time Because of Infrequently Missed Days of Treatment Is Not Associated With Inferior Biochemical Outcome After Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Liauw, Stanley L.; Liauw, Sun H.

    2011-11-01

    Purpose: Prolongation of treatment time with radiation therapy (RT) is associated with inferior disease control for many rapidly proliferating tumors, but it is uncertain whether the same effect is seen in prostate cancer. Methods and Materials: 596 patients underwent with curative-intent RT for adenocarcinoma of the prostate. By National Comprehensive Cancer Network criteria, men were classified as having low-risk (30%), medium-risk (40%), or high-risk (30%) disease. The median RT dose was 72 Gy. Androgen-deprivation therapy (ADT) was used in 45%. The idealized treatment time was defined as the total elapsed time (including weekends) to complete treatment if started on a Monday. Missed days of treatment, defined as the number of days beyond the idealized treatment time, was recorded for all patients. Missed days were added to the end of therapy resulting in a longer treatment time. Analysis was conducted for missed days and other standard prognostic variables against freedom from biochemical failure (FFBF). Results: The median number of missed days was 2 (range, -3 to 22). With a median follow-up of 51 months, men with 5 or more missed days had similar 4-year FFBF rates (79% vs. 83% in men with <5 missed days, p = 0.0809), especially in the subset of men receiving 74 Gy or greater (89% for both groups, p = 0.8008). Analysis of missed days was performed for the subsets of dose, ADT, and risk category. Men without ADT had a lower FFBF rate with more missed days (p = 0.0030), but this association was not seen in men treated to a dose of 74 Gy or greater (p = 0.7425). On multivariate analysis, dose (p = 0.0010), T stage (p = 0.0145), and prostate-specific antigen level (p < 0.0001) were associated with FFBF, but Gleason score (p = 0.1351) and missed days (p = 0.3767) were not. Conclusions: Slight prolongation of treatment time (e.g., {<=}7 days) was not associated with inferior FFBF, especially in men receiving an RT dose of 74 Gy or greater.

  9. Administration-time-dependent effects of hypertension treatment on ambulatory blood pressure in patients with chronic kidney disease.

    PubMed

    Crespo, Juan J; Piñeiro, Luis; Otero, Alfonso; Castiñeira, Carmen; Ríos, María T; Regueiro, Antonio; Mojón, Artemio; Lorenzo, Sonia; Ayala, Diana E; Hermida, Ramón C

    2013-03-01

    Many published prospective trials have reported clinically meaningful morning-evening, treatment-time differences in the blood pressure (BP)-lowering efficacy, duration of action, and safety of most classes of hypertension medications. Most important, it was recently documented that routine ingestion of the full daily dose of ?1 hypertension medications at bedtime, compared with ingestion of all of them upon awakening, significantly reduces cardiovascular disease (CVD) events. Nocturnal hypertension and non-dipping (<10% decline in the asleep relative to the awake BP mean), as determined by ambulatory BP monitoring (ABPM), are frequent in chronic kidney disease (CKD) and both are associated with increased CVD risk. Here, we investigated the influence of hypertension treatment time on the circadian BP pattern and degree of BP control of hypertensive patients with CKD evaluated by 48-h ABPM. This cross-sectional study evaluated 2659 such patients (1585 men/1074 women), 64.9?±?13.2 (mean?±?SD) yrs of age, enrolled in the Hygia Project, involving primary care centers of northwest Spain and designed to evaluate prospectively CVD risk by ABPM; 1446 were ingesting all BP-lowering medications upon awakening, whereas 1213 patients were ingesting ?1 medications at bedtime. Among the latter, 359 patients were ingesting all medications at bedtime, whereas 854 were ingesting the full daily dose of some medications upon awakening and the others at bedtime. Those ingesting all medications upon awakening had significantly higher total cholesterol and low-density lipoprotein (LDL) cholesterol than those ingesting ?1 medications at bedtime. Moreover, patients ingesting all medications at bedtime had the lowest fasting glucose, serum creatinine, and uric acid. Ingestion of ?1 medications at bedtime was significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than treatment with all medications upon awakening. The sleep-time relative SBP decline was significantly attenuated in patients ingesting all medications upon awakening (p?treatment, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of hypertension and avoid treatment-induced nocturnal hypotension, should be the preferred therapeutic scheme for CKD. PMID:23098134

  10. Marked increase in rat red blood cell membrane protein glycosylation by one-month treatment with a cafeteria diet

    PubMed Central

    Oliva, Laia; Baron, Cristian; Fernández-López, José-Antonio; Remesar, Xavier

    2015-01-01

    Background and Objectives. Glucose, an aldose, spontaneously reacts with protein amino acids yielding glycosylated proteins. The compounds may reorganize to produce advanced glycosylation products, which regulatory importance is increasingly being recognized. Protein glycosylation is produced without the direct intervention of enzymes and results in the loss of function. Glycosylated plasma albumin, and glycosylated haemoglobin are currently used as index of mean plasma glucose levels, since higher glucose availability results in higher glycosylation rates. In this study we intended to detect the early changes in blood protein glycosylation elicited by an obesogenic diet. Experimental Design. Since albumin is in constant direct contact with plasma glucose, as are the red blood cell (RBC) membranes, we analyzed their degree or glycosylation in female and male rats, either fed a standard diet or subjected to a hyper-energetic self-selected cafeteria diet for 30 days. This model produces a small increase in basal glycaemia and a significant increase in body fat, leaving the animals in the initial stages of development of metabolic syndrome. We also measured the degree of glycosylation of hemoglobin, and the concentration of glucose in contact with this protein, that within the RBC. Glycosylation was measured by colorimetric estimation of the hydroxymethylfurfural liberated from glycosyl residues by incubation with oxalate. Results. Plasma glucose was higher in cafeteria diet and in male rats, both independent effects. However, there were no significant differences induced by sex or diet in either hemoglobin or plasma proteins. Purified RBC membranes showed a marked effect of diet: higher glycosylation in cafeteria rats, which was more marked in females (not in controls). In any case, the number of glycosyl residues per molecule were higher in hemoglobin than in plasma proteins (after correction for molecular weight). The detected levels of glucose in RBC were lower than those of plasma, even when expressed in molal units, and were practically nil in cafeteria-diet fed rats compared with controls; there was no effect of sex. Conclusions. RBC membrane glycosylation is a sensitive indicator of developing metabolic syndrome-related hyperglycemia, more sensitive than the general measurement of plasma or RBC protein glycosylation. The extensive glycosylation of blood proteins does not seem to be markedly affected by sex; and could be hardly justified from an assumedly sustained plasma hyperglycemia. The low levels of glucose found within RBC, especially in rats under the cafeteria diet, could hardly justify the extensive glycosylation of hemoglobin and the lack of differences with controls, which contained sizeable levels of intracellular glucose. Additional studies are needed to study the dynamics of glucose in vivo in the RBC to understand how such extensive protein glycosylation could take place. PMID:26213657

  11. The effect of respiratory cycle and radiation beam-on timing on the dose distribution of free-breathing breast treatment using dynamic IMRT

    SciTech Connect

    Ding Chuxiong; Li Xiang; Huq, M. Saiful; Saw, Cheng B.; Heron, Dwight E.; Yue, Ning J.

    2007-09-15

    In breast cancer treatment, intensity-modulated radiation therapy (IMRT) can be utilized to deliver more homogeneous dose to target tissues to minimize the cosmetic impact. We have investigated the effect of the respiratory cycle and radiation beam-on timing on the dose distribution in free-breathing dynamic breast IMRT treatment. Six patients with early stage cancer of the left breast were included in this study. A helical computed tomography (CT) scan was acquired for treatment planning. A four-dimensional computed tomography (4D CT) scan was obtained right after the helical CT scan with little or no setup uncertainty to simulate patient respiratory motion. After optimizing based on the helical CT scan, the sliding-window dynamic multileaf collimator (DMLC) leaf sequence was segmented into multiple sections that corresponded to various respiratory phases per respiratory cycle and radiation beam-on timing. The segmented DMLC leaf sections were grouped according to respiratory phases and superimposed over the radiation fields of corresponding 4D CT image set. Dose calculation was then performed for each phase of the 4D CT scan. The total dose distribution was computed by accumulating the contribution of dose from each phase to every voxel in the region of interest. This was tracked by a deformable registration program throughout all of the respiratory phases of the 4D CT scan. A dose heterogeneity index, defined as the ratio between (D{sub 20}-D{sub 80}) and the prescription dose, was introduced to numerically illustrate the impact of respiratory motion on the dose distribution of treatment volume. A respiratory cycle range of 4-8 s and randomly distributed beam-on timing were assigned to simulate the patient respiratory motion during the free-breathing treatment. The results showed that the respiratory cycle period and radiation beam-on timing presented limited impact on the target dose coverage and slightly increased the target dose heterogeneity. This motion impact tended to increase the variation of target dose coverage and heterogeneity between treatment fractions with different radiation beam-on timing. The target dose coverage and heterogeneity were more susceptible to the radiation beam-on timing for patients with long respiratory cycle (longer than 6 s) and large breast motion amplitudes (larger than 0.7 cm). The same results could be found for respiratory cycle up to 8 s and respiratory motion amplitude up to 1 cm. The heart dose distribution did not change significantly regardless of respiratory cycle and radiation beam-on timing.

  12. The effect of Zoledronate treatment timing on lumbar and caudal vertebrae in ovariectomized rats

    E-print Network

    Ruchelsman, Michal (Michal Aliza)

    2007-01-01

    Introduction: While there have been numerous studies demonstrating the effect of bisphosphonates in rats as either a preventative treatment or recovering treatment for osteoporosis, few have directly compared the two ...

  13. Delayed progesterone treatment reduces brain infarction and improves functional outcomes after ischemic stroke: a time-window study in middle-aged rats.

    PubMed

    Yousuf, Seema; Sayeed, Iqbal; Atif, Fahim; Tang, Huiling; Wang, Jun; Stein, Donald G

    2014-02-01

    We evaluated the neuroprotective effects of delayed progesterone (PROG) treatment against ischemic stroke-induced neuronal death, inflammation, and functional deficits. We induced transient focal cerebral ischemia in male rats and administered PROG (8?mg/kg) or vehicle intraperitoneally at 3, 6, or 24?hours post occlusion, subcutaneously 5?hours later and then every 24?hours for 7 days. Behavioral outcomes were evaluated over 22 days. Infarct size and other biomarkers of injury were evaluated by cresyl violet staining, and matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP), and vascular endothelial growth factor (VEGF) by immunofluorescence. Progesterone treatment started at 3 and 6?hours post occlusion significantly (P<0.05) improved behavioral performance at all time points (74.01%) and reduced infarction volume (61.68%) compared with vehicle. No significant difference was observed between the 3 and 6?hour PROG treatment groups. Matrix metalloproteinase-9 and VEGF were upregulated in the PROG groups compared with vehicle. Glial fibrillary acidic protein expression was increased in the vehicle group but markedly lower in the PROG groups. Treatment delayed for 24?hours did not significantly improve functional outcomes or reduce infarction volume. We conclude that, under the right treatment conditions, PROG treatment delayed up to 6?hours can improve functional deficits and reduce brain infarction, possibly by modulating GFAP, VEGF, and MMP-9 expression. PMID:24301297

  14. Impaired Bronchoprotection Is Not Induced by Increased Smooth Muscle Mass in Chronic Treatment In Vivo with Formoterol in Asthmatic Mouse Model

    PubMed Central

    Luo, W; Liu, C-T; Yang, Q-H; Yu, Q; Wang, T

    2014-01-01

    ABSTRACT Objective: Inhaling ?2-adrenoceptor agonist is first-line asthma treatment, which is used for both acute relief of and prevention of bronchoconstriction. However, chronic use of ?-agonists results in impaired bronchoprotection and increasing occurrences of severe asthma exacerbation, even death in clinical practice. The mechanism of ?-adrenoceptor hyposensitivity has not been thoroughly elucidated thus far. Bronchial smooth muscle contraction induces airway narrowing and also mediates airway inflammation. Moreover, bronchial smooth muscle mass significantly increases in asthmatics. We aim to establish an asthmatic model that demonstrated that formoterol induced impaired bronchoprotection and to see whether increased smooth muscle mass played a role in it. Methods: We combined routine allergen challenging (seven weeks) with repeated application of formoterol, formoterol plus budesonide or physiological saline in allergen-sensitized BALB/c mouse. The bronchoprotection mediated by ?-agonist was measured in five consecutive weeks. Smooth muscle mass was shown by morphometric analysis, and ?-actin expression was detected by western blot. Results: The trend of bronchoprotection was wavy in drug interventional groups, which initially increased and then decreased. Chronic treatment with formoterol significantly impaired bronchoprotection. According to the morphometric analysis and ?-actin expression, no significant difference was detected in smooth muscle mass in all groups. Conclusion: This experiment successfully established that a chronic asthmatic mouse model, which manifested typical features of asthmatic patients, when treated chronically with formoterol, showed a loss of bronchoprotection. No significant difference was detected in smooth muscle mass in all groups, which implied some subcellular signalling changes may be the key points. PMID:25803396

  15. Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.

    PubMed

    Bourreau, Eliane; Ginouves, Marine; Prévot, Ghislaine; Hartley, Mary-Anne; Gangneux, Jean-Pierre; Robert-Gangneux, Florence; Dufour, Julie; Sainte-Marie, Dominique; Bertolotti, Antoine; Pratlong, Francine; Martin, Ricardo; Schütz, Frédéric; Couppié, Pierre; Fasel, Nicolas; Ronet, Catherine

    2016-01-01

    Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently ,: we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL. PMID:26123564

  16. Choosing a Hyperacute Stroke Imaging Protocol for Proper Patient Selection and Time Efficient Endovascular Treatment: Lessons from Recent Trials

    PubMed Central

    Lee, Jin Soo; Demchuk, Andrew M.

    2015-01-01

    Recently, several prospective randomized control trials regarding endovascular treatment for patients with intracranial large artery occlusions causing acute ischemic stroke have been successfully reported. Effort to minimize time delays to endovascular treatment, patient selection and the use of retrievable stent were important factors for the success of these trials. The inclusion and exclusion criteria for each of these trials did include differences in imaging protocols. In this review, we focus on the importance of baseline non-invasive angiography prior to deciding endovascular treatment. Then imaging protocols are described for each trial according to measurement of infarct volume and collateral grading. PMID:26437989

  17. Laundry greywater treatment using a fluidized bed reactor: a proposed model based on greywater biodegradation and residence time distribution approach.

    PubMed

    David, Pierre-luc; Bulteau, Gaëlle; Humeau, Philippe; Gérente, Claire; Andrès, Yves

    2013-01-01

    The increasing demand for water and the decrease in global water resources require research into alternative solutions to preserve them. The present study deals with the optimization of a treatment process, i.e. an aerobic fluidized bed reactor and the modelling of the degradation that takes place within it. The methodology employed is based on the hydrodynamics of the treatment process linked to the biodegradation kinetics of greywater coming from a washing machine. The residence time distribution (RTD) approach is selected for the hydrodynamic study. Biodegradation kinetics are quantified by respirometry and dissolved organic carbon (DOC) analysis on several mass quantities of colonized particles. RTD determinations show that there are no dysfunctions in the fluidized bed. Its hydrodynamic behaviour is similar to the one of a continuous stirred-tank reactor. A first-order reaction is obtained from the DOC biodegradation study. A model describing the degradation that takes place into the reactor is proposed, and from a sensitive study, the influence of the operating conditions on DOC biodegradation is defined. The theoretical results calculated from the first-order equation C(t) = 0.593 x C(0) x e(-kt) are compared with the experimental results and validated by a Student test. The value of the kinetic constant k is 0.011 h(-1) in the presence of a biomass carrier. The results highlight that it is possible to design a reactor in order to obtain a carbon content lower than 15 mg C L(-1) when the characteristics of raw greywater are known. PMID:24617067

  18. Relationship Between Time in Therapeutic Range and Comparative Treatment Effect of Rivaroxaban and Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Harrell, Frank E.; Singer, Daniel E.; Becker, Richard C.; Breithardt, Günter; Halperin, Jonathan L.; Hankey, Graeme J.; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2014-01-01

    Background Time in therapeutic range (TTR) is a standard quality measure of the use of warfarin. We assessed the relative effects of rivaroxaban versus warfarin at the level of trial center TTR (cTTR) since such analysis preserves randomized comparisons. Methods and Results TTR was calculated using the Rosendaal method, without exclusion of international normalized ratio (INR) values performed during warfarin initiation. Measurements during warfarin interruptions >7 days were excluded. INRs were performed via standardized finger?stick point?of?care devices at least every 4 weeks. The primary efficacy endpoint (stroke or non?central nervous system embolism) was examined by quartiles of cTTR and by cTTR as a continuous function. Centers with the highest cTTRs by quartile had lower?risk patients as reflected by lower CHADS2 scores (P<0.0001) and a lower prevalence of prior stroke or transient ischemic attack (P<0.0001). Sites with higher cTTR were predominantly from North America and Western Europe. The treatment effect of rivaroxaban versus warfarin on the primary endpoint was consistent across a wide range of cTTRs (P value for interaction=0.71). The hazard of major and non?major clinically relevant bleeding increased with cTTR (P for interaction=0.001), however, the estimated reduction by rivaroxaban compared with warfarin in the hazard of intracranial hemorrhage was preserved across a wide range of threshold cTTR values. Conclusions The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of cTTR. PMID:24755148

  19. Real-time computer treatment of THz passive device images with the high image quality

    NASA Astrophysics Data System (ADS)

    Trofimov, Vyacheslav A.; Trofimov, Vladislav V.

    2012-06-01

    We demonstrate real-time computer code improving significantly the quality of images captured by the passive THz imaging system. The code is not only designed for a THz passive device: it can be applied to any kind of such devices and active THz imaging systems as well. We applied our code for computer processing of images captured by four passive THz imaging devices manufactured by different companies. It should be stressed that computer processing of images produced by different companies requires using the different spatial filters usually. The performance of current version of the computer code is greater than one image per second for a THz image having more than 5000 pixels and 24 bit number representation. Processing of THz single image produces about 20 images simultaneously corresponding to various spatial filters. The computer code allows increasing the number of pixels for processed images without noticeable reduction of image quality. The performance of the computer code can be increased many times using parallel algorithms for processing the image. We develop original spatial filters which allow one to see objects with sizes less than 2 cm. The imagery is produced by passive THz imaging devices which captured the images of objects hidden under opaque clothes. For images with high noise we develop an approach which results in suppression of the noise after using the computer processing and we obtain the good quality image. With the aim of illustrating the efficiency of the developed approach we demonstrate the detection of the liquid explosive, ordinary explosive, knife, pistol, metal plate, CD, ceramics, chocolate and other objects hidden under opaque clothes. The results demonstrate the high efficiency of our approach for the detection of hidden objects and they are a very promising solution for the security problem.

  20. A Comparison of Taped-Problem Interventions to Increase Math Fact Fluency: Does the Length of Time Delay Affect Student Learning Rates?

    ERIC Educational Resources Information Center

    Poncy, Brian C.; Jaspers, Kathryn E.; Hansmann, Paul R.; Bui, Levita; Matthew, William B.

    2015-01-01

    An alternating treatments design with a control condition was used to evaluate and compare the effects of two taped-problem interventions on addition fact fluency. Both taped-problem interventions were identical with the exception of the time delay between the auditory cue of the problem and the answer. One condition used a 2-s delay and the other…

  1. Time loss due to dental problems and treatment in the Canadian population: analysis of a nationwide cross-sectional survey

    PubMed Central

    2013-01-01

    Background The purpose of this study was to quantify time loss due to dental problems and treatment in the Canadian population, to identify factors associated with this time loss, and to provide information regarding the economic impacts of these issues. Methods Data from the 2007/09 Canadian Health Measures Survey were used. Descriptive analysis determined the proportion of those surveyed who reported time loss and the mean hours lost. Linear and logistic regressions were employed to determine what factors predicted hours lost and reporting time loss respectively. Productivity losses were estimated using the lost wages approach. Results Over 40 million hours per year were lost due to dental problems and treatment, with a mean of 3.5 hours being lost per person. Time loss was more likely among privately insured and higher income earners. The amount of time loss was greater for higher income earners, and those who reported experiencing oral pain. Experiencing oral pain was the strongest predictor of reporting time loss and the amount of time lost. Conclusions This study has shown that, potentially, over 40 million hours are lost annually due to dental problems and treatment in Canada, with subsequent potential productivity losses of over $1 billion dollars. These losses are comparable to those experienced for other illnesses (e.g., musculoskeletal sprains). Further investigation into the underlying reasons for time loss, and which aspects of daily living are impacted by this time loss, are necessary for a fuller understanding of the policy implications associated with the economic impacts of dental problems and treatment in Canadian society. PMID:23587069

  2. Increased formation of halomethanes during chlorination of chloramphenicol in drinking water by UV irradiation, persulfate oxidation, and combined UV/persulfate pre-treatments.

    PubMed

    Wenhai, Chu; Tengfei, Chu; Erdeng, Du; Deng, Yang; Yingqing, Guo; Naiyun, Gao

    2016-02-01

    Ultraviolet/persulfate (UV/PS) has been widely used to generate sulfate radicals for degradation of water organic pollutants in previous studies. However, its impacts on disinfection byproduct formation during post-chlorination of degraded compounds is unclear. The objective of this study was to evaluate the impacts of UV irradiation, PS oxidation, and the combined UV/PS advanced oxidation process (AOP) pre-treatments on halomethane formation during the following chlorination of chloramphenicol (CAP), a model antibiotic commonly found in wastewater-impacted water. Results showed that CAP could be transformed to more trichloromethane (TCM) than monochloromethane (MCM) and dichloromethane (DCM) in the presence of excess chlorine. UV photolysis, PS oxidation and UV/PS AOP all directly decomposed CAP to produce halomethanes (HMs) before post-chlorination. Moreover, UV and UV/PS pre-treatments both enhanced the formation of all the HMs in the subsequent chlorination. PS pre-oxidation decreased the TCM formation during post-chlorination, but increased the yields of MCM, DCM and total HMs. UV pre-irradiation significantly increased the bromide utilization of HMs, whereas UV/PS pre-oxidation decreased the bromine incorporation and utilization of HMs from the chlorination of CAP in a low-bromide water. UV irradiation, PS oxidation, and UV/PS AOP can inactivate pathogens and degrade organic pollutants, but this benefit should be weighed against a potential risk of the increased halomethane formation from degraded organic pollutants with and without post-chlorination. PMID:26513530

  3. Increased lead concentration in brain and potentiation of lead-induced neuronal depression in rats after combined treatment with lead and disulfiram

    SciTech Connect

    Oskarsson, A.; Olson, L.; Palmer, M.R.; Lind, B.; Bjoerklund, H.; Hoffer, B.

    1985-12-01

    The effects of disulfiram (tetraethylthiuram disulfide) on blood and brain lead levels and on lead-induced changes in growth and cerebellar Purkinje neuron excitability were assessed in adult Sprague-Dawley rats. Disulfiram is metabolized to diethyldithiocarbamate, which forms a lipophilic complex with lead, and can thereby influence the tissue distribution of lead. Pregnant rats were exposed to 0.25% lead acetate or an equimolar amount of sodium acetate in the drinking water, and these treatments were continued for 4 weeks after birth. Half of the mothers from each group were given 0.1 mmole/kg disulfiram orally twice a week until parturition, after which the treatment was continued for 4 weeks in the respective pups in the form of subcutaneous injections. Although lead exposure markedly increased blood lead levels, the increase in brain lead levels was much more modest. Disulfiram markedly increased brain lead levels while blood lead levels in this group were only slightly elevated as compared to animals receiving lead alone. In addition, the lead + disulfiram group had depressed weight gain during maturation, and Purkinje neuron firing rates were reduced. The lead alone and disulfiram alone groups were not different from controls in these respects. These data suggest that disulfiram potentiates the adverse effects of lead on growth rates and on cerebellar Purkinje neuron function by facilitating the accumulation of lead in brain tissue.

  4. Combination of LC3 shRNA plasmid transfection and genistein treatment inhibited autophagy and increased apoptosis in malignant neuroblastoma in cell culture and animal models.

    PubMed

    Mohan, Nishant; Chakrabarti, Mrinmay; Banik, Naren L; Ray, Swapan K

    2013-01-01

    Malignant neuroblastoma is an extracranial solid tumor that usually occurs in children. Autophagy, which is a survival mechanism in many solid tumors including malignant neuroblastoma, deters the efficacy of conventional chemotherapeutic agents. To mimic starvation, we used 200 nM rapamycin that induced autophagy in human malignant neuroblastoma SK-N-BE2 and IMR-32 cells in cell culture and animal models. Combination of microtubule associated protein light chain 3 short hairpin RNA (LC3 shRNA) plasmid transfection and genistein (GST) treatment was tested for inhibiting rapamycin-induced autophagy and promoting apoptosis. The best synergistic efficacy caused the highest decrease in cell viability due to combination of 50 nM LC3 shRNA plasmid transfection and 25 µM GST treatment in rapamycin-treated SK-N-BE2 cells while combination of 100 nM LC3 shRNA plasmid transfection and 25 µM GST treatment in rapamycin-treated IMR-32 cells. Quantitation of acidic vesicular organelles confirmed that combination of LC3 shRNA plasmid transfection and GST treatment prevented rapamycin-induced autophagy due to down regulation of autophagy promoting marker molecules (LC3 II, Beclin 1, TLR-4, and Myd88) and upregulation of autophagy inhibiting marker molecules (p62 and mTOR) in both cell lines. Apoptosis assays showed that combination therapy most effectively activated mitochondrial pathway of apoptosis in human malignant neuroblastoma in cell culture and animal models. Collectively, our current combination of LC3 shRNA plasmid transfection and GST treatment could serve as a promising therapeutic strategy for inhibiting autophagy and increasing apoptosis in human malignant neuroblastoma in cell culture and animal models. PMID:24205354

  5. Combination of LC3 shRNA Plasmid Transfection and Genistein Treatment Inhibited Autophagy and Increased Apoptosis in Malignant Neuroblastoma in Cell Culture and Animal Models

    PubMed Central

    Mohan, Nishant; Chakrabarti, Mrinmay; Banik, Naren L.; Ray, Swapan K.

    2013-01-01

    Malignant neuroblastoma is an extracranial solid tumor that usually occurs in children. Autophagy, which is a survival mechanism in many solid tumors including malignant neuroblastoma, deters the efficacy of conventional chemotherapeutic agents. To mimic starvation, we used 200 nM rapamycin that induced autophagy in human malignant neuroblastoma SK-N-BE2 and IMR-32 cells in cell culture and animal models. Combination of microtubule associated protein light chain 3 short hairpin RNA (LC3 shRNA) plasmid transfection and genistein (GST) treatment was tested for inhibiting rapamycin-induced autophagy and promoting apoptosis. The best synergistic efficacy caused the highest decrease in cell viability due to combination of 50 nM LC3 shRNA plasmid transfection and 25 µM GST treatment in rapamycin-treated SK-N-BE2 cells while combination of 100 nM LC3 shRNA plasmid transfection and 25 µM GST treatment in rapamycin-treated IMR-32 cells. Quantitation of acidic vesicular organelles confirmed that combination of LC3 shRNA plasmid transfection and GST treatment prevented rapamycin-induced autophagy due to down regulation of autophagy promoting marker molecules (LC3 II, Beclin 1, TLR-4, and Myd88) and upregulation of autophagy inhibiting marker molecules (p62 and mTOR) in both cell lines. Apoptosis assays showed that combination therapy most effectively activated mitochondrial pathway of apoptosis in human malignant neuroblastoma in cell culture and animal models. Collectively, our current combination of LC3 shRNA plasmid transfection and GST treatment could serve as a promising therapeutic strategy for inhibiting autophagy and increasing apoptosis in human malignant neuroblastoma in cell culture and animal models. PMID:24205354

  6. Stearoyl-Coenzyme A Desaturase 1 Gene Expression Increases after Pioglitazone Treatment and Is Associated with Peroxisomal Proliferator-Activated Receptor-? Responsiveness

    PubMed Central

    Yao-Borengasser, Aiwei; Rassouli, Negah; Varma, Vijayalakshmi; Bodles, Angela M.; Rasouli, Neda; Unal, Resat; Phanavanh, Bounleut; Ranganathan, Gouri; McGehee, Robert E.; Kern, Philip A.

    2008-01-01

    Context and Objective: Stearoyl-coenzyme A desaturase (SCD1) is the rate-limiting enzyme that converts palmitoyl- and stearoyl-coenzyme A to palmitoleoyl- and oleoyl-cownzyme A, respectively. SCD-deficient mice are protected from obesity, and the ob/ob mouse has high levels of SCD. This study was designed to better characterize SCD1 gene and protein expression in humans with varying insulin sensitivity. Design, Participants, and Setting: In a university hospital clinical research center setting, SCD1 gene expression was measured in sc adipose and vastus lateralis muscle of 86 nondiabetic subjects; 10 wk of pioglitazone (45 mg daily) and metformin (1000 mg twice daily) treatment were assessed in 36 impaired glucose-tolerant subjects. Adipocytes were treated with pioglitazone, and SCD1 expression was attenuated with small interfering RNA (siRNA) to examine other adipocyte genes. Results: There was no significant relationship between adipose or muscle SCD1 mRNA and either body mass index or insulin sensitivity. After pioglitazone (but not metformin) treatment, there was a 2-fold increase in SCD1 mRNA and protein in adipose tissue. Pioglitazone also increased SCD1 in vitro. There were significant positive correlations between SCD1 and peroxisomal proliferator-activated receptor ? (PPAR?) as well as other PPAR?-responsive genes, including lipin-?, AGPAT2, RBP4, adiponectin receptors, CD68, and MCP1. When SCD1 expression was inhibited with a siRNA, lipin-?, AGPAT2, and the adiponectin R2 receptor expression were decreased, and adipocyte MCP-1 was increased. Conclusions: SCD1 is closely linked to PPAR? expression in humans, and is increased by PPAR? agonists. The change in expression of some downstream PPAR? targets after SCD1 knockdown suggests that PPAR? up-regulation of SCD1 leads to increased lipogenesis and potentiation of adiponectin signaling. PMID:18697866

  7. Prosper and Live Long: Productive Life Span Tracks Increasing Overall Life Span Over Historical Time among Privileged Worker Groups.

    PubMed

    Palacios, Tomas; Solari, Catherine; Bains, William

    2015-06-01

    Life expectancy has increased continuously for at least 150 years, due at least in part to improving life conditions for the majority of the population. A substantial part of this historical increase is due to decreases in early life mortality. In this article, we analyze the longevity of four privileged sets of adults who have avoided childhood mortality and lived a life more similar to the modern middle class. Our analysis is focused on writers and musicians from the 17th through the 21st centuries. We show that their average age at death increased only slightly between 1600 and 1900, but in the 20th century increased at around 2 years/decade. We suggest that this confirms that modern life span extension is driven by delay of death in older life rather than avoidance of premature death. We also show that productive life span, as measured by writing and composition outputs, has increased in parallel with overall life span in these groups. Increase in age of death is confirmed in a group of the minor British aristocracy and in members of the US Congress from 1800 to 2010. We conclude that both life span and productive life span are increasing in the 20th and early 21st century, and that the modern prolongation of life is the extension of productive life and is not the addition of years of disabling illness to the end of life. PMID:25625915

  8. What Motivates an Ever Increasing Number of Students to Enroll in Part-Time Taught Postgraduate Awards?

    ERIC Educational Resources Information Center

    Ho, Amaly; Kember, David; Hong, Celina

    2012-01-01

    There has been a substantial rise in the number of students enrolling in part-time taught postgraduate awards. This study investigates the reasons or motivation for students to spend significant amounts on tutorial fees and find time alongside work, family and social commitments to take a taught postgraduate award. Data were gathered through…

  9. Circulating and in situ lymphocyte subsets and Langerhans cells in patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity during treatment with azathioprine

    SciTech Connect

    Baadsgaard, O.

    1986-04-01

    Circulating and in situ lymphocyte subsets and Langerhans cells in four patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity before and during treatment with azathioprine were estimated. It was found that the number of Leu 6+ Langerhans cells decreased during therapy. This decrease was accompanied by a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, DR+, and Leu M2+ cells in the blood and a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, and DR+ cells in the skin. Concomitantly with the changes in the number of immunocompetent cells, the eczema cleared.

  10. A fast-time study on increasing the capacity of continuous descent approaches through airborne precision spacing 

    E-print Network

    Weitz, Lesley Anne

    2005-11-01

    Research Center (LaRC) in Hampton, Virginia, two parallel research efforts have focusedon terminal area research: one is Airborne Precision Spacing (APS), and the other is the Quiet Aircraft Technologies (QAT) project. The APS objective is to increase...

  11. Comparing drinking water treatment costs to source water protection costs using time series analysis.

    EPA Science Inventory

    We present a framework to compare water treatment costs to source water protection costs, an important knowledge gap for drinking water treatment plants (DWTPs). This trade-off helps to determine what incentives a DWTP has to invest in natural infrastructure or pollution reductio...

  12. Increased Intra-Individual Reaction Time Variability in Attention-Deficit/Hyperactivity Disorder across Response Inhibition Tasks with Different Cognitive Demands

    ERIC Educational Resources Information Center

    Vaurio, Rebecca G.; Simmonds, Daniel J.; Mostofsky, Stewart H.

    2009-01-01

    One of the most consistent findings in children with ADHD is increased moment-to-moment variability in reaction time (RT). The source of increased RT variability can be examined using ex-Gaussian analyses that divide variability into normal and exponential components and Fast Fourier transform (FFT) that allow for detailed examination of the…

  13. Chronic HO-1 Induction with Cobalt Protoporphyrin (CoPP) Treatment Increases Oxygen Consumption, Activity, Heat Production and Lowers Body Weight in Obese Melanocortin-4 Receptor Deficient Mice

    PubMed Central

    Csongradi, Eva; doCarmo, Jussara M.; Dubinion, John H.; Vera, Trinity; Stec, David E.

    2011-01-01

    Objective Heme oxygenase-1 induction (HO-1) elicits chronic weight loss in several rodent models of obesity. Despite these findings, the mechanism by which HO-1 induction reduces body weight is unclear. Chronic HO-1 induction does not alter food intake suggesting other mechanisms such as increases in metabolism and activity may be responsible for the observed reduction of body weight. In this study, we investigated the mechanism of weight loss elicited by chronic HO-1 induction in a model of genetic obesity due to melanocortin-4 receptor (MC4R) deficiency. Design Experiments were performed on loxTB MC4R deficient mice as well as lean controls. Mice were administered cobalt protoporphyrin (CoPP, 5 mg/kg), an inducer of HO-1, once weekly from 4 to 23 weeks of age. Body weights were measured weekly and fasted blood glucose and insulin as well as food intake were determined at 18 weeks of age. O2 consumption, CO2 production, activity, and body heat production were measured at 20 weeks of age. Results Chronic CoPP treatment resulted in a significant decrease in body weight from 5 weeks on in loxTB mice. Chronic CoPP treatment resulted in a significant decrease in fasted blood glucose levels, plasma insulin, and a significant increase in plasma adiponectin levels in MC4R deficient mice. Chronic CoPP treatment increased O2 consumption (47 ± 4 vs. 38 ± 3 ml/kg/min, P<0.05) and CO2 production (44 ± 7 vs. 34 ± 4 ml/kg/min, P<0.05) in treated versus non-treated, MC4R deficient mice (n=4). Heat production (10%) and activity (18%) were also significantly (P<0.05) increased in CoPP treated MC4R deficient mice. Conclusion Our results suggest that chronic HO-1 induction with CoPP induction elicits weight loss by increasing metabolism and activity by an MC4R independent pathway. PMID:21467998

  14. Prenatal Stress-Induced Increases in Placental Inflammation and Offspring Hyperactivity Are Male-Specific and Ameliorated by Maternal Antiinflammatory Treatment

    PubMed Central

    Bronson, Stefanie L.

    2014-01-01

    Adverse experiences during gestation such as maternal stress and infection are known risk factors for neurodevelopmental disorders, including schizophrenia, autism, and attention deficit/hyperactivity disorder. The mechanisms by which these distinct exposures may confer similar psychiatric vulnerability remain unclear, although likely involve pathways common to both stress and immune responses at the maternal-fetal interface. We hypothesized that maternal stress-induced activation of immune pathways within the placenta, the sex-specific maternal-fetal intermediary, may contribute to prenatal stress programming effects on the offspring. Therefore, we assessed for markers indicative of stress-induced placental inflammation, and examined the ability of maternal nonsteroidal antiinflammatory drug (NSAID) treatment to ameliorate placental effects and thereby rescue the stress-dysregulation phenotype observed in our established mouse model of early prenatal stress (EPS). As expected, placental gene expression analyses revealed increased levels of immune response genes, including the proinflammatory cytokines IL-6 and IL-1?, specifically in male placentas. NSAID treatment partially ameliorated these EPS effects. Similarly, in adult offspring, males displayed stress-induced locomotor hyperactivity, a hallmark of dopaminergic dysregulation, which was ameliorated by maternal NSAID treatment. Fitting with these outcomes and supportive of dopamine pathway involvement, expression of dopamine D1 and D2 receptors was altered by EPS in males. These studies support an important interaction between maternal stress and a proinflammatory state in the long-term programming effects of maternal stress. PMID:24797632

  15. Bupropion Increases Selection of High Effort Activity in Rats Tested on a Progressive Ratio/Chow Feeding Choice Procedure: Implications for Treatment of Effort-Related Motivational Symptoms

    PubMed Central

    Randall, Patrick A.; Lee, Christie A.; Podurgiel, Samantha J.; Hart, Evan; Yohn, Samantha E.; Jones, Myles; Rowland, Margaret; López-Cruz, Laura; Correa, Mercè

    2015-01-01

    Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans. PMID:25575584

  16. Ciguatera Incidence in the US Virgin Islands Has Not Increased over a 30-Year Time Period Despite Rising Seawater Temperatures

    PubMed Central

    Radke, Elizabeth G.; Grattan, Lynn M.; Cook, Robert L.; Smith, Tyler B.; Anderson, Donald M.; Morris, J. Glenn

    2013-01-01

    Ciguatera fish poisoning is the most common marine food poisoning worldwide. It has been hypothesized that increasing seawater temperature will result in increasing ciguatera incidence. In St. Thomas, US Virgin Islands, we performed an island-wide telephone survey (N = 807) and a medical record review of diagnosed ciguatera cases at the emergency department of the sole hospital and compared these data with comparable data sources collected in 1980. Annual incidence from both recent data sources remained high (12 per 1,000 among adults in the telephone survey). However, the combined data sources suggest that incidence has declined by 20% or more or remained stable over 30 years, whereas seawater temperatures were increasing. Illness was associated with lower education levels, higher levels of fish consumption, and having previous episodes of ciguatera; population shifts from 1980 to 2010 in these factors could explain an incidence decline of approximately 3 per 1,000, obscuring effects from rising seawater temperature. PMID:23400575

  17. Ciguatera incidence in the US Virgin Islands has not increased over a 30-year time period despite rising seawater temperatures.

    PubMed

    Radke, Elizabeth G; Grattan, Lynn M; Cook, Robert L; Smith, Tyler B; Anderson, Donald M; Morris, J Glenn

    2013-05-01

    Ciguatera fish poisoning is the most common marine food poisoning worldwide. It has been hypothesized that increasing seawater temperature will result in increasing ciguatera incidence. In St. Thomas, US Virgin Islands, we performed an island-wide telephone survey (N = 807) and a medical record review of diagnosed ciguatera cases at the emergency department of the sole hospital and compared these data with comparable data sources collected in 1980. Annual incidence from both recent data sources remained high (12 per 1,000 among adults in the telephone survey). However, the combined data sources suggest that incidence has declined by 20% or more or remained stable over 30 years, whereas seawater temperatures were increasing. Illness was associated with lower education levels, higher levels of fish consumption, and having previous episodes of ciguatera; population shifts from 1980 to 2010 in these factors could explain an incidence decline of approximately 3 per 1,000, obscuring effects from rising seawater temperature. PMID:23400575

  18. The Timing of the Shrew: Continuous Melatonin Treatment Maintains Youthful Rhythmic Activity in Aging Crocidura russula

    PubMed Central

    Magnanou, Elodie; Attia, Joël; Fons, Roger; Boeuf, Gilles; Falcon, Jack

    2009-01-01

    Background Laboratory conditions nullify the extrinsic factors that determine the wild expected lifespan and release the intrinsic or potential lifespan. Thus, wild animals reared in a laboratory often show an increased lifespan, and consequently an increased senescence phase. Senescence is associated with a broad suite of physiological changes, including a decreased responsiveness of the circadian system. The time-keeping hormone melatonin, an important chemical player in this system, is suspected to have an anti-aging role. The Greater White-toothed shrew Crocidura russula is an ideal study model to address questions related to aging and associated changes in biological functions: its lifespan is short and is substantially increased in captivity; daily and seasonal rhythms, while very marked the first year of life, are dramatically altered during the senescence process which starts during the second year. Here we report on an investigation of the effects of melatonin administration on locomotor activity of aging shrews. Methodology/Principal Findings 1) The diel fluctuations of melatonin levels in young, adult and aging shrews were quantified in the pineal gland and plasma. In both, a marked diel rhythm (low diurnal concentration; high nocturnal concentration) was present in young animals but then decreased in adults, and, as a result of a loss in the nocturnal production, was absent in old animals. 2) Daily locomotor activity rhythm was monitored in pre-senescent animals that had received either a subcutaneous melatonin implant, an empty implant or no implant at all. In non-implanted and sham-implanted shrews, the rhythm was well marked in adults. A marked degradation in both period and amplitude, however, started after the age of 14–16 months. This pattern was considerably delayed in melatonin-implanted shrews who maintained the daily rhythm for significantly longer. Conclusions This is the first long term study (>500 days observation of the same individuals) that investigates the effects of continuous melatonin delivery. As such, it sheds new light on the putative anti-aging role of melatonin by demonstrating that continuous melatonin administration delays the onset of senescence. In addition, the shrew appears to be a promising mammalian model for elucidating the precise relationships between melatonin and aging. PMID:19526053

  19. A time dependent density functional treatment of superfluid dynamics: Equilibration of the electron bubble in superfluid 4

    E-print Network

    Apkarian, V. Ara

    A time dependent density functional treatment of superfluid dynamics: Equilibration of the electron by the slow breathing of the cavity. The far-field motion consists of a shock wave, followed by radiating sound waves. The solitonic shock wave propagates at speeds as high as 580 m/s, determined

  20. Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time?

    PubMed

    Cucinotto, Iole; Fiorillo, Lucia; Gualtieri, Simona; Arbitrio, Mariamena; Ciliberto, Domenico; Staropoli, Nicoletta; Grimaldi, Anna; Luce, Amalia; Tassone, Pierfrancesco; Caraglia, Michele; Tagliaferri, Pierosandro

    2013-01-01

    Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms. PMID:23738077

  1. Nanoparticle Albumin Bound Paclitaxel in the Treatment of Human Cancer: Nanodelivery Reaches Prime-Time?

    PubMed Central

    Cucinotto, Iole; Fiorillo, Lucia; Gualtieri, Simona; Arbitrio, Mariamena; Ciliberto, Domenico; Staropoli, Nicoletta; Grimaldi, Anna; Luce, Amalia; Tassone, Pierfrancesco; Caraglia, Michele; Tagliaferri, Pierosandro

    2013-01-01

    Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms. PMID:23738077

  2. Pharmacokinetics of Repeated Sodium Salicylate Administration to Laying Hens: Evidence for Time Dependent Increase in Drug Elimination from Plasma and Eggs

    PubMed Central

    Po?niak, B?a?ej; Grabowski, Tomasz; Motykiewicz-Pers, Karolina; Bobrek, Kamila; Rak, Lech; Bobusia, Katarzyna; Gawe?, Andrzej; ?wita?a, Marcin

    2015-01-01

    Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs) to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus) salicylate (SA) may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS) to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT), minimal plasma concentration (Cmin, C16h) and elimination half-life (T1/2el) of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB) increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment. PMID:25893240

  3. Increased eligibility for treatment of chronic hepatitis C infection with shortened duration of therapy: Implications for access to care and elimination strategies in Canada

    PubMed Central

    Borgia, Sergio M; Rowaiye, Adenike

    2015-01-01

    BACKGROUND: All oral, highly effective direct-acting antiviral combinations, such as sofosbuvir-ledipasvir, have recently been licensed in Canada but cost as much as $67,000 for a 12-week course of therapy, representing a major economic barrier to predominately single-payer health care systems such as that found in Ontario. In hepatitis C virus (HCV) genotype 1 noncirrhotic patients with a baseline viral load of <6×106 IU/mL, treatment with sofosbuvir-ledipasvir can be shortened to eight weeks without compromising ?95% efficacy. The number of HCV-infected patients in Ontario eligible for shortened therapy, and the associated cost savings, are unknown. The authors propose that treating every patient with shortened therapy, regardless of baseline viral load, would lead to significant public cost savings and collateral efficiencies, enabling increased HCV treatment capacity and cure. METHODS: The present study designed a three-part model to investigate the cost of cure per patient and cost savings per patient under three eligibility pathways: conservative, permissive and ideal. In the conservative model, every patient is treated for 12 weeks regardless of baseline viral load, whereas in the permissive model, patients with a baseline viral load <6×106 IU/mL are treated for eight weeks. In the ideal model, every patient receives eight weeks of therapy regardless of baseline viral load. Relapsed patients are retreated for 12 weeks. Data obtained from the Ontario Public Health Laboratory were used to validate the model and generate the outcomes. RESULTS: In Ontario, 75.34% of HCV genotype 1 patients had a baseline viral load of <6×106 IU/mL and were eligible for shortened therapy. The cost of cure per patient in the ideal model was $47,328.44, representing a 29% reduction in the cost of curative therapy and 3.5 weeks of shortened treatment duration compared with the conservative model. The ideal model generated a cost savings per patient of $3,855.17 (8% reduction in treatment cost) and 0.7 weeks of shorter therapy compared with the permissive model, and was the shortest and most efficient while maintaining a cure rate ?95%. CONCLUSIONS: These results demonstrate that recommendations for a shortened treatment course of eight weeks using all-oral direct-acting antivirals in HCV genotype 1 noncirrhotic patients, regardless of baseline viral load, affords significant public cost savings and, on a population level, offers opportunities for expanded HCV treatment and cure. PMID:25855874

  4. Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat

    PubMed Central

    2012-01-01

    Background Excess peroxisome proliferator-activated receptor (PPAR) stimulation has been associated with detrimental health effects including impaired myocardial function. Recently, supplementation with n-3 polyunsaturated fatty acids (PUFA) has been associated with improved left ventricular function and functional capacity in patients with dilated cardiomyopathy. We investigated the long-term effects of the pan-PPAR agonist tetradecylthioacetic acid (TTA) and/or high-dose fish oil (FO) on cardiac fatty acid (FA) composition and lipid metabolism. Male Wistar rats were given one out of four different 25% (w/v) fat diets: control diet; TTA diet; FO diet; or diet containing both TTA and FO. Results After 50?weeks n-3 PUFA levels were increased by TTA and FO in the heart, whereas liver levels were reduced following TTA administration. TTA was associated with a decrease in arachidonic acid, increased activities of carnitine palmitoyltransferase II, fatty acyl-CoA oxidase, glycerol-3-phosphate acyltransferase, and fatty acid synthase in the heart. Furthermore, cardiac Ucp3 and Cact mRNA was upregulated. Conclusions Long-term treatment with the pan-PPAR agonist TTA or high-dose FO induced marked changes in PUFA composition and enzymatic activity involved in FA metabolism in the heart, different from liver. Changes included increased FA oxidation and a selective increase in cardiac n-3 PUFA. PMID:22738017

  5. Does Leisure Time as a Stress Coping Resource Increase Affective Complexity? Applying the Dynamic Model of Affect (DMA).

    PubMed

    Qian, Xinyi Lisa; Yarnal, Careen M; Almeida, David M

    2013-01-01

    Affective complexity, a manifestation of psychological well-being, refers to the relative independence between positive and negative affect (PA, NA). According to the Dynamic Model of Affect (DMA), stressful situations lead to highly inverse PA-NA relationship, reducing affective complexity. Meanwhile, positive events can sustain affective complexity by restoring PA-NA independence. Leisure, a type of positive events, has been identified as a coping resource. This study used the DMA to assess whether leisure time helps restore affective complexity on stressful days. We found that on days with more leisure time than usual, an individual experienced less negative PA-NA relationship after daily stressful events. The finding demonstrates the value of leisure time as a coping resource and the DMA's contribution to coping research. PMID:24659826

  6. Peripheral reflex feedbacks in chronic heart failure: Is it time for a direct treatment?

    PubMed

    Giannoni, Alberto; Mirizzi, Gianluca; Aimo, Alberto; Emdin, Michele; Passino, Claudio

    2015-12-26

    Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF), no single conceptual paradigm for HF has withstood the test of time. The last model that has been developed, the neurohormonal model, has the great virtue of highlighting the role of the heart as an endocrine organ, as well as to shed some light on the key role on HF progression of neurohormones and peripheral organs and tissues beyond the heart itself. However, while survival in clinical trials based on neurohormonal antagonist drugs has improved, HF currently remains a lethal condition. At the borders of the neurohormonal model of HF, a partially unexplored path trough the maze of HF pathophysiology is represented by the feedback systems. There are several evidences, from both animal studies and humans reports, that the deregulation of baro-, ergo- and chemo-reflexes in HF patients elicits autonomic imbalance associated with parasympathetic withdrawal and increased adrenergic drive to the heart, thus fundamentally contributing to the evolution of the disease. Hence, on top of guideline-recommended medical therapy, mainly based on neurohormonal antagonisms, all visceral feedbacks have been recently considered in HF patients as additional potential therapeutic targets. PMID:26730288

  7. Peripheral reflex feedbacks in chronic heart failure: Is it time for a direct treatment?

    PubMed Central

    Giannoni, Alberto; Mirizzi, Gianluca; Aimo, Alberto; Emdin, Michele; Passino, Claudio

    2015-01-01

    Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF), no single conceptual paradigm for HF has withstood the test of time. The last model that has been developed, the neurohormonal model, has the great virtue of highlighting the role of the heart as an endocrine organ, as well as to shed some light on the key role on HF progression of neurohormones and peripheral organs and tissues beyond the heart itself. However, while survival in clinical trials based on neurohormonal antagonist drugs has improved, HF currently remains a lethal condition. At the borders of the neurohormonal model of HF, a partially unexplored path trough the maze of HF pathophysiology is represented by the feedback systems. There are several evidences, from both animal studies and humans reports, that the deregulation of baro-, ergo- and chemo-reflexes in HF patients elicits autonomic imbalance associated with parasympathetic withdrawal and increased adrenergic drive to the heart, thus fundamentally contributing to the evolution of the disease. Hence, on top of guideline-recommended medical therapy, mainly based on neurohormonal antagonisms, all visceral feedbacks have been recently considered in HF patients as additional potential therapeutic targets.

  8. Mathematics Achievement Gaps between Suburban Students and Their Rural and Urban Peers Increase over Time. Issue Brief No. 52

    ERIC Educational Resources Information Center

    Graham, Suzanne E.; Provost, Lauren E.

    2012-01-01

    In this brief, authors Suzanne Graham and Lauren Provost examine whether attending a school in a rural, urban, or suburban community is related to children's mathematics achievement in kindergarten, and whether increases in mathematics achievement between kindergarten and eighth grade differ for children in rural, urban, and suburban schools. They…

  9. FABULOUS FALL FUNGI 2015 Due to increased demand, we are pleased to offer this workshop three times this year

    E-print Network

    Fletcher, Robin

    1 of 3 FABULOUS FALL FUNGI 2015 DATES Due to increased demand, we are pleased to offer diversity of mushrooms and other fungi growing in Southern Ontario. Typically, 130-150 species is the ideal opportunity to become better acquainted with the mysterious world of fungi. CLASS SIZE Each

  10. A microenvironment approach to reducing sedentary time and increasing physical activity of children and adults at a playground

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective. Test whether a micro-environment park intervention in Grand Forks, ND, movement of seating away from a playground, would increase the physical activity and length of stay of park users. Method. STUDY 1, summer 2012: physical activity of children and adults was assessed during baseline (...

  11. An Investigation of the Effectiveness of Increasing Academic Learning Time for College Undergraduate Students' Achievement in Kuwait

    ERIC Educational Resources Information Center

    Al-Shammari, Zaid; Mohammad, Anwar; Al-Shammari, Bandar

    2010-01-01

    The study investigated the effectiveness of increasing ALT for college students' achievement in Kuwait. In Phase 1, 37 students participated (22, experimental; 15, control); in Phase 2, 19 students participated (8, sub-experimental; 11, sub-control). Several experimental research methods used in conducting this study, including development of a…

  12. Length and time for development of laminar flow in tubes following a step increase of volume flux

    NASA Astrophysics Data System (ADS)

    Chaudhury, Rafeed A.; Herrmann, Marcus; Frakes, David H.; Adrian, Ronald J.

    2015-01-01

    Laminar flows starting up from rest in round tubes are relevant to numerous industrial and biomedical applications. The two most common types are flows driven by an abruptly imposed constant pressure gradient or by an abruptly imposed constant volume flux. Analytical solutions are available for transient, fully developed flows, wherein streamwise development over the entrance length is absent (Szymanski in J de Mathématiques Pures et Appliquées 11:67-107, 1932; Andersson and Tiseth in Chem Eng Commun 112(1):121-133, 1992, respectively). They represent the transient responses of flows in tubes that are very long compared with the entrance length, a condition that is seldom satisfied in biomedical tube networks. This study establishes the entrance (development) length and development time of starting laminar flow in a round tube of finite length driven by a piston pump that produces a step change from zero flow to a constant volume flux for Reynolds numbers between 500 and 3,000. The flows are examined experimentally, using stereographic particle image velocimetry and computationally using computational fluid dynamics, and are then compared with the known analytical solutions for fully developed flow conditions in infinitely long tubes. Results show that step function volume flux start-up flows reach steady state and fully developed flow five times more quickly than those driven by a step function pressure gradient, a 500 % change when compared with existing estimates. Based on these results, we present new, simple guidelines for achieving experimental flows that are fully developed in space and time in realistic (finite) tube geometries. To a first approximation, the time to achieve steady spatially developing flow is nearly equal to the time needed to achieve steady, fully developed flow. Conversely, the entrance length needed to achieve fully developed transient flow is approximately equal to the length needed to achieve fully developed steady flow. Beyond this level of description, the numerical results reveal interaction between the effects of space and time development and nonlinear Reynolds number effects.

  13. Programming generalization and maintenance of treatment effects across time and across settings1

    PubMed Central

    Walker, Hill M.; Buckley, Nancy K.

    1972-01-01

    Effects of three experimental and one control strategy were investigated in facilitating generalization and maintenance of treatment effects after two months in a token-economy classroom. At the conclusion of treatment, subjects were randomly assigned to one of three maintenance strategies or a control group and returned to their regular classrooms. The maintenance strategies were peer reprogramming, equating stimulus conditions between the experimental and regular classrooms, and teacher training in behavior management techniques. The maintenance strategies were implemented in the regular classroom for a two-month period and then terminated. Results indicated a powerful treatment effect produced by the token economy. Behavior maintenance effects following treatment were also obtained. The mean per cent appropriate behavior for the peer reprogramming and equating stimulus conditions strategies was significantly greater than the mean for the control subjects. The teacher training and control group means were not significantly different. PMID:16795344

  14. Practical treatment of Helicobacter pylori: a balanced view in changing times.

    PubMed

    Smith, Sinéad M; Haider, Rana B; O'Connor, Humphrey; McNamara, Deirdre; O'Morain, Colm

    2014-08-01

    Eradication rates of first-line triple therapy for Helicobacter pylori infection have fallen in the recent years. The main reasons for treatment failure are poor compliance due to complicated treatment regimens and the emergence of antibiotic-resistant strains of H. pylori. Treatment failure is a cause for concern with regard to the complications of H. pylori infection, which include gastric and peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. This review describes considerations for optimizing standard first-line triple therapy, as well as alternatives to the standard first-line treatment, such as bismuth quadruple therapy, sequential therapy, concomitant therapy and hybrid therapy. Studies using levofloxacin-based and rifabutin-based regimens for the treatment of multiresistant infections have also been reviewed. The current most up-to-date systematic reviews and meta-analyses comparing the efficacy of these treatments have been discussed, in light of the recent antimicrobial susceptibility testing data, regional antibiotic resistance rates and the Maastricht IV guidelines on the management of H. pylori infection. PMID:24892516

  15. Increased Specificity of Wechsler Adult Intelligence Scale-Third Edition Matrix Reasoning Test Instructions and Time Limits

    ERIC Educational Resources Information Center

    Callens, Andy M.; Atchison, Timothy B.; Engler, Rachel R.

    2009-01-01

    Instructions for the Matrix Reasoning Test (MRT) of the Wechsler Adult Intelligence Scale-Third Edition were modified by explicitly stating that the subtest was untimed or that a per-item time limit would be imposed. The MRT was administered within one of four conditions: with (a) standard administration instructions, (b) explicit instructions…

  16. Reduction of Overall Treatment Time in Patients Irradiated for More Than Three Brain Metastases

    SciTech Connect

    Rades, Dirk Kieckebusch, Susanne; Lohynska, Radka; Veninga, Theo; Stalpers, Lukas J.A.; Dunst, Juergen; Schild, Steven E.

    2007-12-01

    Purpose: Patients with multiple brain metastases usually receive whole brain radiotherapy (WBRT). A dose of 30 Gy in 10 fractions (10 x 3 Gy) in 2 weeks is the standard treatment in many centers. Regarding the poor survival of these patients, a shorter RT regimen would be preferable if it provides a similar outcome as that with 10 x 3 Gy. This study compared 20 Gy in five fractions (5 x 4 Gy) within 5 days to 10 x 3 Gy. Methods and Materials: Data from 442 patients treated with WBRT for multiple brain metastases were retrospectively analyzed. Survival and local control within the brain of 232 patients treated with 5 x 4 Gy were compared with the survival and local control within the brain of 210 patients treated with 10 x 3 Gy. Seven additional potential prognostic factors were investigated: age, gender, Karnofsky performance score, tumor type, interval from tumor diagnosis to RT, extracranial metastases, and recursive partitioning analysis class. Results: On univariate analysis, the WBRT program was not associated with survival (p = 0.29) or local control (p = 0.07). On multivariate analyses, improved survival was associated with a lower recursive partitioning analysis class (p < 0.001), age {<=}60 years (p = 0.001), Karnofsky performance score {>=}70 (p = 0.015), and the absence of extracranial metastases (p = 0.005). Improved local control was associated with a lower recursive partitioning analysis class (p < 0.001), Karnofsky performance score {>=}70 (p < 0.001), and breast cancer (p = 0.043). Grade 3 acute toxicity rates were not significantly different between 5 x 4 Gy and 10 x 3 Gy. Conclusions: Shorter course WBRT with 5 x 4 Gy was associated with similar survival and local control as 'standard' WBRT with 10 x 3 Gy in patients with more than three brain metastases. The 5 x 4-Gy regimen appears preferable for most of these patients, because it is less time consuming and more convenient for patients than the 10 x 3-Gy regimen.

  17. Basophil CD203c Levels Are Increased at Baseline and Can Be Used to Monitor Omalizumab Treatment in Subjects with Nut Allergy

    PubMed Central

    Gernez, Yael; Tirouvanziam, Rabindra; Yu, Grace; Ghosn, Eliver E.B.; Reshamwala, Neha; Nguyen, Tammie; Tsai, Mindy; Galli, Stephen J.; Herzenberg, Leonard A.; Herzenberg, Leonore A.; Nadeau, Kari C.

    2011-01-01

    Rationale: Basophils contribute to anaphylaxis and allergies. We examined the utility of assessing basophil-associated surface antigens (CD11b/CD63/CD123/CD203c/CD294) in characterizing and monitoring subjects with nut allergy. Methods: We used flow cytometry to analyze basophils at baseline (without any activation) and after ex vivo stimulation of whole blood by addition of nut or other allergens for 2, 10, and 30 min. We also evaluated whether basophil expression of CD11b/CD63/CD123/CD203c/CD294 was altered in subjects treated with anti-IgE monoclonal antibody (omalizumab) to reduce plasma levels of IgE. Results: We demonstrate that basophil CD203c levels are increased at baseline in subjects with nut allergy compared to healthy controls (13 subjects in each group, p < 0.0001). Furthermore, we confirm that significantly increased expression of CD203c occurs on subject basophils when stimulated with the allergen to which the subject is sensitive and can be detected rapidly (10 min of stimulation, n = 11, p < 0.0008). In 5 subjects with severe peanut allergy, basophil CD203c expression following stimulation with peanut allergen was significantly decreased (p < 0.05) after 4 and 8 weeks of omalizumab treatment but returned toward pretreatment levels after treatment cessation. Conclusions: Subjects with nut allergy show an increase of basophil CD203c levels at baseline and following rapid ex vivo stimulation with nut allergen. Both can be reduced by omalizumab therapy. These results highlight the potential of using basophil CD203c levels for baseline diagnosis and therapeutic monitoring in subjects with nut allergy. PMID:20975283

  18. Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection.

    PubMed

    Ahmad, Fareed; Tufa, Dejene Milkessa; Mishra, Neha; Jacobs, Roland; Schmidt, Reinhold E

    2015-12-01

    HIV-1 infection results in immunological abnormalities of natural killer (NK) cells such as disturbed distribution of NK cell subsets and downmodulation of activating and upregulation of inhibitory receptors thereby diminishing NK cell killing capacity and cytokine secretion. Antiretroviral treatment (ART) is known to restore phenotype and functions of NK cells. However, the effects of ART on NK cell terminal differentiation, activation, and disturbed distribution have not been studied yet longitudinally. Here, we analyzed the effects of ART on these parameters of peripheral blood NK cells in a longitudinal as well as in a cross-sectional study. We observed that expanded CD56(-)CD16(+) NK cell frequency is inversely correlated with the frequency of CD56(dim)CD16(+) NK cells in treatment-naive HIV-1 patients. Loss of CD56(dim)CD16(+) and expansion of CD56(-)CD16(+) NK cells again restore to the levels of healthy controls after ART. Enhanced immune activation of different NK cell subsets is partially restored after ART. Terminal differentiation of CD56(dim)CD16(+) NK cells is enhanced after ART as measured by CD57 expression. Frequencies of CD57(+)CD56(dim)CD16(+) NK cells are directly correlated with the frequencies of total NK cells suggesting that an increase in the frequencies of CD57(+)CD56(dim)CD16(+) NK cells is reflected by increased frequencies of total NK cells after ART. Taken together these data demonstrate that ART has an effect on the immune restoration of NK cells and is enhanced in the terminal differentiation of CD56(dim)CD16(+) NK cells, which is associated with increased frequencies of total NK cells after ART. PMID:26352913

  19. Egg box conformation of oligogalacturonides: the time-dependent stabilization of the elicitor-active conformation increases its biological activity.

    PubMed

    Cabrera, Juan Carlos; Boland, Aurelien; Messiaen, Johan; Cambier, Pierre; Van Cutsem, Pierre

    2008-06-01

    Circular dichroism spectrometry was used on oligogalacturonides (OGAs) and showed the existence of a calcium/sodium-induced conformational state that is intermediate between single-isolated chains and calcium-associated multimer chains. This conformation is interpreted as being egg box dimers. Using the 2F4 monoclonal antibody that specifically binds such an egg box dimer conformation of pectin, the stability of OGA dimers was investigated over a period of 24 hours. The extent to which egg box dimers were recognized by the antibody was dependent on the temperature and duration of preincubation of the OGA. This suggests a "maturation" process of the egg-box structure that consists in a progressive increase in the length of the junction sequences between two chains that slide along each other in order to form a maximum number of calcium bridges and dimer ends. The maturation of egg boxes induced both a significant increase in their binding to wall-associated kinase 1 (WAK1) and an increased extracellular alkalinization when applied to Arabidopsis thaliana cell suspensions. The chemical modification of the reducing end of the OGAs largely diminished their elicitating activity but did not hinder either dimerization or binding of these end-reduced egg boxes to WAK1. We conclude that there are at least two different perception systems for egg box dimers. One binds egg box junctions and the other binds egg box ends. The relevance of these results is discussed in terms of pectic signal perception and plant-pathogen interaction. PMID:18381977

  20. The Effect of Isothermal Heat Treatment Time on the Microstructure and Properties of 2.11% Al Austempered Ductile Iron

    NASA Astrophysics Data System (ADS)

    Erfanian-Naziftoosi, H. R.; Haghdadi, N.; Kiani-Rashid, A. R.

    2012-08-01

    In this article, the bainitic transformation during austempering was studied for a 2.11% Al containing ductile iron under different isothermal holding times. The austenitizing time and temperature were selected to be 60 min and 920 °C, respectively, referring to previous studies. The isothermal austempering heat treatments were performed at 350 °C for different durations. Microstructures have been examined by optical microscopy, scanning electron microscopy, and transmission electron microscopy. Microstructural investigations revealed that austempering treatment at 350 °C for durations up to 100 min results in microstructures consisting of carbide-free bainitic ferrite with considerable amounts of retained austenite while the extension of isothermal transformation time leads to precipitation of carbides. Hardness measurements were also carried out the results of which were shown to be consistent with microstructural evolutions.

  1. Prototype of a Questionnaire and Quiz System for Supporting Increase of Health Awareness During Wait Time in Dispensing Pharmacy

    NASA Astrophysics Data System (ADS)

    Toda, Takeshi; Chen, Poa-Min; Ozaki, Shinya; Ideguchi, Naoko; Miyaki, Tomoko; Nanbu, Keiko; Ikeda, Keiko

    For quit-smoking clinic and its campaign, there was a need for pharmacists to investigate pediatric patient's parent consciousness to tobacco harm utilizing wait time in a pediatric dispensing pharmacy. In this research, we developed the questionnaire and quiz total system using the tablet for user interface, in which people can easily answer the questionnaire/quiz and quickly see the total results on the spot in order to enhance their consciousness to the tobacco harm. The system also provides their tobacco dependence level based on the questionnaire results and some advice for their health and dietary habits due to the tobacco dependence level. From a field trial with one hundred four examinees in the pediatric dispensing pharmacy, the user interface was useful compared to conventional questionnaire form. The system could enhance their consciousness to tobacco harm and make their beneficial use of waiting time in dispensing pharmacy. Some interesting suggestions for improvement and new services were also obtained.

  2. Alternated Prone and Supine Whole-Breast Irradiation Using IMRT: Setup Precision, Respiratory Movement and Treatment Time

    SciTech Connect

    Veldeman, Liv; De Gersem, Werner; Speleers, Bruno; Truyens, Bart; Van Greveling, Annick; Van den Broecke, Rudy; De Neve, Wilfried

    2012-04-01

    Purpose: The objective of this study was to compare setup precision, respiration-related breast movement and treatment time between prone and supine positions for whole-breast irradiation. Methods and Materials: Ten patients with early-stage breast carcinoma after breast-conserving surgery were treated with prone and supine whole breast-irradiation in a daily alternating schedule. Setup precision was monitored using cone-beam computed tomography (CBCT) imaging. Respiration-related breast movement in the vertical direction was assessed by magnetic sensors. The time needed for patient setup and for the CBCT procedure, the beam time, and the length of the whole treatment slot were also recorded. Results: Random and systematic errors were not significantly different between positions in individual patients for each of the three axes (left-right, longitudinal, and vertical). Respiration-related movement was smaller in prone position, but about 80% of observations showed amplitudes <1 mm in both positions. Treatment slots were longer in prone position (21.2 {+-} 2.5 min) than in supine position (19.4 {+-} 0.8 min; p = 0.044). Conclusion: Comparison of setup precision between prone and supine position in the same patient showed no significant differences in random and systematic errors. Respiratory movement was smaller in prone position. The longer treatment slots in prone position can probably be attributed to the higher repositioning need.

  3. Hexa-D-Arginine treatment increases 7B2•PC2 activity in hyp-mouse osteoblasts and rescues the HYP phenotype

    PubMed Central

    Yuan, Baozhi; Feng, Jian Q.; Bowman, Stephen; Liu, Ying; Blank, Robert D.; Lindberg, Iris; Drezner, Marc K.

    2012-01-01

    Inactivating mutations of PHEX/Phex underlie disease in patients with X-linked hypophosphatemia (XLH) and the hyp-mouse, a murine homologue of the human disorder. Although increased serum FGF-23 underlies the HYP phenotype, the mechanism(s) by which PHEX mutations inhibit FGF-23 degradation and/or enhance production remains unknown. Here we show that treatment of wild type mice with the proprotein convertase (PC) inhibitor, Decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone, increases serum FGF-23 and produces the HYP phenotype. Since PC2 is uniquely co-localized with PHEX in osteoblasts/bone, we examined if PC2 regulates PHEX-dependent FGF-23 cleavage and production. Transfection of murine osteoblasts with PC2 and its chaperone protein 7B2 cleaved FGF-23, while Signe1 (7B2) RNAi transfection, which limited 7B2 protein production, decreased FGF-23 degradation and increased Fgf-23 mRNA and protein. The mechanism by which decreased 7B2•PC2 activity influences Fgf-23 mRNA was linked to reduced conversion of proBMP1 to active BMP1, which resulted in limited cleavage of DMP1, and consequent increased Fgf-23 mRNA. The significance of decreased 7B2•PC2 activity in XLH was confirmed by studies of hyp-mouse bone, which revealed significantly decreased Sgne1 (7B2) mRNA and 7B2 protein, and limited cleavage of proPC2 to active PC2. The expected downstream effects of these changes included decreased FGF-23 cleavage and increased FGF-23 synthesis, secondary to decreased BMP1-mediated degradation of DMP1. Subsequent Hexa-D-Arginine treatment of hyp-mice enhanced bone 7B2•PC2 activity, normalized FGF-23 degradation and production, and rescued the HYP phenotype. These data suggest decreased PHEX-dependent 7B2•PC2 activity is central to the pathogenesis of XLH. PMID:22886699

  4. Increased expression of mitochondrial benzodiazepine receptors following low-level light treatment facilitates enhanced protoporphyrin IX production in glioma-derived cells in vitro

    NASA Astrophysics Data System (ADS)

    Bisland, S. K.; Hassanali, N. S.; Johnson, C.; Wilson, B. C.

    2007-02-01

    This study investigates whether low level light treatment (LLLT) can enhance the expression of Peripheral-type mitochondrial benzodiazepine receptors (PBRs) on the glioma-derived tumour cell line, CNS-1, and by doing so promote the synthesis of protoporphyrin IX (PpIX) and increase the photodynamic therapy (PDT)-induced cell kill using 5-aminolevulinic acid (ALA). The endogenous photosensitizer, (PpIX) and related metabolites including coproporphyrin III are known to traffic via the PBRs on the outer mitochondrial membrane on their passage into or out of the mitochondria. Astrocyte-derived cells within the brain express PBRs, while neurons express the central-type of benzodiazepine receptor. CNS-1 cells were exposed to a range of differing low-level light protocols immediately prior to PDT. LLLT involved using broad-spectrum light or monochromatic laser light specific to 635 or 905 nm wavelength. Cells (5?10 5) were exposed to a range of LLLT doses (0, 1 or 5 J/cm2) using a fixed intensity of 10 mW/cm2 and subsequently harvested for cell viability, immunofluorescence or western blot analysis of PBR expression. The amount of PpIX within the cells was determined using chemical extraction techniques. Results confirm the induction of PBR following LLLT is dependent on the dose and wavelength of light used. Broadspectrum light provided the greatest cell kill following PDT, although LLLT with 635 nm or 905 nm also increased cell kill as compared to PDT alone. All LLLT regimens increased PBR expression compared to controls with corresponding increases in PpIX production. These data suggest that by selectively increasing PBR expression in tumour cells, LLLT may facilitate enhanced cell kill using ALA-PDT without damaging surrounding normal brain.

  5. Age-related effects of increased ambient pressure on discrimination reaction time: A study in 105 professional divers at 6.0 atm abs.

    PubMed

    Tikkinen, Janne; Siimes, Martti A

    2015-01-01

    We investigated 105 professional divers using a computerized visual discrimination trial (Cognitrone) to measure the effects of ambient pressure on reaction times. The possible improvement in performance due to practice was anticipated, and the trials were carried out four times prior to pressurization in a hyperbaric chamber. The effect of increased ambient pressure was measured at 6.0 and 1.9 atm abs, and the potential for residual effects was tested after decompression. The results of our study indicate that repeated testing had a systematic influence on the measured time values. The effects of learning, which were independent of diver age, may have independently influenced response times. Exposure to 6.0 atm abs modified the systematic pattern of learning and was associated with increased reaction times. There were also age-related differences in response times associated with exposure to increased ambient pressures. Younger divers were more susceptible to elevated ambient pressure, evidenced by increased response times at 6 atm abs relative to their older colleagues. One out of every four of the younger divers could be considered susceptible to inert gas narcosis (ION) when an increase of one standard deviation/1SD (> 19%) or more in discrimination reaction time is used as an indicator. ION susceptibility appears independent of body composition and physical fitness. The slowed response speed experienced at 6.0 atm abs was of short duration and returned to baseline immediately with decompression. Our results suggest that IGN is demonstrated by an impaired learning process and decreased response speed and that some younger divers appear more susceptible. PMID:26094302

  6. Inhibition of the centrally induced increases in myocardial oxygen demand in rabbits by chronic treatment with baclofen, a selective GABAB agonist.

    PubMed Central

    Tibiriçà, E.; Catelli, M.; Lessa, M. A.; Roegel, J. C.; Feldman, J.; Monassier, L.; Bousquet, P.

    1995-01-01

    1. A previous study from our group demonstrated that neurones of the paraventricular nucleus of the hypothalamus (PVN) are selectively involved in the central control of the cardiac function. Moreover, in that study, it was shown that baclofen, a selective GABAB receptor agonist, is capable of modulating the increases in myocardial contractility and oxygen demand evoked by electrical or pharmacological stimulation of the PVN. Nevertheless, the acute administration of this compound was frequently accompanied by a cardiodepressant effect. 2. In the present study, the effects of a long term treatment (14 days) with baclofen (3 or 10 mg kg-1, i.p.) have been examined on the excitatory haemodynamic responses evoked by central pharmacological stimulation in anaesthetized rabbits. 3. The i.c.v. injection of L-glutamate (3 mg kg-1) induced marked increases in dP/dtmax (32%), mean arterial pressure (39%) and on two indices of myocardial oxygen consumption: the rate-pressure product (34%) and the triple product (78%). 4. Baclofen blunted the positive inotropic response and the increases in myocardial oxygen consumption induced by L-glutamate in a dose-related manner. The higher dose of baclofen (10 mg kg-1, i.p.), reduced by more than 50% these excitatory effects of L-glutamate without eliciting any significant negative effect on basal haemodynamics. The same doses of baclofen were not able to blunt the hypertensive response induced by central stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582565

  7. Increased Delay Discounting on a Novel Real-Time Task among Girls, but not Boys, with ADHD.

    PubMed

    Rosch, Keri S; Mostofsky, Stewart H

    2016-01-01

    The aim of this study was to examine delay discounting in girls and boys with ADHD-Combined type (ADHD-C) relative to typically developing (TD) children on two tasks that differ in the extent to which the rewards and delays were experienced by participants. Children ages 8-12 years with ADHD-C (n=65; 19 girls) and TD controls (n=55; 15 girls) completed two delay discounting tasks involving a series of choices between smaller, immediate and larger, delayed rewards. The classic delay discounting task involved choices about money at delays of 1-90 days and only some of the outcomes were actually experienced by the participants. The novel real-time discounting task involved choices about an immediately consumable reward (playing a preferred game) at delays of 25-100 s, all of which were actually experienced by participants. Participants also provided subjective ratings of how much they liked playing the game and waiting to play. Girls with ADHD-C displayed greater delay discounting compared to boys with ADHD-C and TD girls and boys on the real-time discounting task. Diagnostic group differences were not evident on the classic discounting task. In addition, children with ADHD-C reported wanting to play the game more and liking waiting to play the game less than TD children. This novel demonstration of greater delay discounting among girls with ADHD-C on a discounting task in which the rewards are immediately consumable and the delays are experienced in real-time informs our understanding of sex differences and motivational processes in children with ADHD. (JINS, 2016, 22, 12-23). PMID:26549118

  8. Oxytocin increases eye contact during a real-time, naturalistic social interaction in males with and without autism

    PubMed Central

    Auyeung, B; Lombardo, M V; Heinrichs, M; Chakrabarti, B; Sule, A; Deakin, J B; Bethlehem, R A I; Dickens, L; Mooney, N; Sipple, J A N; Thiemann, P; Baron-Cohen, S

    2015-01-01

    Autism spectrum conditions (autism) affect ~1% of the population and are characterized by deficits in social communication. Oxytocin has been widely reported to affect social-communicative function and its neural underpinnings. Here we report the first evidence that intranasal oxytocin administration improves a core problem that individuals with autism have in using eye contact appropriately in real-world social settings. A randomized double-blind, placebo-controlled, within-subjects design is used to examine how intranasal administration of 24?IU of oxytocin affects gaze behavior for 32 adult males with autism and 34 controls in a real-time interaction with a researcher. This interactive paradigm bypasses many of the limitations encountered with conventional static or computer-based stimuli. Eye movements are recorded using eye tracking, providing an objective measurement of looking patterns. The measure is shown to be sensitive to the reduced eye contact commonly reported in autism, with the autism group spending less time looking to the eye region of the face than controls. Oxytocin administration selectively enhanced gaze to the eyes in both the autism and control groups (transformed mean eye-fixation difference per second=0.082; 95% CI:0.025–0.14, P=0.006). Within the autism group, oxytocin has the most effect on fixation duration in individuals with impaired levels of eye contact at baseline (Cohen's d=0.86). These findings demonstrate that the potential benefits of oxytocin in autism extend to a real-time interaction, providing evidence of a therapeutic effect in a key aspect of social communication. PMID:25668435

  9. Oxytocin increases eye contact during a real-time, naturalistic social interaction in males with and without autism.

    PubMed

    Auyeung, B; Lombardo, M V; Heinrichs, M; Chakrabarti, B; Sule, A; Deakin, J B; Bethlehem, R A I; Dickens, L; Mooney, N; Sipple, J A N; Thiemann, P; Baron-Cohen, S

    2015-01-01

    Autism spectrum conditions (autism) affect ~1% of the population and are characterized by deficits in social communication. Oxytocin has been widely reported to affect social-communicative function and its neural underpinnings. Here we report the first evidence that intranasal oxytocin administration improves a core problem that individuals with autism have in using eye contact appropriately in real-world social settings. A randomized double-blind, placebo-controlled, within-subjects design is used to examine how intranasal administration of 24?IU of oxytocin affects gaze behavior for 32 adult males with autism and 34 controls in a real-time interaction with a researcher. This interactive paradigm bypasses many of the limitations encountered with conventional static or computer-based stimuli. Eye movements are recorded using eye tracking, providing an objective measurement of looking patterns. The measure is shown to be sensitive to the reduced eye contact commonly reported in autism, with the autism group spending less time looking to the eye region of the face than controls. Oxytocin administration selectively enhanced gaze to the eyes in both the autism and control groups (transformed mean eye-fixation difference per second=0.082; 95% CI:0.025-0.14, P=0.006). Within the autism group, oxytocin has the most effect on fixation duration in individuals with impaired levels of eye contact at baseline (Cohen's d=0.86). These findings demonstrate that the potential benefits of oxytocin in autism extend to a real-time interaction, providing evidence of a therapeutic effect in a key aspect of social communication. PMID:25668435

  10. Timing of buprenorphine adoption by privately funded substance abuse treatment programs: The role of institutional and resource-based inter-organizational linkages

    PubMed Central

    Savage, Sarah A.; Abraham, Amanda J.; Knudsen, Hannah K.; Rothrauff, Tanja C.; Roman, Paul M.

    2011-01-01

    Identifying facilitators of more rapid buprenorphine adoption may increase access to this effective treatment for opioid dependence. Using a diffusion of innovations theoretical framework, we examine the extent to which programs’ inter-organizational institutional and resource-based linkages predict the likelihood of being an earlier, later, or non-adopter of buprenorphine. Data were derived from face-to-face interviews with administrators of 345 privately funded substance abuse treatment programs in 2007–2008. Results of multinomial logistic regression models show that inter-organizational and resource linkages were associated with timing of adoption. Programs reporting membership in provider associations were more likely to be earlier adopters of buprenorphine. Programs that relied more on resources linkages, such as the detailing activities by pharmaceutical companies and the NIDA website, were more likely to be earlier adopters of buprenorphine. These findings suggest that institutional and resource-based inter-organizational linkages may expose programs to effective treatments, thereby facilitating more rapid and sustained adoption of innovative treatment techniques. PMID:21831565

  11. LC–MS Metabolomics of Psoriasis Patients Reveals Disease Severity-Dependent Increases in Circulating Amino Acids That Are Ameliorated by Anti-TNF? Treatment

    PubMed Central

    2015-01-01

    Psoriasis is an immune-mediated highly heterogeneous skin disease in which genetic as well as environmental factors play important roles. In spite of the local manifestations of the disease, psoriasis may progress to affect organs deeper than the skin. These effects are documented by epidemiological studies, but they are not yet mechanistically understood. In order to provide insight into the systemic effects of psoriasis, we performed a nontargeted high-resolution LC–MS metabolomics analysis to measure plasma metabolites from individuals with mild or severe psoriasis as well as healthy controls. Additionally, the effects of the anti-TNF? drug Etanercept on metabolic profiles were investigated in patients with severe psoriasis. Our analyses identified significant psoriasis-associated perturbations in three metabolic pathways: (1) arginine and proline, (2) glycine, serine and threonine, and (3) alanine, aspartate, and glutamate. Etanercept treatment reversed the majority of psoriasis-associated trends in circulating metabolites, shifting the metabolic phenotypes of severe psoriasis toward that of healthy controls. Circulating metabolite levels pre- and post-Etanercept treatment correlated with psoriasis area and severity index (PASI) clinical scoring (R2 = 0.80; p < 0.0001). Although the responsible mechanism(s) are unclear, these results suggest that psoriasis severity-associated metabolic perturbations may stem from increased demand for collagen synthesis and keratinocyte hyperproliferation or potentially the incidence of cachexia. Data suggest that levels of circulating amino acids are useful for monitoring both the severity of disease as well as therapeutic response to anti-TNF? treatment. PMID:25361234

  12. Copper sulphate and DCMU-herbicide treatments increase asymmetry between sister cells in the toxic cyanobacteria Microcystis aeruginosa: implications for detecting environmental stress.

    PubMed

    Costas, E; Lopez-Rodas, V

    2006-07-01

    Works correlating fluctuating asymmetry with environmental stress or genetic damages have been largely reported in multicellular organisms but not in single-celled ones. We hypothesize that asymmetry analysis could also be applied to single-celled organisms, because the asymmetry between two sister cells originated from a cellular division event (same genotype in similar environment) must tend to zero in the absence of environmental or genetic perturbations. Laboratory experiments with copper sulphate and DCMU-herbicide treatments as well as experiments in a water reservoir after treatment with copper sulphate algaecide show that environmental stress increases asymmetry between sister cells of Microcystis aeruginosa (Cyanobacteria). Even low Cu(2+) or DCMU doses, which were unable to reduce growth rate, considerably enlarge asymmetry with respect to untreated controls. Asymmetry between sister cells of cyanobacteria seems to be a reliable indicator of environmental perturbation. Analysis of asymmetry in single-celled organisms could become as important as fluctuating asymmetry of multicellular organisms is today. PMID:16762387

  13. Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype.

    PubMed

    Sudduth, Tiffany L; Wilson, Joan G; Everhart, Angela; Colton, Carol A; Wilcock, Donna M

    2012-01-01

    Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3?). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2-/- mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2-/- mice for a period of eight months, followed by water maze testing at 12 months of age, immediately prior to sacrifice. We found that lithium significantly lowered hyperphosphorylated tau levels as measured by Western blot and immunocytochemistry. However, we found no apparent neuroprotection, no effect on spatial memory deficits and an increase in histological amyloid deposition. A? levels measured biochemically were unaltered. We also found that lithium significantly altered the neuroinflammatory phenotype of the brain, resulting in enhanced alternative inflammatory response while concurrently lowering the classical inflammatory response. Our data suggest that lithium may be beneficial for the treatment of tauopathies but may not be beneficial for the treatment of Alzheimer's disease. PMID:22347510

  14. Endovascular image-guided treatment of in-vivo model aneurysms with asymmetric vascular stents (AVS): evaluation with time-density curve angiographic analysis and histology

    NASA Astrophysics Data System (ADS)

    Dohatcu, A.; Ionita, C. N.; Paciorek, A.; Bednarek, D. R.; Hoffmann, K. R.; Rudin, S.

    2008-03-01

    In this study, we compare the results obtained from Time-Density Curve (TDC) analysis of angiographic imaging sequences with histological evaluation for a rabbit aneurysm model treated with standard stents and new asymmetric vascular stents (AVS) placed by image-guided endovascular deployment. AVSs are stents having a low-porosity patch region designed to cover the aneurysm neck and occlude blood flow inside. To evaluate the AVSs, rabbits with elastase-induced aneurysm models (n=20) were divided into three groups: the first (n=10) was treated with an AVS, the second (n=5) with a non-patch standard coronary stent, and third was untreated as a control (n=5). We used TDC analysis to measure how much contrast media entered the aneurysm before and after treatment. TDCs track contrast-media-density changes as a function of time over the region of interest in x-ray DSA cine-sequences. After 28 days, the animals were sacrificed and the explanted specimens were histologically evaluated. The first group showed an average reduction of contrast flow into the aneurysm of 95% after treatment with an AVS with fully developed thrombus at 28 days follow-up. The rabbits treated with standard stents showed an increase in TDC residency time after treatment and partial-thrombogenesis. The untreated control aneurysms displayed no reduction in flow and were still patent at follow-up. The quantitative TDC analysis findings were confirmed by histological evaluation suggesting that the new AVS has great potential as a definitive treatment for cerebro-vascular aneurysms and that angiographic TDC analysis can provide in-vivo verification.

  15. Time delay measurement for linac based treatment delivery in synchronized respiratory gating radiotherapy

    SciTech Connect

    Jin Jianyue; Yin Fangfang

    2005-05-01

    A time delay in a respiratory gating system could cause an unexpected phase mismatch for synchronized gating radiotherapy. This study presents a method of identifying and measuring the time delay in a gating system. Various port films were taken for a motion phantom at different gating window levels with a very narrow window size. The time delay for the gating system was determined by comparing the motion curve (the position of a moving object versus the gating time) measured in the port films to the motion curve determined by the video cameras. The measured time delay for a linac-based gating system was 0.17{+-}0.03 s. This time delay could induce target missing if it was not properly taken into account for the synchronized gating radiotherapy. Measurement/verification of the time delay should be considered as an important part of the accepting/commissioning test before the clinical use of the gating system.

  16. Development of a Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor during a Long-Time Treatment with Sunitinib

    PubMed Central

    Pallotti, Maria Caterina; Pantaleo, Maria Abbondanza; Nannini, Margherita; Centofanti, Francesca; Fabbrizio, Benedetta; Montanari, Mara; Baraldi, Olga; Saponara, Maristella; Lolli, Cristian; Mandrioli, Anna; Biasco, Guido; Prandini, Rita

    2012-01-01

    A patient with advanced gastrointestinal stromal tumor (GIST) receiving second-line treatment with sunitinib developed edema, increase of the serum creatinine, weight gain, nephrotic syndrome with proteinuria of 12 g/24 h, dyslipidemia, hypoalbuminemia and also presented with hypertension. A kidney biopsy showed an immunocomplex glomerulonephritis. Steroid treatment was started, but the clinical conditions and laboratory values did not improve. So in the hypothesis that the nephrotic syndrome was induced by sunitinib, sunitinib was temporarily discontinued with a subsequent reduction of proteinuria and improvement in blood pressure control. In the last years, the introduction of sunitinib has modified the natural history of advanced GIST. However, due to chronic and prolonged intake of this drug, there is increasingly frequent detection of late and unknown toxicities in clinical practice. In particular, the late renal toxicity from sunitinib may be the primary clinical problem with this drug in the case of prolonged treatment. Monitoring of kidney function and blood pressure should be performed for early detection of side effects such as hypertension and kidney dysfunction in advanced GIST patients receiving long-term treatment with sunitinib. A clinical collaboration between oncologists and nephrologists could be useful with the objective to optimize the management of sunitinib. PMID:23275781

  17. Development of a Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor during a Long-Time Treatment with Sunitinib.

    PubMed

    Pallotti, Maria Caterina; Pantaleo, Maria Abbondanza; Nannini, Margherita; Centofanti, Francesca; Fabbrizio, Benedetta; Montanari, Mara; Baraldi, Olga; Saponara, Maristella; Lolli, Cristian; Mandrioli, Anna; Biasco, Guido; Prandini, Rita

    2012-09-01

    A patient with advanced gastrointestinal stromal tumor (GIST) receiving second-line treatment with sunitinib developed edema, increase of the serum creatinine, weight gain, nephrotic syndrome with proteinuria of 12 g/24 h, dyslipidemia, hypoalbuminemia and also presented with hypertension. A kidney biopsy showed an immunocomplex glomerulonephritis. Steroid treatment was started, but the clinical conditions and laboratory values did not improve. So in the hypothesis that the nephrotic syndrome was induced by sunitinib, sunitinib was temporarily discontinued with a subsequent reduction of proteinuria and improvement in blood pressure control. In the last years, the introduction of sunitinib has modified the natural history of advanced GIST. However, due to chronic and prolonged intake of this drug, there is increasingly frequent detection of late and unknown toxicities in clinical practice. In particular, the late renal toxicity from sunitinib may be the primary clinical problem with this drug in the case of prolonged treatment. Monitoring of kidney function and blood pressure should be performed for early detection of side effects such as hypertension and kidney dysfunction in advanced GIST patients receiving long-term treatment with sunitinib. A clinical collaboration between oncologists and nephrologists could be useful with the objective to optimize the management of sunitinib. PMID:23275781

  18. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

    SciTech Connect

    Craig, Zelieann R. Hannon, Patrick R. Flaws, Jodi A.

    2013-11-01

    Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P{sub 4}) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 ?g/mL), pregnenolone (1 ?g/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P{sub 4}, androstenedione (A), testosterone (T), estrone (E{sub 1}), and 17?-estradiol (E{sub 2}) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E{sub 2}. Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P{sub 4}, A, T, and E{sub 1} that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. - Highlights: • Mono-OH MXC inhibited antral follicle steroidogenesis, growth, and survival. • Pregnenolone partially restored steroidogenesis in mono-OH MXC-treated follicles. • Pregnenolone did not prevent mono-OH MXC-induced inhibition of growth and survival.

  19. Timing and rate of Chaparral treatment affects tall fescue seedhead development and pasture plant densities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The herbicide Chaparral™ has been shown to suppress seedhead development in tall fescue (Neotyphodium coenophialum) pastures and reduce the symptoms of tall fescue toxicosis in cattle. However, little is known about the logistics of herbicide treatment on tall fescue pastures. The objective of thi...

  20. Transobturator Tape in Treatment of Stress Urinary Incontinence: It is Time for a New Gold Standard

    PubMed Central

    Magon, Navneet; Chopra, Sanjiv VSM

    2012-01-01

    Background: Stress urinary incontinence (SUI) can significantly impair the quality of life. A variety of treatments, both medical and surgical, have been used to manage it. The transobturator sling, which is a subfascial sling, is relatively a new surgical technique with minimal access. Aim: The objective of this study was to evaluate the effectiveness of transobturator tape (TOT) in the treatment of female SUI and to analyze functional results. Materials and Methods: A total of 59 patients were applied TOT by outside-in technique and various outcome parameters recorded. These patients were followed up 6 months after surgery. Results: Success rate of TOT was 93.2% (95% CI: 86.4–99.5). A total of 51 patients (86.4%) were completely satisfied, whereas 4 (6.8%) were partially satisfied and 4 were unsatisfied with surgical outcome. The procedure-related complications were few and could be managed in the same sitting. Conclusion: The transobturator approach is an effective treatment of SUI with low morbidity, and it has all the potential to be the new Gold Standard in the treatment of female SUI. PMID:22655282

  1. Effects of Antiparasitic Treatment on Dynamically and Statically Tested Cognitive Skills over Time

    ERIC Educational Resources Information Center

    Grigorenko, Elena L.; Sternberg, Robert J.; Jukes, Mathew; Alcock, Katie; Lambo, Jane; Ngorosho, Damaris; Nokes, Catherine; Bundy, Donald A.

    2006-01-01

    The main objective of this work was to investigate two testing procedures, repeated static tests and dynamic testing, that can more clearly demonstrate the impact of treatment for parasites in children. Rural Tanzanian children were assessed for the presence/absence and burden of helminth parasites and assigned to one of three…

  2. Slug-Dependent Upregulation of L1CAM Is Responsible for the Increased Invasion Potential of Pancreatic Cancer Cells following Long-Term 5-FU Treatment

    PubMed Central

    Lund, Kaja; Dembinski, Jennifer L.; Solberg, Nina; Urbanucci, Alfonso; Mills, Ian G.; Krauss, Stefan

    2015-01-01

    Background Pancreatic adenocarcinoma is a lethal disease with 5-year survival of less than 5%. 5-fluorouracil (5-FU) is a principal first-line therapy, but treatment only extends survival modestly and is seldom curative. Drug resistance and disease recurrence is typical and there is a pressing need to overcome this. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc 03.27 cell line by long-term exposure to increasing doses of 5-FU. Results 5-FU-resistant cell lines exhibited increased expression of markers associated with multidrug resistance explaining their reduced sensitivity to 5-FU. In addition, 5-FU-resistant cell lines showed alterations typical for an epithelial-to-mesenchymal transition (EMT), including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, and a significant upregulation of L1CAM was seen on the RNA and protein level. In pancreatic cancer, expression of L1CAM is associated with a chemoresistant and migratory phenotype. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with antibodies, we show that the increased invasiveness observed in the chemoresistant cells functionally depends on L1CAM. Using esiRNA targeting ?-catenin and/or Slug, we demonstrate that in the chemoresistant cell lines, L1CAM expression depends on Slug rather than ?-catenin. Conclusion Our findings establish Slug-induced L1CAM expression as a mediator of a chemoresistant and migratory phenotype in pancreatic adenocarcinoma cells. PMID:25860483

  3. An update on the management of Budd-Chiari syndrome: the issues of timing and choice of treatment.

    PubMed

    Mancuso, Andrea

    2015-03-01

    Because of the rarity of Budd-Chiari syndrome (BCS), the flow chart of management comes from expert opinion and is not evidence based. To report an update on the management of BCS. I performed a review on published papers on BCS in an attempt to speculate in particular on the timing and the choice of treatment. Some authors suggest that the management of BCS should follow a step-wise strategy. Anticoagulation and medical therapy should be the first-line treatment. Revascularization or transjugular intrahepatic portosystemic shunt should be performed in case of no response to medical therapy. Orthotopic liver transplant should be used as a rescue therapy. The biggest criticism of this flow chart is that it is based on the assumption that patients with BCS should receive further treatment only when hemodynamic effects on portal hypertension become clinically evident, thus paying little attention to the chronic ischemic liver damage effects on hepatic function and to the possibility of preventing liver failure by relieving impaired hepatic veins outflow. Recently, I presented a proposal of a new algorithm for the management of BCS, in which medical therapy alone is suggested only for patients without any sign of portal hypertension, irrespective of whether early interventional treatment is suggested when either any symptoms or signs of portal hypertension appear, with the aim of preventing hepatic fibrosis development, disease progression, and finally improving outcome. Given that the benefit of treatments for BCS is not under debate, guidelines for the management of BCS should be re-evaluated and updated, with particular attention to both the timing and the choice of treatment. PMID:25590783

  4. Real-time and post-frac' 3-D analysis of hydraulic fracture treatments in geothermal reservoirs

    SciTech Connect

    Wright, C.A.; Tanigawa, J.J.; Hyodo, Masami; Takasugi, Shinji

    1994-01-20

    Economic power production from Hot Dry Rock (HDR) requires the establishment of an efficient circulation system between wellbores in reservoir rock with extremely low matrix permeability. Hydraulic fracturing is employed to establish the necessary circulation system. Hydraulic fracturing has also been performed to increase production from hydrothermal reservoirs by enhancing the communication with the reservoir's natural fracture system. Optimal implementation of these hydraulic fracturing applications, as with any engineering application, requires the use of credible physical models and the reconciliation of the physical models with treatment data gathered in the field. Analysis of the collected data has shown that 2-D models and 'conventional' 3-D models of the hydraulic fracturing process apply very poorly to hydraulic fracturing in geothermal reservoirs. Engineering decisions based on these more 'conventional' fracture modeling techniques lead to serious errors in predicting the performance of hydraulic fracture treatments. These errors can lead to inappropriate fracture treatment design as well as grave errors in well placement for hydrothermal reservoirs or HDR reservoirs. This paper outlines the reasons why conventional modeling approaches fall short, and what types of physical models are needed to credibly estimate created hydraulic fracture geometry. The methodology of analyzing actual measured fracture treatment data and matching the observed net fracturing pressure (in realtime as well as after the treatment) is demonstrated at two separate field sites. Results from an extensive Acoustic Emission (AE) fracture diagnostic survey are also presented for the first case study aS an independent measure of the actual created hydraulic fracture geometry.

  5. Maternal Behavior by Birth Order in Wild Chimpanzees (Pan troglodytes): Increased Investment by First-Time Mothers.

    PubMed

    Stanton, Margaret A; Lonsdorf, Elizabeth V; Pusey, Anne E; Goodall, Jane; Murray, Carson M

    2014-08-01

    Parental investment theory predicts that maternal resources are finite and allocated among offspring based on factors including maternal age and condition, and offspring sex and parity. Among humans, firstborn children are often considered to have an advantage and receive greater investment than their younger siblings. However, conflicting evidence for this "firstborn advantage" between modern and hunter-gatherer societies raises questions about the evolutionary history of differential parental investment and birth order. In contrast to humans, most non-human primate firstborns belong to young, inexperienced mothers and exhibit higher mortality than laterborns. In this study, we investigated differences in maternal investment and offspring outcomes based on birth order (firstborn vs. later-born) among wild chimpanzees (Pan troglodyte schweinfurthii). During the critical first year of life, primiparous mothers nursed, groomed, and played with their infants more than did multiparous mothers. Furthermore, this pattern of increased investment in firstborns appeared to be compensatory, as probability of survival did not differ by birth order. Our study did not find evidence for a firstborn advantage as observed in modern humans but does suggest that unlike many other primates, differences in maternal behavior help afford chimpanzee first-borns an equal chance of survival. PMID:25328164

  6. Increased survival time of a patient with metastatic malignant melanoma following immunotherapy: A case report and literature review

    PubMed Central

    ZHANG, YONG; SONG, YONGPING; GAO, QUANLI

    2015-01-01

    Metastatic malignant melanoma is treated with chemotherapy and radiotherapy. A number of previous studies have indicated that cytokine-induced killer cells (CIK cells) are a heterogeneous cell population that express cluster of differentiation (CD)3 and CD56, in addition to the natural killer cell NKG2D activating receptor. CIK cells possess major histocompatibility complex-unrestricted cytotoxicity towards cancer, but not towards normal targets. The present study investigated whether the addition of CIK cells resulted in an improved therapeutic response in a patient with metastatic malignant melanoma. In the current case, a patient with metastatic malignant melanoma received CIK therapy, which resulted in a relatively long survival time of 28 months. To the best of our knowledge, there have been no previous studies reporting such positive effects in a patient who received CIK cell immunotherapy. Based on the findings of the present study, CIK cell therapy may be an option that results in a good prognosis in certain patients with metastatic malignant melanoma.

  7. Inoculum potential of Rhizopogon spores increases with time over the first 4 yr of a 99-yr spore burial experiment.

    PubMed

    Bruns, Thomas D; Peay, Kabir G; Boynton, Primrose J; Grubisha, Lisa C; Hynson, Nicole A; Nguyen, Nhu H; Rosenstock, Nicholas P

    2009-01-01

    In disturbed or pioneer settings, spores and sclerotia of ectomycorrhizal fungi serve as the necessary inoculum for establishment of ectomycorrhizal-dependent trees. Yet, little is known about the persistence of these propagules through time. Here, live field soil was inoculated with known quantities of basidiospores from four pine-associated species of Rhizopogon; these samples were then buried in retrievable containers, and pine seedling bioassays of serially diluted spore samples were used to measure spore viability. In the first 4 yr, no evidence of loss of spore viability was found in the four Rhizopogon species tested, but all four species exhibited dormancy in which a maximum of 1-8% of their spores were initially receptive to pine roots. There were some differences between species in overall inoculum potential of their spores, but all species broke dormancy at a statistically similar rate. This result provides evidence for spore dormancy in a common ectomycorrhizal genus, but it also precludes our ability to estimate the longevity of the spores accurately. Nevertheless these results, coupled with the observed patterns of Rhizopogon spore banks, suggest that at least decade-long durations are likely. As this experiment progresses, the true longevity of the spores will eventually be revealed. PMID:19121040

  8. An increase in hemoglobin, platelets and white blood cells levels by iron chelation as single treatment in multitransfused patients with myelodysplastic syndromes: clinical evidences and possible biological mechanisms.