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Sample records for early luteal phase

  1. Early luteal phase endocrine profile is affected by the mode of triggering final oocyte maturation and the luteal phase support used in recombinant follicle-stimulating hormone-gonadotropin-releasing hormone antagonist in vitro fertilization cycles

    DEFF Research Database (Denmark)

    Fatemi, Human M; Polyzos, Nikolaos P; van Vaerenbergh, Inge

    2013-01-01

    To assess endocrine differences during early luteal phase according to mode of triggering final oocyte maturation with or without luteal phase support (LPS).......To assess endocrine differences during early luteal phase according to mode of triggering final oocyte maturation with or without luteal phase support (LPS)....

  2. Improving the luteal phase after ovarian stimulation

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Vilbour Andersen, K

    2014-01-01

    The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final...... follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using...

  3. The relationship between the production and the anti-gonadotrophic action of prostaglandin F 2 alpha in luteal cells from the marmoset monkey (Callithrix jacchus) in the early and mid-luteal phase.

    Science.gov (United States)

    Webley, G E; Michael, A E; Abayasekara, D R E

    2010-04-01

    To address the potential luteolytic role for prostaglandin F(2 alpha) (PGF(2 alpha)) in the corpus luteum of the common marmoset monkey (Callithrix jacchus), the ability of marmoset luteal cells, maintained in monolayer culture, to produce PGF(2 alpha) was determined in vitro in the presence and absence of human chorionic gonadotrophin (hCG) and other established pharmacological modulators of PGF(2 alpha) synthesis. We also assessed the effects of the PGF(2 alpha) analogue, cloprostenol, on progesterone output from luteal cells isolated in the early luteal phase versus the mid-luteal phase (days 3 and 14 post ovulation, respectively). Cloprostenol had no effect on progesterone output from luteal cells isolated on day 3 of the luteal phase, whereas it significantly inhibited both basal and hCG-stimulated progesterone synthesis by day 14 luteal cells during the culture period 48-72 h (Pmarmoset monkey appears to involve changes in both the luteal cell response to and production of PGF(2 alpha).

  4. Evaluation of models to induce low progesterone during the early luteal phase in cattle.

    Science.gov (United States)

    Beltman, M E; Roche, J F; Lonergan, P; Forde, N; Crowe, M A

    2009-10-15

    Two experiments were designed to evaluate models for generation of low circulating progesterone concentrations during early pregnancy in cattle. In Experiment 1, 17 crossbred heifers (Bos taurus) were assigned to either prostaglandin F(2alpha) (PGF(2alpha)) administration on Days 3, 3.5, and 4 (PG3; n=9) or to control (n=8). Blood samples were collected from heifers from Days 1 to 9 for progesterone assay. Progesterone concentrations were decreased (P<0.03) between 18 and 48h after first PGF(2alpha) treatment in heifers assigned to PG3 compared with that of controls. In Experiment 2, 39 crossbred heifers detected in estrus were inseminated (Day 0) and assigned to either (1) PGF(2alpha) administration on Days 3, 3.5, and 4 (PG3; n=10), (2) PGF(2alpha) administration on Days 3, 3.5, 4, and 4.5 (PG4; n=10), (3) Progesterone Releasing Intravaginal Device (PRID) insertion on Day 4.5 with PGF(2alpha) administration on Days 5 and 6 (PRID+PGF(2alpha); n=10), or (4) control (n=9). Blood samples were collected daily until Day 15, and conceptus survival rate was determined at slaughter on Day 16. Progesterone concentrations during the sampling period in the PG3 and PG4 groups did not differ but were less than that of controls (P<0.01). After an initial peak, progesterone concentrations in the PRID+PGF(2alpha) group were similar to that of controls. More heifers in the PG4 group (6 of 10) had complete luteal regression than did those in the PG3 group (3 of 10). Conceptus survival rate on Day 16 did not differ between groups. There was a significant correlation between progesterone concentration on Days 5 and 6 and conceptus size on Day 16. In summary, treatment with PGF(2alpha) on Days 3, 3.5, and 4 postestrus appeared to provide the best model to induce reduced circulating progesterone concentrations during the early luteal phase in cattle.

  5. Improving the luteal phase after ovarian stimulation: reviewing new options.

    Science.gov (United States)

    Yding Andersen, C; Vilbour Andersen, K

    2014-05-01

    The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using the GnRHa trigger suggest an association between the reproductive outcome after IVF treatment and the mid-luteal-phase serum progesterone concentration. It appears that a minimum mid-luteal progesterone threshold of approximately 80-100 nmol/l exists, which, when surpassed, results in reduced early pregnancy loss and an increased live birth rate. Further, the trade off between the HCG bolus and the subsequent risk of ovarian hyperstimulation syndrome has resulted in a trend to reduce the HCG bolus from 10,000 IU to 6500-5000 IU, which augments the HCG/LH deficiency during the early/mid-luteal phase. The mid-luteal HCG/LH shortage results in an altered progesterone profile, showing the highest concentration during the early luteal phase, contrasting with the mid-luteal peak seen in the natural menstrual cycle. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  6. Receptors for gonadotrophin and prostaglandin F2 alpha in bovine corpora lutea of early, mid and late luteal phase.

    Science.gov (United States)

    Rao, C V; Estergreen, V L; Carman, F R; Moss, G E

    1979-07-01

    A total of 15 corpora lutea representing early (day 3), mid (day 13) and late luteal phase (day 20 and 21-24) were obtained by ovariectomy on cycling cows. The luteal weights and peripheral plasma progesterone levels just prior to ovariectomy, were consistent with the above luteal phases. The specific binding of [125I]human chorionic gonadotrophin to membranes prepared from corpora lutea was significantly higher (P less than 0.01) for days 13 and 20 than for days 3 and 21-24. The binding in day 21-24 corpora lutea was higher (P less than 0.01) than day 3. Although there was no different either in number or affinity (apparent dissociation constant (Kd) = 0.04 nM) of gonadotrophin receptors in days 13 and 20 corpora lutea, only in the former did the binding correlate well with plasma progesterone levels. The specific binding of [3H]prostaglanding (PG)F2 alpha to the membranes of the same corpora lutea showed a progressive increase (P less than 0.01) from day 3, reached the highest value at a time when corpora lutea were actively regressing (day 20) and the decline (P less than 0.01) by day 21-24. Although a considerable number of PGF2 alpha receptors existed at day 13, the affinity of these same receptors was 203 times lower (Kd = 3458 nM) than the affinity of receptors in day 20 corpora lutea (Kd = 17 nM). In summary, the above results show that gonadotrophin receptors correlate with luteotrophic, whereas PGF2 alpha receptors correlate with luteolytic phases in bovine corpora lutea.

  7. Leucocyte phagocytosis during the luteal phase in bitches.

    Science.gov (United States)

    Holst, Bodil Ström; Gustavsson, Malin Hagberg; Lilliehöök, Inger; Morrison, David; Johannisson, Anders

    2013-05-15

    Pyometra is a disease that affects a large proportion of intact bitches, and typically is seen during the latter half of dioestrus. Several factors contribute to the development of pyometra, including genetic factors, an infectious component (most often Escherichia coli), and hormonal factors. Hormones may act directly on the endometrium, and also affect the immune system. In dogs, the phagocytic ability has been shown to decrease with age, and ovarian hormones have also been shown to affect immune resistance. The aim of the present study was to examine whether phagocytosis by canine leucocytes varies significantly during the luteal phase. Eight bitches were followed by repeated blood sampling. Samples were taken at the calculated optimal day for mating (Day 1), and thereafter on days 8, 15 and 22 (early luteal phase) and 29, 43, 57 and 71 (late luteal phase). Blood was collected from the cephalic vein into EDTA tubes for leucocyte counts and heparinised tubes for testing of phagocytosis and oxidative burst using commercial kits and flow cytometry. The cell activity of the phagocyting leucocytes, expressed as mean fluorescence activity, MFI, was significantly lower during late luteal phase than during early luteal phase. The proportion of leucocytes that was induced to phagocyte did not differ significantly. The percentage of cells stimulated by E. coli to oxidative burst was significantly lower during late luteal phase. Their activity did not differ between the two periods. The number of cells stimulated to oxidative burst by a low stimulus was too low to evaluate, and leucocytes stimulated with the high stimulus did not vary in oxidative burst between the two periods. The changes in phagocytic activity and in the number of leucocytes that showed oxidative burst were not associated with any change in the proportion of different leucocytes. The decreased phagocytic capacity possibly contributes to the higher incidence of diseases such as pyometra during the latter

  8. Sexual polymorphisms of vomeronasal 1 receptor family gene expression in bulls, steers, and estrous and early luteal-phase heifers.

    Science.gov (United States)

    Kubo, Haruna; Otsuka, Midori; Kadokawa, Hiroya

    2016-02-01

    Vomeronasal 1 receptors (V1R) are a family of receptors for intraspecies chemosignals, including pheromones, and are expressed in the olfactory epithelium (OE) and vomeronasal organ (VO). Even in the well-studied rodents, it is unclear which members of the V1R family cause sexual polymorphisms, as there are numerous genes and it is difficult to quantify their expressions individually. Bovine species carry only 34 V1R homologs, and the OE and VOs are large enough to sample. Here, V1R expression was quantified in the OE and VOs of individual bovines. Based on the 34 gene sequences, we obtained a molecular dendrogram consisting of four clusters and six independent branches. Semi-quantitative RT-PCR was used to obtain gene expression profiles in the VOs and OE of 5 Japanese Black bulls, 5 steers, 7 estrous heifers and 6 early luteal-phase heifers. Ten genes showed significant between-group differences, and 22 showed high expression in VOs than in OE. The bulls showed higher expression of one gene more in OE and another in VOs (both Pexpressed more abundantly in steers than in bulls. The estrous heifers showed higher expression of a gene of the second cluster in OE, and a gene of the third cluster in VOs (both Pexpression exhibits sexual polymorphisms in cattle.

  9. Endometrial gene expression in the early luteal phase is impacted by mode of triggering final oocyte maturation in recFSH stimulated and GnRH antagonist co-treated IVF cycles

    DEFF Research Database (Denmark)

    Humaidan, P; Van Vaerenbergh, I; Bourgain, C

    2012-01-01

    Do differences in endometrial gene expression exist after ovarian stimulation with four different regimens of triggering final oocyte maturation and luteal phase support in the same patient? SUMMARY ANSWER: Significant differences in the expression of genes involved in receptivity and early...... implantation were seen between the four protocols. WHAT IS KNOWN ALREADY: GnRH agonist triggering is an alternative to hCG triggering in GnRH antagonist co-treated cycles, resulting in an elimination of early ovarian hyperstimulation syndrome. Whereas previous studies have revealed a low ongoing clinical...... pregnancy rate after GnRH agonist trigger due to a high early pregnancy loss rate, despite supplementation with the standard luteal phase support, more recent studies, employing a 'modified' luteal phase support including a bolus of 1500 IU hCG on the day of oocyte aspiration, have reported ongoing...

  10. Effect of exogenous progesterone supplementation in the early luteal phase post-insemination on pregnancy per artificial insemination in Holstein-Friesian cows.

    Science.gov (United States)

    Parr, M H; Crowe, M A; Lonergan, P; Evans, A C O; Rizos, D; Diskin, M G

    2014-11-10

    One of the main determining factors of pregnancy per artificial insemination (P/AI) is an optimum concentration of progesterone (P4) in the early luteal phase. This study examined the effects of P4 supplementation on P/AI in lactating Holstein-Friesian cows. A total of 453 cows in 8 spring-calving herds were used in the study. Following AI, cows were randomly assigned to 1 of 2 treatment groups: (1) no subsequent treatment (control; n=221); (2) insertion of a Controlled Internal Drug Release device (CIDR) from day 4 to day 9 post-estrus (supplemented; n=232). Pregnancy per AI was determined by transrectal ultrasonography at day 30 following AI. Insertion of a CIDR increased concentrations of milk P4 in supplemented cows by 4.78ng/mL between day 4 and 4.5 in comparison with a 0.55ng/mL increase in control cows. Progesterone supplementation from day 4 to 9 after AI decreased P/AI by 12 percentage points (56 vs 44%). There was a positive linear and quadratic relationship between P/AI and milk concentration of P4 on day 4 post-estrus in control cows. An optimum concentration of 2.5ng/mL on day 4 was calculated from the logistic regression curve to achieve a probability of P/AI of 65%. When both treatments groups were included in the analysis, there was no association between P/AI and concentrations of P4 on day 4. The results of the study indicate that supplementation with P4 initiated in the early luteal phase had a negative effect on P/AI in dairy cows.

  11. The expression pattern of microRNAs in granulosa cells of subordinate and dominant follicles during the early luteal phase of the bovine estrous cycle.

    Science.gov (United States)

    Salilew-Wondim, Dessie; Ahmad, Ijaz; Gebremedhn, Samuel; Sahadevan, Sudeep; Hossain, M D Munir; Rings, Franca; Hoelker, Michael; Tholen, Ernst; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tesfaye, Dawit

    2014-01-01

    This study aimed to investigate the miRNA expression patterns in granulosa cells of subordinate (SF) and dominant follicle (DF) during the early luteal phase of the bovine estrous cycle. For this, miRNA enriched total RNA isolated from granulosa cells of SF and DF obtained from heifers slaughtered at day 3 and day 7 of the estrous cycle was used for miRNAs deep sequencing. The results revealed that including 17 candidate novel miRNAs, several known miRNAs (n = 291-318) were detected in SF and DF at days 3 and 7 of the estrous cycle of which 244 miRNAs were common to all follicle groups. The let-7 families, bta-miR-10b, bta-miR-26a, bta-miR-99b and bta-miR-27b were among abundantly expressed miRNAs in both SF and DF at both days of the estrous cycle. Further analysis revealed that the expression patterns of 16 miRNAs including bta-miR-449a, bta-miR-449c and bta-miR-222 were differentially expressed between the granulosa cells of SF and DF at day 3 of the estrous cycle. However, at day 7 of the estrous cycle, 108 miRNAs including bta-miR-409a, bta-miR-383 and bta-miR-184 were differentially expressed between the two groups of granulosa cell revealing the presence of distinct miRNA expression profile changes between the two follicular stages at day 7 than day 3 of the estrous cycle. In addition, unlike the SF, marked temporal miRNA expression dynamics was observed in DF groups between day 3 and 7 of the estrous cycle. Target gene prediction and pathway analysis revealed that major signaling associated with follicular development including Wnt signaling, TGF-beta signaling, oocyte meiosis and GnRH signaling were affected by differentially expressed miRNAs. Thus, this study highlights the miRNA expression patterns of granulosa cells in subordinate and dominant follicles that could be associated with follicular recruitment, selection and dominance during the early luteal phase of the bovine estrous cycle.

  12. Corpus luteum development and function after supplementation of long-acting progesterone during the early luteal phase in beef cattle.

    Science.gov (United States)

    Pugliesi, G; Oliveria, M L; Scolari, S C; Lopes, E; Pinaffi, F V; Miagawa, B T; Paiva, Y N; Maio, J R G; Nogueira, G P; Binelli, M

    2014-02-01

    Strategic supplementation of P4 may be used to increase conception rates in cattle, but timing of supplementation in relation to ovulation, mass of supplementary P4 and formulation of the P4-containing supplement has not been determined for beef cattle. Effects of supplementation of long-acting progesterone (P4) on Days 2 or 3 post-ovulation on development, function and regression of corpus luteum (CL) were studied in beef cattle. Cows were synchronized with an oestradiol/P4-based protocol and treated with 150 or 300 mg of long-acting P4 on Day 2 or 3 post-ovulation (6-7 cows/group). Colour-doppler ultrasound scanning and blood sample collection were performed from Day 2-21.5. Plasma P4 concentrations were greater (p  0.05) among groups, suggesting no effect of P4 treatment on luteal development. The frequency of cows that began luteolysis before Day 15 was greater (p beef cattle. © 2013 Blackwell Verlag GmbH.

  13. The Luteal Phase after GnRHa Trigger-Understanding An Enigma

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    Kathrine Leth-Moller

    2014-11-01

    Full Text Available The luteal phase of all stimulated in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI cycles is disrupted, which makes luteal phase support (LPS mandatory. The cause of the disruption is thought to be the multifollicular development achieved during ovarian stimulation which results in supraphysiological concentrations of steroids secreted by a high number of corpora lutea during the early luteal phase. This will directly inhibit luteinizing hormone (LH secretion by the pituitary via negative feedback at the level of the hypothalamic-pituitary axis, leading to a luteal phase defect. With the introduction of the gonadotropin-releasing hormone (GnRH antagonist protocol, it became feasible to trigger final oocyte maturation and ovulation with a single bolus of GnRH agonist (GnRHa as an alternative to human chorionic gonadotropin (hCG. GnRHa triggering presents several advantages, including the reduction in or even elimination of ovarian hyperstimulation syndrome. Despite the potential advantages of GnRHa triggering, previous randomized controlled trials reported a poor clinical outcome with high rates of early pregnancy losses, despite supplementation with a standard LPS in the form of progesterone and estradiol. Following these disappointing results, several studies now report a luteal phase rescue after modifications of the LPS, resulting in a reproductive outcome comparable to that seen after hCG triggering. We herein review luteal phase differences between the natural cycle, hCG trigger and GnRHa trigger and present the most recent data on handling the luteal phase after GnRHa triggering.

  14. The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives

    DEFF Research Database (Denmark)

    Humaidan, Peter; Papanikolaou, E G; Kyrou, D;

    2012-01-01

    is the use of GnRH agonist (GnRHa) which reduces or even prevents ovarian hyperstimulation syndrome (OHSS). Interestingly, the current regimens of luteal support after HCG triggering are not sufficient to secure the early implanting embryo after GnRHa triggering. This review discusses the luteal...... phase - the phase after egg transfer - necessitating hormonal support with vaginally applied progesterone to obtain ongoing pregnancies. With the introduction of the gonadotrophin-releasing hormone (GnRH) antagonist protocol (short protocol) it became possible to perform final oocyte maturation...... with a GnRH agonist instead of human chorionic gonadotrophin (HCG). The first studies applying this concept, however, showed a very poor pregnancy rate, despite standard luteal-phase support with progesterone. This review discusses the reason for the poor results and the newest studies, using GnRH agonist...

  15. Canine herpesvirus during pregnancy and non-pregnant luteal phase.

    Science.gov (United States)

    Ström Holst, B; Hagberg Gustavsson, M; Grapperon-Mathis, M; Lilliehöök, I; Johannisson, A; Isaksson, M; Lindhe, A; Axnér, E

    2012-12-01

    Canine herpesvirus (CHV) is a widespread infection among dogs that typically get latently infected after exposure and can reactivate the infection after stress. The aim of the present study was to study the effects of latent CHV infection during pregnancy on pregnancy outcome, and to study if there are signs of genital viral reactivation during pregnancy or during non-pregnant luteal phase. Twelve mated bitches and eight control bitches were followed and sampled regularly during pregnancy or non-pregnant luteal phase. Blood samples were taken for antibody analysis and vaginal swabs for real-time PCR analysis. Three of the pregnant bitches were vaccinated against CHV during pregnancy. All bitches had antibodies to CHV. Two pregnant bitches that were not vaccinated had a twofold or larger increase in CHV titre, with no negative effects detected on pregnancy. Higher titres were not associated with smaller litters or with vaccination. There was no consistent variation in antibody titres due to pregnancy or non-pregnant luteal phase. Vaginal excretion of CHV was not detected from any of the bitches.

  16. The Luteal Phase after GnRHa Trigger-Understanding An Enigma

    DEFF Research Database (Denmark)

    Leth-Moller, Kathrine; Hammer Jagd, Sandra; Humaidan, Peter

    2014-01-01

    The luteal phase of all stimulated in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles is disrupted, which makes luteal phase support (LPS) mandatory. The cause of the disruption is thought to be the multifollicular development achieved during ovarian stimulation which...... phase defect. With the intro- duction of the gonadotropin-releasing hormone (GnRH) antagonist protocol, it became feasible to trigger final oocyte maturation and ovulation with a single bolus of GnRH agonist (GnRHa) as an alternative to human chorionic gonadotropin (hCG). GnRHa trig- gering presents...... several advantages, including the reduction in or even elimination of ovarian hyperstimulation syndrome. Despite the potential advantages of GnRHa trig- gering, previous randomized controlled trials reported a poor clinical outcome with high rates of early pregnancy losses, despite supplementation...

  17. Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Meenakumari K.J.

    2004-01-01

    Full Text Available The causes of luteal phase progesterone deficiency in polycystic ovary syndrome (PCOS are not known. To determine the possible involvement of hyperinsulinemia in luteal phase progesterone deficiency in women with PCOS, we examined the relationship between progesterone, luteinizing hormone (LH and insulin during the luteal phase and studied the effect of metformin on luteal progesterone levels in PCOS. Patients with PCOS (19 women aged 18-35 years were treated with metformin (500 mg three times daily for 4 weeks prior to the test cycle and throughout the study period, and submitted to ovulation induction with clomiphene citrate. Blood samples were collected from control (N = 5, same age range as PCOS women and PCOS women during the late follicular (one sample and luteal (3 samples phases and LH, insulin and progesterone concentrations were determined. Results were analyzed by one-way analysis of variance (ANOVA, Duncan's test and Karl Pearson's coefficient of correlation (r. The endocrine study showed low progesterone level (4.9 ng/ml during luteal phase in the PCOS women as compared with control (21.6 ng/ml. A significant negative correlation was observed between insulin and progesterone (r = -0.60; P < 0.01 and between progesterone and LH (r = -0.56; P < 0.05 concentrations, and a positive correlation (r = 0.83; P < 0.001 was observed between LH and insulin. The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml in PCOS women treated with metformin. The results suggest that hyperinsulinemia/insulin resistance may be responsible for low progesterone levels during the luteal phase in PCOS. The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.

  18. Follicular and luteal phase characteristics following early cessation of gonadotrophin-releasing hormone agonist during ovarian stimulation for in-vitro fertilization

    NARCIS (Netherlands)

    J.S.E. Laven (Joop); M.J.C. Eijkemans (René); B.C.J.M. Fauser (Bart); N.G.M. Beckers (Nicole)

    2000-01-01

    textabstractGonadotrophin-releasing hormone agonists (GnRHa) are widely used in in-vitro fertilization (IVF) for the prevention of a premature rise in luteinizing hormone (LH) concentrations. However, the administration of GnRHa during the follicular phase may also impa

  19. Women's luteal-phase sexual proceptivity and the functions of extended sexuality.

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    Grebe, Nicholas M; Gangestad, Steven W; Garver-Apgar, Christine E; Thornhill, Randy

    2013-10-01

    Women's sexuality, unlike that of most mammals, is not solely defined by sexual receptivity during the short window of fertility. Women demonstrate extended sexuality (in which they initiate and accept sexual advances outside of the fertile phase) more than any other mammalian female. In this light, surprisingly little research has addressed the functions of women's luteal-phase sexuality. On the basis of theory and comparative evidence, we propose that women's initiation of sex during nonfertile phases evolved in part to garner investment from male partners. If so, women should be particularly prone to initiate luteal-phase sex when the potential marginal gains are greatest. Results from a study of 50 heterosexual couples showed that women increasingly initiate sex in the luteal phase (but not the fertile phase) when they perceive their partners' investment to lag behind their own. These findings provide evidence for the distinct nature of women's extended sexuality and may contribute to a more comprehensive understanding of women's sexuality.

  20. The effect of luteal phase gonadotropin-releasing hormone antagonist administration on IVF outcomes in women at risk of OHSS

    Science.gov (United States)

    Eftekhar, Maryam; Miraj, Sepideh; Mortazavifar, Zahrasadat

    2016-01-01

    Background: Gonadotropin-releasing hormone (GnRH) plays essential roles in embryo implantation, invasion of trophoblastic tissue, and steroid synthesis in the placenta. Objective: The aim of this study was to evaluate the effect of GnRH antagonist administration on pregnancy outcomes in early implantation period. Materials and Methods: In this retrospective study, 94 infertile women undergoing GnRH antagonist protocol who were at risk of ovarian hyperstimulation syndrome (OHSS) were included. Sixty-seven patients (group I) received Cetrorelix 0.25 mg/daily in the luteal phase for 3 days while in 27 participants (group II), it was not administered. Pregnancy outcomes were assessed based on chemical and clinical pregnancy rates. Results: The pregnancy outcomes were not significantly different between two groups (p=0.224). Conclusion: The present study proposed that luteal phase GnRH antagonist administration does not influence the chance of successful pregnancy outcomes. PMID:27679825

  1. Nicotine Pretreatment Increases Dysphoric Effects of Alcohol in Luteal-Phase Female Volunteers

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    Scott E. Lukas

    2009-02-01

    Full Text Available The present report shows that nicotine enhances some of alcohol’s positive and negative effects in women and that these effects are most pronounced during the luteal phase of the menstrual cycle. Ten low progesterone and 10 high progesterone/luteal-phase women received nicotine patch pretreatments (placebo or 21 mg 3 hours before an alcohol challenge (0.4 g/kg. Subjective effects were recorded on mood adjective scales and the Addiction Research Center Inventory (ARCI. Heart rate and skin temperature were recorded. Luteal-phase women reported peak positive (e.g. “stimulated” and peak negative effects (e.g. “clumsy”, “dizzy” almost twice as great as low progesterone women.

  2. Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.

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    Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit; Laursen, Rita Jakubcionyte; Povlsen, Betina Boel; Thomsen, Lise; Humaidan, Peter

    2015-10-01

    Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone. A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014. Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups. The number of patients included is limited and conclusions need to be verified in a larger RCT. Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace

  3. Cytological image of the endometrium in cows in follicular and luteal phases of the ovarian cycle and in cows with follicular and luteal ovarian cysts

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    Brodzki Piotr

    2014-03-01

    Full Text Available The experiment was conducted on 30 Holstein-Friesian cows: 10 cows in the follicular phase of the cycle and in the luteal phase 10 d later, 10 cows with follicular cysts, and 10 with luteal cysts. The presence of the ovarian structures was confirmed by ultrasonography. Serum levels of progesterone and 17β-oestradiol were tested with ELISA. Samples for cytological examination were collected from the uterus of all cows using a cytological brush. Following staining, the smears were evaluated in terms of quality and percentages of endometrial cells. In the follicular phase of the oestrous cycle, cells of type A - superficial cells (64.6 ± 4.48 were proportionally the largest group of cells. Cells of type C - basal cells (19.8 ± 2.75 were also present. In the luteal phase, the highest percentage of cells was of type B - intermediate cells (76.9 ± 4.26. When follicular cysts were present on the ovaries, the cytology resembled the follicular phase of the cycle, but with many younger type C cells (33.1 ± 4.11. In the case of luteal cysts on the ovaries, the cytology was similar to that of the luteal phase of the cycle, however with a lower percentage of type B cells (58.1 ± 5.71, and a slightly higher percentage of the other types. The differences in the cytological image of the uterus when different ovarian structures are present, depend on the hormonal activity of those structures. Due to the lack of literature data, the results of the study are important as a model, and may substantially facilitate identification of phases of the oestrus cycle, or the pathologies described, as well as indicate the current status of the endometrium

  4. Luteal Phase Support in the Intrauterine Insemination (IUI Cycles: A Randomized Double Blind, Placebo Controlled Study.

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    Batool Hossein Rashidi

    2014-12-01

    Full Text Available To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG, in sub fertile couples.This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with clomiphene citrate (100 mg and hMG (75 IU in preparation for the IUI cycle. Study group (n = 127 received luteal phase support in the form of vaginal progesterone (400 mg twice a day, and control group (n = 126 received placebo. Clinical pregnancy and abortion rates were assessed and compared between the two groups.The clinical pregnancy rate was not significantly higher for supported cycles than that for the unsupported ones (15.75% vs. 12.69%, p = 0.3. The abortion rate in the patients with progesterone luteal support compared to placebo group was not statistically different (10% vs. 18.75%, p = 0.45.It seems that luteal phase support with vaginal progesterone was not enhanced the success of IUI cycles outcomes, when clomiphene citrate and hMG were used for ovulation stimulation.

  5. Effect of Estradiol Prescribed during Luteal Phase of Art Cycles and Pregnancy Outcome

    OpenAIRE

    2007-01-01

    Introduction: Implantation is one of the most important steps in ART cycles and it depends upon embryo and endometrial reception. Different protocols have been suggested for getting better endometrium. It seems estrogen increases the endometrial reception and pregnancy rate by inducing changes in the hormonal status. The aim of this study was to evaluate the effect of estradiol(E2) on luteal phase support and pregnancy rate in ART cycles Methods: This prospective randomized study was done in ...

  6. Effect of investigational kisspeptin/metastin analog, TAK-683, on luteinizing hormone secretion at different stages of the luteal phase in goats.

    Science.gov (United States)

    Rahayu, Larasati Puji; El Behiry, Mohammed; Endo, Natsumi; Tanaka, Tomomi

    2017-03-25

    This study aimed to examine the response of luteinizing hormone (LH) secretion and ovarian steroid profile to TAK-683, an investigational metastin/kisspeptin analog, through treatment during different stages of the luteal phase in goats. Nine cycling Shiba goats (4.4 ± 2.3 years old) were assigned to early luteal phase (ELP, n = 4), mid-luteal phase (MLP, n = 4), and control (n = 5) groups. The ELP and MLP groups were administered 50 µg of TAK-683 intravenously on either day 5 or between days 7-14 after ovulation, respectively. The control group received vehicle between days 7-14 after ovulation. Blood samples were collected at 10-min (2-6 h), 2-h (6-24 h), and 24-h (24-96 h) intervals after treatment. Significant increases in plasma LH concentration were detected during the periods of 3 to 5 h and 2 to 5 h in the ELP and MLP groups, respectively. Estradiol concentrations continuously increased with the rise of basal LH secretion after TAK-683 treatment in two goats of the ELP group with a surge-like release of LH, but not in the goats without LH surge, i.e. the MLP and control group ones. Plasma progesterone concentration and the lengths of estrous cycle in all groups did not change significantly from the time before and after treatment. Present findings indicate that the responses of LH and ovarian steroids to treatment with TAK-683 depend on the stage of the luteal phase of the estrous cycle. We suggest that the stimulatory effects of TAK-683 on LH secretion are reduced in the process leading to the mid-luteal phase in cycling goats.

  7. Development of a bovine luteal cell in vitro culture system suitable for co-culture with early embryos.

    Science.gov (United States)

    Batista, M; Torres, A; Diniz, P; Mateus, L; Lopes-da-Costa, L

    2012-10-01

    The cross talk between the corpus luteum (CL) and the early embryo, potentially relevant to pregnancy establishment, is difficult to evaluate in the in vivo bovine model. In vitro co-culture of bovine luteal cells and early embryos (days 2-8 post in vitro fertilization) may allow the deciphering of this poorly understood cross talk. However, early embryos and somatic cells require different in vitro culture conditions. The objective of this study was to develop a bovine luteal cell in vitro culture system suitable for co-culture with early embryos in order to evaluate their putative steroidogenic and prostanoid interactions. The corpora lutea of the different stages of the estrous cycle (early, mid, and late) were recovered postmortem and enriched luteal cell populations were obtained. In experiments 1 and 2, the effects of CL stage, culture medium (TCM, DMEM-F12, or SOF), serum concentration (5 or 10%), atmosphere oxygen tension (5 or 20%), and refreshment of the medium on the ability of luteal cells to produce progesterone (P(4)) were evaluated. The production of P(4) was significantly increased in early CL cultures, and luteal cells adapted well to simple media (SOF), low serum concentrations (5%), and oxygen tensions (5%). In experiment 3, previous luteal cell cryopreservation did not affect the production of P(4), PGF(2α), and PGE(2) compared to fresh cell cultures. This enables the use of pools of frozen-thawed cells to decrease the variation in cell function associated with primary cell cultures. In experiment 4, mineral oil overlaying culture wells resulted in a 50-fold decrease of the P(4) quantified in the medium, but had no effect on PGF(2α) and PGE(2) quantification. In conclusion, a luteal cell in vitro culture system suitable for the 5-d-long co-culture with early embryos was developed.

  8. 'Luteal coasting' after GnRH agonist trigger - individualized, HCG-based, progesterone-free luteal support in 'high responders'

    DEFF Research Database (Denmark)

    Kol, Shahar; Breyzman, Tatiana; Segal, Linoy

    2015-01-01

    ') according to endogenous luteal progesterone concentrations. One patient developed a brief early-onset moderate ovarian hyperstimulation syndrome (OHSS) condition. Six clinical pregnancies were achieved, two of which have resulted in live births thus far. To further individualize the luteal phase support...

  9. Addition of gonadotropin releasing hormone agonist for luteal phase support in in-vitro fertilization: an analysis of 2739 cycles

    Science.gov (United States)

    Şimşek, Erhan; Kılıçdağ, Esra Bulgan; Aytaç, Pınar Çağlar; Çoban, Gonca; Şimşek, Seda Yüksel; Çok, Tayfun; Haydardedeoğlu, Bülent

    2015-01-01

    Objective Luteal phase is defective in in vitro fertilization (IVF) cycles, and many regimens were tried for the very best luteal phase support (LPS). Gonadotropin releasing hormone (GnRH) agonist use, which was administered as an adjunct to the luteal phase support in IVF cycles, was suggested to improve pregnancy outcome measures in certain randomized studies. We analyzed the effects of addition of GnRH agonist to standard progesterone luteal support on pregnancy outcome measures, particularly the live birth rates. Material and Methods This is a retrospective cohort study, including 2739 IVF cycles. Long GnRH agonist and antagonist stimulation IVF cycles with cleavage-stage embryo transfer were included. Cycles were divided into two groups: Group A included cycles with single-dose GnRH agonist plus progesterone LPS and Group B included progesterone only LPS. Live birth rates were the primary outcome measures of the analysis. Miscarriage rates and multiple pregnancy rates were the secondary outcome measures. Results Live birth rates were not statistically different in GnRH agonist plus progesterone (Group A) and progesterone only (Group B) groups in both the long agonist and antagonist stimulation arms (40.8%/41.2% and 32.8%/34.4%, p<0.05 respectively). Moreover, pregnancy rates, implantation rates, and miscarriage rates were found to be similar between groups. Multiple pregnancy rates in antagonist cycles were significantly higher in Group A than those in Group B (12.0% and 6.9%, respectively). Conclusion A beneficial effect of a single dose of GnRH agonist administration as a luteal phase supporting agent is yet to be determined because of the wide heterogeneity of data present in literature. Well-designed randomized clinical studies are required to clarify any effect of luteal GnRH agonist addition on pregnancy outcome measures with different doses, timing, and administration routes of GnRH agonists. PMID:26097392

  10. GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation

    DEFF Research Database (Denmark)

    Al Humaidan, Peter Samir Heskjær; Polyzos, N P; Alsbjerg, B

    2013-01-01

    STUDY QUESTION: Does a GnRH agonist (GnRHa) trigger followed by a bolus of 1.500 IU hCG in a group of patients at risk of ovarian hyperstimulation syndrome (OHSS) reduce the OHSS incidence compared with hCG trigger? SUMMARY ANSWER: A GnRHa trigger followed by early luteal hCG support with one bolus...

  11. Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Oliveira João

    2010-09-01

    Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

  12. Micro-dose hCG as luteal phase support without exogenous progesterone administration

    DEFF Research Database (Denmark)

    Andersen, C Yding; Fischer, R; Giorgione, V;

    2016-01-01

    For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the Gn......RHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple...... corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential...

  13. Effect of Estradiol Prescribed during Luteal Phase of Art Cycles and Pregnancy Outcome

    Directory of Open Access Journals (Sweden)

    M Karimzadeh

    2007-01-01

    Full Text Available Introduction: Implantation is one of the most important steps in ART cycles and it depends upon embryo and endometrial reception. Different protocols have been suggested for getting better endometrium. It seems estrogen increases the endometrial reception and pregnancy rate by inducing changes in the hormonal status. The aim of this study was to evaluate the effect of estradiol(E2 on luteal phase support and pregnancy rate in ART cycles Methods: This prospective randomized study was done in Yazd at the IVF center from March until December, 2002. 68 patients who had undergone IVF or ICSI were enrolled in the study. Exclusion criteria was age>40, endometriosis and ovarian hyper stimulation syndrome. Induction ovulation protocol was long suppression with GnRH analogues.After embryo transfer, patients were divided in two groups randomly. Both groups received 100mg progesterone IM daily from the transfer day. Estradiol valerate 2 mg/day was added from the 7th transfer day to progesterone in Group I and continued if the BhCG became positive. Abortion and malformations were measured in all patients. Data analyzed with SPSS 11.0 and P value <0.05 considered statistically significant. Results: Pregnancy rate in the 34 patients of estradiol group (group I was 26.5%which was significantly higher than 11.8 %( 4 cases in the other group (Pvalue=0.034. Abortion rate was higher in estradiol group (3 cases, but there was no abortion in the progesterone group(P=0.119. 2 cases of major fetal malformations were observed in E2 supplementation group (P=0.246 . Conclusions: E2 suplementation to progesterone in the luteal phase of ART cycles, especially in the long GnRH analogues causes higher endometrial receptivity and pregnancy rate.

  14. Circadian variation of sleep during the follicular and luteal phases of the menstrual cycle.

    Science.gov (United States)

    Shechter, Ari; Varin, France; Boivin, Diane B

    2010-05-01

    Women experience insomnia more frequently than men. Menstrual cycle changes in reproductive hormones and circadian rhythms may contribute to sleep disruptions. Our aim, therefore, was to clarify the interaction between menstrual and circadian processes as it affects sleep. Participants entered the laboratory during the mid-follicular (MF) and mid-luteal (ML) phases of their menstrual cycle for an ultra-rapid sleep-wake cycle (URSW) procedure, consisting of 36 cycles of 60-min wake episodes alternating with 60-min nap opportunities. This procedure concluded with an ad libitum nap episode. Time-isolation suite. Eight unmedicated, physically and mentally healthy females with regular ovulatory menstrual cycles. N/A. Polysomnographic sleep from nocturnal sleep episodes and 60-min naps; subjective alertness; core body temperature (CBT); salivary melatonin; urinary estradiol; and urinary progesterone. Increased CBT values at night and decreased CBT amplitude were observed during ML compared to MF. Circadian phase of CBT and the circadian melatonin profile were unaffected by menstrual phase. All analyzed sleep parameters showed a circadian variation throughout the URSW procedure, with no menstrual phase differences observed for most, including slow wave sleep (SWS). The circadian variation of REM sleep duration, however, was sensitive to menstrual phase, with reduced REM sleep during ML at circadian phase 0 degrees and 30 degrees. Moderate but significant changes in REM sleep across the menstrual and circadian cycles were observed. These results support an interaction between circadian and menstrual processes in the regulation of REM sleep.

  15. Sweet taste threshold for sucrose inversely correlates with depression symptoms in female college students in the luteal phase.

    Science.gov (United States)

    Nagai, Masanori; Matsumoto, Sayaka; Endo, Junko; Sakamoto, Reiko; Wada, Maki

    2015-03-15

    Influences of depression symptoms on the sweet taste threshold were investigated in healthy college students (30 males and 40 females). Depression symptoms were scored by SDS (Self-Rating Depression Scale), and anxiety levels by STAI (State- and Trait-Anxiety Inventory). Recognition thresholds for sucrose were determined. In female students, the menstrual phase on the day of the experiment was self-reported. Depression symptoms, anxiety levels, and the recognition threshold for sucrose were not different among the 3 groups, i.e. males, females in the follicular phase, and females in the luteal phase. Depression symptoms were positively correlated with state and trait anxiety in all groups. The sweet taste threshold was inversely correlated with depression symptoms (r=-0.472, p=0.031) and trait anxiety (r=-0.506, p=0.019) in females in the luteal phase. In males as well as females in the follicular phase, however, no correlation between sweet taste threshold and depression was found. The results show that the recognition threshold for sucrose reduces with increased depression in females with a higher anxiety trait, but only in the luteal phase. It is hypothesized that brain regions, which spatially overlap and are responsible for both aversive emotions and gustatory processing, are susceptible to periodic changes in gonadal hormones due to the menstrual cycle.

  16. Analysis of human mammary fibroadenoma by Ki-67 index in the follicular and luteal phases of menstrual cycle.

    Science.gov (United States)

    Rego, M F; Navarrete, M A L H; Facina, G; Falzoni, R; Silva, R; Baracat, E C; Nazario, A C P

    2009-04-01

    Fibroadenoma is the most common benign mammary condition among women aged 35 or younger. Expression of Ki-67 antigen has been used to compare proliferative activity of mammary fibroadenoma epithelium in the follicular and luteal phases of the menstrual cycle. Ninety eumenorrheic women were selected for tumour excision; they were assigned to either of the two groups, according to their phase of menstrual cycle. At the end of the study, 75 patients with 87 masses were evaluated by epithelial cell Ki-67 expression, blind (no information given concerning group to which any lesion belonged). Both groups were found to be homogeneous relative to age, menarche, body mass index, previous gestation, parity, breastfeeding, number of fibroadenomas, family history of breast cancer and tabagism. Median tumour size was 2.0 cm and no relationship between proliferative activity and nodule diameter was observed. No typical pattern was observed in the expression of Ki-67 in distinct nodules of the same patient. Average values for expression of Ki-67 (per 1000 epithelial cells) in follicular and luteal phases were 27.88 and 37.88, respectively (P = 0.116). Our findings revealed that proliferative activities in the mammary fibroadenoma epithelium did not present a statistically significant difference in the follicular and luteal phases. The present study contributes to clarifying that fibroadenoma is a neoplasm and does not undergo any change in the proliferative activity during the menstrual cycle.

  17. Luteal phase supplementation after gonadotropin-releasing hormone agonist trigger in fresh embryo transfer: the American versus European approaches.

    Science.gov (United States)

    Humaidan, Peter; Engmann, Lawrence; Benadiva, Claudio

    2015-04-01

    The challenges in attaining an adequate luteal phase after GnRH agonist (GnRHa) trigger to induce final oocyte maturation have resulted in different approaches focused on rescuing the luteal phase insufficiency so that a fresh transfer can be carried out without jeopardizing IVF outcomes. Over the years, two different concepts have emerged: intensive luteal support with aggressive exogenous administration of E2 and P; and low-dose hCG rescue in the form of a small dose of hCG either on the day of oocyte retrieva or on the day of GnRHa trigger (the so called "dual trigger"). Both approaches have been shown to be effective in achieving pregnancy rates similar to those obtained after conventional hCG trigger and resulting in a very low risk of ovarian hyperstimulation syndrome (OHSS). Although the idea of freezing all embryos after GnRHa trigger and transferring them in a subsequent frozen-thawed cycle has been gaining momentum, a fresh transfer leading to the live birth of a healthy child is currently considered to be the goal of IVF treatment. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Assessment of progesterone profiles and postpartum onset of luteal activity in spring calving Hereford beef suckler cattle.

    Science.gov (United States)

    Martin, Adam D; Lystad, Marit L; Reksen, Olav; Ropstad, Erik; Waldmann, Andres; Nafstad, Ola; Karlberg, Knut

    2010-06-15

    Reproduction is the single greatest factor limiting beef cattle production. Previous research on beef suckler luteal activity has largely focused on the mechanisms, and duration, of postpartum anoestrus. However, the temporal pattern of luteal activity after resumption of post-partum ovarian activity, and the impact of pattern type on days open (DO) in purebred beef suckler cows, are unknown. Progesterone concentration was measured in milk samples taken thrice weekly from 120 lactations, in 87 animals, on 3 farms, over two years. Onset of luteal activity (OLA) was defined as the first day milk progesterone concentration exceeded 3 ng/ml for two successive measurements, or exceeded 5 ng/ml once. It was defined as delayed if it occurred more than 61 days postpartum. A short initial luteal phase consisted of progesterone concentrations which exceeded 3 ng/ml for fewer than 4 sequential measurements. Temporal progesterone patterns were classified as: 1) Normal cyclicity; 2) Cessation of luteal activity; 3) Prolonged luteal activity; 4) Erratic phase: failure to conform to 1, 2 or 3. Data concerning parity, previous calving interval, breeding values, calf birth and 200-d weight were obtained from the Norwegian Beef Cattle Recording System database. The mean (SD) OLA was 41 d (20). Parity and calf birth weight were inversely correlated with OLA. Delayed OLA occurred in 14.4% of lactations. A short first luteal phase occurred in 61.5% of lactations, but this was unrelated to irregular luteal phase occurrence, pregnancy or DO. Irregular luteal phases occurred in 22% of lactations. The irregularities were: prolonged luteal phase (11%); cessation of luteal activity (5%); erratic luteal activity (6%). Early OLA was associated with prolonged luteal phases. DO was positively correlated with irregular luteal phases and negatively correlated with calf 200-d weight. This study demonstrates that irregular luteal phases negatively affect reproductive performance in purebred beef

  19. Assessment of progesterone profiles and postpartum onset of luteal activity in spring calving Hereford beef suckler cattle

    Directory of Open Access Journals (Sweden)

    Waldmann Andres

    2010-06-01

    Full Text Available Abstract Background Reproduction is the single greatest factor limiting beef cattle production. Previous research on beef suckler luteal activity has largely focused on the mechanisms, and duration, of postpartum anoestrus. However, the temporal pattern of luteal activity after resumption of post-partum ovarian activity, and the impact of pattern type on days open (DO in purebred beef suckler cows, are unknown. Methods Progesterone concentration was measured in milk samples taken thrice weekly from 120 lactations, in 87 animals, on 3 farms, over two years. Onset of luteal activity (OLA was defined as the first day milk progesterone concentration exceeded 3 ng/ml for two successive measurements, or exceeded 5 ng/ml once. It was defined as delayed if it occurred more than 61 days postpartum. A short initial luteal phase consisted of progesterone concentrations which exceeded 3 ng/ml for fewer than 4 sequential measurements. Temporal progesterone patterns were classified as: 1 Normal cyclicity; 2 Cessation of luteal activity; 3 Prolonged luteal activity; 4 Erratic phase: failure to conform to 1, 2 or 3. Data concerning parity, previous calving interval, breeding values, calf birth and 200-d weight were obtained from the Norwegian Beef Cattle Recording System database. Results The mean (SD OLA was 41 d (20. Parity and calf birth weight were inversely correlated with OLA. Delayed OLA occurred in 14.4% of lactations. A short first luteal phase occurred in 61.5% of lactations, but this was unrelated to irregular luteal phase occurrence, pregnancy or DO. Irregular luteal phases occurred in 22% of lactations. The irregularities were: prolonged luteal phase (11%; cessation of luteal activity (5%; erratic luteal activity (6%. Early OLA was associated with prolonged luteal phases. DO was positively correlated with irregular luteal phases and negatively correlated with calf 200-d weight. Conclusions This study demonstrates that irregular luteal phases

  20. A preliminary study on the induction of dioestrous ovulation in the mare – a possible method for inducing prolonged luteal phase

    Directory of Open Access Journals (Sweden)

    Kindahl Hans

    2006-07-01

    Full Text Available Abstract Background Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules, there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. Methods In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG (3000 IU was injected intramuscularly in four mares (experimental group in the luteal phase when a dioestrous follicle ≥ 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles ≥ 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. Results Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. Conclusion HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle ≥ 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness.

  1. Comparing stimulation requirements and final outcome between early follicular and mid luteal pituitary suppression in the long gonadotropin releasing hormone agonist protocol.

    Science.gov (United States)

    Sarhan, Abdulmagid; Harira, Mervat; Elshazly, Sherine; Nouh, Ahmad

    2016-05-01

    To compare stimulation requirements and ICSI outcome when agonist treatment is started in the early follicular phase or in mid luteal phase of the cycle. 181 infertile patients were randomly assigned to: group A (N=66) and group B (N=115). GnRH-a (Triptorelin) subcutaneous daily injections started on day 20-22 of the previous cycle till pituitary suppression is achieved where gonadotropins stimulation commenced. In group A, agonist treatment was started on the first or second days of the cycle, in group B it was started on day 20-22 of the cycle. The agonist treatment was continued till the day of (hCG) administration. The stimulation requirements were similar in the two groups. The days of t agonist treatment required to reach pituitary suppression were higher in group A: 12.5±6.4 than in group B, 11±4.5. Days of stimulation (10.4±1.7 and 10.3±1.6) and number of gonadotropin vials (40.1±8.7and 39.3±9.5) did not differ between both groups. The mean number of oocytes retrieved, mean number of embryos produced (11.7±7.4 and 13.3±9.3) (5.9±4.2and 6±5.2) were similar in both groups. The rates of fertilization and cleavage were similar in the two groups. Pregnancy rates were similar in both groups. The clinical pregnancy rates per cycle was 31.8% and 33%, while pregnancy rates per embryo transfer was 36.2 % and 36.5% in groups A and B respectively. Starting pituitary suppression with GnRH agonist in the early follicular phase or mid luteal phase were comparable regarding stimulation requirements and final outcomes.

  2. Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit

    2015-01-01

    STUDY QUESTION: Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? SUMMARY ANSWER: Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exo......STUDY QUESTION: Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? SUMMARY ANSWER: Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support...... on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. MAIN RESULTS AND THE ROLE OF CHANCE: The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid...... were seen between groups. LIMITATIONS, REASONS FOR CAUTION: The number of patients included is limited and conclusions need to be verified in a larger RCT. WIDER IMPLICATIONS OF THE FINDINGS: Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH...

  3. GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles-A Systematic PRISMA Review and Meta-analysis.

    Science.gov (United States)

    Haahr, Thor; Roque, Matheus; Esteves, Sandro C; Humaidan, Peter

    2017-01-01

    The use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer. We conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates. A total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54). GnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS

  4. GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles—A Systematic PRISMA Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Thor Haahr

    2017-06-01

    Full Text Available IntroductionThe use of GnRH agonist (GnRHa for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer.Material and methodsWe conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS. The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates.ResultsA total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14. OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60. We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54.ConclusionGnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity

  5. Body size in relation to urinary estrogens and estrogen metabolites (EM) among premenopausal women during the luteal phase.

    Science.gov (United States)

    Xie, Jing; Eliassen, A Heather; Xu, Xia; Matthews, Charles E; Hankinson, Susan E; Ziegler, Regina G; Tworoger, Shelley S

    2012-12-01

    Estrogen metabolism profiles may play an important role in the relationship between body size and breast carcinogenesis. Previously, we observed inverse associations between current body mass index (BMI) and plasma levels of parent estrogens (estrone and estradiol) among premenopausal women during both follicular and luteal phases. Using data from the Nurses' Health Study II, we assessed whether height, current BMI, and BMI at age 18 were associated with the urinary concentrations of 15 estrogens and estrogen metabolites (jointly referred to as EM) measured during the luteal phase among 603 premenopausal women. We observed inverse associations with total EM for height (P (trend) = 0.01) and current BMI (P (trend) = 0.01), but not BMI at age 18 (P (trend) = 0.26). Six EMs were 18-27% lower in women with a height 68+ versus ≤62 in., primarily in the methylated catechol pathway (P (trend) = 0.04). Eight EMs were 18-50% lower in women with a BMI of 30+ versus estrogen metabolism profiles in premenopausal women. Further studies with timed urine and blood collections are required to confirm and extend our findings.

  6. Comparison of Intramuscular and Intravaginal Progesterone for Luteal Phase Support in IVF Cycles: a randomized clinical trial

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    Katayon Berjis

    2008-06-01

    Full Text Available Objective: This research was designed to compare the effectiveness of intramuscular progesterone and vaginal progesterone to support luteal phase in IVF cycles. Materials and Methods: In this randomized clinical trial 182 infertile patients between 20-40 years old were selected for rapid ZIFT cycles. In order to support luteal phase Cyclogest suppository (400 mg BID was used for 77 cases and the rest used intramuscular progesterone (100 mg daily. Pregnancy and abortion rates were compared between two groups.Results: Chemical pregnancy rate (positive ß-HCG was %27.3 in Cyclogest group and %30.6 in intramuscular progestrone group (P = 0.7. Clinical pregnancy (gestational sac visible by transvaginal ultrasound was observed in %22.1 of cases in Cyclogest group and %27.1 of cases in intramuscular progestrone group (P = 0.4. Ongoing pregnancy rate (fetal heart action visible by transvaginal ultrasound was %15.6 in Cyclogest group and %18.8 in intramuscular progesterone group (P = 0.6.Conclusion: Chemical pregnancy, clinical pregnancy and ongoing pregnancy rates were similar in vaginal and intramuscular progestrone groups.

  7. Luteal phase HCG support for unexplained recurrent pregnancy loss - a low hanging fruit?

    Science.gov (United States)

    Fox, Chelsea; Azores-Gococo, Denise; Swart, Linda; Holoch, Kristin; Savaris, Ricardo F; Likes, Creighton E; Miller, Paul B; Forstein, David A; Lessey, Bruce A

    2017-03-01

    Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies and accounts for only 1-5% of pregnancy failures. Treatment options for unexplained RPL (uRPL) are limited. Previous studies suggest a link between delayed implantation and pregnancy loss. Based on this, a timely signal for rescue of the corpus luteum (CL) using human chorionic gonadotrophin (HCG) could improve outcomes in women with uRPL. This retrospective cohort study included 98 subjects with uRPL: 45 underwent 135 monitored cycles without HCG support; and 53 underwent 142 cycles with a single mid-luteal HCG injection. Based on Log-rank Mantel-Cox survival curves, miscarriage rate and time to pregnancy decreased in the HCG group (P = 0.0005). Women receiving luteal HCG support had an increased chance of an ongoing pregnancy compared with those not receiving it (RR = 2.4; 95% CI 1.4-3.6; number need to treat (NNT) = 7; 95% CI 4-18). Subjects receiving HCG support had a significant absolute risk reduction (ARR) of miscarriage (P HCG in women with RPL appears warranted. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  8. Assessment of quantitative and qualitative changes of proteoglycans and glycosaminoglycans in normal breast tissue during the follicular and luteal phases of the menstrual cycle.

    Science.gov (United States)

    Júnior, J A Dos Santos; de Lima, C R; Michelacci, Y M C da Silva; Nazário, A C Pinto

    2015-01-01

    The effect of sex hormones on extracellular matrix compounds, such as proteoglycans (PGs) and glycosaminoglycans (GAGs), in mammary tissue remains poorly understood. The elucidation of extracellular matrix component functions could clarify pathophysiological conditions, such as cyclical mastalgia (breast pain). The authors examined the quantitative and qualitative changes of PGs and GAGs in normal breast tissue during the follicular and luteal phases of the menstrual cycle. Twenty-eight eumenorrheic patients with benign breast nodules were divided into groups: Group A included 15 follicular patients and Group B included 13 luteal phase patients. Breast tissue adjacent to the nodules was biochemically analyzed to evaluate the types and concentrations of PGS and GAGs. The distribution of proteoglycans during the menstrual cycle was analyzed with immunofluorescence. PG concentrations were elevated (p < 0.01) during the luteal phase compared with the follicular phase, whereas the concentrations of GAGs did not differ significantly. Immunofluorescence revealed that decorin was mainly found in the intralobular stroma. PG concentrations were elevated during the luteal phase, likely due to the influence of sex hormones on macromolecular synthesis. The PG decorin was observed in normal breast tissue in the intralobular stroma. Although the concentration of GAGs, including dermatan and heparan sulfate, varied cyclically, the differences were not significant.

  9. Proliferation of luteal steroidogenic cells in cattle.

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    Shin Yoshioka

    Full Text Available The rapid growth of the corpus luteum (CL after ovulation is believed to be mainly due to an increase in the size of luteal cells (hypertrophy rather than an increase in their number. However, the relationship between luteal growth and the proliferation of luteal steroidogenic cells (LSCs is not fully understood. One goal of the present study was to determine whether LSCs proliferate during CL growth. A second goal was to determine whether luteinizing hormone (LH, which is known have roles in the proliferation and differentiation of follicular cells, also affects the proliferation of LSCs. Ki-67 (a cell proliferation marker was expressed during the early, developing and mid luteal stages and some Ki-67-positive cells co-expressed HSD3B (a steroidogenic marker. DNA content in LSCs isolated from the developing CL increased much more rapidly (indicating rapid growth than did DNA content in LSCs isolated from the mid CL. The cell cycle-progressive genes CCND2 (cyclin D2 and CCNE1 (cyclin E1 mRNA were expressed more strongly in the small luteal cells than in the large luteal cells. LH decreased the rate of increase of DNA in LSCs isolated from the mid luteal stage but not in LSCs from the developing stage. LH suppressed CCND2 expression in LSCs from the mid luteal stage but not from the developing luteal stage. Furthermore, LH receptor (LHCGR mRNA expression was higher at the mid luteal stage than at the developing luteal stage. The overall results suggest that the growth of the bovine CL is due to not only hypertrophy of LSCs but also an increase in their number, and that the proliferative ability of luteal steroidogenic cells decreases between the developing and mid luteal stages.

  10. Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials

    Science.gov (United States)

    Doblinger, Jakob; Cometti, Barbara; Trevisan, Silvia; Griesinger, Georg

    2016-01-01

    Objective To summarize efficacy and safety data on a new progesterone compound which is available for subcutaneous administration as compared to vaginally administered progesterone for luteal phase support in patients undergoing IVF treatment. Design Data from two randomized phase III trials (07EU/Prg06 and 07USA/Prg05) performed according to GCP standards with a total sample size of 1435 per-protocol patients were meta-analyzed on an individual patient data level. Setting University affiliated reproductive medicine unit. Patients Subcutaneous progesterone was administered to a total of 714 subjects and vaginal progesterone was administered to a total of 721 subjects who underwent fresh embryo transfer after ovarian stimulation followed by IVF or ICSI. The subjects were between 18 and 42 years old and had a BMI <30kg/m2. Interventions Subcutaneous progesterone 25 mg daily vs. either progesterone vaginal gel 90 mg daily (07EU/Prg06) or 100 mg intravaginal twice a day (07USA/Prg05) for luteal phase support in IVF patients. Main outcome measures Ongoing pregnancy rate beyond 10 gestational weeks, live birth rate and OHSS risk. Results The administration of subcutaneous progesterone versus intra-vaginal progesterone had no impact on ongoing pregnancy likelihood (OR = 0.865, 95% CI 0.694 to 1.077; P = n.s.), live birth likelihood (OR = 0.889, 95% CI 0.714 to 1.106; P = n.s.) or OHSS risk (OR = 0.995, 95% CI 0.565 to 1.754; P = n.s.) in regression analyses accounting for clustering of patients within trials, while adjusting for important confounders. Only female age and number of oocytes retrieved were significant predictors of live birth likelihood and OHSS risk. Conclusion No statistical significant or clinical significant differences exist between subcutaneous and vaginal progesterone for luteal phase support. PMID:26991890

  11. Luteal insufficiency in first trimester

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    Duru Shah

    2013-01-01

    Full Text Available Luteal phase insufficiency is one of the reasons for implantation failure and has been responsible for miscarriages and unsuccessful assisted reproduction. Luteal phase defect is seen in women with polycystic ovaries, thyroid and prolactin disorder. Low progesterone environment is created iatrogenically due to interventions in assisted reproduction. Use of gonadotrophin-releasing hormone analogs to prevent the LH surge and aspiration of granulosa cells during the oocyte retrieval may impair the ability of corpus luteum to produce progesterone. Treatment of the underlying disorder and use of progestational agents like progesterone/human chorionic gonadotrophin have been found to be effective in women with a history of recurrent miscarriage. There has been no proved beneficial effect of using additional agents like ascorbic acid, estrogen, prednisolone along with progesterone. Despite their widespread use, further studies are required to establish the optimal treatment. Literature review and analysis of published studies on luteal phase support.

  12. Gender-specific cerebral activation during cognitive tasks using functional MRI: comparison of women in mid-luteal phase and men

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    Gizewski, Elke R.; Wanke, Isabel; Forsting, Michael [University Hospital Essen, Departments of Diagnostic and Interventional Neuroradiology, Essen (Germany); Krause, Eva; Senf, Wolfgang [University Hospital Essen, Department of Psychosomatic Medicine, Essen (Germany)

    2006-01-01

    Previous studies of gender-specific differences in functional imaging during spatial and language tasks have been inconclusive. Furthermore, among women, such differences may occur during mid-luteal phase compared to the rest of the menstrual cycle. In order to examine further gender differences, functional MRI was performed in 12 male volunteers and 12 female volunteers (in the mid-luteal phase) during mental rotation and verb-generation tests. Two-sample t-tests with uncorrected P values of <0.001 for the specific regions of interest (ROIs) revealed cerebral activation differences in both stimuli. During mental rotation tests, higher levels of activation were noted in the right medial frontal, precentral, and bilateral inferior parietal cortex, while in women this occurred in the right inferior and medial temporal, right superior frontal cortex, and left fusiform gyrus. During verb-generation tests, higher levels of activation in men was found in the left medial temporal and precentral cortex. Our results indicate that differences in cerebral activity during cognitive tasks can be shown between men and women in the mid-luteal phase. Gender differences while performing a mental rotation task were more prominent than during a verb-generation task. (orig.)

  13. Luteal-phase support in assisted reproduction treatment: real-life practices reported worldwide by an updated website-based survey.

    Science.gov (United States)

    Vaisbuch, Edi; de Ziegler, Dominique; Leong, Milton; Weissman, Ariel; Shoham, Zeev

    2014-03-01

    An updated worldwide web-based survey assessed the real-life clinical practices regarding luteal-phase supplementation (LPS) in assisted reproduction. This survey looked for changes since a former survey conducted nearly 3years earlier. The survey questions were: If you support the luteal phase, when do you start the regimen you are using?; Which agent/route is your treatment of choice to support the luteal phase?; If you use vaginal progesterone, which formulation do you use?; and How long you continue progesterone supplementation if the patient conceived? Data were obtained from 408 centres (82 countries) representing 284,600 IVF cycles/year. The findings were: (i) most practitioners (80% of cycles) start LPS on the day of egg collection; (ii) in >90%, a vaginal progesterone product is used (77% as a single agent and 17% in combination with i.m. progesterone), while human chorionic gonadotrophin as a single agent for LPS is not being used at all; and (iii) in 72% of cycles, LPS is administered until 8-10weeks' gestation or beyond. When compared with the initial survey, the results of this survey are encouraging as there is a clear shift towards a more unified and evidence-based approach to LPS in IVF cycles. This updated worldwide web-based survey assessed the actual real-life clinical practices regarding luteal-phase supplementation (LPS) in assisted reproduction. Specifically, this survey looked for changes since an initial survey conducted nearly 3years earlier. The survey included the following questions: If you support the luteal phase, when do you start the regimen you are using?; Which agent/route is your treatment of choice to support the luteal phase?; If you use vaginal progesterone, which formulation do you use?; and How long you continue progesterone supplementation if the patient conceived? Data from 408 centres in 82 countries representing a total of 284,600 IVF cycles/year were included. Most practitioners (80% of cycles) start LPS on the day of

  14. Expression of calbindin-D9k and vitamin D receptor in the uterus of Egyptian buffalo during follicular and luteal phases.

    Science.gov (United States)

    Emam, Mahmoud Abdelghaffar; Abouelroos, Mahmoud E A; Gad, Fatma A

    2016-06-01

    Uteri of mature Egyptian buffalo cows (5-10 years old) were collected at follicular (n=12) and luteal (n=16) phases of estrous cycle to investigate the expression of calbindin-D9k (CaPB-9k) and vitamin D receptor (VDR). This study was done using avidin-biotin immunohistochemistry method. In addition, blood levels of calcium (Ca), vitamin D3 (Vit D), estrogen (E2) and progesterone (P4) were measured. The immunohistochemical findings restricted the expressions of CaBP-9k and VDR to the luminal and glandular epithelia of the endometrium implicating the importance of CaBP-9K and VDR in the function of endometrial epithelium, especially the glandular one, in order to prepare a receptive uterus. On the other hand, the myometrium did not express CaBP-9k or VDR that denies the potential role of CaBP-9k and VDR in the uterine contractility during the estrous cycle of Egyptian buffalo. All of Ca, Vit D, and P4 blood levels significantly (P<0.05) increased during luteal phase however, blood level of E2 significantly (P<0.05) increased during follicular phase. The expressions of CaBP-9k and VDR in the uterus of Egyptian buffalo were significantly (P<0.05) higher during luteal (P4 dominant) phase than during the follicular (E2 dominant) phase indicating that P4 up-regulates the expressions of CaBP-9k and VDR. In view of these observations, this study represents the first characterization of CaBP-9K and VDR expression in the uterus of Egyptian buffalo and suggests the pivotal role of CaBP-9k and VDR in the uterine receptivity. Furthermore, it demonstrates the regulatory role of P4 for expressions of CaBP-9k and VDR in buffalo uterus. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. A randomized double-blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer.

    Science.gov (United States)

    Lee, Vivian Chi Yan; Li, Raymond Hang Wun; Yeung, William Shu Biu; Pak Chung, H O; Ng, Ernest Hung Yu

    2017-05-01

    Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate? The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate. The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone. This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015. Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days. The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET. This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support. The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET. No external funding was used and there were no competing interests. clinicaltrial.gov identifier: NCT01931384. 23/8/2013. 30/8/2013.

  16. Lipid droplets in cultured luteal cells in non-pregnant sheep fed different planes of nutrition.

    Science.gov (United States)

    Khanthusaeng, Vilaivan; Thammasiri, Jiratti; Bass, Casie S; Navanukraw, Chainarong; Borowicz, Pawel; Redmer, Dale A; Grazul-Bilska, Anna T

    2016-07-01

    Accumulation of lipid droplets (LD) in luteal cells likely is important for energy storage and steroidogenesis in the highly metabolically active corpus luteum (CL). The objective of this study was to determine the effect of plane of nutrition on progesterone (P4) secretion, and lipid droplet number and size in cultured ovine luteal cells. Ewes were randomly assigned to one of three nutritional groups: control (C; 100% NRC requirements, n=9), overfed (O; 2×C, n=12), or underfed (U; 0.6×C, n=10). Superovulation was induced by follicle stimulating hormone injections. At the early and mid-luteal phases of the estrous cycle, CL were dissected from ovaries, and luteal cells isolated enzymatically. Luteal cells were incubated overnight in medium containing serum in chamber slides. Media were then changed to serum-free and after 24h incubation, media were collected for P4 analysis, and cells were fixed in formalin and stained with BODIPY followed by DAPI staining. Z-stacks of optical sections of large and small luteal cells (LLC and SLC, respectively) were obtained using a laser-scanning microscope. Rendered 3D images of individual LLC and SLC were analyzed for cell volume, and total and individual LD volume, number and percentage of cellular volume occupied by LD by using Imaris software. Concentrations of P4 in serum and media were greater (Pplane. LD total volume and number were greater (Pplane affect selected LD measurements and thus may affect luteal functions. Furthermore, these data confirm that LD dynamics differ among parenchymal steroidogenic luteal cell types.

  17. Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

    Science.gov (United States)

    Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

    2016-10-01

    For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

  18. Comparison of live-birth defects after luteal-phase ovarian stimulation vs. conventional ovarian stimulation for in vitro fertilization and vitrified embryo transfer cycles.

    Science.gov (United States)

    Chen, Hong; Wang, Yun; Lyu, Qifeng; Ai, Ai; Fu, Yonglun; Tian, Hui; Cai, Renfei; Hong, Qingqing; Chen, Qiuju; Shoham, Zeev; Kuang, Yanping

    2015-05-01

    To assess live-birth defects after a luteal-phase ovarian-stimulation regimen (LPS) for in vitro fertilization (IVF) and vitrified embryo transfer (ET) cycles. Retrospective cohort study. Tertiary-care academic medical center. Infants who were born between January 1, 2013 and May 1, 2014 from IVF with intracytoplasmic sperm injection (ICSI) treatments (n = 2,060) after either LPS (n = 587), the standard gonadotropin-releasing hormone-agonist (GnRH-a) short protocol (n = 1,257), or mild ovarian stimulation (n = 216). The three ovarian-stimulation protocols described and assisted reproductive technology (ART) treatment (IVF or ICSI, and vitrified ET) in ordinary practice. The main measures were: gestational age, birth weight and length, multiple delivery, early neonatal mortality, and birth defects. Associations were assessed using logistic regression by adjusting for confounding factors. The final sample included 2,060 live-born infants, corresponding to 1,622 frozen-thawed (FET) cycles, which led to: 587 live-born infants from LPS (458 FET cycles); 1,257 live-born infants from the short protocol (984 FET cycles); and 216 live-born infants from mild ovarian stimulation (180 FET cycles). Birth characteristics regarding gestational age, birth weight and length, multiple delivery, and early neonatal death were comparable in all groups. The incidence of live-birth defects among the LPS group (1.02%) and the short GnRH-a protocol group (0.64%) was slightly higher than in the mild ovarian-stimulation group (0.46%). However, none of these differences reached statistical significance. For congenital malformations, the risk significantly increased for the infertility-duration factor and multiple births; the adjusted odds ratios were 1.161 (95% confidence interval [CI]: 1.009-1.335) and 3.899 (95% CI: 1.179-12.896), respectively. No associations were found between congenital birth defects and various ovarian-stimulation regimens, maternal age, body mass index, parity

  19. Maintenance of the corpus luteum of early pregnancy in the ewe. IV. Changes in luteal sensitivity to prostaglandin F2 alpha throughout early pregnancy.

    Science.gov (United States)

    Silvia, W J; Niswender, G D

    1986-10-01

    Two experiments were conducted to examine the temporal aspects of luteal resistance to the luteolytic effect of prostaglandin (PG) F2 alpha during early pregnancy. In Exp. 1, 14 pregnant and 12 nonpregnant ewes were treated with PGF2 alpha either on d 10 or 13 post-estrus. Jugular venous blood samples were collected at -30 min, 0, 6, 12, 18, 24, 30 and 36 h post-injection for quantification of progesterone. The difference (delta P) between pre-treatment and post-treatment concentrations of progesterone was calculated for each ewe. There was a significant interaction between pregnancy status and day of treatment on delta P (P less than .05). Pregnant and nonpregnant ewes treated on d 10 showed a large delta P. A large delta P also was observed in nonpregnant ewes treated on d 13 post-estrus. However, delta P in pregnant ewes treated on d 13 was smaller than in the other three groups (P less than .05). The temporal patterns of concentrations of progesterone in serum were different among treatment groups (P less than .05). A suppression in the concentration of progesterone was observed by 24 h post-injection in all four treatment groups. Progesterone returned to pre-treatment levels only in pregnant ewes treated on d 13. In Exp. 2, 47 pregnant ewes were treated with PGF2 alpha on d 10, 13, 16, 19, 22, 26 or 30 postestrus. Blood samples were collected and data were analyzed as described for Exp. 1.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization.

    Science.gov (United States)

    Tournaye, Herman; Sukhikh, Gennady T; Kahler, Elke; Griesinger, Georg

    2017-05-01

    Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation? Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin. MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration. Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to Pharmaceuticals Division. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Besins, Ferring and Mithra (now Allergan) and H.T. has received consultancy fees from Finox, Ferring, Abbott, ObsEva and Ovascience. G.S. has nothing to disclose. E.K. is an employee of Abbott GmbH. G.G. has received investigator fees from Abbott during the conduct of the study; outside of this submitted work, G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, Glycotope, as well as personal fees from VitroLife, NMC Healthcare LLC, ReprodWissen LLC and ZIVA LLC. NCT01850030 (clinicaltrials.gov). 19 April 2013. 23 August 2013.

  1. Impact of Mid-Luteal Phase GnRH Agonist Administration on Reproductive Outcomes in GnRH Agonist-Triggered Cycles: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Abdelhamid Benmachiche

    2017-06-01

    Full Text Available ObjectiveTo explore whether the addition of a mid-luteal bolus of GnRH agonist (GnRHa improves the implantation rate (IR in in vitro fertilization (IVF cycles.DesignA randomized controlled trial.SettingPrivate IVF center.Patients328 IVF/intracytoplasmic sperm injection patients were triggered with GnRHa and received 1,500 IU HCG on the day of oocyte pick-up (OPU in addition to a standard luteal phase support (LPS.Intervention(sIn addition, the study group received a bolus of GnRHa 6 days after OPU, whereas the control group did not.Main outcome measureImplantation rate.Secondary outcome measure(sOngoing pregnancy (OP and live birth (LB rates.ResultsAlthough serum concentrations of FSH, LH, E2, and P on day OPU + 7 were significantly higher in the study group compared to the control group, the IR was not statistically different between the treatment group (27% and the control group (23% [odds ratio (OR 1.2 (95% CI 0.9–1.7, P < 0.27]. Similarly, the OP rate was 37% in the treatment group and 31% in the control group [OR 1.3 (95% CI 0.8–2.0, P < 0.23]. The LB rate was 36% in the treatment group and 31% in the control group [OR: 1.3 (95% CI 0.8–2.0, P < 0.27].ConclusionAlthough a trend toward a higher IR and pregnancy rate was observed in the treatment group, this difference was not statistically significant. However, the absolute risk difference of 5% found for LB is clinically relevant, warranting further investigation.NCT02053779.

  2. Effect of increasing maximal aerobic exercise on serum gonadal hormones and alpha-fetoprotein in the luteal phase of professional female soccer players.

    Science.gov (United States)

    Otağ, Aynur; Hazar, Muhsin; Otağ, İlhan; Beyleroğlu, Malik

    2016-03-01

    [Purpose] The performance of female athletes during their menstrual period has attracted the attention of researchers for many years. It is known that the menstrual period changes with exercise. Alpha-fetoprotein (AFP) is an oncofetal protein. In this study, the effect of maximal aerobic exercise in the luteal phase on some hormones and AFP in female athletes was researched. [Subjects and Methods] Twelve volunteers and healthy female footballers with normal menstrual cycles volunteered for this study as subjects. All the participants performed a shuttle run test. Blood samples were taken before, after, and one hour after exercise. Serum AFP, estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) values were measured using an auto analyzer and original kits. Heart rate measurements were performed before and after the exercise. [Results] AFP activity had significantly decreased after 1 h of recovery from the exercise in the female soccer players, and estrogen and LH activity had significantly increased immediately after the exercise. Progesterone activity had significantly decreased immediately after the exercise. FSH values had significantly increased immediately after the exercise. [Conclusion] The results of the present study show there were significant decreases in the values of AFP, which is a cancer parameter, 1 hour after the exercise. This result may be valuable in future physiotherapy studies on the relationship between exercise and cancer.

  3. Role of interleukin-1β in the regulation of porcine corpora lutea during the late luteal phase of the cycle and during pregnancy.

    Science.gov (United States)

    Zmijewska, Agata; Franczak, Anita; Kotwica, Genowefa

    2012-09-01

    Interleukin-1β (IL-1β) may regulate ovarian physiology. In this study, the influence of IL-1β on secretory activity within the corpora lutea (CL) of cyclic and gravid pigs was determined in vitro during different stages of the CL lifespan, e.g. on Days 10-11, 12-13 and 15-16 of the oestrous cycle and pregnancy. IL-1β (10 ng/ml) increased prostaglandin E2 (PGE2) secretion from CL of the cyclic and gravid pigs during studied days of the oestrous cycle and pregnancy. Increase (P < 0.05) of prostaglandin F2α (PGF2α) in IL-1β-treated CL was demonstrated only on Days 10-11 of the oestrous cycle. More potent stimulatory effect of IL-1β on PGE2 than PGF2α secretion resulted in the enhancement of the PGE2:PGF2α ratio in cyclic and early pregnant CL. IL-1β increased (P < 0.05) progesterone (P4) secretion only in gravid CL and had no effect on oestradiol-17β (E2) release. Expression of cyclooxygenase-2 (COX-2) mRNA was stimulated (P < 0.05) in IL-1β-treated cyclic and gravid CL. Expression of prostaglandin synthase mRNAs in response to IL-1β did not increase. In conclusion, IL-1β modulates PGE2, PGF2α and P4 secretion from porcine CL, depending on luteal stage and the surrounding hormonal milieu. The cytokine may act locally in porcine CL for luteotrophic support throughout the PGE2-mediated synthesis and secretion.

  4. Influence of a low-carbohydrate diet on thermoregulatory responses to exercise in women during follicular and luteal phase of the menstrual cycle

    Directory of Open Access Journals (Sweden)

    I Pokora

    2003-12-01

    Full Text Available The aim of this study was to examine the effects of a low-carbohydrate diet on thermoregulatory responses to exercise in women during follicular (F and luteal (L phase of the menstrual cycle. Ten subjects performed a graded bicycle exercise in a thermoneutral environment (23oC, 52-60% relative humidity. Women were tested after consuming, for 3 days, a control diet (C: 60% carbohydrates, 20% fat, 20% protein and after that a low-carbohydrate diet (LCHO: 50% fat, 35% protein and 5% carbohydrates, in each phase of the menstrual cycle. Tympanic temperature (Tty, mean skin temperature (Tsk, electrical skin resistance (ESR, oxygen uptake (VO2, heart rate (HR as well as blood β-hydroxybutyrate acid (β-HB, glucose (Glu and lactate (LA concentrations were measured. On the basis of ESR, dynamics of sweating was estimated. No differences in Tty and Tsk were found between the C and LCHO during exercise tests. However, Tty was significantly higher during L than F phase. Delay time for sweating was shorter after LCHO (F: 10.8 vs 9.4 min, P<0.05, L: 9.9 vs 9.3 N.S., but temperature threshold for this reaction was unchanged (L: 37.22 vs 37.37 and F: 36.91 vs 36.94 oC. Sweating sensitivity was greater after LCHO during both F and L. Resting blood Glu and LA concentrations were similar in women after C and LCHO diet. Before exercise β-HB level was F: 0.45, L: 0.35 mM after LCHO and F: 0.08, L: 0.09 mM after C diet (P<0.05, respectively. At rest and during exercise HR was significantly higher after LCHO diet in women during F phase. In submaximal exercise loads VO2 after LCHO diet were significantly higher than after C diet in all women. It was concluded that the low-carbohydrate diet ingested by young women in both phases of the menstrual cycle have no effect on body temperature, however, it affects heat dissipation mechanism during exercise.

  5. Apoptosis-Related Factors in the Luteal Phase of the Domestic Cat and Their Involvement in the Persistence of Corpora Lutea in Lynx.

    Directory of Open Access Journals (Sweden)

    Olga Amelkina

    Full Text Available The corpus luteum (CL is a transient gland formed in the ovary after ovulation and is the major source of progesterone. In the Iberian and Eurasian lynx, CL physiologically persist after parturition and retain their capacity to produce progesterone, thus suppressing the ovarian activity. This unique reproductive characteristic has a big impact on the success of assisted reproduction techniques in the endangered Iberian lynx. The mechanisms behind CL persistence are not yet understood and require extensive studies on potential luteotropic and luteolytic factors in felids. Because the apoptosis system has been shown to be involved in structural regression of CL in many species, we aimed to investigate the capacity of perCL to undergo apoptosis. In addition, we performed initial studies on the apoptosis system in the luteal phase of the domestic cat. No previous research on this system has been made in this species. Our factors of interest included agents of the intrinsic apoptosis pathway, i.e., pro-survival B-cell CLL/lymphoma 2 (BCL2 and pro-apoptotic BCL2-associated X protein (BAX, the executioner caspase-3 (CASP3, as well as of the extrinsic pathway, i.e., pro-apoptotic receptor FAS, and tumor necrosis factor (TNF and its receptors (pro-apoptotic TNFRSF1A and pro-survival TNFRSF1B. We analyzed the relative mRNA levels of these factors, as well as protein localization of CASP3 and TNF during stages of pregnancy and the non-pregnant luteal phase in CL of domestic cats. The same factors were investigated in freshly ovulated CL (frCL and perCL of Iberian and Eurasian lynx, which were histologically analyzed. All factors were present in the CL tissue of both domestic cat and lynx throughout all analyzed stages. The presence of pro-apoptotic factors BAX, CASP3, FAS and TNFRSF1A in perCL of the Eurasian and Iberian lynx might indicate the potential sensitivity of perCL to apoptotic signals. The expression of pro-survival factors BCL2 and TNFRSF1B was

  6. Difference in expression between AQP1 and AQP5 in porcine endometrium and myometrium in response to steroid hormones, oxytocin, arachidonic acid, forskolin and cAMP during the mid-luteal phase of the estrous cycle and luteolysis.

    Science.gov (United States)

    Skowronska, Agnieszka; Mlotkowska, Patrycja; Nielsen, Soren; Skowronski, Mariusz T

    2015-12-01

    Recently, we demonstrated in vitro that AQP1 and AQP5 in the porcine uterus are regulated by steroid hormones (P4, E2), arachidonic acid (AA), forskolin (FSK) and cAMP during the estrous cycle. However, the potential of the porcine separated uterine tissues, the endometrium and myometrium, to express these AQPs remains unknown. Thus, in this study, the responses of AQP1 and AQP5 to P4, E2 oxytocin (OT), AA, FSK and cAMP in the porcine endometrium and myometrium were examined during the mid-luteal phase of the estrous cycle and luteolysis. Real-time PCR and western blot analysis. Progesterone up-regulated the expression of AQP1/AQP5 mRNAs and proteins in the endometrium and myometrium, especially during luteolysis. Similarly, E2 also stimulated the expression of both AQPs, but only in the endometrium. AA led to the upregulation of AQP1/AQP5 in the endometrium during luteolysis. In turn, OT increased the expression of AQP1/AQP5 mRNAs and proteins in the myometrium during mid-luteal phase. Moreover, a stimulatory effect of forskolin and cAMP on the expression of AQP1/AQP5 mRNAs and proteins in the endometrium and myometrium dominated during luteolysis, but during the mid-luteal phase their influence on the expression of these AQPs was differentiated depending on the type of tissue and the incubation duration. These results seem to indicate that uterine tissues; endometrium and myometrium, exhibit their own AQP expression profiles in response to examined factors. Moreover, the responses of AQP1/AQP5 at mRNA and protein levels to the studied factors in the endometrium and myometrium are more pronounced during luteolysis. This suggests that the above effects of the studied factors are connected with morphological and physiological changes taking place in the pig uterus during the estrous cycle.

  7. Luteal blood flow in patients undergoing GnRH agonist long protocol

    Directory of Open Access Journals (Sweden)

    Takasaki Akihisa

    2011-01-01

    Full Text Available Abstract Background Blood flow in the corpus luteum (CL is closely related to luteal function. It is unclear how luteal blood flow is regulated. Standardized ovarian-stimulation protocol with a gonadotropin-releasing hormone agonist (GnRHa long protocol causes luteal phase defect because it drastically suppresses serum LH levels. Examining luteal blood flow in the patient undergoing GnRHa long protocol may be useful to know whether luteal blood flow is regulated by LH. Methods Twenty-four infertile women undergoing GnRHa long protocol were divided into 3 groups dependent on luteal supports; 9 women were given ethinylestradiol plus norgestrel (Planovar orally throughout the luteal phase (control group; 8 women were given HCG 2,000 IU on days 2 and 4 day after ovulation induction in addition to Planovar (HCG group; 7 women were given vitamin E (600 mg/day orally throughout the luteal phase in addition to Planovar (vitamin E group. Blood flow impedance was measured in each CL during the mid-luteal phase by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a CL-resistance index (CL-RI. Results Serum LH levels were remarkably suppressed in all the groups. CL-RI in the control group was more than the cutoff value (0.51, and only 2 out of 9 women had CL-RI values Conclusion Patients undergoing GnRHa long protocol had high luteal blood flow impedance with very low serum LH levels. HCG administration improved luteal blood flow impedance. This suggests that luteal blood flow is regulated by LH.

  8. CRP at early follicular phase of menstrual cycle can cause misinterpretation for cardiovascular risk assessment.

    Science.gov (United States)

    Gursoy, Asli Yarci; Caglar, Gamze Sinem; Kiseli, Mine; Pabuccu, Emre; Candar, Tuba; Demirtas, Selda

    2015-12-01

    C-reactive protein (CRP) is a well-known marker of inflammation and infection in clinical practice. This study is designed to evaluate CRP levels in different phases of menstrual cycle, which might end up with misleading conclusions especially when used for cardiovascular risk assessment. Twenty-seven women were eligible for the cross-sectional study. Venous blood samples from each participant were collected twice during the menstrual cycle. The first sampling was held at 2nd to 5th days of the menstrual cycle for FSH, estradiol, CRP, and sedimentation, and the second was done at 21st to 24th days of the menstrual cycle for measurement of progesterone, CRP, and sedimentation values. CRP values were significantly higher in the early follicular phase compared to luteal phase (1.8 mg/L [0.3-7.67] vs. 0.7 mg/L [0.1-8.3], p menstrual cycle, sedimentation rate was similar (12.1 ± 6.7 vs. 12.3 ± 7.7; p = 0.717, respectively). CRP levels in early follicular phase of the menstrual cycle (menstruation) are significantly higher than CRP levels in luteal phase of the same cycle. In reproductive age women, detection of CRP for cardiovascular risk assessment during menstruation might not be appropriate.

  9. Effect of Vascular Endothelial Growth Factor on Regulation of Angiogenesis during Early Luteal Development in Livestock%VEGF在家畜黄体早期发育过程中对血管生成的调控作用

    Institute of Scientific and Technical Information of China (English)

    罗倩萍; 张正红; 陈佳洁; 黄晓红; 成勇; 王正朝

    2011-01-01

    对黄体时期VEGF依赖性血管生成的分子机制研究,将有助于我们开发新的策略用于治疗黄体相关的不孕症,以及改善动物的繁殖性能.论文对VEGF在家畜黄体血管生成过程中的调控作用进行综述,旨在为临床研究及畜牧生产提供理论依据及参考资料.%Angiogenesis is a process of vascular growth which is mainly limited to the reproductive system in healthy adult animals. In mammalian, the corpus luteum is a site of intense angiogenesis. Within a short period of the corpus luteum, the angiogenesis is followed either by controlled regression of the micro-vascular tree in the non-fertile cycle, or maintenance and stabilisation of the new vasculature in a conceptual cycle. Therefore, the corpus luteum is a unique model system in which the cellular and molecular regulation of angiogenesis can be studied. The development of new blood vessels in the ovarian corpus luteum is essential for corpus luteum formation to guarantee the necessary supply of nutrients and hormones. At present, the study of the molecular mechanism indicated vascular endothelial growth factor has a major role in the corpus luteum, since significantly inhibitory effects on luteal angiogenesis and function are observed when its action was blocked by antagonists at specific stages of the luteal phase in vivo. Investigations of the mechanisms of vascular endothelial growth factor-dependent angiogenesis in mammalian corpus luteum will provide insights into new strategies in treatment of luteal-based infertility and methods of improving animal reproduction. Based on our previous researches, we reviewed the effect of vascular endothelial growth factor on luteal angiogenesis in livestock, in order to provide some important references for clinic researches and animal husbandry production.

  10. Measurement of plasma human chorionic gonadotropin (hCG) and beta-hCG activities in the late luteal phase: evidence of the occurrence of spontaneous menstrual abortions in infertile women.

    Science.gov (United States)

    Chartier, M; Roger, M; Barrat, J; Michelon, B

    1979-02-01

    Plasma luteinizing hormone (LH-human chorionic gonadotropin (hCG) and beta-hCG activities were measured during the late luteal phase in 321 cycles of 147 infertile women. In 71 cycles the hCG measurement permitted the diagnosis of pregnancy between the 10th and 14th days after the thermal nadir. The slope of the regression line derived from hCG levels during the first 22 days of pregnancy was significantly lower in pregnancies which aborted before the 60th day than in normal pregnancies (P less than 0.01). Among 72 cycles ended by apparently normal menses which exhibited an LH-hCG activity at least equal to 7 mIU of hCG/ml during the late luteal phase, the beta-hCG activity was measured in 49 cycles during which hCG had not been given. Significant beta-hCG activity (greater than or equal to 4 mIU of hCG/ml) was detected in 19 cases. This finding supports the assumption that secretory trophoblastic tissue had been present and that spontaneous menstrual abortions had occurred in these women.

  11. The effect of oxytocin on progesterone secretion, phosphoinositide hydrolysis and intracellular mobilisation of Ca2+ in porcine luteal cells.

    Science.gov (United States)

    Franczak, Anita; Kurowicka, Beata; Kowalik, Magdalena; Ciereszko, Renata Elzbieta; Kotwica, Genowefa

    2009-03-01

    Oxytocin (OT) is involved in the regulation of steroid secretion by the corpus luteum (CL) in pigs, but OT signal transduction in the porcine CL has not been identified. In this study, the effects of OT on in vitro progesterone (P4) secretion, phosphoinositide (PI) hydrolysis and intracellular mobilisation of Ca2+ ([Ca2+]i) were investigated in porcine luteal cells during the early (days 3-5), mid(days 8-10) and late luteal phases (days 12-14) of the oestrous cycle. Basal concentrations of P4 and accumulation of inositol phosphates (IPs) were higher (P < 0.05) on days 3-5 and 8-10 of the oestrous cycle than on days 12-14. Basal [Ca2+]i mobilisation did not differ among studied periods of the oestrous cycle. Oxytocin (10(-7) M) enhanced P4 secretion and PI hydrolysis (P < 0.05) by luteal cells harvested on days 8-10 of the oestrous cycle. Moreover, OT started to increase mobilisation of [Ca2+]i at the 15th (days 3-5 and 8-10) or 30th second (days 12-14) in porcine luteal cells. It was concluded that in pigs OT acts as a regulator of steroidogenesis, stimulating P4 secretion in mature CL. This OT action may be mediated by changes in PI hydrolysis and [Ca2+]i mobilisation.

  12. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment

    NARCIS (Netherlands)

    N.S. Macklon (Nick); M.J.C. Eijkemans (René); M. Ludwig (Michael); R.E. Felberbaum; K. Diedrich; S. Bustion; E. Loumaye; B.C.J.M. Fauser (Bart); N.G.M. Beckers (Nicole)

    2003-01-01

    textabstractReplacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because o

  13. Establishment and characterization of a telomerase immortalized porcine luteal cells.

    Science.gov (United States)

    Zhang, Liang; Huang, Yong; Wang, Zhenyu; Luo, Xiaomao; Zhang, Hongling; Du, Qian; Chang, Lingling; Zhao, Xiaomin; Tong, Dewen

    2017-05-01

    Luteal cells play a crucial role in pregnancy through secreting progesterone to maintain pregnancy and support of fetus. However, low cellular yields and inability to passage primary porcine luteal cells (PLCs) in vitro limit the luteal cell study. Therefore, developing an immortalized porcine luteal cell line is necessary for studying luteal cells activity and function in different diseases. In this study, primary PLCs were obtained from gilts at day 30 to day 50 of gestation and immortalized by human telomerase reverse transcriptase (hTERT). The porcine corpus luteal cell line (hTERT-PLCs) expressed hTERT gene steady, maintained high hTERT activity and normal karyotype. The phase contrast microscope and transmission electron microscope observation showed primary PLCs and hTERT-PLCs were polygonal and exhibited abundant mitochondria, smooth endoplasmic reticulum and lipid droplets. 3β hydroxysteroid dehydrogenase (3βHSD) and Oil-Red-O staining showed that hTERT-PLCs at passage 30 and 50 were similar to primary PLCs. The hTERT-PLCs expressed steroidogenesis-related proteins, enzymes and receptors, such as steroidogenic acute regulatory protein, P450 cholesterol side-chain cleavage, 3βHSD, 20αHSD, luteinizing hormone receptor, progesterone receptor, prolactin receptor, estrogen receptorα/β, as well as primary PLCs. Consequently, hTERT-PLCs could secret progesterone and exhibited similar responses to luteinizing hormone and prostaglandin F2α as primary PLCs. In addition, the hTERT-PLCs did not show neoplastic transformation or anchorage independent growth. In summary, we developed an immortalized porcine luteal cell line which maintained its originally morphological, biological and functional characteristics. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Effect of Administration of Single Dose GnRH Agonist in Luteal Phase on Outcome of ICSI-ET Cycles in Women with Previous History of IVF/ICSI Failure: A Randomized Controlled Trial

    Science.gov (United States)

    Zafardoust, Simin; Jeddi-Tehrani, Mahmood; Akhondi, Mohammad Mehdi; Sadeghi, Mohammad Reza; Kamali, Koroush; Mokhtar, Sara; Badehnoosh, Bita; Arjmand-Teymouri, Fatemeh; Fatemi, Farnaz; Mohammadzadeh, Afsaneh

    2015-01-01

    Background GnRH agonist administration in the luteal phase has been suggested to beneficially affect the outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This blind randomized controlled study evaluates the effect of GnRH (Gonadotropine Releasing Hormone) agonist administration on ICSI outcome in GnRH antagonist ovarian stimulation protocol in women with 2 or more previous IVF/ICSI-ET failures. Methods One hundred IVF failure women who underwent ICSI cycles and stimulated with GnRH antagonist ovarian stimulation protocol, were included in the study. Women were randomly assigned to intervention (received a single dose injection of GnRH agonist (0.1 mg of Decapeptil) subcutaneously 6 days after oocyte retrieval) and control (did not receive GnRH agonist) groups. Implantation and clinical pregnancy rates were the primary outcome measures. Results Although the age of women, the number of embryos transferred in the current cycle and the quality of the transferred embryos were similar in the two groups, there was a significantly higher rate of implantation (Mann Whitney test, p = 0.041) and pregnancy (32.6% vs. 12.5%, p = 0.030, OR = 3.3, 95%CI, 1.08 to 10.4) in the intervention group. Conclusion Our results suggested that, in addition to routine luteal phase support using progesterone, administration of 0.1 mg of Decapeptil 6 days after oocyte retrieval in women with previous history of 2 or more IVF/ICSI failures led to a significant improvement in implantation and pregnancy rates after ICSI following ovarian stimulation with GnRH antagonist protocol. PMID:25927026

  15. Bad基因在黄体期绵羊生殖器官中表达的比较研究%The on comparison of expression of Bad gene in generative organ of sheep at luteal phase

    Institute of Scientific and Technical Information of China (English)

    葛晨霞; 王龙涛; 李向军; 贾博寅; 马磊; 姜怀志

    2011-01-01

    DUring luteal phase (LP) immunohistochemistry was used to confirm and locate apoptosis cells and to detect the expression of Bad in major reproductive organs (ovaries, oviduct and uterus) of Small-tails Han Sheep (SHS) and Suffolk Sheep (SS),which have high and low productivity,respectively. Bad gene was expressed in most of luteal cells. secretory cells and part of ciliated cell in fimbriaend of fallopian tube, ampullae and isthmusthe epithelia at luteal phase of submited positiveness, ciliated cell was stained strongly at luteal phase. The expression inten difference was unsharpness in different position of fimhriae tubae at contemporaneous. Staining was moderate with Bad positive cells in fimbriaend of fallopian tube,ampullae and isthmusthe epithelia. Staining was light with Bad positive cells in endometrial gland and endometrium cotyledon Average optical density and average positive area were measured by computator image analysis software in different of position between Small-tails Hah Sheep (SHS) and Suffolk Sheep (SS) but also had several visible differences in reproductive organs. The ratio of positive cells and AO of endometrium cotyledon stroma of SHS was higher significantly than SS in LP (P<0. 01). The result showed that the difference of apoptosis in reproductive organs and expression of Bad between SHS and SS maybe is agroundwork which result in of their differential productivity.%以黄体期小尾寒羊和萨福克羊为研究对象,采用免疫组织化学技术,针对Bad基因在母羊生殖器官卵巢,输卵管和子宫中的表达与定位进行初步研究,在卵巢中Bad基因均在多数黄体细胞中表达;在输卵管宫管结合部、峡部和壶腹部的分泌细胞Bad基因均有不同程度的表达,未发现纤毛细胞Bad阳性细胞;子宫内膜腺体小泡表达Bad阳性,子宫内膜子叶、基质的阳性细胞数极少,阳性细胞呈轻度着色,显弱阳性.利用计算机图像分析技术测量小尾寒羊和萨福克

  16. Estado nutricional e consumo alimentar de mulheres jovens na fase lútea e folicular do ciclo menstrual Nutritional status and food consumption of young women in the luteal and follicular phases of the menstrual cycle

    Directory of Open Access Journals (Sweden)

    Larissa Almenara Silva dos Santos

    2011-04-01

    percentage of women with above-average body water during the luteal phase (77%. The consumption of foods from the complementary group was higher during the luteal phase. The consumption of foods from all other groups during both phases was below the recommended levels, except for meats. Food cravings were mild during the entire menstrual cycle and there were no significant differences between the phases. Food cravings were positively associated with increased intake of foods from the complementary group. CONCLUSION: In healthy women, the menstrual cycle influences food consumption and the luteal phase causes water retention.

  17. Progesterone, estradiol, arachidonic acid, oxytocin, forskolin and cAMP influence on aquaporin 1 and 5 expression in porcine uterine explants during the mid-luteal phase of the estrous cycle and luteolysis: an in vitro study.

    Science.gov (United States)

    Skowronska, Agnieszka; Młotkowska, Patrycja; Wojciechowicz, Bartosz; Okrasa, Stanisław; Nielsen, Soren; Skowronski, Mariusz T

    2015-02-18

    The cell membrane water channel protein, aquaporins (AQPs), regulate cellular water transport and cell volume and play a key role in water homeostasis. Recently, AQPs are considered as important players in the field of reproduction. In previous studies, we have established the presence of AQP1 and 5 in porcine uterus. Their expression at protein level altered in distinct tissues of the female reproductive system depending on the phase of the estrous cycle. However, the regulation of aquaporin genes and proteins expression has not been examined in porcine uterine tissue. Therefore, we have designed an in vitro experiment to explain whether steroid hormones, progesterone (P4) and estradiol (E2), and other factors: oxytocine (OT), arachidonic acid (AA; substrate for prostaglandins synthesis) as well as forskolin (FSK; adenylate cyclase activator) and cAMP (second messenger, cyclic adenosine monophosphate) may impact AQPs expression. Uterine tissues were collected on Days 10-12 and 14-16 of the estrous cycle representing the mid-luteal phase and luteolysis. Real-time PCR and Western blot analysis were performed to examine the expression of porcine AQP1 and AQP5. Their expression in the uterine explants was also evaluated by immunohistochemistry. The results indicated that uterine expression of AQP1 and AQP5 potentially remains under control of steroid hormones and AA-derived compounds (e.g. prostaglandins). P4, E2, AA, FSK and cAMP cause translocation of AQP5 from apical to the basolateral plasma membrane of the epithelial cells, which might affect the transcellular water movement (through epithelial cells) between uterine lumen and blood vessels. The AC/cAMP pathway is involved in the intracellular signals transduction connected with the regulation of AQPs expression in the pig uterus. This study documented specific patterns of AQP1 and AQP5 expression in response to P4, E2, AA, FSK and cAMP, thereby providing new indirect evidence of their role in maintaining the

  18. Impact of GnRH agonist triggering and intensive luteal steroid support on live-birth rates and ovarian hyperstimulation syndrome

    DEFF Research Database (Denmark)

    Iliodromiti, Stamatina; Lan, Vuong Thi Ngoc; Tuong, Ho Manh;

    2013-01-01

    Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory implanta......Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory...

  19. Mid-luteal phase injection of subcutaneous leuprolide acetate improves live delivered pregnancy and implantation rates in younger women undergoing in vitro fertilization-embryo transfer (IVF-ET).

    Science.gov (United States)

    Check, J H; Wilson, C; Cohen, R; Choe, J K; Corley, D

    2015-01-01

    To see if the single injection of one mg of the gonadotropin releasing hormone agonist (GnRHa) leuprolide acetate given in the mid-luteal phase can increase live delivered pregnancy and implantation rates. Furthermore the purpose was to determine if improvement was found, did the mechanism involve increased secretion of human chorionic gonadotropin (hCG). A prospective study was conducted in women aged 35 who were undergoing in vitro fertilization-embryo transfer (IVF-ET). They were advised of data from Tesarik et al. and a previous pilot study conducted in the present IVF center showing improved pregnancy rates with the injection of a GnRHa three days after embryo transfer. They were offered the option of returning for a one-mg injection s.c. of leuprolide acetate or not. Clinical and live delivered pregnancy rates were compared according to those taking or not the leuprolide acetate one-mg injection. Chi-square analysis was used for statistical comparisons. Serum beta-hCG levels were compared between those conceiving with or without the extra injection of leuprolide. There was a non-significant trend for higher live delivered pregnancy rates in those taking leuprolide (47.8%, 64/134) vs. those not taking it (38.6%, 76/197). For those pregnant there was no difference in hCG levels according to taking the GnRHa or not. The 25% increased live delivered pregnancy rate per transfer was insufficiently powered to detect a significant difference. The results do justify continuing the study. Perhaps the difference could be wider using a slightly older age group whose embryos are frequently less hearty.

  20. Ruptured corpus luteal cyst: Prediction of clinical outcomes with CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Seok; Moon, Min Hoan; Woo, Hyun Sik; Sung, Chang Kyu; Jeon, Hye Won; Lee, Taek Sang [SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2017-08-01

    To evaluate the determinant pretreatment CT findings that can predict surgical intervention for patients suffering from corpus luteal cyst rupture with hemoperitoneum. From January 2009 to December 2014, a total of 106 female patients (mean age, 26.1 years; range, 17–44 years) who visited the emergency room of our institute for acute abdominal pain and were subsequently diagnosed with ruptured corpus luteal cyst with hemoperitoneum were included in the retrospective study. The analysis of CT findings included cyst size, cyst shape, sentinel clot sign, ring of fire sign, hemoperitoneum depth, active bleeding in portal phase and attenuation of hemoperitoneum. The comparison of CT findings between the surgery and conservative management groups was performed with the Mann-Whitney U test or chi-square test. Logistic regression analysis was used to determine significant CT findings in predicting surgical intervention for a ruptured cyst. Comparative analysis revealed that the presence of active bleeding and the hemoperitoneum depth were significantly different between the surgery and conservative management groups and were confirmed as significant CT findings for predicting surgery, with adjusted odds ratio (ORs) of 3.773 and 1.318, respectively (p < 0.01). On the receiver-operating characteristic curve analysis for hemoperitoneum depth, the optimal cut-off value was 5.8 cm with 73.7% sensitivity and 58.6% specificity (Az = 0.711, p = 0.004). In cases with a hemoperitoneum depth > 5.8 cm and concurrent active bleeding, the OR for surgery increased to 5.786. The presence of active bleeding and the hemoperitoneum depth on a pretreatment CT scan can be predictive warning signs of surgery for a patient with a ruptured corpus luteal cyst with hemoperitoneum.

  1. Impact of ovarian stimulation on mid-luteal endometrial tissue and secretion markers of receptivity

    NARCIS (Netherlands)

    van der Gaast, M. H.; Classen-Linke, I.; Krusche, C. A.; Beier-Hellwig, K.; Fauser, B. C. J. M.; Beier, H. M.; Macklon, N. S.

    2008-01-01

    The objective of this study was to investigate the effect of ovarian stimulation for IVF on endometrial secretion and tissue markers of receptivity in the mid-luteal phase. In 10 oocyte donors, endometrial secretions and biopsies were sampled 5 days after spontaneous ovulation and oocyte retrieval i

  2. Colour Doppler Ultrasonography as a Tool to Assess Luteal Function in Santa Inês Ewes.

    Science.gov (United States)

    Figueira, L M; Fonseca, J F; Arashiro, Ekn; Souza-Fabjan, Jmg; Ribeiro, Acs; Oba, E; Viana, Jhm; Brandão, F Z

    2015-08-01

    The aim of this study was to evaluate luteal dynamics in the Santa Inês ewes using colour Doppler (CD) ultrasonography. Oestrus was synchronized in nulliparous females (n = 18), and subsequently, they were only teased (n = 6) or teased and mated (n = 12). Blood samples were collected daily for plasma progesterone (P4 ) concentrations. Ultrasonographic images of corpora lutea (CL) in CD mode were obtained for further analysis in its largest diameter. The CD mode allowed an early sequential monitoring of CL that was visualized by the first time 0.77 ± 0.62 days after ovulation, with luteal area 29.68 ± 13.21 mm(2) . During the luteogenesis, a progressive increase was observed, followed by a plateau of luteal area, vascularization area and plasma concentrations of P4 reaching maximum values in D11 (124.0 ± 38.0 mm(2) , 52.78 ± 24.08 mm(2) and 11.23 ± 4.89 ng/ml, respectively). In the luteolysis, the plasma concentrations of P4 decreased sharply, whereas luteal and vascularization area gradually. The vascularization area was positively correlated with plasma concentrations of P4 during the luteogenesis (r = 0.22) and luteolysis (r = 0.48). The luteal dynamics of Santa Inês ewes showed patterns similar to those observed in other sheep breeds studied. The CD ultrasonography has the potential to be used as a tool to assess luteal function in sheep.

  3. Comparison of the Efficacy of Two Vaginal Progesterone Formulations, Crinone 8% Gel and Utrogestan Capsules, Used for Luteal Support in Blastocyst Stage Embryo Transfers

    Directory of Open Access Journals (Sweden)

    Li-Jung Wang

    2009-12-01

    Conclusion: Luteal phase support with Crinone 8% vaginal gel (90 mg daily resulted in better clinical pregnancy and implantation rates than Utrogestan vaginal capsules (200 mg, 4 times daily in IVF/ICSI–BT cycles.

  4. Corpora lutea of pregnant and pseudopregnant domestic cats reveal similar steroidogenic capacities during the luteal life span.

    Science.gov (United States)

    Zschockelt, Lina; Amelkina, Olga; Siemieniuch, Marta J; Koster, Stefanie; Jewgenow, Katarina; Braun, Beate C

    2014-10-01

    In domestic cats, luteal phases of pregnancy and pseudopregnancy (non-pregnant luteal phase) differ in the course and level of plasma progesterone (P4). Therefore, we assumed differences in luteal steroidogenic capacities. Here we present a comprehensive analysis of intraluteal steroid biogenesis in the domestic cat. We quantitatively measured relative mRNA levels of steroidogenic acute regulatory protein (STAR), cytochrome P450 oxidases (CYP), hydroxysteroid dehydrogenases (HSD), steroid reductase (SRD) and enzymes involved in sulfoconjugation of steroids, i.e. sulfotransferase (SULT) and sulfatase (STS). Protein expression was analysed by Western Blot for HSD3B. Additionally, intraluteal steroid contents were determined. During the pseudopregnant luteal phase, expression of STAR (p=0.005), HSD3B1 (ppregnancy and pseudopregnancy. This was in accordance with decreasing intraluteal levels of P4, oestrogens and androgens. In contrast, expression of SRD5A1 (p0.05), suggesting a permanent capacity of cat CL to convert progestogens via androgen and oestrogen pathways. In general, mRNA expression profiles of steroidogenic enzymes during the pregnant luteal phase reflected the pseudopregnancy profiles. Intraluteal oestrogen (pcat CL of the same histomorphological stage are characterised by identical steroidogenic capacities independently of an on-going pregnancy.

  5. Early Phase Process Evaluation: Industrial Practices

    Directory of Open Access Journals (Sweden)

    Zulfan Adi Putra

    2016-09-01

    Full Text Available Process route evaluation is a part of research and development (R&D works in an industrial chemical project life cycle. In this early phase, good process evaluation, including process synthesis and designs, provide guidance’s on the R&D project. The paper aimed to collect practical methods used in this early phase process route evaluation from author’s 10 years of industrial experiences.  The collected methods range from forward-backward process synthesis, functional process design, use of cost estimation, and applications of Monte Carlo simulation. Led by a good project management (e.g. via a stage-gate approach use of these methods have shown beneficial results. Some important results are strong arguments on whether or not the project will continue, as well as relevant technical and economic issues identified during this early phase process synthesis and design. Later on, these issues become guidance’s to the follow-up project, if it is continued.

  6. Early Work on Defect Driven Phase Transitions

    Science.gov (United States)

    Kosterlitz, J. Michael; Thouless, David J.

    2016-12-01

    This article summarizes the early history of the theory of phase transitions driven by topological defects, such as vortices in superfluid helium films or dislocations and disclinations in two-dimensional solids. We start with a review of our two earliest papers, pointing out their errors and omissions as well as their insights. We then describe the work, partly done by Kosterlitz but mostly done by other people, which corrected these oversights, and applied these ideas to experimental systems, and to numerical and experimental simulations.

  7. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

    Pepe, Margaret S.; Janes, Holly; Li, Christopher I.

    2016-01-01

    BACKGROUND: Many cancer biomarker research studies seek to develop markers that can accurately detect or predict future onset of disease. To design and evaluate these studies, one must specify the levels of accuracy sought. However, justified target levels are rarely available. METHODS: We describe...... for ovarian cancer. CONCLUSIONS: It is feasible to specify target levels of biomarker performance that enable evaluation of the potential clinical impact of biomarkers in early-phase studies. Nevertheless, biomarkers meeting the criteria should still be tested rigorously in studies that measure the actual...

  8. The Influence of Pregnancy Outcomes with Estradiol Valerate in Addition during Luteal Phase in IVF- ET Cycles%移植后补充戊酸雌二醇对IVF-ET妊娠结局的影响

    Institute of Scientific and Technical Information of China (English)

    马兰; 镡颖; 陈静思

    2013-01-01

    Objective To evaluate the influence of pregnancy outcomes with different dosage of estradiol valerate in addition to progesterone for luteal supplementation in IVF-ET cycles. Methods From February 2011 to October 2012, 362 patients undergoing IVF-ET in the second affiliated hospital of Kunming Medical University were selected. The patients were randomly assigned into three groups. Since oocyte retrieval, all of them were injected luteal supplementation with progesterone in oil 60 mg/d, im. Group A as control group (112 cases) did not add with pentanoic acid estradiol;Group B for the experimental group (122 cases), added pentanoic acid estradiol 4 mg/d after embryo transfer;Group C for the experimental group (128 cases) added pentanoic acid estradiol 6 mg/d after embryo transfer. Finally the pregnancy outcome and implantation rate were compared for each group. Results There were no significant differences between group A and group B, group B and group C in the rate of embryos grow and pregnancy rate ( >0.05) . The embryo planting rate and pregnancy rate have significant difference between Group A and group C ( < 0.05) . Conclusion 6 mg/d fill estradiol valerate for luteal supplementation may improve implantation rate and pregnancy rate after IVF.%目的:探讨胚胎移植后黄体期不同剂量戊酸雌二醇对体外受精-胚胎移植(IVF-ET)妊娠结局的影响.方法选取2011年2月至2012年10月在昆明医科大学第二附属医院生殖医学科接受IVF-ET的患者362例,随机分为3组,用标准长方案进行控制性超促排卵,均自取卵日后行黄体酮肌注60 mg/d.A组为对照组,112例,不加用戊酸雌二醇;B组为实验组1,122例,在移植后加用戊酸雌二醇4 mg/d;C组为实验组2,128例在移植后加用戊酸雌二醇6 mg/d;比较各组妊娠结局.结果 A组和B组的胚胎种植率和妊娠率差异无统计学意义(>0.05);B组和C组的胚胎种植率和妊娠率

  9. Transcriptomes of bovine ovarian follicular and luteal cells

    Science.gov (United States)

    RNA expression analysis was performed on four somatic ovarian cell types using a gene array panel: the granulosa cells (GCs) and theca cells (TCs) of the dominant follicle and the large luteal cells (LLCs) and small luteal cells (SLCs) of the corpus luteum. The normalized linear microarray data was ...

  10. 促性腺激素释放激素激动剂用于辅助生殖技术黄体支持的荟萃分析%Effect of luteal-phase gonadotropin-releasing hormone agonist administration on pregnancy outcome in IVF/ICSI cycles:a systematic review and Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    余璐萍; 刘宁; 刘英

    2016-01-01

    目的系统评价促性腺激素释放激素激动剂(GnRH-a)用于辅助生殖技术(ART)黄体支持后,对妊娠结局产生的影响。方法计算机检索PubMed数据库、EMBASE数据库、Cochrane图书馆、随机对照试验(RCT)注册中心[WHO国际临床试验注册平台(ICTRP)和ClinicalTrials.gov]、中国生物医学文献数据库(CBM)、中国知网(CNKI)数据库及万方医学数据库中发表于2015年11月之前的原创性研究论文;收集在体外受精(IVF)或卵母细胞胞质内单精子注射(ICSI)中,GnRH-a应用于黄体支持的RCT文献。根据Cochrane系统评价方法,由2位评价员根据纳入及排除标准独立进行文献筛选、资料提取和质量评价后,采用Stata 13.0软件对符合质量标准的RCT文献进行荟萃分析,分析GnRH-a用于ART黄体支持后对妊娠结局产生的影响。结果共纳入11项研究,3406例患者,3280个周期。以采用标准黄体支持方案的研究人群为对照组,在标准黄体支持方案基础上加入GnRH-a的研究人群为试验组。试验组与对照组比较,出生率或继续妊娠率(RR=1.29,95%CI为1.11~1.51)、临床妊娠率(RR=1.24,95%CI为1.08~1.43)、多胎率(RR=1.95,95%CI为1.21~3.14)均明显增加。结论目前的证据表明,无论采用激动剂方案或拮抗剂方案降调,在黄体支持中加入GnRH-a均可增加出生率或继续妊娠率、临床妊娠率、多胎率,可为ART过程中的黄体支持提供新的治疗方案。%Objective To evaluate the potential efficacy and safety of gonadotropin-releasing hormone agonist(GnRH-a) administration in the luteal-phase on in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles in assisted reproductive technology (ART). Methods The relevant papers published before November 2015 were electronically searched in PubMed, EMBASE, Cochrane Library, WHO ICTRP, ClinicalTrials.gov, CNKI, CBM and Wan

  11. The Effects of Anordrin on Luteal Cells,Decidual Cells and Trophoblast Cells in Vitro

    Institute of Scientific and Technical Information of China (English)

    孙朝霞; 陈浩安; 游根娣; 曹霖; 顾芝萍

    1999-01-01

    By using the morphology and the viability of ceils index,the direct effects of anordrin on serum-free primary cultures of rat luteal cells,human decidual ceils and trophoblast cells were observed.Meanwhile,the effect of anordrin on the secretive function of rat luteal cells was also observed.The results indicated that(1)anordrin has damaging effects on rat luteal cells,human decidual cells and trophoblast ceils.The LDsas were 14.34±0.9 μg/ml,17.33±4.1μg/ml and 34.87±4.9μg/ml re-spectively.(2)With nonlethal dose (5μg/ml),the activity of progesterone secretion of rat lutein cells which was stimulated by hCG and pregnenolone was not influenced by anordrin while the stimulating activity of forskolin was inhibited remarkably.The results suggest that luteolytic action is the main mechanism of the termination of early pregnancy by anordrin and the direct damaging effects of anordrin on decidua and cy-totrophoblasts also play a role in the termination of early pregnancy.

  12. Effects of periovulatory gonadotrophin treatment on luteal function and endometrial expression of selected genes in cyclic pony mares.

    Science.gov (United States)

    Köhne, Martin; Ille, Natascha; Erber, Regina; Adib Razavi, Mahsa S; Walter, Ingrid; Aurich, Christine

    2016-12-01

    Progestin concentration in plasma during the early luteal phase is crucial for endometrial function and conceptus development. We hypothesized that periovulatory gonadotrophin treatment via support of luteal function affects endometrial gene expression in horses. Effect of age was analyzed as well. Shetland mares (n = 8, age 4-25 years) were assigned to the following treatments during five consecutive cycles in alternating order following a cross-over design: treatment hCG/-: preovulatory injection of hCG, but no gonadotrophin injection at detection of ovulation, treatment -/hCG: no preovulatory gonadodrophin injection, but injection of hCG at detection of ovulation, treatment eCG/-: preovulatory injection of eCG, but no gonadotrophin injection at detection of ovulation, treatment -/eCG: no preovulatory gonadotrophin injection, but injection of eCG at detection of ovulation, treatment control: no treatment. Concentration of progestin was analyzed by ELISA from the day of ovulation until Day 10. On Day 10, endometrial cells were collected transvaginally by cytobrush technique. Expression of mRNA of cyclooxygenase-2 (COX-2), prostaglandin F2α-synthase, prostaglandin E-synthase, progesterone receptor (PR), estradiol receptor (E2R), acyl-CoA-dehydrogenase (ACAD), uteroglobin (UGB), uteroferrin, and uterocalin was analyzed by RT qPCR. Immunohistological staining of endometrial tissue, obtained via biopsy, was performed for COX-2, PR and UGB. The P4 concentration was influenced by day of cycle (P PR positive stromal cells (e.g. mare 1 (4 years): 65.5 ± 2.6, mare 2 (24 years): 82.7 ± 2.2%, P function and expression of PRs in the endometrium can at least in part be explained by differences in the reproductive physiology between horses and ponies. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Impact of GnRH agonist triggering and intensive luteal steroid support on live-birth rates and ovarian hyperstimulation syndrome: a retrospective cohort study.

    Science.gov (United States)

    Iliodromiti, Stamatina; Lan, Vuong Thi Ngoc; Tuong, Ho Manh; Tuan, Phung Huy; Humaidan, Peter; Nelson, Scott M

    2013-12-26

    Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory implantation rates can be sustained. The objective of this study was to assess the live-birth rate and incidence of OHSS after GnRHa trigger and intensive luteal steroid support compared to traditional hCG trigger and conventional luteal support in OHSS high risk Asian patients. We conducted a retrospective cohort study of 363 women exposed to GnRHa triggering with intensive luteal support compared with 257 women exposed to conventional hCG triggering. Women at risk of OHSS were defined by ovarian response ≥15 follicles ≥12 mm on the day of the trigger. Live-birth rates were similar in both groups GnRHa vs hCG; 29.8% vs 29.2% (p = 0.69). One late onset severe OHSS case was observed in the GnRHa trigger group (0.3%) compared to 18 cases (7%) after hCG trigger. GnRHa trigger combined with intensive luteal steroid support in this group of OHSS high risk Asian patients can facilitate fresh embryo transfer, however, in contrast to previous reports the occurrence of late onset OHSS was not completely eliminated.

  14. Gelatinases, endonuclease and Vascular Endothelial Growth Factor during development and regression of swine luteal tissue

    Directory of Open Access Journals (Sweden)

    Bacci Maria

    2006-11-01

    Full Text Available Abstract Background The development and regression of corpus luteum (CL is characterized by an intense angiogenesis and angioregression accompanied by luteal tissue and extracellular matrix (ECM remodelling. Vascular Endothelial Growth Factor (VEGF is the main regulator of angiogenesis, promoting endothelial cell mitosis and differentiation. After the formation of neovascular tubes, the remodelling of ECM is essential for the correct development of CL, particularly by the action of specific class of proteolytic enzymes known as matrix metalloproteinases (MMPs. During luteal regression, characterized by an apoptotic process and successively by an intense ECM and luteal degradation, the activation of Ca++/Mg++-dependent endonucleases and MMPs activity are required. The levels of expression and activity of VEGF, MMP-2 and -9, and Ca++/Mg++-dependent endonucleases throughout the oestrous cycle and at pregnancy were analyzed. Results Different patterns of VEGF, MMPs and Ca++/Mg++-dependent endonuclease were observed in swine CL during different luteal phases and at pregnancy. Immediately after ovulation, the highest levels of VEGF mRNA/protein and MMP-9 activity were detected. On days 5–14 after ovulation, VEGF expression and MMP-2 and -9 activities are at basal levels, while Ca++/Mg++-dependent endonuclease levels increased significantly in relation to day 1. Only at luteolysis (day 17, Ca++/Mg++-dependent endonuclease and MMP-2 spontaneous activity increased significantly. At pregnancy, high levels of MMP-9 and VEGF were observed. Conclusion Our findings, obtained from a precisely controlled in vivo model of CL development and regression, allow us to determine relationships among VEGF, MMPs and endonucleases during angiogenesis and angioregression. Thus, CL provides a very interesting model for studying factors involved in vascular remodelling.

  15. Early Phases of Protoplanetary Disk Evolution

    NARCIS (Netherlands)

    Kamp, Inga; Macchetto, FD

    2010-01-01

    It is widely accepted that planetary systems form from protoplanetary disks, and observations of the dust reveal significant grain growth over timescales of a few million years. However, we know little about the gas processing in the first 10-20 Myr of disk evolution. This is the phase where protopl

  16. Steady-state concentrations of mRNA encoding two inhibitors of protein kinase C in ovine luteal tissue.

    Science.gov (United States)

    Juengel, J L; Melner, M H; Clapper, J A; Turzillo, A M; Moss, G E; Nett, T M; Niswender, G D

    1998-07-01

    Prostaglandin F2 alpha (PGF2 alpha) decreases secretion of progesterone from the corpus luteum in domestic ruminants. However, it is less effective during the early part of the oestrous cycle (Louis et al., 1973) and at the time of maternal recognition of pregnancy (Silvia and Niswender, 1984; Lacroix and Kann, 1986). Decreased luteal responsiveness may be due to failure of PGF2 alpha to activate fully its normal second messenger system, protein kinase C (PKC). Alternatively, increased resistance of the corpus luteum to PGF2 alpha might be attributable to greater concentrations of recently identified biological inhibitors of PKC. These possibilities were addressed by measuring steady-state concentrations of mRNA encoding PGF2 alpha receptor and two inhibitors of PKC, protein kinase C inhibitor-1 (PKCI-1) and kinase C inhibitor protein-1 (KCIP-1, brain 14-3-3 protein), in corpora lutea collected from ewes on days 4, 10 and 15 of the oestrous cycle (n = 5 per day) and day 15 of pregnancy (n = 7). There were no differences in mean concentrations of mRNA encoding PGF2 alpha receptor among the groups. However, concentrations of mRNA encoding both inhibitors of PKC were higher (P day 4 of the oestrous cycle compared with the other groups. Treatment of ewes with a luteolytic dose of PGF2 alpha, which activates PKC, did not change concentrations of mRNA encoding either PKCI-1 or KCIP-I up to 24 h later. Luteal expression of mRNA encoding the PKC inhibitors and PGF2 alpha receptor was also examined in ewes treated with oestradiol in vivo for 16 h in the midluteal phase. High concentrations of oestradiol in serum (20 and 70 pg ml-1) did not influence quantities of any of the mRNAs examined. Therefore, an increase in PKC inhibitors may be involved in resistance of the corpus luteum to PGF2 alpha during the early part of the oestrous cycle but does not appear to mediate the increased resistance of the corpus luteum to PGF2 alpha during maternal recognition of pregnancy

  17. Chandra Catches Early Phase of Cosmic Assembly

    Science.gov (United States)

    2004-08-01

    A NASA Chandra X-ray Observatory image has revealed a complex of several intergalactic hot gas clouds in the process of merging. The superb Chandra spatial resolution made it possible to distinguish individual galaxies from the massive clouds of hot gas. One of the clouds, which that envelops hundreds of galaxies, has an extraordinarily low concentration of iron atoms, indicating that it is in the very early stages of cluster evolution. "We may be seeing hot intergalactic gas in a relatively pristine state before it has been polluted by gas from galaxies," said Q. Daniel Wang of the University of Massachusetts in Amherst, and lead author on an upcoming Astrophysical Journal article describing the study. "This discovery should provide valuable insight into how the most massive structures in the universe are assembled." 3-Panel Image of Abell 2125, Its Core & Galaxy C153 3-Panel Image of Abell 2125, Its Core & Galaxy C153 The complex, known as Abell 2125,is about 3 billion light years from Earth, and is seen at a time about 11 billion years after the Big Bang, when many galaxy clusters are believed to have formed. The Chandra Abell 2125 image shows several huge elongated clouds of multimillion degree gas coming together from different directions. These hot gas clouds, each of which contains hundreds of galaxies, appear to be in the process of merging to form a single massive galaxy cluster. Chandra, Hubble Space Telescope, and Very Large Array radio telescope data show that several galaxies in the Abell 2125 core cluster are being stripped of their gas as they fall through surrounding high-pressure hot gas. This stripping process has enriched the core cluster's gas in heavy elements such as iron. Abell 2125's Core & Galaxy C153 Abell 2125's Core & Galaxy C153 The gas in the pristine cloud, which is still several million light years away from the core cluster, is conspicuous for its lack of iron atoms. This anemic cloud must be in a very early evolutionary stage. The

  18. Effects of Different Levels of Diet on Plasma Physiochemical Indexes and Folliculogenesis in Hu Sheep During the Luteal Phase%不同营养水平对湖羊黄体期血液理化指标及卵泡发育的影响

    Institute of Scientific and Technical Information of China (English)

    应诗家; 王锋; 聂海涛; 张国敏; 吴勇聪; 王子玉; 庞训胜; 王昌龙; 何东洋; 贾若欣

    2012-01-01

    [Objective ] The present study was designed to investigate the effects of different plasma physiochemical indexes on folliculogenesis in Hu sheep fed with different levels of diet during the luteal phase. [Method] Twenty-eight multiparous Hu sheep were assigned into 3 groups and received a maintenance diet (C group), 0.5*M (R group) and 1.5*M (S group), respectively, for 6 days of their estrous cycle. Six ewes in each group were laughtered on day 12 of the estrous cycle. The remaining ewes were received a maintenance diet until the next estrus. Blood was sampled on days 7,8,10 and 12 of the estrous cycle. [Result] As dietary intake increased, the number of follicles of ≥3.5 mm was significantly increased (P0.05), however, there was a significant effect of day on plasma uric acid, ammonia, low density lipoprotein concentrations and aspartate transaminase activity (P<0.05). [Conclusion] Different nutritional requirements and metabolic features were present in different physiological periods during ovine luteal phaseand the mechanism by which dietary restriction inhibited folliculogenesis may involve responses to the increased capacity of lipolysis and protein degradation and the decreased capacity of lipid and protein synthesis.%[目的]研究不同营养水平对湖羊黄体期血液理化指标及卵泡发育的影响.[方法]选择28只经产母羊,于发情周期第6天分别按0.5倍体重维持需要量(R组),1倍体重维持需要量(C组)和1.5倍体重维持需要量(S组)饲喂6d,第12天每组屠宰6头;剩下的湖羊用于观察发情;分别于发情周期第7、8、10和12天采血.[结果]随着营养水平的提高,≥3.5 mm的卵泡数量显著增加(P<0.05)、2.5-3.5 mm的卵泡数量显著降低(P<0.05),平均发情周期缩短(P<0.05),血液尿素、胆固酵和游离脂肪酸含量显著下降(P<0.05),甘油三酯含量显著提高(p<0.05);S组乳酸脱氢酶活性显著高于C组(P<0.05);血液尿酸、血氨、高密度

  19. GnRH agonist ovulation trigger and hCG-based, progesterone-free luteal support: a proof of concept study

    DEFF Research Database (Denmark)

    Kol, Shahar; Humaidan, Peter; Itskovitz-Eldor, Joseph

    2011-01-01

    BACKGROUND It is now well established that a GnRH agonist (GnRHa) ovulation trigger completely prevents ovarian hyperstimulation syndrome. However, early studies, using conventional luteal support, showed inferior clinical results following a GnRHa trigger compared with a conventional hCG trigger...

  20. Natural influence of season on follicular, luteal, and endocrinological turnover in Indian crossbred cows.

    Science.gov (United States)

    Satheshkumar, S; Brindha, K; Roy, A; Devanathan, T G; Kathiresan, D; Kumanan, K

    2015-07-01

    The study was aimed at investigating the effect of seasonal changes on follicular and luteal dynamics in vivo in normally cycling crossbred cows during summer and winter months of the year. Six healthy regularly cycling Jersey crossbred nonlactating pluriparous cows were used for the study. Follicular and luteal developmental pattern was studied every other day throughout the estrous cycle by scanning the ovaries during two periods of a year viz., hot season (April to June; n = 16) and cold season (December to February; n = 12). Plasma progesterone (P4) concentrations were measured on Days 0 (estrus), 6, and 12 of the estrous cycle. Among the 12 cycles studied during the cold season, 11 (91.7%) had three waves and one had two waves. Of 16 cycles studied during the hot season, eight (50%) had two waves, four (25%) had three waves, and the remaining four cycles had single (n = 2) and four waves (n = 2). High P4 concentrations during the midcycle would have suppressed the dominant follicle of the second follicular wave and induced the emergence of the third wave during the cold season. The first follicular wave (wave I) of the cycle emerged much earlier (Day 0.5 ± 0.3) during the cold season than that in the hot season (Day 1.7 ± 0.4). The ovulatory wave emerged significantly earlier during the hot season (Day 11.5 ± 1.3) than in the cold season (Day 14.8 ± 0.4), and hence, the growth phase of ovulatory follicle significantly increased during the former season (11.0 ± 1.4 days) than the latter (5.8 ± 0.2 days). The ovulatory follicle attained a significantly larger diameter (12.8 ± 0.8 mm) to express the estrus during the hot season when compared to the cold season (11.3 ± 0.4 mm), which might be indicative of alterations in steroidogenic activity within the follicular microenvironment. During the midphase of the cycle, a period critical for embryonic sustenance, the P4 level was significantly reduced in the hot months indicating suppression of luteal activity

  1. Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates.

    Science.gov (United States)

    Vohs, Jenifer L; Hummer, Tom A; Yung, Matthew G; Francis, Michael M; Lysaker, Paul H; Breier, Alan

    2015-06-29

    Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis.

  2. Early Phase Observations of the KVN+VERA Joint Array

    CERN Document Server

    Sawada-Satoh, S

    2013-01-01

    The KVN+VERA array is a joint VLBI project of seven VLBI stations spread throughout Korea and Japan. Since the first fringe detection in 2008, the early phase observations of the KVN+VERA have been carried out every several months. Currently, two observing bands of 22 and 43 GHz are available. We are aiming for early realization of science observations with the 1-Gbps recording system from 2012.

  3. Improving decision making in the early phases of configuration projects

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik; Hvam, Lars; Harlou, Ulf

    2011-01-01

    During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system and qual......During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system......) customers with very convincing results. © International Journal of Industrial Engineering....

  4. Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients

    Directory of Open Access Journals (Sweden)

    Irigoyen Marcela

    2010-10-01

    Full Text Available Abstract Background Various endometrial abnormalities have been associated with luteal phase deficiency: a significant dyssynchrony in the maturation of the glandular epithelium and the stroma and a prevalence of out-of-phase endometrial biopsy specimens. Out-of phase endometrium is a controversial disorder related to failed implantation, infertility and early pregnancy loss. Given that the regulation of the apoptotic process in endometrium of luteal phase deficiency is still unknown, the aim of this study was to evaluate cell proliferation, apoptosis and the levels of the main effector caspase, caspase-3 in the luteal in-phase and out-of-phase endometrium. Methods Thirty-seven endometrial samples from sterile or recurrent abortion patients were included in this study: 21 in-phase samples (controls and 16 samples with out-of-phase endometrium. Biopsy specimens of eutopic endometrium were obtained from all subjects during days 21-25 of the menstrual cycle. The endometrium with endometrial maturity of cycle day 25 or less at the time of menstruation was considered out-of phase. Endometrial tissues were fixed in 10% buffered formaldehyde. For apoptosis quantification, sections were processed for in situ immunohistochemical localization of nuclei exhibiting DNA fragmentation, by the terminal deoxynucleotidyl transferase (TdT-mediated dUTP digoxygenin nick-end labeling (TUNEL technique. Expressions of Proliferating Cell Nuclear Antigen (PCNA as a marker of cell proliferation, and of cleaved caspase-3 as a marker of apoptosis, were assessed by immunohistochemistry in the luteal in-phase and out-of-phase endometrium from infertile and recurrent abortion patients. Results Luteal out-of-phase endometrium had increased apoptosis levels compared to in-phase endometrium (p Conclusions this study represents the first report describing variations at the cell proliferation and cell death levels in the out-of-phase endometrium in comparison with in-phase

  5. Improving early clinical trial phase identification of promising therapeutics.

    Science.gov (United States)

    Kent, Thomas A; Shah, Shreyansh D; Mandava, Pitchaiah

    2015-07-21

    This review addresses decision-making underlying the frequent failure to confirm early-phase positive trial results and how to prioritize which early agents to transition to late phase. While unexpected toxicity is sometimes responsible for late-phase failures, lack of efficacy is also frequently found. In stroke as in other conditions, early trials often demonstrate imbalances in factors influencing outcome. Other issues complicate early trial analysis, including unequally distributed noise inherent in outcome measures and variations in natural history among studies. We contend that statistical approaches to correct for imbalances and noise, while likely valid for homogeneous conditions, appear unable to accommodate disease complexity and have failed to correctly identify effective agents. While blinding and randomization are important to reduce selection bias, these methods appear insufficient to insure valid conclusions. We found potential sources of analytical errors in nearly 90% of a sample of early stroke trials. To address these issues, we recommend changes in early-phase analysis and reporting: (1) restrict use of statistical correction to studies where the underlying assumptions are validated, (2) select dichotomous over continuous outcomes for small samples, (3) consider pooled samples to model natural history to detect early therapeutic signals and increase the likelihood of replication in larger samples, (4) report subgroup baseline conditions, (5) consider post hoc methods to restrict analysis to subjects with an appropriate match, and (6) increase the strength of effect threshold given these cumulative sources of noise and potential errors. More attention to these issues should lead to better decision-making regarding selection of agents to proceed to pivotal trials.

  6. Early phase Technology Assessment of nanotechnology in oncology.

    Science.gov (United States)

    Retèl, Valesca P; Hummel, Marjan J M; van Harten, Willem H

    2008-01-01

    To perform early Technology Assessment (TA) of nanotechnology in oncology. The possibilities of nanotechnology for detection (imaging), diagnosis and treatment of cancer are subject of different research programs where major investments are concerned. As a range of bio- nanotechnologies is expected to enter the oncology field it is relevant to consider the various aspects involved in especially early TA. This article provides two cases of early assessment of (predecessors of) nanotechnologies: Microarray Analysis and Photodynamic Therapy implementation, which methodology can be extrapolated to other nanotechnologies in oncology. Constructive Technology Assessment (CTA) is used for the introduction of technologies that are still in a dynamic phase of development or in an early stage of diffusion. The selection of studied aspects in CTA is based on: clinical aspects (safety, efficacy, and effectiveness), economic (cost-effectiveness), patient related (QoL, ethical/juridical and psychosocial), organizational aspects (diffusion and adoption) and scenario drafting. The features of the technology and the phase of implementation are decisive for choices and timing of the specific aspects to be studied. A framework was drafted to decide on the relevant aspects. In the first case, early implementation of Microarray Analysis; clinical effectiveness, logistics, patient centeredness and scenario drafting were given priority. Related to the diffusion-phase of Photodynamic Therapy however other aspects were evaluated, such as early cost-effectiveness analysis for possible reimbursement. Often CTA will result in a mixed method design. Especially scenario drafting is a powerful instrument to predict possible developments that can be anticipated upon in the assessment. CTA is appropriate for the study of early implementation of new technologies in oncology. In early TA small series often necessitate a mix of quantitative and qualitative methods. The features of nanotechnology

  7. Early Phase Requirements Assessment of a Teletreatment Trial

    NARCIS (Netherlands)

    Widya, I.A.; van Beijnum, Bernhard J.F.; Bults, Richard G.A.; Sandjö, L.; Schaake, L.; Huis in 't Veld, M.H.A.; Jones, Valerie M.; Hermens, Hermanus J.; Shin, S.Y.; Ossowski, S.

    2009-01-01

    This paper presents the early phase requirements elicitation of a teletreatment trial and the assessment of the requirements in respect of their importance to the trial and the feasibility of the corresponding adaptations of the telemedicine system within the trial project constraints. The

  8. Improving decision making in the early phases of configuration projects

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik; Harlou, Ulf; Haug, Anders

    2008-01-01

    During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system and qual......During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system......¬eling in configuration projects. Each of the five phases is sup¬ported by a set of tools. The main idea of the pro¬cedure is utili¬zation of a so-called Product Family Master Plan, which is a formal description of the product assortment and its variation. The procedure has been tested at one of Baan's cus¬tomers...

  9. Early phase of acute pancreatitis: Assessment and management

    Institute of Scientific and Technical Information of China (English)

    Veit; Phillip; Jrg; M; Steiner; Hana; Algül

    2014-01-01

    Acute pancreatitis(AP) is a potentially life-threatening disease with a wide spectrum of severity. The overall mortality of AP is approximately 5%. According to the revised Atlanta classification system, AP can be classified as mild, moderate, or severe. Severe AP often takes a clinical course with two phases, an early and a late phase, which should both be considered separately. In this review article, we first discuss general aspects of AP, including incidence, pathophysiology, etiology, and grading of severity, then focus on the assessment of patients with suspected AP, including diagnosis and risk stratification, followed by the management of AP during the early phase, with special emphasis on fluid therapy, pain management, nutrition, and antibiotic prophylaxis.

  10. Improving decision making in the early phases of configuration projects

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik; Harlou, Ulf; Haug, Anders

    2008-01-01

    During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system and qual......During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system......¬eling in configuration projects. Each of the five phases is sup¬ported by a set of tools. The main idea of the pro¬cedure is utili¬zation of a so-called Product Family Master Plan, which is a formal description of the product assortment and its variation. The procedure has been tested at one of Baan's cus...

  11. Improving decision making in the early phases of configuration projects

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik; Hvam, Lars; Harlou, Ulf

    2011-01-01

    During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system and qual......During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system...... in configuration projects. Each of the five phases is supported by a set of tools. The main idea of the procedure is utilization of a so-called Product Family Master Plan, which is a formal description of the product assortment and its variation. The procedure has been tested at one of Baan's (SSA Global...

  12. Horava-Lifshitz early universe phase transition beyond detailed balance

    Energy Technology Data Exchange (ETDEWEB)

    Kheyri, F.; Khodadi, M.; Sepangi, H.R. [Shahid Beheshti University, Department of Physics, Tehran (Iran, Islamic Republic of)

    2013-01-15

    The early universe is believed to have undergone a QCD phase transition to hadrons at about 10 {mu}s after the big bang. We study such a transition in the context of the non-detailed balance Horava-Lifshitz theory by investigating the effects of the dynamical coupling constant {lambda} in a flat universe. The evolution of the relevant physical quantities, namely the energy density {rho}, temperature T, scale factor a and the Hubble parameter H is investigated before, during and after the phase transition, assumed to be of first order. Also, in view of the recent lattice QCD simulations data, we study a cross-over phase transition of the early universe whose results are based on two different sets of lattice data. (orig.)

  13. Follicle Development during Luteal Phase and Altrenogest Treatment in Pigs

    NARCIS (Netherlands)

    Soede, N.M.; Bouwman, E.G.; Langendijk, P.; Laan, van der I.; Kanora, A.; Kemp, B.

    2007-01-01

    Synchronization of the oestrous cycle of gilts using altrenogest treatment has been found to increase ovulation rate. The current experiment investigated if the increase in ovulation rate after altrenogest treatment is related to increased follicle size at the end of altrenogest treatment compared w

  14. Epithelial lining of the endometrium during the luteal phase in ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-15

    Dec 15, 2009 ... underwent two endometrial biopsies 2-7 days after human chronic gonadotrophin (HCG) administration. ... epithelial cells lining the uterine cavity loses their ... by dehydration in graded series of ethanol, followed by a graded.

  15. Endometrial Prostaglandins in Menstrual Cycle and Early Pregnancy:Effects of Antigestogens

    Institute of Scientific and Technical Information of China (English)

    DavidTBaird

    1992-01-01

    Antigestogens such as mifepristone oppose the action of endogenous progesteroneby blocking the progesterone receptor in the uterus. There is a modest increase in thecapacity of endonterium from the luteal phase of the cyele and.from decidua of early pregnancy to generate prostaglandins after the administration of antigestogens. Coup-led with a decrease in the metabolism of prostaglandins, this may lead to an increase inconcentration of PGF, and other prostaglandins which cause myometrial contractionsand decidual necrosis.

  16. Entropy production in the early-cosmology pionic phase

    CERN Document Server

    Dobado, Antonio; Rodriguez-Fernandez, David

    2015-01-01

    We point out that in the early universe, for temperatures in the approximate interval 175-80 MeV (after the quark-gluon plasma), pions carried a large share of the entropy and supported the largest inhomogeneities. Thus, we examine the production of entropy in a pion gas, particularizing to inhomogeneities of the temperature, for which we benefit from the known thermal conductivity. We finally put that entropy produced in relaxing such thermal inhomogeneities in the broad context of this relatively unexplored phase of early-universe cosmology.

  17. The retention of academics in the early career phase

    Directory of Open Access Journals (Sweden)

    Coenraad Bester

    2008-12-01

    Full Text Available The purpose of the study was to determine to what extent academics in the early career phase at a South African higher education institution are committed to the institution in question and the impact which this commitment has on labour turnover. More than 21% of the original respondents left the institution while this research was still underway. Insufficient financial remuneration was the most important reason why the respondents considered leaving the institution.

  18. THROMBOCYTOPENIA & RUPTURED CORPUS LUTEAL CYST : A DEADLY COMBINATION: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Baidya

    2015-07-01

    Full Text Available Ovarian corpus luteal cyst occurs during reproductive years, at end of menstrual cycle, or during pregnancy. The presentation of ruptured luteal cyst may vary from no symptoms to symptoms and signs of acute abdomen . 1 Ruptured corpus luteal cyst in some instances causes massive intraperitoneal hemorrhage leading to death in patient , 2 particularly those with bleeding diathesis. Fitzgerald & Berrigan (1959 called it an “ovarian accident”& it is rarely accurately diagnosed before operation . 3 In this case report, we will depict a case of ruptured corpus luteal cyst which became catastrophic for the patient with thrombocytopenia.

  19. Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

    Science.gov (United States)

    Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

    2016-01-01

    Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, poptimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (poptimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

  20. Information about robustness, reliability and safety in early design phases

    DEFF Research Database (Denmark)

    Marini, Vinicius Kaster

    This thesis is motivated by the need for support in considerations of robustness, reliability and safety during early design phases. The thesis deals with the question of how to codify and communicate failures and hazards, and devises measures against these. Current methods to robustness, reliabi......This thesis is motivated by the need for support in considerations of robustness, reliability and safety during early design phases. The thesis deals with the question of how to codify and communicate failures and hazards, and devises measures against these. Current methods to robustness......, reliability and safety reviewed have shortcomings including the complexity of using them and dependence on expert input for mitigating uncertainty and ambiguity among solution alternatives. This research is carried out using case studies: a pilot case to assess information requirements from reliability...... methods, and an industrial case to assess how the use of information about robustness, reliability and safety as practised by current methods influences concept development. Current methods cannot be used in early design phases due to their dependence on detailed design information for the identification...

  1. Physiotherapy in early phase of low back pain

    Directory of Open Access Journals (Sweden)

    Markku Paatelma

    2011-03-01

    Full Text Available Markku PaatelmaDepartment of Education, Auron – OMT Center, Helsinki, FinlandAbstract: Low back pain (LBP is a substantial health problem and has subsequently attracted a considerable amount of research both in the early and chronic phases. Chronic, nonspecific LBP indicates limited effectiveness from most commonly applied interventions and approaches, but it seems to be opposite in the early phase. Intervention is more effective than advice on staying active in acute LBP, leading to more rapid improvement in function, mood, quality of life, and general health. We compared physiotherapy (PT that involved 3–7 treatment sessions based on subclassification in early phase LBP (acute and subacute LBP lasting <3 months to one session of PT that advised staying active, in 134 LBP patients. Low back and leg pain, disability, and days of sick-leave were evaluated. After 12 months, all groups had only minimal pain and disability. In the advice-only group, those patients who had radiating pain had less improvement compared with other groups, and increasing days of sick-leave because of LBP after 12 months. Compared with the advice-only group, orthopedic manual therapy and McKenzie methods seemed to be slightly more effective than one session of assessment in pain and disability.Keywords: OMT, advice, low back pain 

  2. Quark-Hadron Phase Transitions in Viscous Early Universe

    CERN Document Server

    Tawfik, A

    2011-01-01

    Based on hot big bang theory, the cosmological matter is conjectured to undergo QCD phase transition(s) to hadrons, when the universe was about $1-10 \\mu$s old. In the present work, we study the quark-hadron phase transition, by taking into account the effect of the bulk viscosity. We analyze the evolution of the quantities relevant for the physical description of the early universe, namely, the energy density $\\rho$, temperature $T$, Hubble parameter $H$ and scale factor $a$ before, during and after the phase transition. To study the cosmological dynamics and the time evolution we use both analytical and numerical methods. By assuming that the phase transition may be described by an effective nucleation theory (prompt {\\it first-order} phase transition), we also consider the case where the universe evolved through a mixed phase with a small initial supercooling and monotonically growing hadronic bubbles. The numerical estimation of the cosmological parameters, $a$ and $H$ for instance, makes it clear that th...

  3. Phase relationship between alternans of early and late phases of ventricular action potentials.

    Directory of Open Access Journals (Sweden)

    Linyuan eJing

    2012-06-01

    Full Text Available Background: Alternans of early phase and of duration of action potential (AP critically affect dispersion of refractoriness through their influence on conduction and repolarization. We investigated the phase relationship between the two alternans and its effect on conduction. Methods and Results: Transmembrane potentials recorded from ventricles of 8 swine and 3 canines during paced activation intervals of ≤ 300 ms were used to quantify alternans of maximum rate of depolarization (|dv/dt|max and of APD. Incidence of APD alternans was 62% and 76% in swine and canines. Alternans of APD was frequently accompanied with alternans of |dv/dt|max. Of these, 4 and 26 % were out of phase in swine and canines, i.e. low |dv/dt|max preceded long APD. Computer simulations show that out of phase alternans attenuate variation of wavelength and thus minimize formation of spatially discordant alternans. Conclusions: The spontaneous switching of phase relationship between alternans of depolarization and repolarization suggests that mechanisms underlying these alternans may operate independent of each other. The phase between these alternans can critically impact spatial dispersion of refractoriness and thus stability of conduction, with the in phase relation promoting transition from concord to discord while out of phase preventing formation of discord.

  4. Luteal maintenance of pregnancy in the African elephant (Loxodonta africana).

    Science.gov (United States)

    Stansfield, F J; Allen, W R

    2012-06-01

    The ovaries of eight African elephant foetuses and their mothers between 2 and 22 months of gestation, and those of two cycling and two lactating elephants, were examined grossly, histologically and immunocytochemically, with emphasis on the development and regression of accessory corpora lutea (CL) of pregnancy and the steroidogenic capacities of the accessory CL and the foetal ovaries. The results supported recent findings that the accessory CL form as a result of luteinisation, with and without ovulation, of medium-sized follicles during the 3-week inter-luteal period of the oestrous cycle. They enlarge significantly and become steroidogenically active around 5 weeks of gestation, probably in response to the placental lactogen which is secreted by the implanting trophoblast of the conceptus. The large luteal cells stained strongly for 3β hydroxysteroid dehydrogenase (3βHSD) activity throughout the 22-month gestation period although they showed vacuolation and other degenerative changes in the final months of gestation coincident with hypertrophy and hyperplasia of 3βHSD-positive interstitial cells in the foetal gonads. It is proposed that the progestagens secreted by the enlarged gonads of the elephant foetus may function both to assist the maternal ovaries in supporting the pregnancy state and to induce torpor and intrauterine immobility of the rapidly growing foetus.

  5. Effect of antiprogestin ZK 98. 734 on the ovarian cycle, early pregnancy, and on its binding to progesterone receptors in the myometrium of marmoset Callithrix jacchus

    Energy Technology Data Exchange (ETDEWEB)

    Puri, C.P.; Kholkute, S.D.; Pongubala, J.M.; Patil, R.K.; Elger, W.A.; Jayaraman, S.

    1988-04-01

    The antiprogestin ZK 98.734 (11 beta-(4-dimethylaminophenyl-17 beta-hydroxy-17 alpha-(3-hydroxy-prop-1(Z)-enyl-4,9(10)-estradien-3-one) was administered i.m. (5 mg/day) for three consecutive days to two groups of common marmosets. In one group (nonpregnant, n = 6), it was injected during the luteal phase, and to the second group (pregnant, n = 7), it was injected during early pregnancy, on Days 24-26 of the mid-cycle estradiol peak. Administration of ZK 98.734 during the luteal phase caused a sharp drop in plasma progesterone levels. The luteal phase was shortened whether the drug was administered during the early or the late luteal phase. Similarly, administration of ZK 98.734 during early pregnancy caused a significant drop in progesterone levels, and pregnancy was terminated in all of the animals. The post-treatment cycles in both groups of animals were ovulatory and of normal duration. /sup 3/H-ZK 98.734 showed specific binding to myometrial cytosol fraction. ZK 98.734 also displaced the binding of /sup 3/H-progesterone to progesterone receptors. However, progesterone had higher binding affinity than did ZK 98.734. The antifertility action of ZK 98.734 could be a result either of its luteolytic action or of its blocking the progesterone receptors in the target tissue. This study, therefore, indicates that in the common marmoset ZK 98.734 is a progesterone antagonist with a potential to terminate early pregnancy.

  6. Effects of endocannabinoid 1 and 2 (CB1; CB2) receptor agonists on luteal weight, circulating progesterone, luteal mRNA for luteinizing hormone (LH) receptors, and luteal unoccupied and occupied receptors for LH in vivo in ewes.

    Science.gov (United States)

    Tsutahara, Nicole M; Weems, Yoshie S; Arreguin-Arevalo, J Alejandro; Nett, Torrance M; LaPorte, Magen E; Uchida, Janelle; Pang, Janelle; McBride, Tonya; Randel, Ronald D; Weems, Charles W

    2011-02-01

    Thirty to forty percent of ruminant pregnancies are lost during the first third of gestation due to inadequate progesterone secretion. During the estrous cycle, luteinizing hormone (LH) regulates progesterone secretion by small luteal cells (SLC). Loss of luteal progesterone secretion during the estrous cycle is increased via uterine secretion of prostaglandin F(2α) (PGF(2α)) starting on days 12-13 post-estrus in ewes with up to 4-6 pulses per day. Prostaglandin F(2α) is synthesized from arachidonic acid, which is released from phospholipids by phospholipase A2. Endocannabinoids are also derived from phospholipids and are associated with infertility. Endocannabinoid-induced infertility has been postulated to occur primarily via negative effects on implantation. Cannabinoid (CB) type 1 (CB1) or type 2 (CB2) receptor agonists and an inhibitor of the enzyme fatty acid amide hydrolase, which catabolizes endocannabinoids, decreased luteal progesterone, prostaglandin E (PGE), and prostaglandin F(2α) (PGF(2α)) secretion by the bovine corpus luteum in vitro by 30 percent. The objective of the experiment described herein was to determine whether CB1 or CB2 receptor agonists given in vivo affect circulating progesterone, luteal weights, luteal mRNA for LH receptors, and luteal occupied and unoccupied LH receptors during the estrous cycle of ewes. Treatments were: Vehicle, Methanandamide (CB1 agonist; METH), or 1-(4-chlorobenzoyl)-5-methoxy-1H-indole-3-acetic acid morpholineamide (CB2 agonist; IMMA). Ewes received randomized treatments on day 10 post-estrus. A single treatment (500 μg; N=5/treatment group) in a volume of 1 ml was given into the interstitial tissue of the ovarian vascular pedicle adjacent to the luteal-containing ovary. Jugular venous blood was collected at 0 h and every 6-48 h for the analysis of progesterone by radioimmunoassay (RIA). Corpora lutea were collected at 48 h, weighed, bisected, and frozen in liquid nitrogen until analysis of unoccupied and

  7. Probing early-universe phase transitions with CMB spectral distortions

    Science.gov (United States)

    Amin, Mustafa A.; Grin, Daniel

    2014-10-01

    Global, symmetry-breaking phase transitions in the early universe can generate scaling seed networks which lead to metric perturbations. The acoustic waves in the photon-baryon plasma sourced by these metric perturbations, when Silk damped, generate spectral distortions of the cosmic microwave background (CMB). In this work, the chemical potential distortion (μ ) due to scaling seed networks is computed and the accompanying Compton y -type distortion is estimated. The specific model of choice is the O (N ) nonlinear σ -model for N ≫1 , but the results remain the same order of magnitude for other scaling seeds. If CMB anisotropy constraints to the O (N ) model are saturated, the resulting chemical potential distortion μ ≲2 ×1 0-9 .

  8. Probing early-universe phase transitions with CMB spectral distortions

    CERN Document Server

    Amin, Mustafa A

    2014-01-01

    Global, symmetry-breaking phase transitions in the early universe can generate scaling seed networks which lead to metric perturbations. The acoustic waves in the photon-baryon plasma sourced by these metric perturbations, when Silk damped, generate spectral distortions of the cosmic microwave background (CMB). In this work, the chemical potential distortion ($\\mu$) due to scaling seed networks is computed and the accompanying Compton $y$-type distortion is estimated. The specific model of choice is the $O(N)$ nonlinear $\\sigma$-model for $N\\gg 1$, but the results remain the same order of magnitude for other scaling seeds. If CMB anisotropy constraints to the $O(N)$ model are saturated, the resulting chemical potential distortion $\\mu \\lesssim 2\\times 10^{-9}$.

  9. Phase-Synchronization Early Epileptic Seizure Detector VLSI Architecture.

    Science.gov (United States)

    Abdelhalim, K; Smolyakov, V; Genov, R

    2011-10-01

    A low-power VLSI processor architecture that computes in real time the magnitude and phase-synchronization of two input neural signals is presented. The processor is a part of an envisioned closed-loop implantable microsystem for adaptive neural stimulation. The architecture uses three CORDIC processing cores that require shift-and-add operations but no multiplication. The 10-bit processor synthesized and prototyped in a standard 1.2 V 0.13 μm CMOS technology utilizes 41,000 logic gates. It dissipates 3.6 μW per input pair, and provides 1.7 kS/s per-channel throughput when clocked at 2.5 MHz. The power scales linearly with the number of input channels or the sampling rate. The efficacy of the processor in early epileptic seizure detection is validated on human intracranial EEG data.

  10. Creating an information quantum leap in early design phases

    DEFF Research Database (Denmark)

    Jensen, Lotte Bjerregaard; Heller, Alfred; Hurup-Felby, Brian

    2014-01-01

    urban environment climatic conditions, broad multi-­‐criteria sustainability certification in early design phases aiming a.o. at meeting the obligations defined by smart cities challenges. Civil and Environmental Engineering has special challenges concerning design processes. These design projects...... are always influenced by their location and the topography (be it natural or manmade), climate, etc. This means that each project is unique and must be viewed in its own right. This reduces the benefits of mass production and standardization that are so heavily emphasized in mechanical design...... and behavior. This is more true than ever when considering the challenge of climate change. The requirements and behavior of the human users also vary in time. To meet these challenges, Civil and Environmental Engineering projects must be designed to be flexible so they can adjust for temporary changes...

  11. Hilar Cholangiocarcinoma Diagnosed and Treated Early, in Prejaundice Phase

    Directory of Open Access Journals (Sweden)

    Denes M.

    2014-08-01

    Full Text Available Hilar cholangiocarcinoma, Klatskin tumor or proximal bile duct cancer, is a tumor growing in the right hepatic duct, left hepatic duct or at their confluence. It is a relatively rare but devastating disease. The tight stricture of the biliary ducts and the development of obstructive jaundice are the main characteristics of the disease. In the early phase, symptoms are nonspecific and jaundice is not present, leading to delayed diagnosis and denying the possibility of curative treatment. We present the case of a 74 years old woman who was referred to us with ambiguous symptomatology and without jaundice. The ultrasound and CT scan showed dilation of the left biliary tree, without increase of the cholestatic enzymes. Magnetic resonance cholangiography depicted a tumor in the left hepatic duct (3X3 cm. with enlargement of the bile ducts above. The surgical treatment consisted of left hepatectomy and hilar lymph nodes dissection. The pathology findings showed a cholangiocarcinoma with a few hilar nodes involvement. Our approach was potentially curative. Unfortunately these situations are seldom because in the majority of cases the patients have obstructive jaundice at presentation and the tumors are unresectable. We consider that a magnetic resonance cholangiography made when we suspect a bile duct tumor, leads us to an early diagnosis and gives us the possibility of a potential curative surgical treatment.

  12. Cardiovascular response to short-term fasting in menstrual phases in young women: an observational study.

    Science.gov (United States)

    Ohara, Kumiko; Okita, Yoshimitsu; Kouda, Katsuyasu; Mase, Tomoki; Miyawaki, Chiemi; Nakamura, Harunobu

    2015-08-28

    Menstrual cycle-related symptoms are an important health issue for many women, and some may affect cardiac autonomic regulation. In the present study, we evaluated the cardiovascular and physiological stress response to 12-h short-term fasting in the menstrual phases of healthy young women. We performed a randomized crossover study. Subjects were seven female university students (age: 22.3 ± 1.0 years). The experiments comprised four sessions: meal intake in the follicular phase, meal intake in the luteal phase, fasting in the follicular phase, and fasting in the luteal phase. All subjects participated in a total of four experimental sessions during two successive phases (follicular and luteal phase in the same menstrual cycle, or luteal phase and follicular phase in the next menstrual cycle) according to a randomized crossover design. R-R intervals were continuously recorded before and after meals, and power spectral analysis of heart rate variability was performed. Other physiological data were obtained before and 20, 40, 60, and 80 min after meal intake or after the corresponding time point of meal intake (fasting in the follicular or luteal phase). Heart rate decreased during fasting in the follicular and luteal phases. High frequency power increased during fasting in the follicular and luteal phases. In addition, salivary cortisol concentrations decreased during fasting in the luteal phase. In the present study, short-term fasting resulted in higher parasympathetic activity and lower cortisol levels in the luteal phase in these young women. These results indicate a possibility to produce an anti-stress effect in the luteal phase, which may reduce menstrual symptoms.

  13. The effects of prolactin and gonadotropin on luteal function and morphology in the cyclic golden hamster.

    Science.gov (United States)

    Kon, Hiroe; Kishi, Hisashi; Arai, Koji Y; Shinoda, Motoo; Watanabe, Gen; Taya, Kazuyoshi

    2008-12-01

    The present study was conducted to evaluate the endocrinological effects of the pituitary on luteal maintenance and regression in the cyclic golden hamster (Mesocritus auratus). After hypophysectomy (Hypox) at 0900 h on day 1 of the estrous cycle (the day of ovulation), the animals received injection of prolactin (PRL) or PRL plus equine chorionic gonadotropin (eCG). They were decapitated at 1500 h on day 3 of the cycle, and trunk blood was collected for measurement of progesterone (P4). Corpora lutea (CLs) were dissected from one ovary for DNA ladder detection by electrophoresis, determination of DNA fragmentation ratio by fluorometric measurement method and measurement of P4. The other ovary was used for histological observation. After the Hypox, the daily injection of 1 mg ovine PRL restrained the DNA fragmentation ratio and number of apoptotic cell in the CLs. The PRL treatment maintained the luteal morphology and increased the luteal P4 concentration, but not in the plasma P4 concentration. In addition to PRL, injection of 2 IU eCG after the Hypox also restrained the DNA fragmentation ratio and number of apoptotic cells in the CLs to the level of a pregnant animal. The PRL plus eCG treatment maintained the luteal morphology in the same manner as the PRL only treatment and increased not only the luteal but also the plasma P4 concentration. These results suggest that PRL restrains luteal apoptosis and maintains luteal morphology and that the combination of PRL and eCG restrains not only structural but also functional luteal regression in the cyclic hamster.

  14. 78 FR 8184 - DEEPWATER HORIZON Oil Spill; Final Phase II Early Restoration Plan and Environmental Review

    Science.gov (United States)

    2013-02-05

    ... Early Restoration Plan and Environmental Review (Phase II ERP/ER) describing the second set of... availability of the Phase II ERP/ER. ADDRESSES: Obtaining Documents: You may download the Phase II ERP/ER and... the Phase II ERP/ER at any of the public repositories listed at...

  15. The Effect of Gossypol and Misoprostol on Luteal and Decidual Cells in Vitro

    Institute of Scientific and Technical Information of China (English)

    陈咏; 曹霖; 杨波; 顾芝萍

    1997-01-01

    Gossypol and Misoprostol could directly damage the luteal and decldual cells cultured in vitro. The LDso of gossypol alone to luteal and decidual cells were 1.27±0.09μg/ml and 3.06±0.23μg/ml, respectively; however when combined with misoprostol (to luteal cells 5μg/ml, or to decidual cells 10μg/ml), the LDso of gossypol significantly decreased to 0.89±0.25μg/ml and 1.88±0.26μg/ml, respectively. The LD50 of misoprostol alone to luteal and decidual cells were 14.29±1.29μg/ml and 24.37±4.49μg/ml, respectively; but it decreased to 8.79±2.18μg/ml and 17.29±1.56μg/ml, respectively when combined with gossypol (to IuteaI cells 0.5 μg/ml, or to decgdual cells 1.0 μg/ml), also showing statistical difference. The results suggested that the combination of gossypol with misoprostol had syner gistie effect on the degeneration of luteal and decidual cells in vitro.

  16. The relationship between fatty acid profiles in milk identified by Fourier transform infrared spectroscopy and onset of luteal activity in Norwegian dairy cattle.

    Science.gov (United States)

    Martin, A D; Afseth, N K; Kohler, A; Randby, Å; Eknæs, M; Waldmann, A; Dørum, G; Måge, I; Reksen, O

    2015-08-01

    To investigate the feasibility of milk fatty acids as predictors of onset of luteal activity (OLA), 87 lactations taken from 73 healthy Norwegian Red cattle were surveyed over 2 winter housing seasons. The feasibility of using frozen milk samples for dry-film Fourier transform infrared (FTIR) determination of milk samples was also tested. Morning milk samples were collected thrice weekly (Monday, Wednesday, Friday) for the first 10 wk in milk (WIM). These samples had bronopol (2-bromo-2-nitropropane-1,3-diol) added to them before being frozen at -20°C, thawed, and analyzed by ELISA to determine progesterone concentration and the concentrations of the milk fatty acids C4:0, C14:0, C16:0, C18:0, and cis-9 C18:1 as a proportion of total milk fatty acid content using dry-film FTIR, and averaged by WIM. Onset of luteal activity was defined as the first day that milk progesterone concentrations were >3 ng/mL for 2 successive measurements; the study population was categorized as early (n=47) or late (n=40) OLA, using the median value of 21 DIM as the cutoff. Further milk samples were collected 6 times weekly, from morning and afternoon milkings, these were pooled by WIM, and one proportional sample was analyzed fresh for fat, protein, and lactose content by the dairy company Tine SA, using traditional FTIR spectrography in the wet phase of milk. Daily energy-balance calculations were performed in 42 lactations and averaged by WIM. Animals experiencing late OLA had a more negative energy balance in WIM 1, 3, 4, and 5, with the greatest differences been seen in WIM 3 and 4. A higher proportion of the fatty acids were medium chained, C14:0 and C16:0, in the early than in the late OLA group from WIM 1. In WIM 4, the proportion of total fatty acid content that was C16:0 predicted late OLA, with 74% sensitivity and 80% specificity. The long-chain proportion of the fatty acids C18:0 and cis-9 C18:1 were lower in the early than in the late OLA group. Differences were greatest in

  17. Effects of orexins A and B on expression of orexin receptors and progesterone release in luteal and granulosa ovarian cells.

    Science.gov (United States)

    Cataldi, Natalia I; Lux-Lantos, Victoria A R; Libertun, Carlos

    2012-10-10

    Orexin-A and orexin-B are neuropeptides controlling sleep-wakefulness, feeding and neuroendocrine functions via their G protein-coupled receptors, orexin-1R and orexin-2R. They are synthesized in the lateral hypothalamus and project throughout the brain. Orexins and orexin receptors have also been described outside the brain. Previously we demonstrated the presence of both receptors in the ovary, their increased expression during proestrous afternoon and the dependence on the gonadotropins. Here we studied the effects of orexins on the mRNA expression of both receptors, by quantitative real-time PCR, on luteal cells from superovulated rat ovaries and granulosa cells from diethylstilbestrol-treated rat ovaries. Effects on progesterone secretion were also measured. In luteal cells, 1 nM of either orexin-A or orexin-B decreased progesterone secretion. Orexin-A treatment increased expression of both orexin-1R and orexin-2R mRNA. The effect on orexin-1R mRNA expression was abolished by an orexin-1R selective receptor antagonist SB-334867 and the effect on orexin-2R mRNA expression was abolished by a selective orexin-2R antagonist JNJ-10397049. Orexin-B did not modify orexin-1R mRNA expression, but increased orexin-2R mRNA expression. The effect of orexin-B on orexin-2R was abolished by a selective orexin-2R antagonist. Neither the expression of orexin receptors nor progesterone secretions by granulosa cells were affected by orexins. FSH, as positive control, increased both steroid hormones secretion, but did not induce the expression of OX receptors in granulosa cells isolated from late preantral/early antral follicles. Finally in ovaries obtained immediately after sacrifice, the expression of orexin-1R and orexin-2R was higher in superovulated rat ovaries compared to control or diethylstilbestrol treated rat ovaries. A selective presence and function of both orexinergic receptors in luteal and granulosa cells is described, suggesting that the orexinergic system may

  18. Effects of single dose GnRH agonist as luteal support on pregnancy outcome in frozen-thawed embryo transfer cycles: an RCT

    Directory of Open Access Journals (Sweden)

    Robab Davar

    2015-08-01

    Full Text Available Background: There is no doubt that luteal phase support is essential to enhance the reproductive outcome in IVF cycles. In addition to progesterone and human chorionic gonadotropin, several studies have described GnRH agonists as luteal phase support to improve implantation rate, pregnancy rate and live birth rate, whereas other studies showed dissimilar conclusions. All of these studies have been done in fresh IVF cycles. Objective: To determine whether an additional GnRH agonist administered at the time of implantation for luteal phase support in frozen-thawed embryo transfer (FET improves the embryo developmental potential. Materials and Methods: This is a prospective controlled trial study in 200 FET cycles, patients were randomized on the day of embryo transfer into group 1 (n=100 to whom a single dose of GnRH agonist (0.1 mg triptorelin was administered three days after transfer and group 2 (n=100, who did not receive agonist. Both groups received daily vaginal progesterone suppositories plus estradiol valerate 6 mg daily. Primary outcome measure was clinical pregnancy rate. Secondary outcome measures were implantation rate, chemical, ongoing pregnancy rate and abortion rate. Results: A total of 200 FET cycles were analyzed. Demographic data and embryo quality were comparable between two groups. No statistically significant difference in clinical and ongoing pregnancy rates was observed between the two groups (26% versus 21%, p=0.40 and 21% versus 17%, p=0.37, respectively. Conclusion: Administration of a subcutaneous GnRH agonist at the time of implantation does not increase clinical or ongoing pregnancy.

  19. The Early Neolithic phases of Beidha in a regional context

    DEFF Research Database (Denmark)

    Jensen, Charlott Hoffmann

    2007-01-01

    The paper is a preliminary account of the new analyses of the Beidha material and concentrates on the earliest levels from the site: the pre-architectural levels as well as a sample of material from Phase A1 buildings. A contextual analysis of some of the phase A1 buildings is introduced and the ...... and the development from temporary shelters to stone-built architecture in the area is discussed....

  20. Robust and flexible mapping for real-time distributed applications during the early design phases

    DEFF Research Database (Denmark)

    Gan, Junhe; Pop, Paul; Gruian, Flavius

    2012-01-01

    We are interested in mapping hard real-time applications on distributed heterogeneous architectures. An application is modeled as a set of tasks, and we consider a fixed-priority preemptive scheduling policy. We target the early design phases, when decisions have a high impact on the subsequent...... implementation choices. However, due to a lack of information, the early design phases are characterized by uncertainties, e.g., in the worst-case execution times (wcets), or in the functionality requirements. We model uncertainties in the wcets using the “percentile method”. The uncertainties...... of taking into account the uncertainties during the early design phases....

  1. LACK OF INHIBITORY ACTION OF OXYTOCIN,VASOTOCIN AND VASOPRESSIN ON PROGESTERONE PRODUCTION BY HUMAN LUTEAL CELLS

    Institute of Scientific and Technical Information of China (English)

    WANGHan-Zheng; HANXiang-Jun; LUShu-Hua; SUNZhi-Da; SHENWei-Xiong; ZHOUWei

    1989-01-01

    The direct effects of oxytocin and relatcd peptides on human luteal cells were attudied Suslxmsions of luteal cells were prepared enzymatically from human corpora htae, obtained during cycle days 19-25. Afar incubation with hCG (liu / ml) for 3 h, the

  2. Development of Heart Rate Variaty in the Early and Rehabilitation Phase of AMI

    Institute of Scientific and Technical Information of China (English)

    R. Tanhbalouti; Feng Jianzhang; Feng Xiuhua

    2000-01-01

    Heart rate variaty (HRV) of 85 cases with AMI was observed in the early phase after onset and rehabilitation phase at first month and sixth month, and was contrasted with six time threshold indices of 111 cases with coronary heart disease and that of 35 normal control. We found the HRV of AMI was apperantly lower in the acute phase than that of coronary heart disease and normal controls. HRV recovered gradually with inclining to be stable after half a year, but it was still lower than that of controls. Low HRV in early phase of AMI suggested the poor prognosis.

  3. Early phase Technology Assessment of nanotechnology in oncology

    NARCIS (Netherlands)

    Retèl, Valesca P.; Hummel, Marjan J.M.; Harten, van Willem H.

    2008-01-01

    To perform early Technology Assessment (TA) of nanotechnology in oncology. The possibilities of nanotechnology for detection (imaging), diagnosis and treatment of cancer are subject of different research programs where major investments are concerned. As a range of bio- nanotechnologies is expected

  4. Naive Fault Trees for Safety Evaluations in Early Project Phase

    NARCIS (Netherlands)

    Rajabali Nejad, Mohammadreza

    2016-01-01

    Naive Fault Trees (NFT) aim to extend the application of Fault Trees (FT) and make them appealing for system designers in the early project life cycle. NFT use input intervals and values to estimate the frequency of a top event. This extension facilitates the assignment of failure probability to

  5. Transvaginal sonographic evaluation at different menstrual cycle phases in diagnosis of uterine lesions

    Directory of Open Access Journals (Sweden)

    Hajishaiha M

    2011-10-01

    Full Text Available Masomeh Hajishaiha1, Mohammad Ghasemi-rad2, Nazila Karimpour1, Nikol Mladkova3, Farzaneh Boromand11Department of Gynecology, 2Student Research Committee (SRC, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran; 3Institute of Cell and Molecular Science, London, UKPurpose: Intrauterine lesions (IULs are a common finding in women of reproductive age, particularly infertile women. Transvaginal sonography (TVS is a popular tool for IUL detection, but there are conflicting data with respect to its accuracy.Methods: Five hundred and six women were enrolled into the study. Of these, 496 underwent hysterosalpingography and subsequent TVS six different times during the course of their menstrual cycle. If a lesion was detected, it was further evaluated by sonohysterography (SHG and hysteroscopy.Results: Of 496 women, 41 were shown to have IULs by TVS and those lesions were confirmed in 39 by SHG and hysteroscopy. All 39 lesions were detectable during the ovulatory and early luteal phase (days 16–19 of the menstrual cycle. Accuracy of TVS during different phases was largely dependent on the size of the lesion. TVS falsely detected two lesions and missed fine adhesions in two patients.Conclusion: Accuracy of TVS in detection of IULs is highly dependent on the menstrual cycle phase, with the ovulatory and early luteal phase being the optimal time for this examination.Keywords: menstrual cycle phase, space occupying lesions, transvaginal sonography

  6. 76 FR 9583 - Draft Guidance for Industry on Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase...

    Science.gov (United States)

    2011-02-18

    ... guidance for industry entitled ``Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase Clinical Studies.'' The draft guidance is intended to assist the pharmaceutical industry and other investigators... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Clinical...

  7. Cosmological Consequences of QCD Phase Transition(s) in Early Universe

    CERN Document Server

    Tawfik, A

    2008-01-01

    We discuss the cosmological consequences of QCD phase transition(s) on the early universe. We argue that our recent knowledge about the transport properties of quark-gluon plasma (QGP) should throw additional lights on the actual time evolution of our universe. Understanding the nature of QCD phase transition(s), which can be studied in lattice gauge theory and verified in heavy ion experiments, provides an explanation for cosmological phenomenon stem from early universe.

  8. Early-phase clinical trials of anti-HIV Drugs——understanding and discussion

    Institute of Scientific and Technical Information of China (English)

    LI YaJie; ZHAO Ming; ZHAO DeHeng

    2009-01-01

    Innovative anti-HIV drugs developed by local sponsors in China have come into the stage of early-phase clinical trials. How to systemically design the clinical trials of innovative anti-HIV drugs still remains a challenge for them. This article references the literature and the experience of reviewers, to introduce general considerations concerning early-phase clinical trials of innovative anti-HIV drugs.

  9. Early-phase clinical trials of anti-HIV Drugs——understanding and discussion

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Innovative anti-HIV drugs developed by local sponsors in China have come into the stage of early-phase clinical trials.How to systemically design the clinical trials of innovative anti-HIV drugs still remains a challenge for them.This article references the literature and the experience of reviewers,to introduce general considerations concerning early-phase clinical trials of innovative anti-HIV drugs.

  10. Motor memory in childhood: early expression of consolidation phase gains.

    Science.gov (United States)

    Ashtamker, Lilach; Karni, Avi

    2013-11-01

    Are children faster than adults in consolidating procedural knowledge? In adults, the expression of the full benefits of motor practice requires a few hours of consolidation and sleep. Here we show that, although the processes generating the delayed gains continued beyond the first few hours post-training, children expressed significant gains as early as 1 h post-training, in the awake state. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Control of Early Age Concrete. Phase 3: Creep in Concrete

    DEFF Research Database (Denmark)

    Hauggaard-Nielsen, Anders Boe; Damkilde, Lars; Hansen, Per Freiesleben

    1997-01-01

    The mechanical properties of the "Road Directorate Concrete" at early ages are studied. Creep in tension at 24 and 72 maturity hours are measured on dogbone shaped specimens. The development of tensile modulus of elasticity and strength are measured with a method developed here. The results...... are compared to compression values and splitting strengths. It is found that the properties of creep in tension are similar to the properties in compression. Further the influence form temperature on creep is found to be significant....

  12. Biomarkers in early phase development of central nervous system drugs : a conceptual framework

    NARCIS (Netherlands)

    Post, Jeroen-Paul van der

    2006-01-01

    The main objective of this thesis is to provide a conceptual framework for the use of Central Nervous System (CNS) biomarkers in early phase clinical drug development. In the Introduction the current use of biomarkers in early CNS drug development is discussed. A conceptual framework for the classif

  13. Role of Early Arterial Phase Multislice Helical CT Angiography in Evaluation of Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    TANGBinghang; HEYaqi; LILiangcai; HUANGDecheng; WURenguo; YUYuanlong

    2005-01-01

    Objective: To investigate the clinical application of early arterial phase multislice CT angiography (MSCTA) of hepatic vessels in evaluation of middle or advanced stage hepatocellular carcinoma.Methods: Trigger Bolus program was used to carry out MSCTA in early and late arterial phases and portal vein phase with single breath holding. Hepatic vessels were reconstructed from the original images of early arterial phase by post processing. The blood supply of tumor and normal liver tissue and the appearances of venous thrombosis and arteriovenous shunts were analyzed. Results: The MSCTA with early arterial phase could perfectly display the origin, shape and amount of feeding vessels to normal liver tissue and tumor in middle or advanced stage hepatocellular carcinoma. It had the ability of displaying the arteriovenous shunts better than that in conventional dual phased liver scanning. Conclusion: MSCTA of hepatic vessels with early arterial phase acquisition using multislice helical CT in middle or advance stage hepatocellular carcinoma has favorable and promising application. It can be used as an imaging method for comprehensive assessment of the hepatocellular carcinoma before treatment.

  14. [Occupational therapy: benefit of early intervention in the manic phase].

    Science.gov (United States)

    Riou, Gaëlle

    When people experiencing a manic episode arrive in hospital, restrictive measures are often put in place. The priority is to avoid all sources of stimulation, especially anything likely to activate the patient. The prescribing of occupational therapy sessions in a well-defined framework may however be appropriate at an early stage in the care. Aside from its effect on the therapeutic alliance, occupational therapy can help on the cognitive and temporal level, increasing awareness of the condition and engagement in the care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. ATF3 Expression in the corpus luteum: possible role in luteal regression

    Science.gov (United States)

    The present study investigated the induction and possible role of activating transcription factor 3 (ATF3) in the corpus luteum. Postpubertal cattle were treated at midcycle with prostaglandin F2alpha(PGF) for 0–4 hours. Luteal tissue was processed for immunohistochemistry, in situ hybridization, an...

  16. Mid-luteal progesterone concentrations are associated with live birth rates during ovulation induction

    DEFF Research Database (Denmark)

    Arce Saez, Jane; Balen, A; Platteau, P

    2011-01-01

    This retrospective study investigated whether mid-luteal serum progesterone concentrations are associated with live birth rates in women with WHO group II anovulatory infertility undergoing ovulation induction. Data were from women (n=335) stimulated with gonadotrophins using a low-dose step...

  17. EFFECT OF RU486 ON THE LUTEAL FUNCTION IN THE PREGNANT MOUSE

    Institute of Scientific and Technical Information of China (English)

    LIShu-Xiang; GUDun-Yu; WUXiao-Yun; ZHUJian-Yu; JIANGWen-Jue; SUNPei-Long; YANGYi-Qian

    1989-01-01

    The effect of RU486, an antiprogestin, on luteal functions in the post-implantation mouse was studied. (1) In vivo experiment: Female adult mice were treated with RU486 at an oral dose of 100 mg/kg on day 1 and day 2 of pregnancy. Autopsy was performed

  18. Effects of IL8 and immune cells on the regulation of luteal progesterone secretion

    Science.gov (United States)

    Recent studies suggest that chemokines may mediate the luteolytic action of PGF2a (PGF). Our objective was to identify chemokines induced by PGF in vivo and to determine the effects of IL8 on specific luteal cell types in vitro. Midcycle cows were injected with saline or PGF, ovaries were removed ...

  19. Effects and Interactions of Prostaglandins and Interferon-γ on Steroidogenesis of Human Luteal Cells

    Institute of Scientific and Technical Information of China (English)

    王寒正; 沈维维; 孙志达; 张翔; 龚岳亭

    1996-01-01

    Previous work from our laboratory has demonstrated that T lymphocyte-derived cytokine, interferon-gamma (IFN-γ) may play a role in human luteal regression by inhibiting luteal progesterone production. Prostaglandin F2a has been known as an important luteolytic factor in a wide range of mammalian species. It was of interest to investigate the effects of IFN-γ on prostaglandin synthesis and their possible interaction with the inhibition on human luteal steroidogenesis. Human luteal cells were cultured for four days in the presence or absence of IFN-γ. Simultaneously, the productions of progesterone, prostaglandin F2a ( PGF2a ), prostaglandin E2 ( PGE2 ), and 6-ketoprostaglandin F1a(PGF1a) were evaluated. Concomitant with the inhibition of progesterone production induced by IFN-γ, a biphasic pattern of response of. prostaglandin synthesis was observed, i.e. a slight decrease of PGF2a and PGF1a after a 48 h exposure to IFN-γ while an increase of PGE2 after 96 h. In a separate experiment, a luteotropic action of PGE2 and PGF2a on human luteal cells from different stages was observed during 48 and 96 h periods of culture. In addition, while indomethacin (INDO) treatment markedly blocked the prostaglandin synthesis, the basal as well as hCG stimulated progesterone production was still inhibited by IFN-γ as usual. These results suggested that prostaglandins appeared to be not responsible for the observed inhibition of progesterone production since the inhibitory effect was not influenced by concurrent treatment with INDO which suppressed prostaglandin synthesis,

  20. Profiling of Burkholderia cepacia secretome at mid-logarithmic and early-stationary phases of growth.

    Directory of Open Access Journals (Sweden)

    Vanitha Mariappan

    Full Text Available BACKGROUND: Burkholderia cepacia is a Gram-negative pathogen that causes serious respiratory infections in immunocompromised patients and individuals with cystic fibrosis. This bacterium is known to release extracellular proteins that may be involved in virulence. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, B. cepacia grown to mid-logarithmic and early-stationary phases were investigated on their ability to invade and survive intracellularly in A549 lung epithelial cells in order to discern the fate of these bacteria in the pathogenesis of B. cepacia lung infections in in vitro condition. The early-stationary phase B. cepacia was demonstrated to be more invasive than mid-logarithmic phase. In addition, culture supernatants of B. cepacia obtained from these phases of growth were also demonstrated to cause different cytotoxic potency on the A549 human lung epithelial cells. Profiling of the supernatants using the gel-based proteomics approach identified 43 proteins that were commonly released in both the growth phases and 40 proteins newly-released at the early-stationary phase. The latter proteins may account for the higher cytotoxic activity of the early-stationary culture supernatant compared to that obtained at the mid-logarithmic phase. Among the newly-released proteins in the early-stationary phase supernatant were flagellar hook-associated domain protein (FliD, flagellar hook-associated protein (FlgK, TonB-dependent siderophore (Fiu, Elongation factor G (FusA, phosphoglycerate kinase (Pgk and sulfatase (AslA which are known for their virulence. CONCLUSION/SIGNIFICANCE: Differences in the ability of B. cepacia to invade and survive intracellularly inside the epithelial cells at different phases of growth may improve our understanding of the varied disease progressions associated with B. cepacia infections. In addition, the identified culture supernatant proteins may be used as targets for the development of new strategies to

  1. Specification of Requirements for Safety in the Early Development Phases - Misuse Case and HAZOP in the Concept Phase

    OpenAIRE

    Maringa, Joshua; Sæther, Thorbjørn

    2011-01-01

    In the course TDT4520 - Specialization Project, the preparatory course to this thesis, we looked at several safety analysis methods and how they could be exploited to identify software hazards in the early stages of development. After our evaluation, and with the results from a survey conducted on experts in the field, we proposed a procedure to improve software hazard identification in the concept phase of projects. The procedure consisted of a Misuse Case analysis with a sub-sequential HAZO...

  2. Modelling production system architectures in the early phases of product development

    DEFF Research Database (Denmark)

    Guðlaugsson, Tómas Vignir; Martin Ravn, Poul; Mortensen, Niels Henrik;

    2016-01-01

    on – leading to an improved basis for prioritizing activities in the project. Requirements for the contents of the framework are presented, and literature on production and system models is reviewed. The production system architecture modelling framework is founded on methods and approaches in literature......This article suggests a framework for modelling a production system architecture in the early phases of product development.The challenge in these phases is that the products to be produced are not completely defined and yet decisions need to be made early in the process on what investments...... and adjusted to fit the modelling requirements of a production system architecture at an early phase of development. The production system architecture models capture and describe the structure, capabilities and expansions of the production system architecture underdevelopment. The production system...

  3. Early-phase thin-slice CT in the diagnosis of small insulinomas.

    Science.gov (United States)

    Ishioka, Hideki; Sata, Naohiro; Ishiguro, Yasunao; Lefor, Alan; Yasuda, Yoshikazu

    2015-01-31

    Insulinomas, which are generally smaller than 2 cm, may be difficult to detect by routine imaging modalities including abdominal ultrasonography, computed tomography, and magnetic resonance imaging. Although preoperative detection of insulinomas is essential for operative planning, it is often challenging due to their small size. While arterial stimulation and venous sampling has been used in patients with insulinomas it has been largely supplanted by early-phase thin-slice computed tomography. We report three patients with insulinomas, which were not detected by routine computed tomography scan, but were successfully imaged using early-phase thin-slice computed tomography. Enucleation was performed in all patients based on preoperative imaging. All three patients had an unremarkable postoperative course. Early-phase thin-slice computed tomography is recommended for the preoperative identification of insulinomas. This non-invasive imaging technique should be considered before performing arterial stimulation and venous sampling.

  4. Fish meal supplementation increases bovine plasma and luteal tissue omega-3 fatty acid composition.

    Science.gov (United States)

    White, N R; Burns, P D; Cheatham, R D; Romero, R M; Nozykowski, J P; Bruemmer, J E; Engle, T E

    2012-03-01

    The objective of this experiment was to determine if dietary inclusion of fish meal would increase plasma and luteal tissue concentrations of eicosapentaenoic and docosahexaenoic acids. Seventeen nonlactating Angus cows (2 to 8 yr of age) were housed in individual pens and fed a corn silage-based diet for approximately 60 d. Diets were supplemented with fish meal at 5% DMI (a rich source of eicosapentaenoic acid and docosahexaenoic acid; n = 9 cows) or corn gluten meal at 6% DMI (n = 8 cows). Body weights and jugular blood samples were collected immediately before the initiation of supplementation and every 7 d thereafter for 56 d to monitor plasma n-3 fatty acid composition and BW. Estrous cycles were synchronized using 2 injections of PGF(2α) administered at 14-d intervals. The ovary bearing the corpus luteum was surgically removed at midcycle (between d 10 and 12) after estrus synchronization, which corresponded to approximately d 60 of supplementation. The ovary was transported to the laboratory, and approximately 1.5 g of luteal tissue was stored at -80°C until analyzed for n-3 fatty acid content. Initial and ending BW did not differ (P > 0.10) between cows supplemented with fish meal and those with corn gluten meal. Plasma eicosapentaenoic acid was greater (P < 0.05) beginning at d 7 of supplementation and docosahexaenoic was greater (P < 0.05) beginning at d 14 of supplementation for cows receiving fish meal. Luteal tissue collected from fish meal-supplemented cows had greater (P < 0.05) luteal n-3 fatty acids and reduced (P < 0.05) arachidonic acid and n-6 to n-3 ratio as compared with tissue obtained from cows supplemented with corn gluten meal. Our data show that fish meal supplementation increases luteal n-3 fatty acid content and reduces available arachidonic acid content, the precursor for PGF(2α). The increase in luteal n-3 fatty acids may reduce PGF(2α) intraluteal synthesis after breeding resulting in increased fertility in cattle.

  5. Biomarkers in early phase development of central nervous system drugs: a conceptual framework

    OpenAIRE

    Post, Jeroen-Paul van der

    2006-01-01

    The main objective of this thesis is to provide a conceptual framework for the use of Central Nervous System (CNS) biomarkers in early phase clinical drug development. In the Introduction the current use of biomarkers in early CNS drug development is discussed. A conceptual framework for the classification of biomarkers is suggested, based on general questions that these markers should provide information on. The body of this thesis (Chapters 1-7) exemplifies the use of these markers within t...

  6. The role of ambiguity and discrepancy in the early phases of innovation

    DEFF Research Database (Denmark)

    Laursen, Linda Nhu; Tollestrup, Christian H. T.

    2015-01-01

    Innovation literature mainly focuses on eliminating ambiguity and discrepancy from the early phases of innovation. This study questions this implicit assumption, as it may provide an oversimplified view on, how to attain proficiency. Instead of narrowly focusing on reducing ambiguity...... and discrepancy, we seek to understand if it might be there for a reason. Through a laboratory experiment, we propose ambiguity and discrepancy actually have a function in concept development. Accordingly the paper contributes with a better understanding of, the role ambiguity and discrepancy as triggers of sense...... making in conceptualisation in the early phases of innovation....

  7. Challenges and perspective of drug repurposing strategies in early phase clinical trials

    OpenAIRE

    Kato, Shumei; Moulder, Stacy L.; Ueno, Naoto T; Wheler, Jennifer J.; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

    2015-01-01

    Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment ...

  8. A Case Study of Idea Work in the Early Phases of Product Development

    DEFF Research Database (Denmark)

    Gish, Liv; Clausen, Christian; Hansen, Claus Thorp

    2009-01-01

    Focus in this paper is on the early innovation activities, in particular idea work. Based on a case study from industrial practice on the development of a new circulator (the Alpha Pro circulator) we aim at getting a better understanding of the work with ideas in the early phases of product...... development. Based on our case we will point out four central findings: 1) Early idea work is a complex process and interlinked with many other activities both inside and outside the organization. 2) Ideas evolve,combine and change over time. 3) Idea work involves a wide range of actors. 4) Carrying ideas...

  9. Implementing Effective Mission Systems Engineering Practices During Early Project Formulation Phases

    Science.gov (United States)

    Moton, Tryshanda

    2016-01-01

    Developing and implementing a plan for a NASA space mission can be a complicated process. The needs, goals, and objectives of any proposed mission or technology must be assessed early in the Project Life Cycle. The key to successful development of a space mission or flight project is the inclusion of systems engineering in early project formulation, namely during Pre-phase A, Phase A, and Phase B of the NASA Project Life Cycle. When a space mission or new technology is in pre-development, or "pre-Formulation", feasibility must be determined based on cost, schedule, and risk. Inclusion of system engineering during project formulation is key because in addition to assessing feasibility, design concepts are developed and alternatives to design concepts are evaluated. Lack of systems engineering involvement early in the project formulation can result in increased risks later in the implementation and operations phases of the project. One proven method for effective systems engineering practice during the pre-Formulation Phase is the use of a mission conceptual design or technology development laboratory, such as the Mission Design Lab (MDL) at NASA's Goddard Space Flight Center (GSFC). This paper will review the engineering process practiced routinely in the MDL for successful mission or project development during the pre-Formulation Phase.

  10. Serum Electrolytes During Different Phases Of Menstrual Cycle

    Directory of Open Access Journals (Sweden)

    Dr. M. A. Lanje,

    2010-11-01

    Full Text Available Background: Although the coordinated sequence of hormonal changes during the normal menstrual cycle are well characterized, whether similar or parallel changes occur in the distribution of various electrolytes has not been clearly established. Materials and methods: This corollary follow up study on 50 healthy normal menstruating females presents variation in serum calcium, magnesium, sodium and potassium during menstrual, follicular and luteal phases of menstrual cycle. Results: The study demonstrated that serum calcium levels were significantly (p < 0.001 higher in follicular phase than menstrual and luteal phases. Serum magnesium levels were significantly (p < 0.001 lower in follicular phase than menstrual and luteal phases. Serum sodium levels were significantly lower in luteal phase than the menstrual and follicular phases. Serum potassium levels were higher (non-significant in luteal phase than menstrual and follicular phases. Conclusion: The concurrence of these cyclical changes in these electrolytes supports the claim of many women that they suffer changes in fluid and electrolyte balance in the premenstrual days. Moreover, these changes may have significance in terms of the normal reference interval, hence necessitate small but significant lterations to the normal reference interval.

  11. Role of P2X7 on steroid synthesis in murine luteal cells

    Directory of Open Access Journals (Sweden)

    Chunping Zhang

    2016-03-01

    Full Text Available The extracellular adenosine triphosphate (ATP regulates different cellular functions through activating purinergic receptors as a signalling molecule or neurotransmitter. P2X7 is highly expressed in murine small luteal cells. In this study, murine luteal cells were cultured in vitro and treated with P2X7 agonists – ATP and 2′(3′-O-(4-benzoyl-benzoyl-adenosine 50-triphosphate (BzATP and with P2X7 antagonist – brilliant blue G (BBG. We found that ATP and BzATP increased the production of progesterone and had no influence on the production of estradiol. BBG reversed the effect of BzATP and ATP. Further studies demonstrated that ATP and BzATP promoted the expression of CYP11A. These results revealed that P2X7 receptor activation is involved in the steroid synthesis in corpus luteum.

  12. Internalization of 125I-human choriogonadotropin in bovine luteal slices. A biochemical study.

    Science.gov (United States)

    Chegini, N; Rao, C V; Carman, F R

    1984-04-01

    Various intracellular organelles as well as outer cell membranes of bovine corpora lutea intrinsically contain gonadotropin receptors (Rao et al., J biol chem 256 (1981) 2628 [5]). In order to investigate whether exogenously added human choriogonadotropin (hCG) can internalize and bind to the intracellular sites, bovine luteal slices that had been carefully checked with respect to structural and functional integrity were incubated with 0.1 nM 125I-hCG. Following incubation, specific radioactivity was found to be associated with various intracellular organelles, but not with cytosol. The order of radioactivity uptake by subcellular organelles following a 2-h incubation was: Golgi medium greater than Golgi heavy greater than Golgi light greater than plasma membranes = rough endoplasmic reticulum greater than mitochondria-lysosomes- greater than nuclei. The 5'-nucleotidase activity and electron microscopic examination of the fractions revealed that the presence of radioactivity in the intracellular organelles cannot be attributed solely to plasma membrane contamination. The internalization and intracellular binding of 125I-hCG was time and temperature-dependent. Only excess unlabeled hCG and hLH (but not hCG subunits, FSH and PRL) competed with 125I-hCG for internalization in luteal slices. Very little or no 125I-hCG added was internalized in liver or kidney slices; luteal, liver and kidney slices accumulated neither 125I-BSA nor 125I. The radioactivity eluted from various luteal subcellular organelles was able to rebind to fresh corresponding organelles and came off Sepharose 6B columns in a position corresponding to native 125I-hCG. The gel filtration profile of detergent-solubilized radioactivity revealed that 125I-hCG was macromolecular bound. The degraded and altered 125I-hCG was found in the incubation media.

  13. Webcam Delivery of the Lidcombe Program for Early Stuttering: A Phase I Clinical Trial

    Science.gov (United States)

    O'Brian, Sue; Smith, Kylie; Onslow, Mark

    2014-01-01

    Purpose: The Lidcombe Program is an operant treatment for early stuttering shown with meta-analysis to have a favorable odds ratio. However, many clients are unable to access the treatment because of distance and lifestyle factors. In this Phase I trial, we explored the potential efficacy, practicality, and viability of an Internet webcam Lidcombe…

  14. Histone modifications induced by MDV infection at early cytolytic and latency phases

    Science.gov (United States)

    Background: Marek’s disease (MD) is a highly contagious, lymphomatous disease of chickens induced by a herpesvirus, Marek’s disease virus (MDV) that is the cause of major annual losses to the poultry industry. MD pathogenesis involves multiple stages including an early cytolytic phase and latency, a...

  15. Teachers' Beliefs on Foreign Language Teaching Practices in Early Phases of Primary Education: A Case Study

    Science.gov (United States)

    Caner, Mustafa; Subasi, Gonca; Kara, Selma

    2010-01-01

    The purpose of the study was to examine whether teacher beliefs would play a role in their actual practices while teaching target language in early phases of primary education, principally, in kindergarten and first grades in a state school. As it is a very broad research area, the researchers exclusively analyzed teaching practices and teaching…

  16. Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies.

    Science.gov (United States)

    Wages, N A; Slingluff, C L; Petroni, G R

    2017-04-01

    In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma.

  17. 77 FR 23741 - DEEPWATER HORIZON Oil Spill; Final Phase I Early Restoration Plan and Environmental Assessment

    Science.gov (United States)

    2012-04-20

    ... Fish and Wildlife Service DEEPWATER HORIZON Oil Spill; Final Phase I Early Restoration Plan and... DEEPWATER HORIZON Oil Spill (Framework Agreement), notice is hereby given that ] the Federal and State... the DEEPWATER HORIZON oil spill, which occurred on or about April 20, 2010, in the Gulf of Mexico....

  18. Men Managing, Not Teaching Foundation Phase: Teachers, Masculinity and the Early Years of Primary Schooling

    Science.gov (United States)

    Moosa, Shaaista; Bhana, Deevia

    2017-01-01

    In this article we argue that eliminating the divisions of labour between men and women could work towards counteracting gender inequality within professions. Globally women are over-represented in the teaching of young children in the early years of primary school, or Foundation Phase (FP), as it is known in South Africa. We are concerned to go…

  19. Effects of testosterone and 5alpha-dihydrotestosterone on luteal lifespan in dairy heifers.

    Science.gov (United States)

    Silvia, W J; Jacobs, A L; Hayes, S H

    1989-11-01

    Endogenous concentrations of testosterone increase approximately 7 d prior to estrus in cattle and goats. Inhibition of testosterone synthesis results in a delay of luteal regression in both species. The purpose of this experiment was to determine if treatment with testosterone or 5alpha-dihydrotestosterone (DHT), 2 to 6 d prior to the endogenous rise in testosterone, would result in premature luteal regression. Sixteen heifers were randomly assigned to one of three treatment groups: 1) Control (n = 6); 2) testosterone (100 mug, n = 5); or 3) DHT (100 mug, n = 5). Each heifer received a single injection of the appropriate steriod on Day 8, 9, 10, 11 or 12 post estrus. Jugular venous blood samples were collected at frequent intervals for 24 h to quantify testosterone, and then daily for 14 d to quantify progesterone. Concentrations of testosterone increased within 15 min of injection of testosterone, and reached a maximum at 30 min. Concentrations were maintained at > 2 ng/ml throughout the first 24 h after injection. Based on concentrations of progesterone, neither androgen had any effect on the lifespan of the corpus luteum or the level of luteal function.

  20. N-acetylcysteine impairs survival of luteal cells through mitochondrial dysfunction.

    Science.gov (United States)

    Löhrke, Berthold; Xu, Jinxian; Weitzel, Joachim M; Krüger, Burkhard; Goldammer, Tom; Viergutz, Torsten

    2010-04-01

    N-acetylcysteine (NAC) is known as an antioxidant and used for mucus viscosity reduction. However, this drug prevents or induces cell death depending on the cell type. The response of steroidogenic luteal cells to NAC is unknown. Our data shows that NAC can behave as an antioxidant or prooxidant in dependency on the concentration and mitochondrial energization. NAC elevated the flowcytometric-measured portion of hypodiploid (dying) cells. This rise was completely abolished by aurintricarboxylic acid, an inhibitor of topoisomerase II. NAC increased the secretion of nitric oxide and cellular nitrotyrosine. An image analysis indicated that cells pretreated with NAC and loaded with DHR showed a fluorescent structure probably elicited by the oxidative product of DHR, rhodamine 123 that sequesters mitochondrially. Pretreating luteal cells with NAC or adding NAC directly to mitochondrial fractions followed by assessing the mitochondrial transmembrane potential difference (Deltapsi) by the JC-1 technique demonstrated a marked decrease in Deltapsi. A protonophore restored Deltapsi and rotenone (an inhibitor of respiratory chain complex I) inhibited mitochondrial recovering. Thus, in steroidogenic luteal cells from healthy mature corpus luteum, NAC impairs cellular survival by interfering with mitochondrial metabolism. The protonophore-induced recovering of NAC-provoked decrease in Deltapsi indicates that an ATP synthase-favored route of H(+) re-entry to the matrix is essentially switched off by NAC while other respiratory chain complexes remain intact. These data may be important for therapeutic timing of treatments with NAC. (c) 2010 International Society for Advancement of Cytometry.

  1. Activation of P2X7 receptors decreases the proliferation of murine luteal cells.

    Science.gov (United States)

    Wang, Jing; Liu, Shuangmei; Nie, Yijun; Wu, Bing; Wu, Qin; Song, Miaomiao; Tang, Min; Xiao, Li; Xu, Ping; Tan, Ximin; Zhang, Luyin; Li, Gang; Liang, Shangdong; Zhang, Chunping

    2015-11-01

    Extracellular ATP regulates cellular function in an autocrine or paracrine manner through activating purinergic signalling. Studies have shown that purinergic receptors were expressed in mammalian ovaries and they have been proposed as an intra-ovarian regulatory mechanism. P2X7 was expressed in porcine ovarian theca cells and murine and human ovarian surface epithelium and is involved in ATP-induced apoptotic cell death. However, the role of P2X7 in corpus luteum is still unclear. The aim of this study was to investigate the role of ATP signalling in murine luteal cells and the possible mechanism(s) involved. We found that P2X7 was highly expressed in murine small luteal cells. The agonists of P2X7, ATP and BzATP, inhibited the proliferation of luteal cells. P2X7 antagonist BBG reversed the inhibition induced by ATP and BzATP. Further studies showed that ATP and BzATP inhibited the expression of cell cycle regulators cyclinD2 and cyclinE2. ATP and BzATP also inhibited the p38-mitogen-activated protein kinase (MAPK) signalling pathway. These results reveal that P2X7 receptor activation is involved in corpus luteum formation and function.

  2. Improved oxygen uptake efficiency slope in acute myocardial infarction patients after early phase I cardiac rehabilitation.

    Science.gov (United States)

    Tsai, Yun-Jeng; Li, Min-Hui; Chen, Chia-Hsin; Tuan, Sheng-Hui; Chen, Yi-Jen; Lin, Ko-Long

    2017-09-01

    A predischarge submaximal exercise test is often recommended after acute myocardial infarction (AMI) as part of phase I cardiac rehabilitation. In this study, a submaximal exercise parameter, oxygen uptake efficiency slope (OUES), was used to monitor the benefit of early mobilization within 48 h after AMI. An early mobilization protocol within 48 h after AMI has been initiated since 1 September 2012 in our center. Patients with onset time of AMI within 1 year before and 1 year after initiation of the early mobilization protocol were recruited for comparisons. Sixty patients were analyzed on the basis of this criterion, and were subjected to predischarge submaximal exercise tests. The OUES calculated with 100% exercise duration (OUES100) and calculated with the first 50% of exercise duration (OUES50) were obtained and analyzed. Both OUES100 and OUES50 of the AMI patients with early mobilization were significantly higher than those without early mobilization (P=0.025 and 0.007, respectively). The OUES100 and OUES50 were also highly correlated (r=0.891, P<0.001). The subgroup analysis using patients within 3 months before and 3 months after initiation of the protocol also showed a significant difference. OUES could be used to measure the exercise capacity and monitor the effect of phase I cardiac rehabilitation in patients soon after AMI. Early mobilization within 48 h following AMI significantly enhanced the patient's exercise capacity.

  3. Early phase in e-money development: from Edvard Bellamy to Frank Macknamary

    Directory of Open Access Journals (Sweden)

    O.S. Vysochan

    2016-03-01

    Full Text Available The article examines the phases of e-money development from the first mentioning of «a credit card» in literary sources to the appearance of Diners Club which preceded modern credit cards. The author has used the historical and geographic method for the decomposition of the early phase in the e-money development concerning the basic motives that induced emitters to develop and implement particular credit-payment systems. The article singles out three stages within the early phase of the e-money development, namely, the beginning of the ХХ-th century (supplying with short-term credits to obtain consumer’s goods, from 1920 to 1940 (guarantee of consumer’s loyalty to a brand, increasing the safety of clearing transactions by payer’s authorization, and 1950-ies (the use of the same credit for payment to various enterprises. It establishes the main features of the early phase in the e-money development; they are such as the absence of the necessary technical supply; emission, sale, guaranty on credits, on the cards issued take place outside the banking system; the lack of corporation credit card segment; the limitation of the application area; the low level of safety of the transactions accomplished.

  4. The flat decay phase in the early X-ray afterglows of Swift GRBs

    CERN Document Server

    Granot, J

    2006-01-01

    Many Swift GRBs show an early phase of shallow decay in their X-ray afterglows, lasting from $t \\sim 10^{2.5} $s to $\\sim 10^4 $s after the GRB, where the flux decays as $\\sim t^{-0.2}-t^{-0.8}$. This is perhaps the most mysterious of the new features discovered by Swift in the early X-ray afterglow, since it is still not clear what causes it. I discuss different possible explanations for this surprising new discovery, as well as their potential implications for the gamma-ray efficiency, the afterglow kinetic energy, and perhaps even for the physics of collisionless relativistic shocks.

  5. Limits on the early afterglow phase of gamma-ray burst sources from TAROT-1

    CERN Document Server

    Boër, M; Bringer, M; Gendre, B; Klotz, A H; Malina, R; De Pacheco, J A F; Pedersen, H

    2001-01-01

    The T\\'elescope \\`a Action Rapide pour les Objets Transitoires (TAROT-1) has as prime objective the observation of the prompt and delayed emission of cosmic gamma-ray bursts (GRBs). We have performed a search for optical emission from 6 GRBs detected by BATSE. The positioning error circle was fully covered within typically thirty minutes after the trigger. No detection of the early afterglow phase was made, and magnitude limits in the range of $ \\mathrm{m}_{\\mathrm{R}} = 13-15 $ were estimated using 20s exposures. These limits are compared to optical afterglow data obtained in later phases and the results are interpreted in terms of source distances. They correspond to a median redshift of z = 0.5. With HETE-2 and the planned instrument upgrade, TAROT-1 will be able to detect the early optical emission of GRBs up to a redshift of the order of 5.

  6. Sustainability certification systems as guidelines for early-phase urban design processes

    DEFF Research Database (Denmark)

    Jensen, Lotte Bjerregaard; Bjerre, Lærke; Mansfelt, Lise

    2016-01-01

    The German Sustainable Building Council (Deutsche Gesellschaft für Nachhaltiges Bauen or DGNB) has one of the most comprehensive sustainability certification systems for urban districts (UD). Their explicit aim is that the system should impact the very earliest design decisions. The Technical...... University of Denmark has tested the DGNB-UD system in two experimental design projects for similar locations to find out how it can be used in the early-phase design process. This paper describes these two independent design processes, compares them and discusses their general features. We found that DGNB......-UD addresses a broad sustainable focus and can be used as a tool for setting sustainability goals from the very first design steps. The system tends to promote multifunctional compromise solutions that meet several criteria at the same time. Using the DGNB-UD certification system in the early design phases...

  7. Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations

    Science.gov (United States)

    Nandal, Savita; Burt, Tal

    2017-01-01

    Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development. PMID:28218733

  8. Bayesian Decision Theory and its Applications in Early Phase Clinical Trails

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ying-hui

    2004-01-01

    Bayes'theorem is named after the Reverend Thomas Bayes who proposed the idea in the 18th century[1].It has been adapted by scientists for many different applications.One of the applications is clinical trials,where decisions are guided by clinical expertise as well as by data,especially in early phases.This paper reviews Bayes' theorem,decision theory and their applications in clinical trials.

  9. Research Biopsies in the Context of Early Phase Oncology Studies: Clinical and Ethical Considerations

    OpenAIRE

    Matilde Saggese; Divyanshu Dua; Emily Simmons; Charlotte Lemech; Hendrik-Tobias Arkenau

    2013-01-01

    The Personalized Medicine approach in oncology is a direct result of an improved understanding of complex tumor biology and advances in diagnostic technologies. In recent years, there has been an increased demand for archival and fresh tumor analysis in early clinical trials to foster proof-of-concept biomarker development, to understand resistance mechanisms, and ultimately to assess biological response. Although phase I studies are aimed at defining drug safety, pharmacokinetics, and to rec...

  10. Muscle fiber conduction velocity in different gait phases of early and late-stage diabetic neuropathy.

    Science.gov (United States)

    Suda, Eneida Yuri; Gomes, Aline A; Butugan, Marco Kenji; Sacco, Isabel C N

    2016-10-01

    We investigated the muscle fiber conduction velocity (MFCV) during gait phases of the lower limb muscles in individuals with various degrees of diabetic peripheral neuropathy (DPN). Forty-five patients were classified into severity degrees of DPN by a fuzzy model. The stages were absent (n=11), mild (n=14), moderate (n=11) and severe (n=9), with 10 matched healthy controls. While walking, all subjects had their sEMG (4 linear electrode arrays) recorded for tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL) and biceps femoris (BF). MFCV was calculated using a maximum likelihood algorithm with 30ms standard deviation Gaussian windows. In general, individuals in the earlier stages of DPN showed lower MFCV of TA, GM and BF, whilst individuals with severe DPN presented higher MFCV of the same muscles. We observed that mild patients already showed lower MFCV of TA at early stance and swing, and lower MFCV of BF at swing. All diabetic groups showed a markedly reduction in MFCV of VL, irrespective of DPN. Severe patients presented higher MFCV mainly in distal muscles, TA at early and swing phases and GM at propulsion and midstance. The absent group already showed MFCV of VL and GM reductions at the propulsion phase and of VL at early stance. Although MFCV changes were not as progressive as the DPN was, we clearly distinguished diabetic patients from controls, and severe patients from all others.

  11. Evaluation of early phase nuclear accident clean-up procedures for Nordic residential areas

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, K.G. [Risoe National Lab., Roskilde (Denmark)

    1996-12-01

    The work reported was carried out as a part of the EKO-5 project under the framework of the Nordic co-operative NKS programme. The project is aimed at giving guidelines relating to Nordic conditions for the reduction of external doses in the early phase of a major accidental airborne nuclear contamination (essentially with {sup 137}Cs) situation in urban areas. The material in this report describes the expected effects, in terms of immediate dose rate reduction and of reduction of the integrated doses over 70 years, of implementation of the methods which were considered to be feasible for early phase treatment of contaminated urban surfaces. Also given are estimates of the integrated doses if no action were taken. The given estimates were based on the experience obtained through large amounts of in situ measurements on different types of surface, mainly since the Chernobyl accident in 1986. The computer model URGENT, was used to apply the information on the migration of the radioactive material with time, together with the results of Monte Carlo photon transport calculations, for the time-integrated dose estimates. 66 data sheets describe the beneficial effects, costs and disadvantages of application of a feasible method for cleaning in the early phase of a specific type of surface in one of five different urban or suburban environments. These data form the foundation for the recommendations on guidelines, which are the ultimate goal of the EKO-5 project. References are given to recommended supplementary reading. (EG).

  12. Thermal to Nonthermal Energy Partition at the Early Rise Phase of Solar Flares

    CERN Document Server

    Altyntsev, Alexander A; Lesovoi, Sergey V; Meshalkina, Natalia S

    2012-01-01

    In some flares the thermal component appears much earlier than the nonthermal component in X-ray range. Using sensitive microwave observations we revisit this finding made by Battaglia et al. (2009) based on RHESSI data analysis. We have found that nonthermal microwave emission produced by accelerated electrons with energy of at least several hundred keV, appears as early as the thermal soft X-ray emission indicative that the electron acceleration takes place at the very early flare phase. The non-detection of the hard X-rays at that early stage of the flares is, thus, an artifact of a limited RHESSI sensitivity. In all considered events, the microwave emission intensity increases at the early flare phase. We found that either thermal or nonthermal gyrosynchrotron emission can dominate the low-frequency part of the microwave spectrum below the spectral peak occurring at 3-10 GHz. In contrast, the high-frequency optically thin part of the spectrum is always formed by the nonthermal, accelerated electron compon...

  13. Early mortality estimates for different nuclear accidents. Final Phase I report, October 1977-April 1979

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F.F.

    1979-08-01

    Several studies have previously been made of the number of early deaths which might be expected in a population exposed to a cloud of radionuclides which could result from a nuclear accident. These analyses, however, have been limited to one accident scenario or to exposures involving limited numbers of radionuclides. The purpose of this Phase I study was to examine the existing data on the early health effects of inhaled radioactive materials and determined what, if any, new studies were needed to make reasonable estimates of early mortality after exposure of a population to a cloud of radionuclides of any type. The approach used in the Phase I project was to analyze the data bases available on the health effects of inhaled radioactive materials and document those which were adequate and useful. Using these data, a computer based simulation model was developed depicting exposure to a radioactive aerosol, the dose to an individual exposed to the aerosol and the probability of dying from early effects.

  14. RODOS and decision conferencing on early phase protective actions in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Haemaelaeinen, R.P.; Lindstedt, M. [Helsinki Univ. of Technology, Espoo (Finland). Systems Analysis Lab.; Sinkko, K.; Ammann, M. [Radiation and Nuclear Safety Authority, Helsinki (Finland); Salo, A

    1998-12-01

    This work was undertaken in order to study the utilisation of decision conferencing and of the RODOS system when considering early phase protective actions in the case of a nuclear accident. Altogether four meetings with various people were organised. The meetings were attended by competent national safety authorities and technical level decision-makers, i.e., those who are responsible for preparing advice or making presentations of matters for decision-makers responsible for practical implementation of actions. In the first set of meetings the aim was to elicit the factors/attributes that have to be considered when making a decision on sheltering, evacuation and iodine tablets. No uncertainties nor a threat phase were considered but everything was assumed to happen as described in the given scenario. The theme in the second set of meetings was to study the implications of probabilities. All information was calculated with the support of the RODOS system. In the early phases of a nuclear accident time is limited. Prestructured generic value trees or a list of possible attributes can help to save time. A possible approach is to present a large generic value tree. Either the decision-makers select the attributes that are suitable for the case in hand or the facilitator offers a choice between more structured value trees. The decision-makers then just examine the suggested value trees, check the generic tree to make sure that no important factors have been omitted and choose the appropriate one. As in previous RODOS exercises, the participants felt that RODOS could be used for providing information but found it more problematic to use decision analysis methods when deciding on countermeasures in the early phase of a nuclear accident. Furthermore, it was noted that understanding the actual meaning of `soft` attributes, such as socio-psychological impacts or political cost, was not a straightforward issue. Consequently, the definition of attributes in advance would be

  15. Differential association with cellular substructures of pseudorabies virus DNA during early and late phases of replication

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Porat, T.; Veach, R.A.; Blankenship, M.L.; Kaplan, A.S.

    1984-12-01

    Pseudorabies virus DNA synthesis can be divided into two phases, early and late, which can be distinguished from each other on the basis of the structures of the replicating DNA. The two types of replicating virus DNA can also be distinguished from each other on the basis of the cellular substructures with which each is associated. Analysis by electron microscopic autoradiography showed that during the first round of replication, nascent virus DNA was found in the vicinity of the nuclear membrane; during later rounds of replication the nascent virus DNA was located centrally within the nucleus. The degree of association of virus DNA synthesized at early and late phases with the nuclear matrix fractions also differed; a larger proportion of late than of early nascent virus DNA was associated with this fraction. While nascent cellular DNA only was associated in significant amounts with the nuclear matrix fraction, a large part (up to 40%) of all the virus DNA remained associated with this fraction. However, no retention of specific virus proteins in this fraction was observed. Except for two virus proteins, which were preferentially extracted from the nuclear matrix, approximately 20% of all virus proteins remained in the nuclear matrix fraction. The large proportion of virus DNA associated with the nuclear fraction indicated that virus DNA may be intimately associated with some proteins.

  16. High-frequency rTMS on leg motor area in the early phase of stroke.

    Science.gov (United States)

    Sasaki, Nobuyuki; Abo, Masahiro; Hara, Takatoshi; Yamada, Naoki; Niimi, Masachika; Kakuda, Wataru

    2017-03-01

    Although repetitive transcranial magnetic stimulation (rTMS) for upper limb motor area in stroke patients is beneficial, it has been poorly investigated in rTMS for leg motor area. Furthermore, no study has examined the usefulness of rTMS for leg motor area in patients in the early phase of stroke. Twenty-one patients with a hemispheric stroke lesion in the early phase were randomly assigned into two groups: the high-frequency (HF)-rTMS group [N = 11] and the sham stimulation group [N = 10]. Patients received rTMS for 5 consecutive days, beginning 10.9 ± 6.6 days on average after the onset. Brunnstrom Recovery Stages (BRS) for the lower limbs and the Ability for Basic Movement Scale Revised (ABMS II) were assessed before and after the intervention. The improvement in BRS for the lower limbs was significant after the intervention in the HF-rTMS group. Although both the HF-rTMS and sham stimulation groups had significant improvements in ABMS II scores, the extent of improvement in the AMBS II was significantly greater in the HF-rTMS group than in the sham stimulation group. Application of HF-rTMS over the bilateral leg motor areas has potential to be a new rehabilitation therapy for patients in the acute phase of stroke.

  17. Variations in Unrealistic Optimism Between Acceptors and Decliners of Early Phase Cancer Trials.

    Science.gov (United States)

    Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Degnin, Catherine; Sulmasy, Daniel P

    2017-10-01

    Research has found that patient-subjects in early phase cancer trials exhibit unrealistic optimism regarding the risks and possible benefits of trial participation. Unrealistic optimism is associated with therapeutic misconception and failures to appreciate research-related information. This is the first study to assess whether those who decline to participate in these trials also exhibit unrealistic optimism. It is also the first study to assess whether there are significant differences in appreciation of research-related risks/benefits and therapeutic misconception between these two groups. We approached 261 patients at two academic medical centers who were offered enrollment in a Phase I, II, or I/II cancer trial (between 2012 and 2016). Two hundred thirty-three patients agreed to enroll in an early phase cancer trial, 171 of whom agreed to be interviewed for the study. Twenty-eight patients declined the offer to enroll, 15 of whom agreed to be interviewed for the study. Subjects participated in a structured face-to-face interview with a research associate trained to administer the study questionnaires. Acceptors demonstrated a significantly higher level of unrealistic optimism than decliners ( p optimism is consequential for the decision to participate in these trials. The different levels of unrealistic optimism exhibited by these groups suggest that it may be a factor that affects the decision to participate.

  18. Coagulation parameters do not change during luteal phase and pregnancy in cats.

    Science.gov (United States)

    Rivera del Álamo, Maria Montserrat; Meléndez-Lazo, Antonio; Ferré-Dolcet, Lluis; Pastor, Josep; Rigau, Teresa; Santos, Laura; Fresno, Laura

    2014-07-15

    Changes in coagulation parameters depending on reproductive status and pregnancy have been previously reported in both human and other veterinary species. The objective of this study was to determine if different reproductive status affects coagulation parameters in queens. Blood samples from 66 queens submitted to spay surgery were obtained. A hemostatic panel including platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and D-dimer and also progesterone concentrations were measured before surgery. According to progesterone results and embryo vesicles diameter, four groups were established: (1) nonpregnant queens with low (≤1 ng/mL) progesterone concentration (LP) (n = 33); (2) nonpregnant queens with high (≥2 ng/mL) progesterone concentration (n = 8) (HP); (3) first half of pregnancy (n = 12); and (4) second half of pregnancy (n = 13). None of the evaluated parameters showed statistically significant differences among the different groups. There was no significant linear correlation between progesterone values and coagulation parameters. In conclusion, neither the presence of the embryo nor the higher values of progesterone concentration induced statistically significant changes in the coagulation profile studied.

  19. Blunted Myoglobin and Quadriceps Soreness after Electrical Stimulation during the Luteal Phase or Oral Contraception

    Science.gov (United States)

    Anderson, Lindsey J.; Baker, Lucinda L.; Schroeder, E. Todd

    2017-01-01

    Purpose: Acute muscle damage after exercise triggers subsequent regeneration, leading to hypertrophy and increased strength after repeated exercise. It has been debated whether acute exercise-induced muscle damage is altered under various premenopausal estrogen conditions. Acute contraction-induced muscle damage was compared during exogenous (oral…

  20. 2-bromopalmitate inhibition of stimulatory effect on LH in isolated luteal cells.

    Science.gov (United States)

    Tan, C H; Robinson, J

    1982-04-05

    The effect of 2-bromopalmitate, an inhibitor of fatty acids oxidation, on progesterone synthesis in isolated luteal cells was studied. Incubation of the cells with increasing concentrations (0 - 2 mM) of the inhibitor resulted in an initial enhancement of progesterone synthesis, both in the presence and absence of LH (1 microgram/ml). In the LH-treated cells, this stimulation in steroid synthesis becomes markedly impaired at 2 mM 2-bromopalmitate. In the control cells, however, progesterone synthesis was sustained at the elevated level. At high concentrations of 2-bromopalmitate, the stimulatory effect of LH (relative to the controls) on steroidogenesis was progressively diminished, until it was completely abolished at an inhibitor concentration of 2 mM. The oxidation of labelled palmitic acid by luteal cells was also effectively inhibited by 2-bromopalmitate (1 mM). The results indicate that the steroidogenic effect of LH is mediated, in part, by fatty acid oxidation, and were explained in terms of the interaction between carbohydrate and fatty acid oxidation in supporting ovarian steroidogenesis.

  1. Patellar Subluxation With Early-Phase Synovial Chondromatosis of the Knee.

    Science.gov (United States)

    Bashaireh, Khaldoon M

    2016-01-01

    Primary synovial chondromatosis is a rare, benign, monoarticular disease process that affects the synovial membrane of the joint, the synovial sheath, or the bursa around the joint. The etiology is unknown, but it has been associated with trauma in some cases. Although it is a benign lesion, if left untreated, it may lead to early secondary osteoarthritis of the joint. The knee joint is affected in 50% to 65% of cases, followed by the elbow and the hip. This article reports a 30-year-old active woman who presented to the author's clinic with a large infrapatellar mass that caused lateral subluxation of the patella, swelling, and episodic pain with crepitations 14 months after direct trauma to the knee. Clinical examination, magnetic resonance imaging, and arthroscopy revealed a large infrapatellar mass causing lateral subluxation of the patella with no loose bodies. Hoffa's disease, para-articular osteochondroma, and early-phase synovial chondromatosis were considered in the differential diagnosis. The histopathologic and clinical features were consistent with early synovial chondromatosis. The patient underwent local excision of the mass through a medial parapatellar arthrotomy. At 5 years of follow-up, she had no recurrence of the lesion or progression of the disease. Early diagnosis of synovial chondromatosis with local excision offers a reliable cure. However, long-term follow-up is advised because of the high recurrence rates as well as the risk of metaplastic transformation.

  2. Radicular dysfunction preponderance at early phase clinical evaluation in myelitis by Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Claudio Henrique Fernandes Vidal

    2011-04-01

    Full Text Available In neuroschistosomiasis, the spinal cord is the most common place of the disease. In high prevalent areas for schistosomiasis mansoni, the clinical alertness is important for an early diagnostic, in order to decrease the final neurological damage. This study provides some useful neurologic information about a series of patients with schistosomal myelitis. METHOD: The sample consisted of 13 schistosomiasis mansoni carriers examined at the moment of the diagnosis of myelitis. RESULTS: The classical triad (lumbago, weakness at the lower limbs and urinary dysfunctions was documented in 11 (86.61% patients. The distribution of the clinical forms was: myeloradicular in six patients (46.15%, radicular in four (30.76% and myelitic in three (23.07%. CONCLUSION: The radicular dysfunction and their clinical associated forms were the most prominent pattern during the early phase of this disease.

  3. Ultrastructural Complexity of Nuclear Components During Early Apoptotic Phases in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Christian Castelli

    2001-01-01

    Full Text Available Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK‐BR‐3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 μM calcimycin (A23187 for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD values indicating that their plasma membranes were less rough (lower FD than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process.

  4. Efficient runner safety assessment during early design phase and root cause analysis

    Science.gov (United States)

    Liang, Q. W.; Lais, S.; Gentner, C.; Braun, O.

    2012-11-01

    Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

  5. Numerical investigation of the early flight phase in ski-jumping.

    Science.gov (United States)

    Gardan, N; Schneider, A; Polidori, G; Trenchard, H; Seigneur, J M; Beaumont, F; Fourchet, F; Taiar, R

    2017-07-05

    The purpose of this study is to develop a numerical methodology based on real data from wind tunnel experiments to investigate the effect of the ski jumper's posture and speed on aerodynamic forces in a wide range of angles of attack. To improve our knowledge of the aerodynamic behavior of the ski jumper and his equipment during the early flight phase of the ski jump, we applied CFD methodology to evaluate the influence of angle of attack (α=14°, 21.5°, 29°, 36.5° and 44°) and speed (u=23, 26 and 29m/s) on aerodynamic forces in the situation of stable attitude of the ski jumper's body and skis. The standard k-ω turbulence model was used to investigate both the influence of the ski jumper's posture and speed on aerodynamic performance during the early flight phase. Numerical results show that the ski jumper's speed has very little impact on the lift and drag coefficients. Conversely, the lift and drag forces acting on the ski jumper's body during the early flight phase of the jump are strongly influenced by the variations of the angle of attack. The present results suggest that the greater the ski jumper's angle of inclination, with respect to the relative flow, the greater the pressure difference between the lower and upper parts of the skier. Further studies will focus on the dependency of the parameters with both the angle of attack α and the body-ski angle β as control variables. It will be possible to test and optimize different ski jumping styles in different ski jumping hills and investigate different environmental conditions such as temperature, altitude or crosswinds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Dispositional optimism and therapeutic expectations in early-phase oncology trials.

    Science.gov (United States)

    Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

    2016-04-15

    Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; Poptimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (Poptimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early-phase oncology research. © 2016 American Cancer Society.

  7. Quantum chromodynamics phase transition in the early Universe and quark nuggets

    Indian Academy of Sciences (India)

    Abhijit Bhattacharyya; Shibaji Banerjee; Sanjay K Ghosh; Sibaji Raha; Bikash Sinha; Hiroshi Toki

    2003-05-01

    A first-order quark hadron phase transition in the early Universe may lead to the formation of quark nuggets. The baryon number distribution of these quark nuggets have been calculated and it has been found that there are sizeable number of quark nuggets in the stable sector. The nuggets can clump and form bigger objects in the mass range of 0.0003$M_{\\odot}$ to 0.12$M_{\\odot}$. It has been discussed that these bigger objects can be possible candidates for cold dark matter.

  8. The role of ambiguity and discrepancy in the early phases of innovation

    DEFF Research Database (Denmark)

    Laursen, Linda Nhu; Tollestrup, Christian H. T.

    2015-01-01

    and discrepancy, we seek to understand if it might be there for a reason. Through a laboratory experiment, we propose ambiguity and discrepancy actually have a function in concept development. Accordingly the paper contributes with a better understanding of, the role ambiguity and discrepancy as triggers of sense......Innovation literature mainly focuses on eliminating ambiguity and discrepancy from the early phases of innovation. This study questions this implicit assumption, as it may provide an oversimplified view on, how to attain proficiency. Instead of narrowly focusing on reducing ambiguity...

  9. Across an early Holocene humid phase in western Sahara:Pollen and isotope stratigraphy

    Science.gov (United States)

    Lézine, Anne-Marie; Casanova, Joël; Hillaire-Marcel, Claude

    1990-03-01

    Paleohydrology and paleoecology of the region around the Chemchane sabkha (Mauritania) are reconstructed from the comparative analyses of mineralogy, stable isotope ratios of bulk carbonates, and palynology from sediment cores. The age of the section is from ca. 13.5 ka to the middle Holocene. Maximum lake expansion between about 8.3 and 6.5 ka is recorded in a girdle of stromatolite carbonates. These document a lower-salinity lake concomitant with a general establishment of Sahel-Sudan vegetation. The Chemchane area is the northernmost (lat 21°N) occurrence of humid- phase elements that are related to maximum intensity of monsoon activity during the early Holocene.

  10. A Tale of Two Timescales: Mixing, Mass Generation, and Phase Transitions in the Early Universe

    CERN Document Server

    Dienes, Keith R; Thomas, Brooks

    2015-01-01

    Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically --- such as during cosmological mass-generating phase transitions --- the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this paper, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the tot...

  11. Feasibility study for early removal of HEU from CPP-651-Phase II

    Energy Technology Data Exchange (ETDEWEB)

    Smith, C.V.; Henry, R.; Milligan, C.; Harmon, B.; Peterson, J.; Thom, M.A.; Campbell, R.; Hendrix, B.

    1997-09-01

    A two-phase feasibility study was initiated in late 1996 to identify a way to expedite the removal of SNM from the CPP-651 vault. The first phase of this study provided preliminary information that appeared promising, but needed additional detailed planning and evaluate to validate the concepts and conclusions. The focus of Phase 2 was to provide the validation via resource-loaded schedules and more detailed cost estimates. Section 1 describes the purpose and objectives of the Phase 2 tasks and the programmatic drivers that influence related CPP-651 high-enriched uranium (HEU) management issues. Section 2 identifies the evaluation criteria and methodology and the transfer issues and barriers preventing shipment. Section 3 provides site-specific background information for the CPP-651 facility and the Idaho National Engineering and Environmental Laboratory (INEEL) and describes the development of the basic material removal schedule, the proposed base case plan for removal of SNM, and the proposed HEU material management/shipping issues and strategies. Section 4 identifies the proposed options for accelerated removal of SNM and how they were evaluated via detailed scheduling, resource histograms, and cost analysis. Section 5 summarizes principal tasks for implementing this plan and other related HEU CPP-651 management issues that require continued planning efforts to assure successful implementation of this proposed early removal strategy.

  12. Impact of gender and menstrual cycle phase on plasma cytokine concentrations.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    OBJECTIVE: The lifetime prevalence of major depression is twice as high in females as in males. Depression is known to increase at periods where there are changes in gonadal hormones. We examined pro- and anti-inflammatory cytokine levels during the normal menstrual cycle of healthy females compared to similar time points in healthy males. METHODS: Plasma concentrations of interleukin (IL)-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-alpha) and soluble IL-6 receptor (sIL-6R) were measured with enzyme-linked immunosorbent assays in healthy females during the normal ovulatory menstrual cycle and also in males at similar time points. RESULTS: The luteal phase of the menstrual cycle is associated with increased production of sIL-6R, IL-4 and TNF-alpha compared to the early follicular phase. No change was observed in IL-6, IL-8 and IL-10 concentration throughout the menstrual cycle. We found IL-4 positively correlated with oestrogen while TNF-alpha positively correlated with progesterone. Females were found to have significantly higher concentrations of TNF-alpha and sIL-6R across all phases of the menstrual cycle, compared to males across similar time points. CONCLUSION: The normal menstrual cycle is associated with increased production of sIL-6R, IL-4 and TNF-alpha in the luteal phase compared to the early follicular phase. Females have significantly higher concentrations of sIL-6R and TNF-alpha at all time points across the menstrual cycle than males.

  13. Effect of perioperative lfuid therapy on early phase prognosis after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Guo-Qing Jiang; Min-Hao Peng; Ding-Hua Yang

    2008-01-01

    BACKGROUND:Although liver transplantation (LT) has made rapid progress, early pulmonary complications still occur. More attention should be paid to lfuid therapy that may be an important factor leading to these complications. It is necessary to investigate the correlation between intraoperative and postoperative lfuid therapy and early pulmonary complications after LT, then attempt to provide a reasonable lfuid therapy in the perioperative period. METHODS:Sixty-two patients who had undergone LT were enrolled and analyzed retrospectively. Based on early phase prognosis after LT, the 62 patients were divided into a non-pulmonary complication group and a pulmonary complication group. Twenty perioperative variables were analyzed in both groups to screen out several factors causing early pulmonary complications, then the parameters relfecting postoperative recovery were analyzed. RESULTS:The pulmonary complication group had 29 patients (46.77%), 3 (4.84%) of whom died during the perioperative period. Using monofactorial analysis for each variable, the two groups differed in the following variables:preoperative lung function, volume of intraoperative transfusion, volume of intraoperative bleeding, and volume of intraoperative net lfuid retention and lfuid balance (≤-500 ml) in≥2 of the ifrst 3 days after operation. Analysis of the relationship between multivariate factors and pulmonary complications after LT by logistic multivariate regression analysis showed that preoperative lung function, volume of intraoperative bleeding, and lfuid balance (≤-500 ml) in≥2 of the ifrst 3 days after operation were inlfuential factors. CONCLUSIONS:It is important to maintain lfuid balance during the perioperative period of LT. If the hemodynamics are stable, appropriate negative lfuid balance in the ifrst 3 days after operation apparently decreases the incidence of early pulmonary complications after LT. These measures are associated with better postoperative recovery.

  14. Liver CT for vascular mapping during radioembolisation workup : comparison of an early and late arterial phase protocol

    NARCIS (Netherlands)

    van den Hoven, Andor F; Braat, Manon N G J A; Prince, Jip F; van Doormaal, Pieter J; van Leeuwen, Maarten S; Lam, Marnix G E H; van den Bosch, Maurice A A J

    2017-01-01

    OBJECTIVES: To compare right gastric (RGA) and segment 4 artery (A4) origin detection rates during radioembolisation workup between early and late arterial phase liver CT protocols. METHODS: 100 consecutive patients who underwent liver CT between May 2012-January 2015 with early or late arterial pha

  15. Child Developmental Impact of Pittsburgh's Early Childhood Initiative (ECI) in High-Risk Communities: First-Phase Authentic Evaluation Research.

    Science.gov (United States)

    Bagnato, Stephen J.; Suen, Hoi K.; Brickley, Dale; Smith-Jones, Janell; Dettore, Ernie

    2002-01-01

    This study used an "enhanced constructed comparison group" statistical model to conduct longitudinal research on the child developmental impact of Pittsburgh's early childhood initiative (ECI), a partnership to provide high-quality early care and education for children in high-risk neighborhoods. First-phase findings indicate that…

  16. The early phase of /see symbol/ production development in adult Japanese learners of English.

    Science.gov (United States)

    Saito, Kazuya; Munro, Murray J

    2014-12-01

    Although previous research indicates that Japanese speakers' second language (L2) perception and production of English /see symbol/ may improve with increased L2 experience, relatively little is known about the fine phonetic details of their /see symbol/ productions, especially during the early phase of L2 speech learning. This cross-sectional study examined acoustic properties of word-initial /see symbol/ from 60 Japanese learners with a length of residence of between one month and one year in Canada. Their performance was compared to that of 15 native speakers of English and 15 low-proficiency Japanese learners of English. Formant frequencies (F2 and F3) and F1 transition durations were evaluated under three task conditions--word reading, sentence reading, and timed picture description. Learners with as little as two to three months of residence demonstrated target-like F2 frequencies. In addition, increased LOR was predictive of more target-like transition durations. Although the learners showed some improvement in F3 as a function of LOR, they did so mainly at a controlled level of speech production. The findings suggest that during the early phase of L2 segmental development, production accuracy is task-dependent and is influenced by the availability of L1 phonetic cues for redeployment in L2.

  17. Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections.

    Science.gov (United States)

    Yu, Yanbao; Kwon, Keehwan; Tsitrin, Tamara; Bekele, Shiferaw; Sikorski, Patricia; Nelson, Karen E; Pieper, Rembert

    2017-01-01

    Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs. The effector proteins were further enriched in DNA-protein complexes isolated in native PAGE gels. Immunofluorescence microscopy revealed a flattened morphology of neutrophils associated with decondensed chromatin, remnants of granules in the cell periphery, and myeloperoxidase co-localized with extracellular DNA, features consistent with early-phase NETs. Nuclear staining revealed that a considerable fraction of bacterial cells in these structures were dead. The proteomes of two pathogens, Staphylococcus aureus and Escherichia coli, were indicative of adaptive responses to early-phase NETs, specifically the release of virulence factors and arrest of ribosomal protein synthesis. Finally, we discovered patterns of proteolysis consistent with widespread cleavage of proteins by neutrophil elastase, proteinase 3 and cathepsin G and evidence of citrullination in many nuclear proteins.

  18. The early phases of the type Iax supernova SN 2011ay

    CERN Document Server

    Szalai, Tamás; Sárneczky, Krisztián; Takáts, Katalin; Benkő, József M; Kelemen, János; Kuli, Zoltán; Silverman, Jeffrey M; Marion, G Howie; Wheeler, J Craig

    2015-01-01

    We present a detailed study of the early phases of the peculiar supernova 2011ay based on BVRI photometry obtained at Konkoly Observatory, Hungary, and optical spectra taken with the Hobby-Eberly Telescope at McDonald Observatory, Texas. The spectral analysis carried out with SYN++ and SYNAPPS confirms that SN 2011ay belongs to the recently defined class of SNe Iax, which is also supported by the properties of its light and color curves. The estimated photospheric temperature around maximum light, T_{phot} ~8,000 K, is lower than in most Type Ia SNe, which results in the appearance of strong Fe II features in the spectra of SN 2011ay, even during the early phases. We also show that strong blending with metal features (those of Ti II, Fe II, Co II) makes the direct analysis of the broad spectral features very difficult, and this may be true for all SNe Iax. We find two alternative spectrum models that both describe the observed spectra adequately, but their photospheric velocities differ by at least 3,000 km/s...

  19. Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections

    Science.gov (United States)

    Yu, Yanbao; Kwon, Keehwan; Tsitrin, Tamara; Sikorski, Patricia; Nelson, Karen E.; Pieper, Rembert

    2017-01-01

    Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs. The effector proteins were further enriched in DNA-protein complexes isolated in native PAGE gels. Immunofluorescence microscopy revealed a flattened morphology of neutrophils associated with decondensed chromatin, remnants of granules in the cell periphery, and myeloperoxidase co-localized with extracellular DNA, features consistent with early-phase NETs. Nuclear staining revealed that a considerable fraction of bacterial cells in these structures were dead. The proteomes of two pathogens, Staphylococcus aureus and Escherichia coli, were indicative of adaptive responses to early-phase NETs, specifically the release of virulence factors and arrest of ribosomal protein synthesis. Finally, we discovered patterns of proteolysis consistent with widespread cleavage of proteins by neutrophil elastase, proteinase 3 and cathepsin G and evidence of citrullination in many nuclear proteins. PMID:28129394

  20. A Simplified Method for Evaluating Building Sustainability in the Early Design Phase for Architects

    Directory of Open Access Journals (Sweden)

    Jernej Markelj

    2014-12-01

    Full Text Available With society turning increasingly to sustainable development, sharper demands are being made concerning energy efficiency and other properties that mean reductions in the negative effects of the building on the environment and people. This means that architects must have a suitably adapted solution already in the early design phase, as this has the greatest influence on the final result. Current tools and methods used for this are either focused only on individual topics or are too complex and not adapted for independent use by architects. The paper presents a simplified method for evaluating building sustainability (SMEBS which addresses these needs. It is intended as a tool to aid architects in the early project planning phases as it allows a quick evaluation of the extent to which the demands of sustainable building are fulfilled. The method was developed on the basis of a study of international building sustainability assessment methods (BSAM and standards in this field. Experts in sustainable construction were invited to determine weights for assessment parameters using the analytical hierarchy process (AHP. Their judgments reflect the specific characteristics of the local environment.

  1. Perceptions of control and unrealistic optimism in early-phase cancer trials.

    Science.gov (United States)

    Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Degnin, Catherine; Sulmasy, Daniel P

    2017-08-03

    Recent research has found unrealistic optimism (UO) among patient-subjects in early-phase oncology trials. Our aim was to investigate the cognitive and motivational factors that evoke this bias in this context. We expected perceptions of control to be a strong correlate of unrealistic optimism. A study of patient-subjects enrolled in early-phase oncology trials was conducted at two sites in the USA. Respondents completed questionnaires designed to assess unrealistic optimism and several risk attribute variables that have been found to evoke the bias in other contexts. One hundred and seventy-one patient-subjects agreed to be interviewed for our study. Significant levels of perceived controllability were found with respect to all nine research-related questions. Perceptions of control were found to predict unrealistic optimism. Two other risk attribute variables, awareness of indicators (p=0.024) and mental image (p=0.022), were correlated with unrealistic optimism. However, in multivariate regression analysis, awareness and mental image dropped out of the model and perceived controllability was the only factor independently associated with unrealistic optimism (poptimism about benefiting personally from trial participation. Effective interventions to counteract unrealistic optimism may need to address the psychological factors that give rise to distorted risk/benefit processing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Internal Dose from Food and Drink Ingestion in the Early Phase after the Accident

    Science.gov (United States)

    Kawai, Masaki; Yoshizawa, Nobuaki; Hirakawa, Sachiko; Murakami, Kana; Takizawa, Mari; Sato, Osamu; Takagi, Shunji; Miyatake, Hirokazu; Takahashi, Tomoyuki; Suzuki, Gen

    2017-09-01

    Activity concentrations in food and drink, represented by water and vegetables, have been monitored continuously since the Fukushima Daiichi Nuclear Power Plant accident, with a focus on radioactive cesium. On the other hand, iodine-131 was not measured systematically in the early phase after the accident. The activity concentrations of iodine-131 in food and drink are important to estimate internal exposure due to ingestion pathway. When the internal dose from ingestion in the evacuation areas is estimated, water is considered as the main ingestion pathway. In this study, we estimated the values of activity concentrations in water in the early phase after the accident, using a compartment model as an estimation method. The model uses measurement values of activity concentration and deposition rate of iodine-131 onto the ground, which is calculated from an atmospheric dispersion simulation. The model considers how drinking water would be affected by radionuclides deposited into water. We estimated the activity concentrations of water on Kawamata town and Minamisouma city during March of 2011 and the committed effective doses were 0.08 mSv and 0.06 mSv. We calculated the transfer parameters in the model for estimating the activity concentrations in the areas with a small amount of measurement data. In addition, we estimated the committed effective doses from vegetables using atmospheric dispersion simulation and FARMLAND model in case of eating certain vegetables as option information.

  3. Gene expression profiling of bovine ovarian follicular and luteal cells provides insight into cellular identities and functions

    Science.gov (United States)

    After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

  4. A comparison of ovarian follicular and luteal cell gene expression profiles provides insight into cellular identities and functions

    Science.gov (United States)

    After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

  5. Enabling Parametric Optimal Ascent Trajectory Modeling During Early Phases of Design

    Science.gov (United States)

    Holt, James B.; Dees, Patrick D.; Diaz, Manuel J.

    2015-01-01

    During the early phases of engineering design, the costs committed are high, costs incurred are low, and the design freedom is high. It is well documented that decisions made in these early design phases drive the entire design's life cycle. In a traditional paradigm, key design decisions are made when little is known about the design. As the design matures, design changes become more difficult -- in both cost and schedule -- to enact. Indeed, the current capability-based paradigm that has emerged because of the constrained economic environment calls for the infusion of knowledge acquired during later design phases into earlier design phases, i.e. bring knowledge acquired during preliminary and detailed design into pre-conceptual and conceptual design. An area of critical importance to launch vehicle design is the optimization of its ascent trajectory, as the optimal trajectory will be able to take full advantage of the launch vehicle's capability to deliver a maximum amount of payload into orbit. Hence, the optimal ascent trajectory plays an important role in the vehicle's affordability posture as the need for more economically viable access to space solutions are needed in today's constrained economic environment. The problem of ascent trajectory optimization is not a new one. There are several programs that are widely used in industry that allows trajectory analysts to, based on detailed vehicle and insertion orbit parameters, determine the optimal ascent trajectory. Yet, little information is known about the launch vehicle early in the design phase - information that is required of many different disciplines in order to successfully optimize the ascent trajectory. Thus, the current paradigm of optimizing ascent trajectories involves generating point solutions for every change in a vehicle's design parameters. This is often a very tedious, manual, and time-consuming task for the analysts. Moreover, the trajectory design space is highly non-linear and multi

  6. Multiphoton microscopic imaging of esophagus during the early phase of tumor progression.

    Science.gov (United States)

    Xu, Jian; Kang, Deyong; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Chen, Jianxin

    2013-01-01

    Esophageal cancer is one of the most common cancer and leading cause of cancer death worldwide. Multiphoton microscopy (MPM) has become a novel optical tool of choice for imaging tissue architecture and cellular morphology based on two-photon excited fluorescence and second harmonic generation. In this study, we used MPM to image microstructure of human normal esophagus, carcinoma in situ, and early invasive carcinoma in order to investigate the morphological change of tissue structure during the early phase of tumor progression. The diagnostic features such as the appearance of cancerous cells, the absence of the basement membrane were extracted to distinguish between normal and cancerous esophagus tissue. The infiltration depth during tumor progression was determined by the appearance of cancerous cells. The significant change of layer structure between cancerous tissue and normal esophagus was described. We also quantitatively described the differences of morphology between normal and cancerous cells. These results correlated well with the corresponding histological findings. With the advancement of clinically miniaturized MPM and the multi-photon probe, combining MPM with standard endoscopy will therefore allow us to make a real-time in vivo diagnosis of early esophageal cancer at the cellular level. © Wiley Periodicals, Inc.

  7. Analysis of Early Severe Accident Initiated by LBLOCA for Qinshan Phase II Nuclear Power Project

    Directory of Open Access Journals (Sweden)

    Shi Xing-Wei

    2013-07-01

    Full Text Available The purpose of this study is to simulate an early Severe Accident (SA scenario more detail through transferring the thermal-hydraulic status of the plant predicted by RELAP5 computer code to SA Program (SAP. Based on the criterion of date extract time, the RELAP5 thermal-hydraulic calculation data is extracted to form a file for SAP input card at 1477K of cladding surface. Relying on the thermal-hydraulic boundary parameters calculated by RELAP5 code, analysis of early SA initiated by the Large Break Loss-of-Coolant Accident (LBLOCA without mitigation measures for Qinshan Phase II Nuclear Power Plant (QSP-II performed by SAP through finding the key events of accident sequence, estimating the amount of hydrogen generation and oxidation behavior of the cladding and evaluating the relocation order of the materials collapsed in the central region of the core. The results of this study are expected to improve the SA analysis methodology more detail through analyzing early SA scenario.

  8. Individualized peri-operative fluid therapy facilitating early-phase recovery after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Guo-Qing Jiang; Ping Chen; Dou-Sheng Bai; Jing-Wang Tan; Hao Su; Min-Hao Peng

    2012-01-01

    AIM:To investigate the correlation between peri-operative fluid therapy and early-phase recovery after liver transplantation (LT) by retrospectively reviewing 102 consecutive recipients.METHODS:Based on whether or not the patients had pulmonary complications,the patients were categorized into non-pulmonary and pulmonary groups.Twentyeight peri-operative variables were analyzed in both groups to screen for the factors related to the occurrence of early pulmonary complications.RESULTS:The starting hemoglobin (Hb) value,an intra-operative transfusion > 100 mL/kg,and a fluid balance ≤-14 mL/kg on the first day and the second or third day post-operatively were significant factors for early pulmonary complications.The extubation time,time to initial passage of flatus,or intensive care unit length of stay were significantly prolonged in patients who had not received an intra-operative transfusion ≤100 mL/kg or a fluid balance ≤-14 mL/kg on the first day and the second or the third day post-operatively.Moreover,these patients had poorer results in arterial blood gas analysis.CONCLUSION:It is important to offer a precise and individualized fluid therapy during the peri-operative period to the patients undergoing LT for cirrhosis-associated hepatocellular carcinoma.

  9. Methisoprinol for children with early phase dengue infection: a pilot study

    Directory of Open Access Journals (Sweden)

    Melissa G. Ompico

    2013-11-01

    Full Text Available Background Dengue fever is associated with many health complications and medical costs. Furthermore, there is currently no approved dengue antiviral medication or vaccine. Empiric evidence has suggested that patients who received supplemental methisoprinol therapy had faster recovery times and fewer complications. Objective To determine the effects of oral methisoprinol on the clinical course and laboratory findings of children with early phase dengue infection. Methods We conducted a randomized, double-blind study from June to September 2012 on 22 children aged 2.7-16.8 years with laboratory-confirmed early dengue infection. Subjects had not previously received antithrombotic agents, nor did they have bleeding disorders or immunodeficiency. We randomized the subjects to receive either oral methisoprinol (100 mg/kg BW/day, divided into four doses or placebo for 72 hours, with 11 subjects per group. The primary endpoint was fever clearance time (FCT, and secondary endpoints were platelet nadir, white blood cell (WBC nadir, maximum hemoconcentration, length of hospital stay, and development of complications. Results The mean decrease in WBC count was less with methisoprinol than with placebo [1.14 (SD 0.84 vs 2.60 (SD 3.12 x 109/L; P=0.004]. In addition, the mean decrease in platelet count was less in patients on methisoprinol [38.36 (SD 58.3 vs. 50.46 (SD 73.42 x 109/L; P=0.046]. No significant differences between the two groups were found for FCT (P=0.158, length of hospital stay (P=0.511, hemoconcentration, or dengue complications. Conclusion Methisoprinol initiated at an early phase in dengue infection reduced the anticipated leukopenia by 56% and thrombocytopenia by 24%. Hence it can be used along with standard approved fluid and antipyretic therapy. [Paediatr Indones. 2013;53:320-7.].

  10. Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice.

    Directory of Open Access Journals (Sweden)

    Melanie Haffner-Luntzer

    Full Text Available The growth and differentiation factor midkine (Mdk plays an important role in bone development and remodeling. Mdk-deficient mice display a high bone mass phenotype when aged 12 and 18 months. Furthermore, Mdk has been identified as a negative regulator of mechanically induced bone formation and it induces pro-chondrogenic, pro-angiogenic and pro-inflammatory effects. Together with the finding that Mdk is expressed in chondrocytes during fracture healing, we hypothesized that Mdk could play a complex role in endochondral ossification during the bone healing process. Femoral osteotomies stabilized using an external fixator were created in wildtype and Mdk-deficient mice. Fracture healing was evaluated 4, 10, 21 and 28 days after surgery using 3-point-bending, micro-computed tomography, histology and immunohistology. We demonstrated that Mdk-deficient mice displayed delayed chondrogenesis during the early phase of fracture healing as well as significantly decreased flexural rigidity and moment of inertia of the fracture callus 21 days after fracture. Mdk-deficiency diminished beta-catenin expression in chondrocytes and delayed presence of macrophages during early fracture healing. We also investigated the impact of Mdk knockdown using siRNA on ATDC5 chondroprogenitor cells in vitro. Knockdown of Mdk expression resulted in a decrease of beta-catenin and chondrogenic differentiation-related matrix proteins, suggesting that delayed chondrogenesis during fracture healing in Mdk-deficient mice may be due to a cell-autonomous mechanism involving reduced beta-catenin signaling. Our results demonstrated that Mdk plays a crucial role in the early inflammation phase and during the development of cartilaginous callus in the fracture healing process.

  11. Discriminating among stellar population synthesis models of the TP-AGB phase in early quiescent galaxies

    Science.gov (United States)

    MacDougall, Mason; Newman, Andrew; Belli, Sirio; Ellis, Richard S.

    2017-01-01

    Galactic evolution at high redshifts is largely understood through stellar population synthesis (SPS) modeling of spectra and photometry integrated over all starlight of a galaxy. However, complex and poorly understood stellar phases like the unstable thermally-pulsating asymptotic giant branch (TP-AGB) phase make SPS modeling a difficult task. Recent models fail to agree on the TP-AGB contribution to the infrared luminosity, leading to significant discrepancy among the properties derived from modern SPS models when applied to early galaxies. Here we provide a thorough assessment of each of the most widely used SPS models by comparing their results and assessing their accuracy in modeling our unique dataset. We combine high-resolution spectroscopic observations from Keck/MOSFIRE with photometric data for 21 early quiescent galaxies with redshifts of z ~ 2. These galaxies are around the age of peak TP-AGB activity, between ~0.3 and 2 Gyr, and therefore provide an ideal test of the models. We find that models with a “light” TP-AGB contribution provide much better descriptions of our galaxies at ages of ~1 Gyr or less. This is true at high statistical significance and holds for models with or without dust reddening. However, contrary to previous studies, the model-dependent photometrically estimated ages are similar among the models, but they show only moderate agreement with the more model-independent spectroscopic ages derived from stellar absorption lines. The largest discrepancies are found for the Charlot & Bruzual (2007) models which show an artificial clustering of ages around 1 Gyr. The TP-AGB “light” models require more reddening, which can be independently tested by examining dust emission in the mid-infrared. The modeled fluxes are also mostly consistent with mid-infrared observations, with the exception of one model. Resolving these differences among the models will substantially strengthen our estimates of the properties of early quiescent

  12. Transference patterns and working alliance during the early phase of psychodynamic psychotherapy.

    Science.gov (United States)

    Samardzić, Ljiljana; Nikolić, Gordana

    2014-02-01

    Working alliance, as a collaborative part of the therapeutic relationship has been proven to be one of the most powerful therapeutic factors in psychotherapy in general, regardless many technical differences between numerous psychotherapeutic modalities. On the other hand, transference is the basic concept of psychodynamic psychotherapy, and, according to the psychoanalytic theory and practice, it forms a major part of the therapeutic relationship. The aim of our paper was to determine the differences between the groups of patients with low, middle, and high working alliance scores and the dropout group in transference patterns, sociodemographic and clinical parameters, during the early phase of psychodynamic psychotherapy. Our sample consisted of 61 non-psychotic patients, randomly selected by the method of consecutive admissions and treated with psychoanalytic psychotherapy in the outpatient clinical setting. The patients were prospectively followed during 5 initial sessions of the therapeutic process. The working alliance inventory and Core conflictual relationship theme method were used for the estimation of working alliance and transference patterns, respectively. According to the Working Alliance Inventory scores, four groups of patients were formed and than compared. Our results show a significant difference between the groups of patients with low, middle, and high working alliance inventory scores and the dropout group on the variable--transference patterns in the therapeutic relationship. Disharmonious transference patterns are more frequent in patients who form poor quality working alliance in the early phase of psychotherapy, or early dropout psychotherapy. It is of great importance to recognize transference patterns of a patient at the beginning of the psychotherapeutic process, because of their potentially harmful influence on the quality of working alliance.

  13. Shallow Decay Phase of the Early X-Ray Afterglow from External Shock in a Wind Environment

    Institute of Scientific and Technical Information of China (English)

    雷海东; 汪九洲; 吕静; 邹远川

    2011-01-01

    We investigate the shallow decay phase of an early x-ray afterglow in gamma-ray bursts discovered by Swift, and suggest that both the shallow decay phase and the normal phase are from external shock in a wind environment, while the transferring time is the deceleration time. We apply this model to GRBs 050319 and 081008, and find that they can be explained by choosing a proper set of parameters.%We investigate the shallow decay phase of an early x-ray afterglow in gamma-ray bursts discovered by Swift,and suggest that both the shallow decay phase and the normal phase are from external shock in a wind environment,while the transferring time is the deceleration time.We apply this model to GRBs 050319 and 081008,and find that they can be explained by choosing a proper set of parameters.

  14. Fault instability on a finite and planar fault related to early phase of nucleation

    Science.gov (United States)

    Mitsui, Yuta; Hirahara, Kazuro

    2011-06-01

    We numerically investigate the early phase of nucleation on a planar fault with the rate- and state-dependent friction law, loaded externally by steady slip, to clarify its relation to fault instability. We define Rn as the invasion distance of the inward creep to characterize that phase. For a circular fault, the dependence of Rn on the dimensionless parameters lb, lb-a, and lRA (all of these are proportional to the rigidity and the characteristic distance of the state evolution L and inversely proportional to the normal stress and the fault radius) can be compiled. We found that Rn is proportional to lb (both aging law and slip law of the state evolution) and lb-a (aging law). In the case of the aging law only, there are two regimes (ordinary events and slow events) separated by the value of lRA. The regimes have different trend lines, although we could not measure Rn for the case of lRA < 0.35 because of breaking of the mirror symmetry of instability along the loading direction. Rn in the slow event regime is smaller. Moreover, we investigated the effect of fault shape and found that a model with a long radius along the mode 2 direction has similar parameter dependence to circular faults, but a model with a long radius along the mode 3 direction has different ones. Our results imply that we can qualitatively estimate the fault instability parameters from the early phase of nucleation, although further research is necessary to enable application to actual faults.

  15. Phase-field simulations of nuclei and early stage solidification microstructures

    Science.gov (United States)

    Nestler, B.; Selzer, M.; Danilov, D.

    2009-11-01

    To investigate the local properties of heterogeneous nuclei on substrates, a phase-field model is extended to incorporate volume constraints and a third order line tension in the gradient free energy density formulation. The new model is applied to sessile drop simulations of Cu nuclei on Ni substrates to precisely analyse 3D equilibrium shapes and diffusion processes across the phase boundaries. In particular, the formalism with higher order potentials is used to investigate the length-scale dependent effect of the line tension on Young's force balance at triple lines in 3D. The employment of parallel and adaptive simulation techniques is essential for three-dimensional numerical computations. Early stage solidification microstructures of cubic Ni crystals are simulated by scale-bridging molecular dynamics (MD) and phase-field (PF) simulations. The domain of the PF computations is initialized by transferring MD data of the atomic positions and of the shape of the nuclei. The combined approach can be used to study the responses of microstructures upon nucleation.

  16. Phase-field simulations of nuclei and early stage solidification microstructures

    Energy Technology Data Exchange (ETDEWEB)

    Nestler, B; Selzer, M; Danilov, D [Institute of Materials and Processes (IMP), Karlsruhe University of Applied Sciences, Moltkestrasse 30, 76133 Karlsruhe (Germany)

    2009-11-18

    To investigate the local properties of heterogeneous nuclei on substrates, a phase-field model is extended to incorporate volume constraints and a third order line tension in the gradient free energy density formulation. The new model is applied to sessile drop simulations of Cu nuclei on Ni substrates to precisely analyse 3D equilibrium shapes and diffusion processes across the phase boundaries. In particular, the formalism with higher order potentials is used to investigate the length-scale dependent effect of the line tension on Young's force balance at triple lines in 3D. The employment of parallel and adaptive simulation techniques is essential for three-dimensional numerical computations. Early stage solidification microstructures of cubic Ni crystals are simulated by scale-bridging molecular dynamics (MD) and phase-field (PF) simulations. The domain of the PF computations is initialized by transferring MD data of the atomic positions and of the shape of the nuclei. The combined approach can be used to study the responses of microstructures upon nucleation.

  17. SURVIVAL OF INTERSTELLAR MOLECULES TO PRESTELLAR DENSE CORE COLLAPSE AND EARLY PHASES OF DISK FORMATION

    Energy Technology Data Exchange (ETDEWEB)

    Hincelin, U. [Department of Chemistry, University of Virginia, Charlottesville, VA 22904 (United States); Wakelam, V.; Hersant, F.; Guilloteau, S. [University of Bordeaux, LAB, UMR 5804, F-33270 Floirac (France); Commerçon, B., E-mail: ugo.hincelin@virginia.edu [Laboratoire de radioastronomie, LERMA, Observatoire de Paris, Ecole Normale Supérieure (UMR 8112 CNRS), 24 rue Lhomond, F-75231 Paris Cedex 05 (France)

    2013-09-20

    An outstanding question of astrobiology is the link between the chemical composition of planets, comets, and other solar system bodies and the molecules formed in the interstellar medium. Understanding the chemical and physical evolution of the matter leading to the formation of protoplanetary disks is an important step for this. We provide some new clues to this long-standing problem using three-dimensional chemical simulations of the early phases of disk formation: we interfaced the full gas-grain chemical model Nautilus with the radiation-magnetohydrodynamic model RAMSES, for different configurations and intensities of the magnetic field. Our results show that the chemical content (gas and ices) is globally conserved during the collapsing process, from the parent molecular cloud to the young disk surrounding the first Larson core. A qualitative comparison with cometary composition suggests that comets are constituted of different phases, some molecules being direct tracers of interstellar chemistry, while others, including complex molecules, seem to have been formed in disks, where higher densities and temperatures allow for an active grain surface chemistry. The latter phase, and its connection with the formation of the first Larson core, remains to be modeled.

  18. Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

    Science.gov (United States)

    Farid, Karim; Hong, Young T; Aigbirhio, Franklin I; Fryer, Tim D; Menon, David K; Warburton, Elizabeth A; Baron, Jean-Claude

    2015-01-01

    Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1-6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD.

  19. Phase noise reveals early category-specific modulation of the event-related potentials.

    Science.gov (United States)

    Németh, Kornél; Kovács, Petra; Vakli, Pál; Kovács, Gyula; Zimmer, Márta

    2014-01-01

    Previous studies have found that the amplitude of the early event-related potential (ERP) components evoked by faces, such as N170 and P2, changes systematically as a function of noise added to the stimuli. This change has been linked to an increased perceptual processing demand and to enhanced difficulty in perceptual decision making about faces. However, to date it has not yet been tested whether noise manipulation affects the neural correlates of decisions about face and non-face stimuli similarly. To this end, we measured the ERPs for faces and cars at three different phase noise levels. Subjects performed the same two-alternative age-discrimination task on stimuli chosen from young-old morphing continua that were created from faces as well as cars and were calibrated to lead to similar performances at each noise-level. Adding phase noise to the stimuli reduced performance and enhanced response latency for the two categories to the same extent. Parallel to that, phase noise reduced the amplitude and prolonged the latency of the face-specific N170 component. The amplitude of the P1 showed category-specific noise dependence: it was enhanced over the right hemisphere for cars and over the left hemisphere for faces as a result of adding phase noise to the stimuli, but remained stable across noise levels for cars over the left and for faces over the right hemisphere. Moreover, noise modulation altered the category-selectivity of the N170, while the P2 ERP component, typically associated with task decision difficulty, was larger for the more noisy stimuli regardless of stimulus category. Our results suggest that the category-specificity of noise-induced modulations of ERP responses starts at around 100 ms post-stimulus.

  20. Prolonged Administration of Twice-Daily Bolus Intravenous Tacrolimus in the Early Phase After Lung Transplantation.

    Science.gov (United States)

    Hirano, Yutaka; Sugimoto, Seiichiro; Mano, Toshifumi; Kurosaki, Takeshi; Miyoshi, Kentaroh; Otani, Shinji; Yamane, Masaomi; Kobayashi, Motomu; Miyoshi, Shinichiro; Oto, Takahiro

    2017-08-11

    BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

  1. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  2. Traumatic Brain Injury Pathophysiology and Treatments: Early, Intermediate, and Late Phases Post-Injury

    Directory of Open Access Journals (Sweden)

    Hanna Algattas

    2013-12-01

    Full Text Available Traumatic Brain Injury (TBI affects a large proportion and extensive array of individuals in the population. While precise pathological mechanisms are lacking, the growing base of knowledge concerning TBI has put increased emphasis on its understanding and treatment. Most treatments of TBI are aimed at ameliorating secondary insults arising from the injury; these insults can be characterized with respect to time post-injury, including early, intermediate, and late pathological changes. Early pathological responses are due to energy depletion and cell death secondary to excitotoxicity, the intermediate phase is characterized by neuroinflammation and the late stage by increased susceptibility to seizures and epilepsy. Current treatments of TBI have been tailored to these distinct pathological stages with some overlap. Many prophylactic, pharmacologic, and surgical treatments are used post-TBI to halt the progression of these pathologic reactions. In the present review, we discuss the mechanisms of the pathological hallmarks of TBI and both current and novel treatments which target the respective pathways.

  3. REMIR: The REM infrared camera to follow up the early phases of GRBs afterglows

    Science.gov (United States)

    Calzoletti, L.; Melandri, A.; Testa, V.; Antonelli, L. A.; Vitali, F.; D'Alessio, F.; di Paola, A.; Zerbi, F. M.; Chincarini, G.; Cunniffe, R.; Jordan, B.; Rodonò, M.; Conconi, P.; Covino, S.; Cutispoto, G.; Molinari, E.; Tosti, G.; Ross/Rem Team

    2005-07-01

    REMIR is a near-infrared camera, covering the 0.95-2.3 μm range with 5 filters (z,J,H,Ks and H2), mounted at one of the Nasmyth foci of the REM (Rapid Eye Mount) telescope. REM is a fully robotic fast-slewing 60 cm telescope, primarily designed to follow-up the early phases of the afterglow of GRBs detected by dedicated instruments onboard satellites (like SWIFT, a satellite entirely dedicated to GRBs science launched the 12 November 2004). Moreover REM hosts a slitless spectrograph covering the range 0.45-0.95 μm, with 30 sample points and with the possibility to perform broad-band V,R,I photometry (ROSS, REM Optical Slitless Spectrograph). The main task of REMIR is to perform realtime NIR observations of GRBs detected by gamma-ray monitors onboard satellites, looking for any possible infrared transient source. As soon as a transient source is detected in the IR images, larger telescopes are promptly alerted to perform early spectroscopy of the afterglow. All the above operations are performed in a fully automatic way and without any human supervision. We present the results of on-site tests that have been done to characterize the REMIR camera and the performances of the dedicated reduction pipeline AQuA (Automatic Quick Analysis), suited for fast transients detection.

  4. Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats.

    Science.gov (United States)

    Ahn, Hyo-Jin; An, Beum-Soo; Jung, Eui-Man; Yang, Hyun; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-09-01

    Parabens are widely used as anti-microbial agents in the cosmetic and pharmaceutical industries. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In the present study, 55 female pups were given daily subcutaneous injections of methyl-, propyl-, and butyl-paraben or 17beta-estradiol (E2) during neonatal Day 1-7. The ovaries were excised on postnatal Day 8, then fixed and stained with hematoxylin and eosin for histological analysis. The follicles were counted and classified as being in the primordial, early primary, or primary stages. The number of primordial follicles increased while early primary follicles decreased at the high doses of propyl- and butyl-paraben. The levels of anti-Mullerian hormone (AMH) and Foxl2 mRNA increased by propyl- and butyl-parabens whereas kit ligand/stem cell factor (KITL) expression was up regulated only by butyl-paraben. The mRNA levels of StAR and Cyp11a1 were significantly decreased after treatment with methyl-, propyl-, and butyl-parabens. Consistent with its use as a positive control, E2 regulated the expression of KITL, StAR, and Cyp11a1 genes, but surprisingly did not affect AMH and Foxl2 levels. Thus, E2 and parabens had different effects on the regulation of folliculogenic and steroidogenic genes, demonstrating the estrogenic and nonestrogenic properties of parabens in the ovary. Taken together, our data show that parabens stimulated AMH mRNA expression and consequently inhibited the early phase of folliculogenesis in the ovaries of neonatal female rat. The levels of steroidogenic enzymes, indicators of follicle differentiation, appeared to be regulated by parabens through inhibition of their transcriptional repressor, Foxl2. Copyright © 2012 Wiley Periodicals, Inc.

  5. Teachers’ Beliefs on Foreign Language Teaching Practices in Early Phases of Primary Education: A case study

    Directory of Open Access Journals (Sweden)

    Mustafa Caner

    2010-07-01

    Full Text Available The purpose of the study was to examine whether teacher beliefs would play a role in their actual practices while teaching target language in early phases of primary education, principally, in kindergarten and first grades in a state school. As it is a very broad research area, the researchers exclusively analyzed teaching practices and teaching activities of two teachers and their beliefs about teaching English to young children within the frame of early childhood education principles. One of the data gathering instruments in this case study was a questionnaire that inquires the participants beliefs related to the classroom practices and how these beliefs influence their classroom practices in early childhood education. In addition to the questionnaire, semi structured interviews with participants were held to examine their beliefs in detail. Finally, in order to see whether participants’ beliefs matched with their actual practices in their classrooms or not, the sample courses of the participants were observed and video-recorded for triangulation for the data. The classroom observations of the courses as well as video recordings of those courses were also examined by the researchers, and the findings were verified by another co-rater in order to increase the trustworthiness of the data. The analysis of responses of participants to the questionnaire, video-recorded classroom observations and interviews were presented qualitatively in the findings section. The results showed that both of the teachers took into account how their students could learn best with regards to their age, level and interest through using different activities and materials suitable for teaching English to young learners. It was also observed that teachers placed room for repetition, role-play, singing songs, picture drawings and coloring in their classes with young learners.

  6. Very early multi-color observations of the plateau phase of GRB 041006 afterglow

    CERN Document Server

    Urata, Y; Qiu, Y L; Hu, J; Kuo, P H; Tamagawa, T; Ip, W H; Kinoshita, D; Fukushi, H; Isogai, M; Miyata, T; Nakada, Y; Aoki, T; Soyano, T; Tarusawa, K; Mito, H; Onda, K; Ibrahimov, M; Pozanenko, A; Makishima, K

    2006-01-01

    Observations of the optical afterglow of GRB 041006 with the Kiso Observatory 1.05 m Schmidt telescope, the Lulin Observatory 1.0 m telescope and the Xinglong Observatory 0.6 m telescope. Three-bands (B, V and R) of photometric data points were obtained on 2004 October 6, 0.025-0.329 days after the burst. These very early multi band light curves imply the existence of a color dependent plateau phase. The B-band light curve shows a clear plateau at around 0.03 days after the burst. The R band light curve shows the hint of a plateau, or a possible slope change, at around 0.1 days after the burst. The overall behavior of these multi-band light curves may be interpreted in terms of the sum of two separate components, one showing a monotonic decay the other exhibiting a rising and a falling phase, as described by the standard afterglow model.

  7. Association between GSTP1 CpG methylation and the early phase of lead exposure.

    Science.gov (United States)

    Li, Chunping; Yang, Xiaolin; Xu, Ming; Zhang, Jinlong; Sun, Na

    2014-02-01

    GSTP1 is induced by lead, and thus serves as a biomarker of lead exposure. Lead exposure changes DNA methylation status. We attempted to prove that the methylation of the GSTP1 promoter plays an important role in lead toxicity. We conducted a case-control study of 53 workers from a battery plant and 53 age and sex matched healthy volunteers to determine whether the methylation level of the GSTP1 promoter is associated with the risk of lead poisoning. We employed methylation-specific PCR (MSP) in cell models to determine the relationship between the GSTP1 methylation level and lead exposure. We found no association between GSTP1 methylation and lead exposure. The difference in methylation frequencies between the exposure group and the controls was not statistically significant (p = 0.401), and individuals with the methylated GSTP1 gene was not associated with the risk of lead poisoning (adjusted OR = 1.36, 95% CI, 0.22-8.24). This study suggests that GSTP1 methylation is not involved in the early phase of lead toxicity. Further studies should be performed to detect the association between GSTP1 methylation and the risk of lead poisoning in later phases.

  8. Flare Ribbons In The Early Phase Of An SDO Flare: Emission Measure And Energetics

    Science.gov (United States)

    Fletcher, Lyndsay; Hannah, I. G.; Hudson, H. S.; Innes, D. E.

    2012-05-01

    We report on the M1.0 flare of 7th August 2010, which displayed extended early phase chromospheric ribbons, well observed by SDO/AIA and RHESSI. Most large flares saturate rapidly in the high-temperature AIA channels, however this event could be followed in unsaturated AIA images for ten minutes in the build-up to and first few minutes of the impulsive phase. Analysis of GOES, RHESSI and SDO/AIA demonstrates the presence of high temperature ( 10MK), compact plasma volumes in the chromospheric flare ribbons, with a column emission measure of on average 3-7 x 1028 cm-5. We construct a time-resolved energy budget for the ribbon plasma, including also SDO/EVE data, and discuss the implications of the observed ribbon properties for flare energisation. This work was supported by the UK’s Science and Technology Facilities Council (ST/1001801), and by the European Commission through the FP7 HESPE project (FP7-2010-SPACE-263086).

  9. 添加GnRH-a黄体支持的辅助生殖技术治疗后妊娠结局及子代随访结局分析%Analysis of the follow-up results concerning pregnancy, delivery and infants after assisted reproductive technique with GnRH-a for luteal support

    Institute of Scientific and Technical Information of China (English)

    周卫琴; 潘艳平; 庄燕燕; 夏飞; 茅彩萍

    2016-01-01

    RH-a in luteal support on the safety of mother and infant. Methods A retrospective analysis was carried out on the medical record from 215 patients who got clinically pregnant after luteal phase long regimen fresh-cycle transfer was operated. According to the differences in luteal support methods, the patients were assigned to Group A (124 patients, progesterone+dydrogesterone group), Group B (91 patients, GnRH-a added group). The patients′ pregnancy course, delivery time, and the growth and development of infants within 1-2 years were followed up. Results (1)There was no obvious difference between Group A and Group B in terms of the abortion ratio during the early pregnancy (8.1%, 12.1%), the rate of abortion villous deformity (50.0%, 9.1%), the rate of heterotopic pregnancy (10.5%, 5.5%) and rate of twin pregnancy (19.4%, 28.6%;all P>0.05).(2)Compared to group A, during the middle and late pregnancy of single or twin pregnancy in Group B , there was no obvious difference in the rate of fetal chromosomal abnormality, organ malformation incidence, late abortion rate and stillbirth rate (all P>0.05).(3)As to childbirth, in the case of twin pregnancy, there was a higher rate of premature delivery (60.0%, 39.1%;P=0.041), as well as rate of lower birth weight of newborn (56.0%, 34.8%; P=0.037) in group B.(4)The statistics on general growth and development as well as infantile common diseases within 2 years after birth indicated that there was no obvious difference between the two groups in single birth and twin birth subgroup (all P>0.05). Conclusion On the basis of controlling of implanted embryos and reducing the occurrence of twins, GnRH-a luteal support maybe relatively safe and effective.

  10. Risk factors for and impact of respiratory failure on mortality in the early phase of acute pancreatitis

    DEFF Research Database (Denmark)

    Dombernowsky, Tilde; Kristensen, Marlene Østermark; Rysgaard, Sisse

    2016-01-01

    : Retrospective cohort study including 359 patients admitted with acute pancreatitis. Information was gathered from electronic patient records. We defined respiratory failure based on the modified Marshall scoring system in the revised Atlanta criteria. Predictors of respiratory failure were evaluated......, or pneumonia may develop respiratory failure, suggests that acute lung injury, possibly associated with systemic inflammation, may be important.......BACKGROUND: The incidence of respiratory failure and other respiratory complications in the early phase of acute pancreatitis (AP) is not well investigated. OBJECTIVE: To evaluate the incidence and risk factors of respiratory failure, and its impact on mortality in the early phase AP. METHODS...

  11. Liver CT for vascular mapping during radioembolisation workup: comparison of an early and late arterial phase protocol

    Energy Technology Data Exchange (ETDEWEB)

    Hoven, Andor F. van den; Braat, Manon N.G.J.A.; Prince, Jip F.; Doormaal, Pieter J. van; Leeuwen, Maarten S. van; Lam, Marnix G.E.H.; Bosch, Maurice A.A.J. van den [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands)

    2017-01-15

    To compare right gastric (RGA) and segment 4 artery (A4) origin detection rates during radioembolisation workup between early and late arterial phase liver CT protocols. 100 consecutive patients who underwent liver CT between May 2012-January 2015 with early or late arterial phase protocol (n = 50 each, 10- vs. 20-s post-threshold delay) were included. RGA/A4 origin detection rates, assessed by two raters, and contrast-to-noise ratio (CNR) of the hepatic artery relative to the portal vein were compared between the protocols. The first-second rater scored the RGA origin as visible in 58-65 % (specific proportion of agreement 82 %, κ = 0.62); A4 origin in 96-89 % (94 %, κ = 0.54). Thirty-six percent of RGA origins not detectable by DSA were identified on CT. Origin detection rates were not significantly different for early/late arterial phases. Mean CNR was higher in the early arterial phase protocol (1.7 vs. 1.2, p < 0.001). A 10-s delay arterial phase CT protocol does not significantly improve detection of small intra- and extrahepatic branches. RGA origin detection requires further optimization, whereas A4/MHA origin detection is adequate, with good inter-rater reproducibility. CT remains important for preprocedural planning, because it may reveal arterial anatomy not discernible on DSA. (orig.)

  12. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  13. Immunohistochemical Localization of Estrogen and Progesterone Receptorin Decidua and Villi of Human Early Pregnancy

    Institute of Scientific and Technical Information of China (English)

    王介东; 伏耀; 施文良; 朱逢第; 乔根梅; 王幼劬

    1992-01-01

    Imtnunohistochemical assessment of estrogen recceptor(ER) and progesterone receptors(PR) were performed using monoetonat antibodies to the receptors. A totalof 81 samples. from pregnant women at 5-13 weeks of gestation were immunostained by peroxidase anti-peroxidase method (PAP). hnmunostaining pattern of PR in early pregnant decidua was similar to that of the late luteal phase of normal endometrium characterized by little reaction in supecfieiat glandular epithelia and retatively intense in stroma. Positive stainig was atsa revealed in structure of blood vessels including pericyte and smooth muscle cells. An interesting finding is that endothelial cells Of the vessels expressed PR which has not been reported in normal cyclic endometrium. The endothelial nature of their PR partitive cell was further confirmed by immunostaining of specific endothelial marker, Factor VⅢ. The trophoblast population in villi anddecidua also showed positive reaction inctnding villous trophoblast, column andinterstitial trophobtast. In eontrast to PR, little ER were revealed in deteected tissue.

  14. The Clinical Study on Effect of a Combination of Mifepristone with Misoprostol on Late Luteal Fertility Regulation

    Institute of Scientific and Technical Information of China (English)

    杨婕; 桂幼伦; 郑娥香; 贺昌海

    2002-01-01

    Objective To investigate the efficacy, safety and acceptability of mifepristone com-bined with misoprostol used for late luteal fertility regulationtreatment cycles in total. Subjects were planned to receive treatment with 25 mg ofmifepristone, Q12 h × 4 orally for five days prior to expected menstruation followedby 400 μg of misoprostol 48 h later for up to six cycles.Results There were 13 pregnancies in the 267 treatment cycles and among them com-plete abortion and continuing pregnancy occurred in 7 and 6 cycles respectively. So theoverall pregnancy rate was 4. 87% (13/267) and the rate of continuing pregnancywas 2. 25% (6/267), while the failure rate per pregnant cycle was 46. 15% (6/13).In treatment cycles the vaginal bleeding patterns changed insignificantly as comparedwith those in control cycles.Conclusion The efficacy, compliance and acceptability of the regimen should befurther improved when it was administered for late luteal fertility regulation.

  15. Psychosocial Interventions in Reducing Cannabis Use in Early Phase Psychosis: A Canadian Survey of Treatments Offered.

    Science.gov (United States)

    Aydin, Cristina; Tibbo, Philip G; Ursuliak, Zenovia

    2016-06-01

    Cannabis use in people with early phase psychosis (EPP) can have a significant impact on long-term outcomes. The purpose of this investigation was to describe current cannabis use treatment practices in English-speaking early intervention services (EISs) in Canada and determine if their services are informed by available evidence. Thirty-five Canadian English-speaking EISs for psychosis were approached to complete a survey through email, facsimile, or online in order to collect information regarding their current cannabis use treatment practices. Data were acquired from 27 of the 35 (78%) programs approached. Only 12% of EISs offered formal services that targeted cannabis use, whereas the majority (63%) of EISs offered informal services for all substance use, not specifically cannabis. In programs with informal services, individual patient psychoeducation (86%) was slightly more common than individual motivational interviewing (MI) (76%) followed by group patient psychoeducation (52%) and information handouts (52%). Thirty-seven percent of EISs offered formal services for substance use, and compared to programs with informal services, more MI, cognitive-behavioural therapy, and family services were offered, with individual treatment modalities more common than groups. No EISs used contingency management, even though it has some preliminary evidence in chronic populations. Evidence-based service implementation barriers included appropriate training and administrative support. While most English-speaking Canadian EIS programs offer individual MI and psychoeducation, which is in line with the available literature, there is room for improvement in cannabis treatment services based on current evidence for both people with EPP and their families. © The Author(s) 2016.

  16. Nitric Oxide Chemical Donor Affects the Early Phases of In Vitro Wound Healing Process.

    Science.gov (United States)

    La Torre, Cristina; Cinque, Benedetta; Lombardi, Francesca; Miconi, Gianfranca; Palumbo, Paola; Evtoski, Zoran; Placidi, Giuseppe; Fanini, Donatella; Cimini, Anna Maria; Benedetti, Elisabetta; Giuliani, Maurizio; Cifone, Maria Grazia

    2016-10-01

    An artificial wound in a confluent monolayer of human keratinocyte HaCaT cells or mouse embryo fibroblast Swiss NIH 3T3 cells was used to analyze the effects of the nitric oxide (NO) chemical donor, S-nitroso-N-acetylpenicillamine (SNAP). SNAP exposure promoted an enhanced rate of wound closure and accelerated motility of both keratinocytes and fibroblasts compared to control cells. The wounded monolayer cultures of HaCaT and NIH 3T3 cells, treated with or without SNAP, were monitored under a phase contrast microscope. Structural and ultrastructural modifications were analyzed by scanning electron microscopy (SEM). The images were captured by a digital camera at different time points (0-28 h) and the wound area was analyzed through software included in Matlab®. As early as 15 min, SNAP induced significant cytoskeletal remodeling, as shown by immunostaining (phalloidin-labelling), which in turn was associated with increased filopodium number and length rise. NO donor treatment also induced overexpression of Ki-67 protein, a typical marker of cell proliferation, as shown by immunostaining. Both SNAP-induced migration and proliferation were antagonized by the NO-sensitive GC inhibitor 1H-[1,2,4]oxadiazolo[-4,3-a]quinoxalin-1-one (ODQ), which suggests activation of the NO/cGMP signalling cascade in the observed SNAP-induced effects in the early stages of the healing process. Moreover, we provide evidence that PPAR-β antagonist (GSK0660) may interfere with NO-mediated wound healing process. J. Cell. Physiol. 231: 2185-2195, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Phase III randomized trial of toremifene versus tamoxifen for Japanese postmenopausal patients with early breast cancer.

    Science.gov (United States)

    Kimura, Morihiko; Tominaga, Takeshi; Kimijima, Izo; Takatsuka, Yuichi; Takashima, Shigemitsu; Nomura, Yasuo; Kasumi, Fujio; Yamaguchi, Akihiro; Masuda, Norikazu; Noguchi, Shinzaburo; Eshima, Nobuoki

    2014-05-01

    Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen. The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events. A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated. Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.

  18. Changes of inflammation-associated cytokine expressions during early phase of experimental endotoxic shock in macaques

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Ji; Ke-Yi Sun; Yan-Hong Feng; Guo-Qing Yin

    2004-01-01

    AIM: To study changes of inflammation-associated cytokine expressions during early phase of endotoxic shock in macague.METHODS: Experiments were performed in Macaque mulatta treated with LPS 2.8 mg/kg in shock model group or with normal saline in control group. Blood samples were collected before, or 60 min, or 120 min after LPS injection,respectively. Liver and spleen tissues were obtained at 120 min after LPS injection. The plasma levels of TNF-α,IL-1 β, IL-10 and IL-12P40 were determined by doubleantibody sandwich ELISA with antibodies against human cytokines. The mRNA levels of TNF-α, IL-1 β, and IL-18 in peripheral blood mononuclear cells (PBMCs), liver and spleen were examined by real-time fluorescence semi-quantitative RT-PCR with the primers based on human genes.RESULTS: Mean systemic arterial pressure (MAP), systemic vascular resistance index (SVRI) and left ventricular work index (LVWI) of macaques were significant declined in shock model group on average 60 min after LPS injection. The plasma levels of TNF-α and IL-10 were significantly increased 60 min after LPS injection and then decreased.The plasma levels of IL-1 β and IL-12P40 were significantly increased at 120 min after LPS injection. The mRNA levels of TNF-α and IL-1 β were significantly increased 60 min after LPS stimulation in PBMCs and 120 min after LPS stimulation in livers. The mRNA level of IL-18 was significantly increased 120 min after LPS stimulation in PBMCs and livers. But in spleen, only TNF-α mRNA level in LPS group was significantly higher 120 min after LPS stimulation, compared with that in control group.CONCLUSION: An endotoxic shock model of Macaque mulatta was successfully established. Both antibodies for ELISA and PCR primers based on human cytokine assays were successfully applied to detect macaque cytokines. In the model, inflammatory cytokines, such as TNF-α, IL-1 β,IL-12 and IL-18 as well as anti-inflammation cytokine IL-10,were released at very early phase of

  19. Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase.

    Science.gov (United States)

    Carroll, Marilyn E; Kohl, Emily A; Johnson, Krista M; LaNasa, Rachel M

    2013-06-01

    In previous studies with male and female rhesus monkeys, withdrawal of access to oral phencyclidine (PCP) self-administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females, and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer impulsive choice for SACC increased during PCP withdrawal more in males than females. The goal of the present study was to examine the effect of PCP (0.25 or 0.5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle. In component 1, PCP and water were available from two drinking spouts for 1.5 h sessions under concurrent FR 16 schedules. In component 2, a SACC solution was available for 45 min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6 ml) or six delayed SACC deliveries, and the delay was increased by 1 s after a response on the delayed lever and decreased by 1 s after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP withdrawal, that occurred during the mid-follicular phase (days 7-11) or the late luteal phase (days 24-28) of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases. PCP deliveries were higher during the luteal (vs follicular) phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration. PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys.

  20. Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists

    Directory of Open Access Journals (Sweden)

    Roth Robert

    2006-02-01

    Full Text Available Abstract Background Cytokine production is critical in ischemia/reperfusion (IR injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury. Methods Adult male mice underwent 90-min of partial liver ischemia followed by reperfusion. The AChR agonists (1,1-dimethyl-4-phenyl-L-pioperazinium-iodide [DMPP], and nicotine or saline-vehicle were administered i.p. before ischemia. Plasma cytokine tumor necrosis factor (TNF-α, macrophage inflammatory protein-2, and Interleukin-6 were measured. Liver injury was assessed by plasma alanine transaminase (ALT and liver histopathology. Results A reperfusion time-dependent hepatocellular injury occurred as was indicated by increased plasma-ALT and histopathology. The injury was associated with marked elevation of plasma cytokines/chemokines. Pre-ischemic treatment of mice with DMPP or nicotine significantly decreased plasma-ALT and cytokines after 3 h of reperfusion. After 6 h of reperfusion, the protective effect of DMPP decreased and reached a negligible level by 24 h of reperfusion, despite significantly low levels of plasma cytokines. Histopathology showed markedly diminished hepatocellular injury in DMPP- and nicotine-pretreated mice during the early-phase of hepatic-IR, which reached a level comparable to saline-treated mice at late-phase of IR. Conclusion Pharmacological modulation of the cholinergic pathway provides a means to modulate cytokine production and to delay IR-induced heaptocellular injury.

  1. Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility

    OpenAIRE

    Kimani, Peter K.; Todd, Susan; Stallard, Nigel

    2013-01-01

    Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point esti...

  2. Experimental infection with Toxocara cati in pigs: migratory pattern and pathological response in early phase.

    Science.gov (United States)

    Sommerfelt, Irma Estela; Duchene, Adriana; Daprato, Betina; Lopez, Clara María; Cardillo, Natalia; Franco, Aníbal Juan

    2014-01-01

    Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi). Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident.

  3. EXPERIMENTAL INFECTION WITH Toxocara cati IN PIGS: MIGRATORY PATTERN AND PATHOLOGICAL RESPONSE IN EARLY PHASE

    Directory of Open Access Journals (Sweden)

    Irma Estela Sommerfelt

    2014-07-01

    Full Text Available Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi. Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident.

  4. The Role of Galaxy Mergers and Molecular Gas in the Early Phase of Galaxy Cluster Assembly

    Science.gov (United States)

    Hung, Chao-Ling

    2017-08-01

    High-redshift protoclusters are ideal places to study the formation of the largest structures in the Universe and the early environmental influences on galaxy evolution. Recent discoveries of z>2 protoclusters with extremely rich populations of dusty star-forming galaxies (DSFGs; SFR>100 Msun/yr) represent the most active assembly phases of massive galaxy clusters. Understanding the triggering mechanisms of these unusual concentrations of extreme star-forming galaxies can provide critical insights into the formation of most massive galaxies in these clusters and the assembly of massive clusters themselves. For example, an increased probability of galaxy interactions and/or enhanced gas supply may trigger an excess of DSFGs. Using the extensive ancillary data in the COSMOS field, we study the role of galaxy mergers through measuring the frequency of galaxy pairs in two such DSFG-rich protoclusters at z=2.10 and 2.47, respectively. We also investigate the mean molecular gas content of protocluster galaxies by stacking SCUBA-2 850 micron images. These independent investigations provide complementary views into the physical nature of these DSFG-rich protoclusters.

  5. 2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

    Science.gov (United States)

    2015-12-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors.

  6. Effects of Ligustrazine on Hematopoiesis in the Early Phase of Bone Marrow Transplantation Mice

    Institute of Scientific and Technical Information of China (English)

    周银莉; 刘文励; 孙汉英; 徐惠珍; 路武; 孙岚; 孟凡凯

    2002-01-01

    Summary: To investigate the effects of Ligustrazine on histogenesis of bone marrow in the early phase of hematopoietic reconstruction in bone marrow transplantation (BMT) mice. The syngeneic BMT mice model was established. The syngeneic BMT mice were orally given 2 mg Ligustrazine twice a day. 1, 3, 5, 7, 10, 15 and 21 day(s) after BMT, peripheral blood granulocytes and bone marrow nucleated cells (BMNC) were counted and the diameter of central vein and the area of micro-vessel in femur were measured. The effect of Ligustrazine on hematopoietic stem cells was observed by colony forming unit of spleen (CFU-S). The effect of Ligustrazine on hemopoietic progenitors was studied by observing the number of progenitors of Granulocytes/Macrophage on day 10 and day 20 after BMT. In Ligustrazine-treated group, the diameter of center veins and the area of micro-vessel of femur were all significantly less than the control group 7, 10, 15, 21 days after BMT (P<0. 01). In addition, Ligustrazine significantly increased the number of CFU-S on day 10and the number of CFU-GM on day 10, 20 after BMT. These results indicate that Ligustrazine can accelerate the histogenesis of hemopoietic bone marrow, which may be one mechanism by which Ligustrazine promotes hematopoietic reconstitution after BMT.

  7. Distribution of CCS and HC3N in L1147, an Early Phase Dark Cloud

    CERN Document Server

    Suzuki, Taiki; Hirota, Tomoya

    2014-01-01

    We used the Nobeyama 45 m radio telescope to reveal spatial distributions of CCS and HC$_3$N in L1147, one of carbon-chain producing regions (CCPRs) candidates, where carbon-chain molecules are dominant rather than NH$_3$. We found that three cores (two CCS cores and one HC$_3$N core) exist along the NE-SW filament traced by the 850 micron dust continuum, which are away from a Very Low Luminosity Object (VeLLO - a source that may turn into sub-stellar mass brown dwarf). The column densities of CCS are 3-7x10$^{12}$ cm$^{-2}$ and those of HC$_3$N are 2-6x10$^{12}$ cm$^{-2}$, respectively, much lower than those previously reported towards other CCPRs. We also found that two CCS peaks are displaced from that of HC$_3$N. In order to interpret such interleaved distributions, we conducted chemical reaction network simulations, and found that slightly different gas densities could lead to large variation of CCS-to-HC$_3$N ratio in the early phase of dark cloud evolution. Such a chemical "variation" may be seen in ot...

  8. A little inflation in the early universe at the QCD phase transition

    CERN Document Server

    Boeckel, Tillmann

    2009-01-01

    We explore a scenario that allows for a strong first order phase-transition of QCD at non-negligible baryon number in the early universe and its possible cosmological observable consequences. The main assumption is a quasi-stable QCD-vacuum state that leads to a short period of inflation, consequently diluting the net baryon to photon ratio to it's today observed value. A strong mechanism for baryogenesis is needed to start out with a baryon asymmetry of order unity, e.g. as provided by Affleck-Dine baryogenesis. The cosmological implications are direct effects on primordial density fluctuations up to dark matter mass scales of 1 - 10 solar masses, change in the spectral slope up to mass scales of 10^6 - 10^7 solar masses, production of primordial magnetic fields with initial strength up to 10^12 Gauss and a gravitational wave spectrum with present day peak strain amplitude of at most h_c = 4.7 * 10^-15 around a frequency of 4*10^-8 Hz. The little QCD inflation scenario could be probed with the upcoming heavy...

  9. A little inflation in the early universe at the QCD phase transition.

    Science.gov (United States)

    Boeckel, Tillmann; Schaffner-Bielich, Jürgen

    2010-07-23

    We explore a scenario that allows for a strong first order phase transition of QCD at a non-negligible baryon number in the early Universe and its possible observable consequences. The main assumption is a quasistable QCD-vacuum state that leads to a short period of inflation, consequently diluting the net baryon to photon ratio to today's observed value. A strong mechanism for baryogenesis is needed to start out with a baryon asymmetry of order unity, e.g., as provided by Affleck-Dine baryogenesis. The cosmological implications are direct effects on primordial density fluctuations up to dark matter mass scales of M{max}∼1-10M{⊙}, change in the spectral slope up to M{max}∼10{6}-10{8}M{⊙}, production of strong primordial magnetic fields and a gravitational wave spectrum with present day peak strain amplitude of up to h{c}(ν{peak})∼5×10{-15} around ν{peak}∼4×10{-8}  Hz.

  10. Media Messages and Perceptions of the Affordable Care Act during the Early Phase of Implementation.

    Science.gov (United States)

    Fowler, Erika Franklin; Baum, Laura M; Barry, Colleen L; Niederdeppe, Jeff; Gollust, Sarah E

    2017-02-01

    Public opinion about the Affordable Care Act (ACA) has been polarized since the law's passage. Past research suggests these conditions would make any media influence on the public limited at best. However, during the early phase of implementation, locally broadcast ACA-related media messages-in the form of paid health insurance and political advertisements and news media stories-abounded as advocates, insurance marketers, and politicians sought to shape the public's perceptions of the law. To what extent did message exposure affect ACA perceptions during the first open enrollment period? We merge data on volumes of messaging at the media market level with nationally representative survey data to examine the relationship between estimated exposure to media messaging and the public's perceptions of how informed they were about and favorable toward the ACA in October 2013. We find that higher volumes of insurance advertising and local news coverage are associated with participants' perceptions of being informed about the law. Volumes of insurance advertising and of local news coverage are also associated with participants' favorability toward the law, but the relationship varies with partisanship, supporting the growing body of research describing partisan perceptual bias.

  11. In vivo measurement of dynamic rectus femoris function at postures representative of early swing phase.

    Science.gov (United States)

    Hernández, Antonio; Dhaher, Yasin; Thelen, Darryl G

    2008-01-01

    Forward dynamic models suggest that muscle-induced joint motions depend on dynamic coupling between body segments. As a result, biarticular muscles may exhibit non-intuitive behavior in which the induced joint motion is opposite to that assumed based on anatomy. Empirical validation of such predictions is important for models to be relied upon to characterize muscle function. In this study, we measured, in vivo, the hip and knee accelerations induced by electrical stimulation of the rectus femoris (RF) and the vastus medialis (VM) at postures representatives of the toe-off and early swing phases of the gait cycle. Seven healthy young subjects were positioned side-lying with their lower limb supported on air bearings while a 90 ms pulse train stimulated each muscle separately or simultaneously. Lower limb kinematics were measured and compared to predictions from a similarly configured dynamic model of the lower limb. We found that both RF and VM, when stimulated independently, accelerated the hip and knee into extension at these postures, consistent with model predictions. Predicted ratios of hip acceleration to knee acceleration were generally within 1 s.d. of average values. In addition, measured responses to simultaneous RF and VM stimulation were within 13% of predictions based on the assumption that joint accelerations induced by activating two muscles simultaneously can be found by adding the joint accelerations induced by activating the same muscles independently. These results provide empirical evidence of the importance of considering dynamic effects when interpreting the role of muscles in generating movement.

  12. Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children.

    Science.gov (United States)

    The, Hao Chung; Florez de Sessions, Paola; Jie, Song; Pham Thanh, Duy; Thompson, Corinne N; Nguyen Ngoc Minh, Chau; Chu, Collins Wenhan; Tran, Tuan-Anh; Thomson, Nicholas R; Thwaites, Guy E; Rabaa, Maia A; Hibberd, Martin; Baker, Stephen

    2017-08-02

    Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions.

  13. Ultra-Fast Flash Observatory: Fast Response Space Missions for Early Time Phase of Gamma Ray Bursts

    DEFF Research Database (Denmark)

    Park, I.H.; Ahmad, S.; Barrillon, P.

    2013-01-01

    One of the unexplored domains in the study of gamma-ray bursts (GRBs) is the early time phase of the optical light curve. We have proposed Ultra-Fast Flash Observatory (UFFO) to address this question through extraordinary opportunities presented by a series of small space missions. The UFFO is eq...

  14. 78 FR 69690 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Science.gov (United States)

    2013-11-20

    ...The Food and Drug Administration (FDA) is extending the comment period for the draft guidance for industry entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products'' that appeared in the Federal Register of July 2, 2013 (78 FR 39736). The draft guidance document provides sponsors of Investigational New Drug......

  15. Bridging the gap between selection decisions of facade systems at the early design phase: Issues, challenges and solutions

    Directory of Open Access Journals (Sweden)

    Mohamad Kassema

    2015-11-01

    Full Text Available Building facade has a significant impact on the environmental and economic performance of buildings and projects. The specification of their elements at the early design phase depends on numerous technical, environmental and economic factors and involves several stakeholders. The procurement and delivery of the facade work package from the early design phase, through detailed design and manufacture, to installation is a process with several inherent risk factors due to the involved cost, technical and engineering complexities and its position on the critical path in all projects. This research investigates the process of selection and specification of building facade elements at the early design phases with the overarching aim of identifying the issues affecting specification decisions, their root causes and impact on projects. The research utilizes a mixed research approach which combines a retrospective case study and an industry survey as two research methods that build on each other. The findings suggest that the complexity of specification at the early design phases is exacerbated by factors such as the inadequate technical knowledge of stakeholders involved in the decision making process, the non-involvement of building facade consultants, the late involvement of specialist facade subcontractors, and in a few cases by some commercial exclusivity agreements that restricts specification decisions. 

  16. Soleus stretch reflex inhibition in the early swing phase of gait using deep peroneal nerve stimulation in spastic stroke participants

    NARCIS (Netherlands)

    Voormolen, Marco M.; Ladouceur, Michel; Veltink, Petrus H.; Sinkjaer, Thomas

    2000-01-01

    Objectives: To investigate the feasibility of inhibiting the stretch reflex of the soleus muscle by a conditioning stimulus applied to the deep peroneal nerve in spastic stroke participants during the early swing phase of gait. - Materials and Methods: This study investigated the effect of an

  17. Effect of Repeated Stress Treatments During the Follicular Phase and Early Pregnancy on Reproductive Performance of Gilts

    NARCIS (Netherlands)

    Soede, N.M.; Roelofs, J.B.; Verheijen, R.J.E.; Schouten, W.G.P.; Hazeleger, W.; Kemp, B.

    2007-01-01

    In pig husbandry, stress is being considered an important cause of impaired reproductive performance. Therefore, an experiment was performed to quantify effects of repeated stressors during the follicular phase and/or during early pregnancy on reproductive performance of gilts. Eighty-one cyclic

  18. Explorative immunohistochemical study to evaluate the addition of a topical corticosteroid in the early phase of alefacept treatment for psoriasis.

    NARCIS (Netherlands)

    Bovenschen, H.J.; Gerritsen, W.J.; Rens, D.W.A. van; Seyger, M.M.B.; Jong, E.M.G.J. de; Kerkhof, P.C.M. van de

    2007-01-01

    The aim of this study was to explore the additional effect of betamethasone dipropionate cream in the early phase of an intramuscular (IM) alefacept course, on plaque severity and on modulating T-cell subsets, cells expressing NK-receptors, epidermal proliferation and keratinocyte differentiation in

  19. The cytoskeleton proteins and LH-regulated steroidogenesis in porcine luteal cells

    Energy Technology Data Exchange (ETDEWEB)

    Gregoraszczuk, Ewa L.; Slomczynska, Maria [Uniwersytet Jagiellonski, Cracow (Poland)

    1996-12-31

    The involvement of microtubules (MT) and microflilaments (MF) in LH-regulation of luteal cell stereoidogenesis was assessed at the middle stage of corpus luteum development. The influence microtubule- and microfilament-altering agents on basal and LH-stimulated progesterone (P4) production and secretion into the incubation medium was determined by RIA. LH-stimulated P4 production was 2.5 times higher than in the control cultures. Cytochalasis B (Cyt B) was without effect on basal P4 synthesis but increased the basal fraction of P4 secreted into the incubation medium, while colchicine (Col) increased both basal P4 synthesis and the fraction of P4 secreted into the incubation medium. LH-stimulated progesterone synthesis was reduced by Col, but the fraction secreted into the incubation medium increased. Cyt B had no effect on LH-stimulated synthesis but it decreased the fraction of P4 secreted into the incubation medium. Our findings demonstrate significant differences in the effect of Cyt B and Col on steroidogenesis in corpus luteum. We conclude that microtubules play an important role in the process of LH-stimulated P4 synthesis, while microfilaments act in the process of basal and LH-stimulated P4 secretion. (author). 23 refs, 4 figs.

  20. Neddylation is required for herpes simplex virus type I (HSV-1)-induced early phase interferon-beta production.

    Science.gov (United States)

    Zhang, Xueying; Ye, Zhenjie; Pei, Yujun; Qiu, Guihua; Wang, Qingyang; Xu, Yunlu; Shen, Beifen; Zhang, Jiyan

    2016-09-01

    Type I interferons such as interferon-beta (IFN-β) play essential roles in the host innate immune response to herpes simplex virus type I (HSV-1) infection. The transcription of type I interferon genes is controlled by nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF) family members including IRF3. NF-κB activation depends on the phosphorylation of inhibitor of κB (IκB), which triggers its ubiqitination and degradation. It has been reported that neddylation inhibition by a pharmacological agent MLN4924 potently suppresses lipopolysaccharide (LPS)-induced proinflammatory cytokine production with the accumulation of phosphorylated IκBα. However, the role of neddylation in type I interferon expression remains unknown. Here, we report that neddylation inhibition with MLN4924 or upon UBA3 deficiency led to accumulation of phosphorylated IκBα, impaired IκBα degradation, and impaired NF-κB nuclear translocation in the early phase of HSV-1 infection even though phosphorylation and nuclear translocation of IRF3 were not affected. The blockade of NF-κB nuclear translocation by neddylation inhibition becomes less efficient at the later time points of HSV-1 infection. Consequently, HSV-1-induced early phase IFN-β production significantly decreased upon MLN4924 treatment and UBA3 deficiency. NF-κB inhibitor JSH-23 mimicked the effects of neddylation inhibition in the early phase of HSV-1 infection. Moreover, the effects of neddylation inhibition on HSV-1-induced early phase IFN-β production diminished in the presence of NF-κB inhibitor JSH-23. Thus, neddylation contributes to HSV-1-induced early phase IFN-β production through, at least partially, promoting NF-κB activation.

  1. Major role for cysteine proteases during the early phase of Acanthamoeba castellanii encystment.

    Science.gov (United States)

    Leitsch, David; Köhsler, Martina; Marchetti-Deschmann, Martina; Deutsch, Andrea; Allmaier, Günter; Duchêne, Michael; Walochnik, Julia

    2010-04-01

    Acanthamoeba castellanii is a facultative pathogen that has a two-stage life cycle comprising the vegetatively growing trophozoite stage and the dormant cyst stage. Cysts are formed when the cell encounters unfavorable conditions, such as environmental stress or food deprivation. Due to their rigid double-layered wall, Acanthamoeba cysts are highly resistant to antiamoebic drugs. This is problematic as cysts can survive initially successful chemotherapeutic treatment and cause relapse of the disease. We studied the Acanthamoeba encystment process by using two-dimensional gel electrophoresis (2DE) and found that most changes in the protein content occur early in the process. Truncated actin isoforms were found to abound in the encysting cell, and the levels of translation elongation factor 2 (EF2) were sharply decreased, indicating that the rate of protein synthesis must be low at this stage. In the advanced stage of encystment, however, EF2 levels and the trophozoite proteome were partly restored. The protease inhibitors PMSF (phenylmethylsulfonyl fluoride) and E64d [(2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester] inhibited the onset of encystment, whereas the protein synthesis inhibitor cycloheximide was ineffective. Changes in the protein profile, similar to those of encysting cells, could be observed with trophozoite homogenates incubated at room temperature for several hours. Interestingly, these changes could be inhibited significantly by cysteine protease inhibitors but not by inhibitors against other proteases. Taken together, we conclude that the encystment process in A. castellanii is of a bipartite nature consisting of an initial phase of autolysis and protein degradation and an advanced stage of restoration accompanied by the expression of encystment-specific genes.

  2. Interleukin-1 receptor antagonist modulates the early phase of liver regeneration after partial hepatectomy in mice.

    Directory of Open Access Journals (Sweden)

    Antonino Sgroi

    Full Text Available BACKGROUND: Cytokine administration is a potential therapy for acute liver failure by reducing inflammatory responses and favour hepatocyte regeneration. The aim of this study was to evaluate the role of interleukin-1 receptor antagonist (IL-1ra during liver regeneration and to study the effect of a recombinant human IL-1ra on liver regeneration. METHODS: We performed 70%-hepatectomy in wild type (WT mice, IL-1ra knock-out (KO mice and in WT mice treated by anakinra. We analyzed liver regeneration at regular intervals by measuring the blood levels of cytokines, the hepatocyte proliferation by bromodeoxyuridin (BrdU incorporation, proliferating cell nuclear antigen (PCNA and Cyclin D1 expression. The effect of anakinra on hepatocyte proliferation was also tested in vitro using human hepatocytes. RESULTS: At 24h and at 48 h after hepatectomy, IL-1ra KO mice had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-1β and MCP-1 and a reduced and delayed hepatocyte proliferation measured by BrdU incorporation, PCNA and Cyclin D1 protein levels, when compared to WT mice. IGFBP-1 and C/EBPβ expression was significantly decreased in IL-1ra KO compared to WT mice. WT mice treated with anakinra showed significantly decreased levels of IL-6 and significantly higher hepatocyte proliferation at 24h compared to untreated WT mice. In vitro, primary human hepatocytes treated with anakinra showed significantly higher proliferation at 24h compared to hepatocytes without treatment. CONCLUSION: IL1ra modulates the early phase of liver regeneration by decreasing the inflammatory stress and accelerating the entry of hepatocytes in proliferation. IL1ra might be a therapeutic target to improve hepatocyte proliferation.

  3. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants

    Science.gov (United States)

    Palac, Hannah L.; Yogev, Ram; Ernst, Linda M.; Mestan, Karen K.

    2017-01-01

    Background Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. Methods In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. Results cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. Conclusion This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and

  4. Musculoskeletal Symptoms in Nurses in the Early Implementation Phase of California's Safe Patient Handling Legislation.

    Science.gov (United States)

    Lee, Soo-Jeong; Lee, Joung Hee; Gershon, Robyn R M

    2015-06-01

    Musculoskeletal injuries and symptoms are prevalent in nurses and are largely associated with strenuous patient handling. In 2011, California enacted legislation that required acute-care hospitals to implement safe patient handling (SPH) policies and programs. To assess the early phase of this legislation, we conducted an epidemiological assessment of organizational SPH practices, musculoskeletal symptoms, and perceptions in a random sample of 396 registered nurses. Among those who worked in hospitals and had patient handling duties (n = 220), the 12 month prevalence of work-related musculoskeletal symptoms was 69% (lower back 54%, neck 41%, shoulders 34%, and hands/wrists 26%). Twenty-two percent of the nurses reported that their hospitals had a "no-lift" policy, 37% reported that their hospitals had lift teams, and 61% reported the availability of mechanical lift equipment such as floor or ceiling lifts. Nurses whose facilities employed lift teams were significantly less likely to report low back pain (OR = 0.54, 95% CI [0.30-0.97]). Nurses whose units had ceiling lifts were significantly less likely to report shoulder pain than nurses with no access to lifts (OR = 0.32, 95% CI [0.10-0.98]). Roughly 60% of respondents were aware of the SPH law, and 33% reported changes in their hospital's patient handling policies or programs since the law went into effect. Hospital SPH practices reported by the nurses in our sample were generally sub-optimal, but our findings suggest positive effects of elements required by SPH legislation. These data will serve as the baseline for future evaluation of the impact of this law in California.

  5. High-content analysis of sequential events during the early phase of influenza A virus infection.

    Science.gov (United States)

    Banerjee, Indranil; Yamauchi, Yohei; Helenius, Ari; Horvath, Peter

    2013-01-01

    Influenza A virus (IAV) represents a worldwide threat to public health by causing severe morbidity and mortality every year. Due to high mutation rate, new strains of IAV emerge frequently. These IAVs are often drug-resistant and require vaccine reformulation. A promising approach to circumvent this problem is to target host cell determinants crucial for IAV infection, but dispensable for the cell. Several RNAi-based screens have identified about one thousand cellular factors that promote IAV infection. However, systematic analyses to determine their specific functions are lacking. To address this issue, we developed quantitative, imaging-based assays to dissect seven consecutive steps in the early phases of IAV infection in tissue culture cells. The entry steps for which we developed the assays were: virus binding to the cell membrane, endocytosis, exposure to low pH in endocytic vacuoles, acid-activated fusion of viral envelope with the vacuolar membrane, nucleocapsid uncoating in the cytosol, nuclear import of viral ribonucleoproteins, and expression of the viral nucleoprotein. We adapted the assays to automated microscopy and optimized them for high-content screening. To quantify the image data, we performed both single and multi-parametric analyses, in combination with machine learning. By time-course experiments, we determined the optimal time points for each assay. Our quality control experiments showed that the assays were sufficiently robust for high-content analysis. The methods we describe in this study provide a powerful high-throughput platform to understand the host cell processes, which can eventually lead to the discovery of novel anti-pathogen strategies.

  6. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

    Science.gov (United States)

    Mithal, Leena B; Palac, Hannah L; Yogev, Ram; Ernst, Linda M; Mestan, Karen K

    2017-01-01

    Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

  7. Effect of menstrual cycle phase on background parenchymal uptake on molecular breast imaging

    Science.gov (United States)

    Hruska, Carrie B.; Conners, Amy Lynn; Vachon, Celine M.; O’Connor, Michael K.; Shuster, Lynne T.; Bartley, Adam C.; Rhodes, Deborah J.

    2015-01-01

    Rationale and Objectives The level of Tc-99m sestamibi uptake within normal fibroglandular tissue on molecular breast imaging (MBI), termed background parenchymal uptake (BPU), has been anecdotally observed to fluctuate with menstrual cycle. Our objective was to assess the impact of menstrual cycle phase on BPU appearance. Materials and Methods Premenopausal volunteers who reported regular menstrual cycles and no exogenous hormone use were recruited to undergo serial MBI exams during the follicular and luteal phase. A study radiologist, blinded to cycle phase, categorized BPU as either photopenic, minimal-mild, moderate, or marked. Change in BPU with cycle phase was determined as well as correlations of BPU with mammographic density and hormone levels. Results Among 42 analyzable participants, high BPU (moderate or marked) was observed more often in luteal phase compared to follicular (p = 0.016). BPU did not change with phase in 30 of 42 (71%) and increased in the luteal phase compared to follicular in 12 (29%). High BPU was more frequent in dense breasts compared to non-dense breasts at both the luteal phase (58% [15/26] vs. 13% [2/16], p= 0.004) and follicular phase (35% [9/26] vs. 6% [1/16], p=0.061). Spearman’s correlation coefficients did not show any correlation of BPU with hormone levels measured at either cycle phase, and suggested a weak correlation between change in BPU and changes in estrone and estradiol between phases. Conclusion We observed variable effects of menstrual cycle on BPU among our cohort of premenopausal women, however, when high BPU was observed, it was most frequently seen during the luteal phase compared to follicular phase, and in women with dense breasts compared to non-dense breasts. PMID:26112057

  8. Early-time solution of the horizontal unconfined aquifer in the build-up phase

    Science.gov (United States)

    Gravanis, Elias; Akylas, Evangelos

    2017-04-01

    goes away. Nonetheless, no analogue of the kinematic wave or the Boussinesq separable solution exists in this case. The late time state of the build-up phase under constant recharge rate is very simply the steady state solution. Our aim is to construct the early time asymptotic solution of this problem. The solution is expressed as a power series of a suitable similarity variable, which is constructed so that to satisfy the boundary conditions at both ends of the aquifer, that is, it is a polynomial approximation of the exact solution. The series turn out to be asymptotic and it is regularized by re-summation techniques which are used to define divergent series. The outflow rate in this regime is linear in time, and the (dimensionless) coefficient is calculated to eight significant figures. The local error of the series is quantified by its deviation from satisfying the self-similar Boussinesq equation at every point. The local error turns out to be everywhere positive, hence, so is the integrated error, which in turn quantifies the degree of convergence of the series to the exact solution.

  9. 7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

    Science.gov (United States)

    van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients.

  10. Stopping rules employing response rates, time to progression, and early progressive disease for phase II oncology trials

    Directory of Open Access Journals (Sweden)

    Goffin John R

    2011-12-01

    Full Text Available Abstract Background Response rate (RR, the most common early means of assessing oncology drugs, is not suitable as the sole endpoint for phase II trials of drugs which induce disease stability but not regression. Time to progression (TTP may be more sensitive to such agents, but induces recruitment delays in multistage studies. Early progressive disease (EPD is the earliest signal of time to progression, but is less intuitive to investigators, To study drugs with unknown anti-tumour effect, we designed the Combination Stopping Rule (CSR, which allows investigators to establish a hypothesis using RR and TTP, while the program also employs early progressive disease (EPD to assess for drug inactivity during the first stage of study accrual. Methods A computer program was created to generate stopping rules based on specified error rates, trial size, and RR and median TTP of interest and disinterest for a two-stage phase II trial. Rules were generated for stage II such that the null hypothesis (Hnul was rejected if either RR or TTP met desired thresholds, and accepted if both did not. Assuming an exponential distribution for progression, EPD thresholds were determined based on specified TTP values. Stopping rules were generated for stage I such that Hnul was accepted and the study stopped if both RR and EPD were unacceptable. Results Patient thresholds were generated for RR, median TTP, and EPD which achieved specified error rates and which allowed early stopping based on RR and EPD. For smaller proportional differences between interesting and disinteresting values of RR or TTP, larger trials are required to maintain alpha error, and early stopping is more common with a larger first stage. Conclusion Stopping rules are provided for phase II trials for drugs which have either a desirable RR or TTP. In addition, early stopping can be achieved using RR and EPD.

  11. Systematic analysis of early phase clinical studies for patients with breast cancer: Inclusion of patients with brain metastasis.

    Science.gov (United States)

    Costa, R; Gill, N; Rademaker, A W; Carneiro, B A; Chae, Y K; Kumthekar, P; Gradishar, W J; Kurzrock, R; Giles, F J

    2017-04-01

    This systematic review aims to better define the limitations and patterns with which patients with MBC and CNS metastasis are enrolled into early phase developmental therapeutics trials. In June 2016, PubMed search was conducted using the following keywords: "Breast cancer". Drug-development phase 1, phase 2 or phase 1/2 trials for patients with MBC were included. Multiple-histology trials and trials without an efficacy endpoint were excluded. In total, 1474 studies were included; Inclusion criteria for 423 (29%) allowed for CNS metastasis, 770 (52%) either excluded or did not document eligibility of patients with CNS disease. Trials accruing patients with HER2-positive MBC and including targeted therapies had higher odds of allowing for patients with CNS disease (adjusted OR 1.56, 95% CI 1.08-2.2.6; p=0.019 and 1.49, 95% 1.08-2.06; p=0.014, respectively). There were also higher odds of accrual of patients with CNS involvement into clinical trials over time (odds ratio=1.10, 95% CI 1.07-1.12; pphase clinical trials either did not clearly document or did not allow for accrual of patients with CNS disease. Early phase trials with targeted agents or enrolling HER2+ MBC had higher odds of permitting CNS metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. STUDY ON THE MECHANISM AND EFFECTS OF GLY-TYR-NH2 AND GLY-TYR-LYS ON RAT LUTEAL CELLS IN VITRO

    Institute of Scientific and Technical Information of China (English)

    王乃功; 关慕贞; 王德心; 鲁桂琛

    1994-01-01

    The action of Gly-Tyr-NH2,(GY-NH2) and Gly-Tyr-LYS(GYK) on 125I-LH binding,cAMP accumulation and progesterone production was investigated.Incubation of rat luteal cells for 2.5h with GH-NH2 and GYK at dosage of 0.2mmol/L caused a significant inhibition of basal and gonadotropin-stimulated steroidogenesis.GYNH2 and GYK were also foumnd to reduce cAMP formation in response to hCG.The activity of adenylate cyclase of luteal cells was inhibitd by 0.2mmol/LGY-NH2 and GYK.GY-NH2 and GYK at a concentration of 0.2mmol/L were not found to have an inhibitory effect on 8Br-cAMP-stimulated progesterone production.GY-NH2 and GYK did not affect 125I-LH binding to LH receptors on the luteal cellsurface.These results suggest that GY-NH2 and GYK inhibit steroidogenesis at the step of gonadotropin-stimulated c AMP for mation in luteal cells.Adenylate cyclase in luteal cells was also inhibited.

  13. A Statistical Index for Early Diagnosis of Ventricular Arrhythmia from the Trend Analysis of ECG Phase-portraits

    CERN Document Server

    Cappiello, Grazia; Mazomenos, Evangelos B; Maharatna, Koushik; Koulaouzidis, George; Morgan, John; Puddu, Paolo Emilio

    2016-01-01

    In this paper, we propose a novel statistical index for the early diagnosis of ventricular arrhythmia (VA) using the time delay phase-space reconstruction (PSR) technique, from the electrocardiogram (ECG) signal. Patients with two classes of fatal VA - with preceding ventricular premature beats (VPBs) and with no VPBs have been analysed using extensive simulations. Three subclasses of VA with VPBs viz. ventricular tachycardia (VT), ventricular fibrillation (VF) and VT followed by VF are analyzed using the proposed technique. Measures of descriptive statistics like mean ({\\mu}), standard deviation ({\\sigma}), coefficient of variation (CV = {\\sigma}/{\\mu}), skewness ({\\gamma}) and kurtosis (\\{beta}) in phase-space diagrams are studied for a sliding window of 10 beats of ECG signal using the box-counting technique. Subsequently, a hybrid prediction index which is composed of a weighted sum of CV and kurtosis has been proposed for predicting the impending arrhythmia before its actual occurrence. The early diagnos...

  14. Hyperhomocysteinemia, a biochemical tool for differentiating ischemic and nonischemic central retinal vein occlusion during the early acute phase.

    Science.gov (United States)

    Lahiri, Kapil Deb; Mukherjee, Somnath; Ghosh, Sambuddha; Mukherjee, Suman; Dutta, Jayanta; Datta, Himadri; Das, Harendra Nath

    2015-04-01

    The purpose of the study was to differentiate ischemic central retinal vein occlusion (CRVO) from nonischemic CRVO during the early acute phase using plasma homocysteine as a biochemical marker. Fasting plasma homocysteine, serum vitamin B12, and folate levels were measured in 108 consecutive unilateral elderly adult (age >50 years) ischemic CRVO patients in the absence of local and systemic disease and compared with a total of 144 age and sex matched nonischemic CRVO patients and 120 age and sex matched healthy control subjects. Homocysteine level was significantly increased in the patients with ischemic CRVO in comparison with nonischemic CRVO patients (p = 0.009) and also in comparison with control subjects (p 0.1). Hyperhomocysteinemia can be regarded as useful in differentiating nonischemic and ischemic CRVO during the early acute phase in absence of local and systemic disease in the elderly adult (age >50 years) population.

  15. The progress of early phase bone healing using porous granules produced from calcium phosphate cement

    Directory of Open Access Journals (Sweden)

    Jungbluth P

    2010-05-01

    phosphate self-setting cement powder after 6 weeks. In the early phase of bone-healing, the sole application of CPG appears to be inferior to the autologous cancellous grafts in an in vivo critical size defect on load-bearing long bones of mini-pigs.

  16. Transformation abrogates an early G1-phase arrest point required for specification of the Chinese hamster DHFR replication origin.

    Science.gov (United States)

    Wu, J R; Keezer, S M; Gilbert, D M

    1998-03-16

    The origin decision point (ODP) was originally identified as a distinct point during G1-phase when Chinese hamster ovary (CHO) cell nuclei experience a transition that is required for specific recognition of the dihydrofolate reductase (DHFR) origin locus by Xenopus egg extracts. Passage of cells through the ODP requires a mitogen-independent protein kinase that is activated prior to restriction point control. Here we show that inhibition of an early G1-phase protein kinase pathway by the addition of 2-aminopurine (2-AP) prior to the ODP arrests CHO cells in G1-phase. Transformation with simian virus 40 (SV40) abrogated this arrest point, resulting in the entry of cultured cells into S-phase in the presence of 2-AP and a disruption of the normal pattern of initiation sites at the DHFR locus. Cells treated with 2-AP after the ODP initiated replication specifically within the DHFR origin locus. Transient exposure of transformed cells to 2-AP during the ODP transition also disrupted origin choice, whereas non-transformed cells arrested in G1-phase and then passed through a delayed ODP after removal of 2-AP from the medium. We conclude that mammalian cells have many potential sites at which they can initiate replication. Normally, events occurring during the early G1-phase ODP transition determine which of these sites will be the preferred initiation site. However, if chromatin is exposed to S-phase-promoting factors prior to this transition, mammalian cells, like Xenopus and Drosophila embryos, can initiate replication without origin specification.

  17. Representations of sensory experiences in the early phases of architectural design: there is more than meets the eye

    OpenAIRE

    Elsen, Catherine; Heylighen, Ann

    2014-01-01

    In response to questions about designers’ visual way of knowing and working, this article explores how sensory experience is conveyed during the early phases of architectural design. By processing 985 graphic components issued from a three-month ethnographic observation inside an architecture firm, and proposing an original methodology for their analysis, we identify and analyse graphic expressions of sensory-related design intentions. Multi-sensory dimensions of experiencing an architectural...

  18. Effects of Type I Collagen Degradation on the Durability of Three Adhesive Systems in the Early Phase of Dentin Bonding

    OpenAIRE

    Lin Hu; Yu-hong Xiao; Ming Fang; Yu Gao; Li Huang; An-qi Jia; Ji-hua Chen

    2015-01-01

    Objective This study was designed to evaluate the effects of type I collagen degradation on the durability of three adhesive systems in the early phase of dentin bonding. Methods Bonded dentin specimens were prepared using three different types of adhesive systems. Micro-tensile bond strength and degradation of collagen were tested before, and after 1 month or 4 months of aging in artificial saliva. The relationship between micro-tensile bond strength and collagen degradation was analyzed by ...

  19. A very early rehabilitation trial for stroke (AVERT) phase II safety and feasibility

    NARCIS (Netherlands)

    Bernhardt, Julie; Dewey, Helen; Thrift, Amanda; Collier, Janice; Donnan, Geoffrey

    2008-01-01

    Background and Purpose - Very early rehabilitation, with an emphasis on mobilization, may contribute to improved outcomes after stroke. We hypothesized that a very early rehabilitation protocol would be safe and feasible. Methods - We performed a randomized, controlled trial with blinded outcome ass

  20. Adverse influence of coumestrol on secretory function of bovine luteal cells in the first trimester of pregnancy.

    Science.gov (United States)

    Młynarczuk, J; Wróbel, M H; Kotwica, J

    2013-07-01

    Coumestrol is one of a few biologically active substances present in leguminous plants, which are widely used as fodder for ruminants. Depending on the doses, coumestrol acts on the reproductive processes as an estrogen-like factor or antiestrogen to evoke a decrease in ovulation frequency, elongation of estrous cycle duration. The aim of the current investigations was to study the influence of coumestrol on secretory function of luteal cells obtained from first trimester of pregnant cows. Luteal cells (2.5 × 10(5) /mL) from 3rd to 5th, 6th to 8th, and 9th to 12th week of pregnancy were preincubated for 24 h and incubated with coumestrol (1 × 10(-6) M) for successive 48 h and the medium concentrations of progesterone (P4), oxytocin (OT), prostaglandin (PG) E2 and F2α were determined. Moreover, the expression of mRNA for neurophysin-I/oxytocin (NP-I/OT; precursor of OT) and peptidyl-glycine-α-amidating mono-oxygenase (PGA, an enzyme responsible for post-translational OT synthesis) was determined after 8 h of treatment. Coumestrol did not affect P4 secretion but increased the secretion of OT from the cells collected at all stages of gestation studied. Hence, the ratio of P4 to OT was markedly decreased. Simultaneously, coumestrol increased the expression of NP-I/OT mRNA during 9th to 12th weeks of pregnancy, and mRNA for PGA during 3rd to 5th and 9th to 12th weeks of gestation. Furthermore, coumestrol decreased PGE2 secretion from luteal cells in all studied stages of pregnancy, while it affected PGF2α metabolite (PGFM) concentration only from week 3 to 5 of pregnancy. Obtained results suggest that coumestrol impairs secretory function of the corpus luteum (CL) and this way it can affect the maintenance of pregnancy in the cow.

  1. Texture analyses show synergetic effects of biomechanical and biochemical stimulation on mesenchymal stem cell differentiation into early phase osteoblasts.

    Science.gov (United States)

    Park, So Hee; Shin, Ji Won; Kang, Yun Gyeong; Hyun, Jin-Sook; Oh, Min Jae; Shin, Jung-Woog

    2014-02-01

    We investigated the structural complexity and texture of the cytoskeleton and nucleus in human mesenchymal stem cells during early phase differentiation into osteoblasts according to the differentiation-induction method: mechanical and/or chemical stimuli. For this, fractal dimension and a number of parameters utilizing the gray-level co-occurrence matrix (GLCM) were calculated based on single-cell images after confirmation of differentiation by immunofluorescence staining. The F-actin and nuclear fractal dimensions were greater in both stimulus groups compared with the control group. The GLCM values for energy and homogeneity were lower in fibers of the F-actin cytoskeleton, indicating a dispersed F-actin arrangement during differentiation. In the nuclei of both stimulus groups, higher values for energy and homogeneity were calculated, indicating that the chromatin arrangement was chaotic during the early phase of differentiation. It was shown and confirmed that combined stimulation with mechanical and chemical factors accelerated differentiation, even in the early phase. Fractal dimension analysis and GLCM methods have the potential to provide a framework for further investigation of stem cell differentiation.

  2. Treatment response in acute/early infection versus advanced AIDS: equivalent first and second phases of HIV RNA decline.

    Science.gov (United States)

    Kilby, J Michael; Lee, Ha Youn; Hazelwood, J Darren; Bansal, Anju; Bucy, R Patterson; Saag, Michael S; Shaw, George M; Acosta, Edward P; Johnson, Victoria A; Perelson, Alan S; Goepfert, Paul A

    2008-05-11

    Compare the initial phases of virologic decay when acute/early and advanced HIV-infected adults are administered the same treatment regimen. Mathematical modeling of a previously completed prospective treatment pilot study involving treatment-naive patients with early and advanced immunosuppression. We analyzed data from a treatment protocol in which 18 individuals with acute or recent HIV-1 seroconversion and six patients with advanced AIDS were administered the same four-drug antiretroviral regimen. Initial treatment responses were compared by fitting a mathematical model to frequent viral load measurements in order to calculate the first and second phase kinetics of viral clearance, and also by comparing viral load suppression over 24 weeks. Patients were also comprehensively compared in terms of protease inhibitor drug levels, HIV-specific immune responses at baseline, and the presence of drug resistance-conferring mutations. There was no statistically meaningful difference in first phase clearance of comparable high-level viremia in the two groups, whether protease inhibitor levels were inserted into the model or 100% antiviral drug effectiveness was assumed. In contrast, acute/early patients had inferior sustained responses than advanced patients, reflecting erratic adherence. Despite many years of intervening immune destruction, the initial virologic decay on therapy appears to be the same at the extremes of the HIV disease spectrum.

  3. Biochemical DSB-repair model for mammalian cells in G1 and early S phases of the cell cycle.

    Science.gov (United States)

    Taleei, Reza; Nikjoo, Hooshang

    2013-08-30

    The paper presents a model of double strand breaks (DSB) repair in G1 and early S phases of the cell cycle. The model is based on a plethora of published information on biochemical modification of DSB induced by ionizing radiation. So far, three main DSB repair pathways have been identified, including nonhomologous end-joining (NHEJ), homologous recombination (HR), and microhomology-mediated end-joining (MMEJ). During G1 and early S phases of the cell cycle, NHEJ and MMEJ repair pathways are activated dependent on the type of double strand breaks. Simple DSB are a substrate for NHEJ, while complex DSB and DSB in heterochromatin require further end processing. Repair of all DSB start with NHEJ presynaptic processes, and depending on the type of DSB pursue simple ligation, further end processing prior to ligation, or resection. Using law of mass action the model is translated into a mathematical formalism. The solution of the formalism provides the step by step and overall repair kinetics. The overall repair kinetics are compared with the published experimental measurements. Our calculations are in agreement with the experimental results and show that the complex types of DSBs are repaired with slow repair kinetics. The G1 and early S phase model could be employed to predict the kinetics of DSB repair for damage induced by high LET radiation.

  4. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    Science.gov (United States)

    Race, Margaret; Conley, Catharine

    discussed by the study participants to date have set the agenda for additional work that will continue for at least another year, culminating in a final report that should be useful to current and new nations and partnerships in planning human missions beyond LEO. In addition, over the past two years, NASA has made progress in integrating planetary protection considerations into mission designs along with other important human, environmental and science needs. Details about planetary protection have also been incorporated into the latest Addendum of the Design Reference Architecture (DRA) for human missions to Mars. Other ongoing studies of Mars human mission architecture, technologies and operations have likewise been integrating PP requirements and guidelines into cross-cutting measures of various types. An important objective of all these studies is to proactively gather and communicate PP information to the broad community of planners, engineers and assorted partners who are facing the challenges of future human exploration missions. By analyzing ways to integrate PP provisions effectively into early mission phases in synergism with other needs, these projects and studies will help ensure that all institutions and organizations avoid releasing harmful contamination on bodies with biological potential, thereby ensuring protection of the Earth and astronauts throughout their missions and safeguarding the integrity of science exploration—all in compliance with the 1967 Outer Space Treaty.

  5. Implementation of “PLST” Assessment Model to Detect Development of Language Skill in Early Childhood (Phase II

    Directory of Open Access Journals (Sweden)

    Nelva Rolina

    2015-05-01

    Full Text Available This research will be done for 3 years (3 phases. The first year had been done on 2013 ago. 2014 is the second year of research (phase II. Research phase of this study (second year, namely development phase: the prototype of model is developed to be a model. The activities carried out in phase II include: expert validation test, readability test, revision, kindergarten teacher training, limited trial, and the trial was extended to find models that fit between the theoretical concepts with empirical data in the field. And finally (second year, from all kindergarten which be the sample study, it was found that all kindergarten were using the general assessment without special assessment for development of children’s language, so it is necessary to create assessment “PLST” to detect the development of language skill for early childhood (kindergarten student. It has to continue in second to third year. The final research, which is at the end of the third year (phase III is expected to match model assessment “PLST” as well as the guidance in learning in kindergarten, which can be used by teachers to detect and monitor the development of language skills, identifying the amount of vocabulary and sentences are mastered children, and the stages of language development next. To achieve these objectives, the researcher adopted a model of research, development, and diffusion by Hopkins & Clark (Havelock, 1976

  6. Online User Feedback in Early Phases of the Design Process: Lessons Learnt from Four Design Cases

    Directory of Open Access Journals (Sweden)

    Asbjørn Følstad

    2010-01-01

    Full Text Available Online user feedback, collected by means of internet survey tools, is a promising approach to obtain early user feedback on concepts and early prototypes. In this study, the collection and utilization of online user feedback was investigated in four design cases: all master student projects for industry clients involving seven student designers. A total of 272 user participants provided quantitative feedback. Half of these also provided qualitative feedback. One third of the qualitative feedback was perceived as useful by the student designers. The main usefulness of the feedback was related to strategic concept decisions rather than the interaction design of the early prototype. Lessons learnt are provided.

  7. Early-stage Widmanstaetten growth of the {gamma} phase in a duplex steel

    Energy Technology Data Exchange (ETDEWEB)

    Shek, C.H.; Dong, C.; Lai, J.K.L.; Wong, K.W.

    2000-01-01

    The present work studies the Widmanstaetten {gamma}-phase morphology and crystallographic orientation relationships with ferrite during its initial-stage growth in a duplex steel. Transmission electron microscopy (TEM) and convergent-beam electron diffraction (CBED) analyses have been applied to determine the orientation relationship with high precision. When the secondary {gamma} phase and the {alpha} phase have special orientation relationships close to the K-S (Kurdjumov-Sachs) relation, the preferential growth involves {gamma} phase, protruding into {alpha} phase and this leads, finally, to the formation of Widmanstatten needles. The needles grow nearly along the invariant-line direction, but they do not satisfy exactly the K-S relation, and a slight angular deviation ({theta}{sub [110]{alpha}}) is always present. This deviation is explained by a compromise between the well-known invariant-line condition, which offers the easiest way for directional growth of the {gamma} phase, and a good atomic matching of the close-packed (1{ovr 11}){gamma} and (110){sub {alpha}} planes of both phases. A matching minimum at {theta}{sub [110]{alpha}} = 2.3 deg is obtained when only three pairs of the nearest-neighbor atoms are considered in an atomic misfit calculation.

  8. Topical dorzolamide for macular edema in the early phase after vitrectomy and epiretinal membrane removal

    Directory of Open Access Journals (Sweden)

    Suzuki T

    2013-04-01

    /ms and the control group (467.8 µm, 64.0 pc/ms. Differences in mean intraocular pressure preoperatively and at 2 weeks, 1 month, and 3 months after surgery were not statistically significant between the two groups. Intraocular pressure never exceeded 21 mmHg.Conclusion: Topical dorzolamide significantly reduced mean central macular thickness at 1 month and mean aqueous flare at 2 weeks after surgery for epiretinal membrane compared with controls. Although further investigation of more cases and longer follow-up are needed, this study suggests that topical dorzolamide can be efficacious in reducing macular edema in the early phase after vitrectomy via its anti-inflammatory effect.Keywords: macular edema, dorzolamide, epiretinal membrane, vitrectomy, anti-inflammatory

  9. Sexual behavior in lesbian and heterosexual women: relations with menstrual cycle phase and partner availability.

    Science.gov (United States)

    Burleson, Mary H; Trevathan, Wenda R; Gregory, W Larry

    2002-05-01

    Using a prospective design over three complete menstrual cycles, 147 heterosexual and 89 lesbian women made daily recordings of their basal body temperature (BBT), cervical mucus status, menses, and completed a daily checklist of various sexual behaviors (including sexual self-stimulation and sexual activity with a partner). They also gave their age, height, weight, age at menarche, number of pregnancies, duration of sleep, tobacco, caffeine, and alcohol use, and whether they had a live-in sexual partner. Using BBT, cervical mucus status, and menses information, cycle days were grouped into five discrete phases: menses, follicular, ovulatory, early luteal, and premenstrual. Daily frequencies of sexual behavior with a partner and autosexual behavior were computed for each phase. Mixed ANOVAs on the resultant proportional data revealed similar patterns for autosexual behavior across the phases for both heterosexuals and lesbians who did not have a live-in partner, in which autosexual behavior was highest during the follicular and ovulatory phases. For those with live-in partners, autosexual behavior did not vary across the phases. Lesbians engaged in more autosexual behavior overall. Allosexual behavior peaked during the follicular phase for both heterosexuals and lesbians, and the phasic pattern was unrelated to live-in partner status. Additional analyses suggest that the observed patterns were unrelated to anticipated changes in sexual activity due to menses. Results are discussed in terms of social variables and hormonal fluctuations associated with the menstrual cycle.

  10. Early and Delayed Myocardial Enhancement in Myocardial Infarction Using Two-Phase Contrast-Enhanced Multidetector-Row CT

    Science.gov (United States)

    Kim, Young-Whan; Han, Seong-Wook; Seo, Joon-Beom

    2007-01-01

    Objective The purpose of this study was to describe the myocardial enhancement patterns in patients with myocardial infarction using two-phase contrast-enhanced multidetector-row computed tomography (MDCT). Materials and Methods Twenty-three patients with clinically proven myocardial infarction (17 acute myocardial infarction [AMI] and 6 chronic myocardial infarction [CMI]) were examined with two-phase contrast-enhanced ECG-gated MDCT. The presence, location, and patterns of myocardial enhancement on two-phase MDCT images were compared with infarcted myocardial territories determined by using electrocardiogram, echocardiography, thallium-201 single photon emission computed tomography, catheter and MDCT coronary angiography. Results After clinical assessment, the presence of myocardial infarctions were found in 27 territories (19 AMI and 8 CMI) of 23 patients. Early perfusion defects were observed in 30 territories of all 23 patients. Three territories not corresponding to a myocardial infarction were detected in three patients with AMI and were associated with artifacts. Fourteen of perfusion defects were in the left anterior descending artery territory, four in the left circumflex artery territory, and nine in the right coronary artery territory. Delayed enhancement was observed in 25 territories (17 AMI and 8 CMI) of 21 patients. Delayed enhancement patterns were variable. Transmural early perfusion defects (n =12) were closely associated with transmural late enhancement (n = 5) and subendocardial residual defect with subepicardial late enhancement (n = 5). Conclusion Myocardial infarction showed early perfusion defects and variable delayed enhancement patterns on two-phase contrast-enhanced MDCT. Delayed enhancement technique of MDCT could provide additional information of the location and extent of infarcted myocardium, and could be useful to plan appropriate therapeutic strategies in patients with AMI. PMID:17420626

  11. Early and Delayed Myocardial Enhancement in Myocardial Infarction Using Two-Phase Contrast-Enhanced Multidetector-Row CT

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Sung-Min; Kim, Young-Whan; Han, Seong-Wook [University of Keimyung College of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of); Seo, Joon-Beom [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2007-04-15

    The purpose of this study was to describe the myocardial enhancement patterns in patients with myocardial infarction using two-phase contrast enhanced multidetector-row computed tomography (MDCT). Twenty-three patients with clinically proven myocardial infarction (17 acute myocardial infarction [AMI] and 6 chronic myocardial infarction [CMI]) were examined with two-phase contrast-enhanced ECG-gated MDCT. The presence, location, and patterns of myocardial enhancement on two phase MDCT images were compared with infarcted myocardial territories determined by using electrocardiogram, echocardiography, thallium-201 single photon emission computed tomography, catheter and MDCT coronary angiography. After clinical assessment, the presence of myocardial infarctions were found in 27 territories (19 AMI and 8 CMI) of 23 patients. Early perfusion defects were observed in 30 territories of all 23 patients. Three territories not corresponding to a myocardial infarction were detected in three patients with AMI and were associated with artifacts. Fourteen of perfusion defects were in the left anterior descending artery territory, four in the left circumflex artery territory, and nine in the right coronary artery territory. Delayed enhancement was observed in 25 territories (17 AMI and 8 CMI) of 21 patients. Delayed enhancement patterns were variable. Transmural early perfusion defects (n =12) were closely associated with transmural late enhancement (n = 5) and subendocardial residual defect with subepicardial late enhancement (n = 5). Myocardial infarction showed early perfusion defects and variable delayed enhancement patterns on two-phase contrast-enhanced MDCT. Delayed enhancement technique of MDCT could provide additional information of the location and extent of infarcted myocardium, and could be useful to plan appropriate therapeutic strategies in patients with AMI.

  12. Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement.

    Science.gov (United States)

    Yovich, John L; Conceicao, Jason L; Stanger, James D; Hinchliffe, Peter M; Keane, Kevin N

    2015-08-01

    This study explores the relevance of mid-luteal serum hormonal concentrations in cryopreserved embryo transfer cycles conducted under hormone replacement therapy (HRT) control and which involved single-embryo transfer (SET) of 529 vitrified blastocysts. Widely ranging mid-luteal oestradiol and progesterone concentrations ensued from the unique HRT regimen. Oestradiol had no influence on clinical pregnancy or live birth rates, but an optimal progesterone range between 70 and 99 nmol/l (P decreased implantation rates. There was no clear interaction between oestradiol and progesterone concentrations but embryo quality grading did show a significant influence on outcomes (P pregnancy and live birth rates, respectively). Multiple comparison analysis showed that the progesterone effect was influential regardless of embryo grading, body mass index or the woman's age, either at vitrification or at cryopreserved embryo transfer. The results support the argument that careful monitoring of serum progesterone concentrations in HRT-cryopreserved embryo transfer is warranted and that further studies should explore pessary adjustments to optimize concentrations for individual women to enhance implantation rates.

  13. Culture of porcine luteal cells as a substrate for in vitro maturation of porcine cumulus oocyte complexes. Establishment and characterization

    Directory of Open Access Journals (Sweden)

    Teplitz MA

    2016-12-01

    Full Text Available The aim of this study was to establish and characterize the porcine luteal cells (PLC culture for the subsequent coculture with porcine COC. The final purpose is to promote the oocyte maturation. The PLC was established using corpora lutea obtained from slaughterhouse ovaries. Corpora lutea were dissected and luteal tissue submitted to a mechanical and enzymatic digestion with collagenase IV. The cell suspension was filtered and centrifuged and the cells obtained were diluted in 15 mL of DMEM-F12 supplemented media. Diluted cells were seeded in 3 culture flasks T25, staying in a controlled environment and changing the medium every 2 days. For the analysis and characterization, the cells were assessed by the Nile red staining to detect intracellular lipids, immunocytochemistry (ICC for 3β-hydroxy steroid dehidrogenase (3β-HSD and ELISA for P4 determination. We observed the presence of lipid intracellular droplets. Also, we observed an increase of P4 concentration at 48, 96 y 144 h of primary culture and almost all the cells were positive to the ICC evaluation for 3β-HSD, showing the steroidogenic capacity of the culture cells.

  14. Species-driven phases and increasing structure in early-successional plant communities.

    Science.gov (United States)

    Zaplata, Markus K; Winter, Susanne; Fischer, Anton; Kollmann, Johannes; Ulrich, Werner

    2013-01-01

    Successional phases describe changes in ecological communities that proceed in steps rather than continuously. Despite their importance for the understanding of ecosystem development, there still exists no reliable definition of phases and no quantitative measure of phase transitions. In order to obtain these data, we investigated primary succession in an artificial catchment (6 ha) in eastern Germany over a period of 6 years. The data set consists of records of plant species and their cover values, and initial substrate properties, both from plots in a regular grid (20 m × 20 m) suitable for spatial data analysis. Community assembly was studied by analyses of species co-occurrence and nestedness. Additionally, we correlated lognormal and log series distributions of species abundance to each community. We here introduce a new general method for detection of successional phases based on the degree of transient spatial homogeneity in the study system. Spatially coherent vegetation patterns revealed nonoverlapping partitions within this sequence of primary succession and were characterized as two distinct ecological phases. Patterns of species co-occurrence were increasingly less random, and hence the importance of demographic stochasticity and neutral community assembly decreased during the study period. Our findings highlight the spatial dimension of successional phases and quantify the degree of change between these steps. They are an element for advancing a more reliable terminology of ecological successions.

  15. Cyclin CYB-3 controls both S-phase and mitosis and is asymmetrically distributed in the early C. elegans embryo.

    Science.gov (United States)

    Michael, W Matthew

    2016-09-01

    In early C. elegans embryos the timing of cell division is both invariant and developmentally regulated, yet how the cell cycle is controlled in the embryo and how cell cycle timing impacts early development remain important, unanswered questions. Here, I focus on the cyclin B3 ortholog CYB-3, and show that this cyclin has the unusual property of controlling both the timely progression through S-phase and mitotic entry, suggesting that CYB-3 is both an S-phase-promoting and mitosis-promoting factor. Furthermore, I find that CYB-3 is asymmetrically distributed in the two-cell embryo, such that the somatic precursor AB cell contains ∼2.5-fold more CYB-3 than its sister cell, the germline progenitor P1 CYB-3 is not only physically limited in P1 but also functionally limited, and this asymmetry is controlled by the par polarity network. These findings highlight the importance of the CYB-3 B3-type cyclin in cell cycle regulation in the early embryo and suggest that CYB-3 asymmetry helps establish the well-documented cell cycle asynchrony that occurs during cell division within the P-lineage.

  16. Mortality and dust expulsion in early phases of stellar clusters. Evidence from NIR photometry of nearby, spiral galaxies

    CERN Document Server

    Grosboel, P

    2013-01-01

    It is often argued that young stellar clusters suffer a significant infant mortality that is partly related to the expulsion of dust and gas in their early phases caused by radiation pressure from hot stars and supernovae. Near-infrared (J-K)-Mk diagrams of young stellar clusters in nearby spiral galaxies show a bi-modal distribution that is consistent with a fast decline of their intrinsic extinction at an early epoch. The distinct features in the color-magnitude diagrams (CMD) and the fast change of colors for the youngest clusters allow us to place constraints on their early evolutionary phases, including the time scale for the decreasing extinction caused for instance by gas and dust expulsion. Monte Carlo simulations of cluster populations were performed using the power-law distribution function g(M, t) ~ M^a t^gam. Integrated colors were computed from Starburst99 models. The simulated near-infrared CMD were compared with those observed for six grand-design, spiral galaxies using statistical goodness-of-...

  17. Catastrophic shifts in ecosystems: spatial early warnings and management procedures (Inspired in the physics of phase transitions)

    Energy Technology Data Exchange (ETDEWEB)

    Fort, H [Complex Systems Group, Instituto de Fisica, Facultad de Ciencias, Universidad de la Republica, Igua 4225, 11400 Montevideo (Uruguay); Mazzeo, N [Depto. de EcologIa, Facultad de Ciencias, Universidad de la Republica, Igua 4225, 11400 Montevideo (Uruguay); Scheffer, M; Nes, E van, E-mail: hugo@fisica.edu.u [Wageningen Agricultural University, Aquatic Ecology and Water Quality Management Group, PO Box 47, 6700 AA Wageningen (Netherlands)

    2010-09-01

    Ecosystems are complex systems which can respond to gradual changes of their conditions by a sudden shift to a contrasting regime or alternative stable state (ASS). Predicting such critical points before they are reached is extremely difficult and providing early warnings is fundamental to design management protocols for ecosystems. Here we study different spatial versions of popular ecological models which are known to exhibit ASS. The spatial heterogeneity is introduced by a local parameter varying from cell to cell in a regular lattice. Transport of biomass among cells occurs by simple diffusion. We investigate whether different quantities from statistical mechanics -like the variance, the two-point correlation function and the patchiness-may serve as early warnings of catastrophic phase transitions between the ASS. In particular, we find that the patch-size distribution follows a power law when the system is close to the catastrophic transition. We also provide links between spatial and temporal indicators and analyze how the interplay between diffusion and spatial heterogeneity may affect the earliness of each of the observables. Finally, we comment on similarities and differences between these catastrophic shifts and paradigmatic thermodynamic phase transitions like the liquid-vapor change of state for a fluid like water.

  18. A dynamic model of the windlass mechanism of the foot: evidence for early stance phase preloading of the plantar aponeurosis.

    Science.gov (United States)

    Caravaggi, Paolo; Pataky, Todd; Goulermas, John Y; Savage, Russel; Crompton, Robin

    2009-08-01

    In the present study we have estimated the temporal elongation of the plantar aponeurosis (PA) during normal walking using a subject-specific multi-segment rigid-body model of the foot. As previous studies have suggested that muscular forces at the ankle can pre-load the PA prior to heel-strike, the main purpose of the current study was to test, through modelling, whether there is any tension present in the PA during early stance phase. Reflective markers were attached to bony landmarks to track the kinematics of the calcaneus, metatarsus and toes during barefoot walking. Ultrasonography measurements were performed on three subjects to determine both the location of the origin of the PA on the plantar aspect of the calcaneus, and the radii of the metatarsal heads. Starting with the foot in a neutral, unloaded position, inverse kinematics allowed calculation of the tension in the five slips of the PA during the whole duration of the stance phase. The results show that the PA experienced tension significantly above rest during early stance phase in all subjects (P<0.01), thus providing support for the PA-preloading hypothesis. The amount of preloading and the maximum elongation of the slips of the PA decreased from medial to lateral. The mean maximum tension exerted by the PA was 1.5 BW (body weight) over the three subjects.

  19. Cosmological QCD phase transition in steady non-equilibrium dissipative Ho\\v{r}ava-Lifshitz early universe

    CERN Document Server

    Khodadi, M

    2014-01-01

    We study the phase transition from quark-gluon plasma to hadrons in the early universe in the context of non-equilibrium thermodynamics. According to the standard model of cosmology, a phase transition associated with chiral symmetry breaking after the electro-weak transition has occurred when the universe was about $1-10\\mu s$ old. We focus attention on such a phase transition in the presence of a viscous relativistic cosmological background fluid in the framework of non-detailed balance Ho\\v{r}ava-Lifshitz cosmology within an effective model of QCD. We consider a flat Friedmann-Robertson-Walker Universe filled with a non-causal and causal bulk viscous cosmological fluid respectively and investigate the effects of the running coupling constants of Ho\\v{r}ava-Lifshitz gravity, $\\lambda$, on the evolution of the physical quantities relevant to a description of the early universe, namely, the temperature $T$, scale factor $a$, deceleration parameter $q$ and dimensionless ratio of the bulk viscosity coefficient ...

  20. Early molecular changes in Alzheimer disease : can we catch the disease in its presymptomatic phase?

    NARCIS (Netherlands)

    Wirz, Kerstin T S; Keitel, Stella; Swaab, Dick F; Verhaagen, J.; Bossers, K.

    2014-01-01

    Alzheimer disease (AD) is the most common form of dementia and characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles consisting of hyperphosphorylated tau, atrophy, and progressive neurodegeneration. While the familial, early onset form of AD is known to be caused by specifi

  1. Systemic oxidative DNA and RNA damage are not increased during early phases of psychosis

    DEFF Research Database (Denmark)

    Nordholm, Dorte; Poulsen, Henrik Enghusen; Hjorthøj, Carsten;

    2016-01-01

    It has been suggested that patients with schizophrenia develop higher levels of oxidative stress, which may contribute to deteriorating mental illness. In order to examine oxidative stress in the early stages of severe mental illness, we examined the levels of systemic Deoxyribonucleic Acid (DNA...

  2. The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

    Directory of Open Access Journals (Sweden)

    Paulina Dumnicka

    2017-02-01

    Full Text Available Acute pancreatitis (AP is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1 we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2 we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

  3. Early Origins of Child Obesity: Bridging Disciplines and Phases of Development - September 30–October 1, 2010

    Directory of Open Access Journals (Sweden)

    Xiaobin Wang

    2012-04-01

    Full Text Available This report summarizes a conference: “Early Origins of Child Obesity: Bridging Disciplines and Phases of Development”, held in Chicago on September 30–October 1, 2010. The conference was funded in part by the National Institutes of Health and the Williams Heart Foundation, to achieve the conference objective: forging a next-step research agenda related to the early origins of childhood obesity. This research agenda was to include working with an array of factors (from genetic determinants to societal ones along a continuum from prenatal life to age 7, with an emphasis on how the developing child deals with the challenges presented by his/her environment (prenatal, parental, nutritional, etc.. The conference offered a unique opportunity to facilitate communication and planning of future work among a variety of researchers whose work separately addresses different periods in early life. Over the span of two days, speakers addressed existing, critical research topics within each of the most-studied age ranges. On the final day, workshops fostered the discussion needed to identify the highest priority research topics related to linking varied early factor domains. These are presented for use in planning future research and research funding.

  4. The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

    Science.gov (United States)

    Dumnicka, Paulina; Maduzia, Dawid; Ceranowicz, Piotr; Olszanecki, Rafał; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

    2017-01-01

    Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients. PMID:28208708

  5. Tracking the Distribution of 26Al and 60Fe during the Early Phases of Star and Disk Evolution

    DEFF Research Database (Denmark)

    Küffmeier, Michael; Mogensen, Troels Frostholm; Haugbølle, Troels;

    2016-01-01

    that the 26Al/27Al and 60Fe/56Fe ratios of accreting gas within a vicinity of 1000 au of the stars follow the predicted decay curves of the initial abundances at the time of star formation without evidence of spatial or temporal heterogeneities for the first 100 kyr of star formation. Therefore, the observed...... the admixing of the 26Al nuclides during the early formative phase of the Sun. We use giant molecular cloud scale adaptive mesh-refinement numerical simulations to trace the abundance of 26Al and 60Fe in star-forming gas during the early stages of accretion of individual low-mass protostars. We find...... system formation....

  6. Reduced early and late phase insulin response to glucose in isolated spiny mouse (Acomys cahirinus) islets: a defective link between glycolysis and adenylate cyclase.

    Science.gov (United States)

    Nesher, R; Abramovitch, E; Cerasi, E

    1989-09-01

    The spiny mouse (Acomys cahirinus) exhibits low insulin responsiveness to glucose with a nearly absent early phase release. The alternative fuel-secretagogue glyceraldehyde (10 mmol/l) produced a maximal early insulin response in rat islets but failed to affect early response in Acomys; however, it potentiated the late insulin response in both species alike. Glucagon (1.5 mumol/l) potentiated the early insulin response to intermediate (8.3 mmol/l) glucose in rat and Acomys islets by two- and four-fold, respectively. Glucose doubled cyclic AMP levels in rat islets but no significant response was noted in Acomys islets. Isobutylmethylxanthine (0.1 mmol/l) and forskolin (25 mumol/l) caused a significant rise in islet cyclic AMP levels in both types of islets; however, neither agent restored the glucose stimulation of cyclic AMP in spiny mouse islets. Forskolin and isobutylmethylxanthine potentiated early and late phase insulin release in both species; however, neither augmented the early response in the Acomys to the degree observed in rat islets. Thus: (1) A deficient link exists in Acomys between glycolysis and subsequent signals. (2) These islets contain a glucose-insensitive adenylate cyclase. (3) The early insulin response may be potentiated by direct activation of adenylate cyclase. (4) The glucose effects on early and late phase insulin release are probably mediated by distinct pathways. (5) In the spiny mouse the signals mediating the early response are deranged to a greater extent than those activating the late phase insulin release.

  7. Which System Variables Carry Robust Early Signs of Upcoming Phase Transition? An Ecological Example

    Science.gov (United States)

    Negahbani, Ehsan; Steyn-Ross, D. Alistair; Steyn-Ross, Moira L.; Aguirre, Luis A.

    2016-01-01

    Growth of critical fluctuations prior to catastrophic state transition is generally regarded as a universal phenomenon, providing a valuable early warning signal in dynamical systems. Using an ecological fisheries model of three populations (juvenile prey J, adult prey A and predator P), a recent study has reported silent early warning signals obtained from P and A populations prior to saddle-node (SN) bifurcation, and thus concluded that early warning signals are not universal. By performing a full eigenvalue analysis of the same system we demonstrate that while J and P populations undergo SN bifurcation, A does not jump to a new state, so it is not expected to carry early warning signs. In contrast with the previous study, we capture a significant increase in the noise-induced fluctuations in the P population, but only on close approach to the bifurcation point; it is not clear why the P variance initially shows a decaying trend. Here we resolve this puzzle using observability measures from control theory. By computing the observability coefficient for the system from the recordings of each population considered one at a time, we are able to quantify their ability to describe changing internal dynamics. We demonstrate that precursor fluctuations are best observed using only the J variable, and also P variable if close to transition. Using observability analysis we are able to describe why a poorly observable variable (P) has poor forecasting capabilities although a full eigenvalue analysis shows that this variable undergoes a bifurcation. We conclude that observability analysis provides complementary information to identify the variables carrying early-warning signs about impending state transition. PMID:27631984

  8. Which System Variables Carry Robust Early Signs of Upcoming Phase Transition? An Ecological Example.

    Science.gov (United States)

    Negahbani, Ehsan; Steyn-Ross, D Alistair; Steyn-Ross, Moira L; Aguirre, Luis A

    2016-01-01

    Growth of critical fluctuations prior to catastrophic state transition is generally regarded as a universal phenomenon, providing a valuable early warning signal in dynamical systems. Using an ecological fisheries model of three populations (juvenile prey J, adult prey A and predator P), a recent study has reported silent early warning signals obtained from P and A populations prior to saddle-node (SN) bifurcation, and thus concluded that early warning signals are not universal. By performing a full eigenvalue analysis of the same system we demonstrate that while J and P populations undergo SN bifurcation, A does not jump to a new state, so it is not expected to carry early warning signs. In contrast with the previous study, we capture a significant increase in the noise-induced fluctuations in the P population, but only on close approach to the bifurcation point; it is not clear why the P variance initially shows a decaying trend. Here we resolve this puzzle using observability measures from control theory. By computing the observability coefficient for the system from the recordings of each population considered one at a time, we are able to quantify their ability to describe changing internal dynamics. We demonstrate that precursor fluctuations are best observed using only the J variable, and also P variable if close to transition. Using observability analysis we are able to describe why a poorly observable variable (P) has poor forecasting capabilities although a full eigenvalue analysis shows that this variable undergoes a bifurcation. We conclude that observability analysis provides complementary information to identify the variables carrying early-warning signs about impending state transition.

  9. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever.

    Science.gov (United States)

    Cui, Liang; Lee, Yie Hou; Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R

    2016-04-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (1.5) in the serum, among which are two products of tryptophan metabolism-serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved the prognosis performance (AUC = 0.92, sensitivity = 77.8%, specificity = 95.8%), suggesting this duplex panel as accurate metrics for the early prognosis of DHF.

  10. The prototyping/early construction phase of the BAIKAL-GVD project

    Energy Technology Data Exchange (ETDEWEB)

    Avrorin, A.D.; Avrorin, A.V.; Aynutdinov, V.M. [Institute for Nuclear Research, 60th October Anniversary pr. 7a, Moscow 117312 (Russian Federation); Bannasch, R. [EvoLogics GmbH, Berlin (Germany); Belolaptikov, I.A. [Joint Institute for Nuclear Research, Dubna 141980 (Russian Federation); Bogorodsky, D.Yu. [Irkutsk State University, Irkutsk 664003 (Russian Federation); Brudanin, V.B. [Joint Institute for Nuclear Research, Dubna 141980 (Russian Federation); Budnev, N.M. [Irkutsk State University, Irkutsk 664003 (Russian Federation); Danilchenko, I.A.; Domogatsky, G.V.; Doroshenko, A.A. [Institute for Nuclear Research, 60th October Anniversary pr. 7a, Moscow 117312 (Russian Federation); Dyachok, A.N. [Irkutsk State University, Irkutsk 664003 (Russian Federation); Dzhilkibaev, Zh-A.M., E-mail: djilkib@yandex.ru [Institute for Nuclear Research, 60th October Anniversary pr. 7a, Moscow 117312 (Russian Federation); Fialkovsky, S.V. [Nizhni Novgorod State Technical University, Nizhni Novgorod 603950 (Russian Federation); Gafarov, A.R. [Irkutsk State University, Irkutsk 664003 (Russian Federation); Gaponenko, O.N.; Golubkov, K.V. [Institute for Nuclear Research, 60th October Anniversary pr. 7a, Moscow 117312 (Russian Federation); Gress, T.I. [Irkutsk State University, Irkutsk 664003 (Russian Federation); Honz, Z. [Joint Institute for Nuclear Research, Dubna 141980 (Russian Federation); Kebkal, K.G. [EvoLogics GmbH, Berlin (Germany); and others

    2014-04-01

    The prototyping phase of the BAIKAL-GVD project has been started in April 2011 with the deployment of a three string engineering array which comprises all basic elements and systems of the Gigaton Volume Detector (GVD) in Lake Baikal. In April 2012 the version of engineering array which comprises the first full-scale string of the GVD demonstration cluster had been deployed and operated during 2012. The first stage of the GVD-cluster which consists of three strings was deployed in April 2013. We review the prototyping phase of the BAIKAL-GVD project and describe the configuration and design of the 2013 engineering array.

  11. 6S RNA regulation of relA alters ppGpp levels in early stationary phase

    OpenAIRE

    Cavanagh, Amy T.; Chandrangsu, Pete; Wassarman, Karen M.

    2010-01-01

    6S RNA is a small, non-coding RNA that interacts directly with ? 70-RNA polymerase and regulates transcription at many ? 70-dependent promoters. Here, we demonstrate that 6S RNA regulates transcription of relA, which encodes a ppGpp synthase. The 6S RNA-dependent regulation of relA expression results in increased ppGpp levels during early stationary phase in cells lacking 6S RNA. These changes in ppGpp levels, although modest, are sufficient to result in altered regulation of transcription fr...

  12. A Bayesian three-parameter logistic model for early- and late-onset DLTs in oncology Phase I studies.

    Science.gov (United States)

    Zheng, Wei; Zhao, Yang; Lu, Yuefeng; Miao, Harry; Liu, Hengchang

    2016-01-01

    We introduce a three-parameter logistic model to analyze the dose limiting toxicity (DLT) as a time-to-event endpoint in oncology Phase I trials. In the proposed model, patients are allowed to stay on trial without the constraint of a maximum follow-up time. Our model accommodates late-onset DLT as well as early-onset DLT, by both of which the dose recommendation is informed. A Bayesian approach is used to incorporate prior knowledge of the test treatment into dose recommendation. Simulation examples show that our proposed model has good operating characteristics in assessing the maximum tolerated dose (MTD).

  13. Factors associated with reduced early survival in the Oxford phase III medial unicompartment knee replacement

    NARCIS (Netherlands)

    Kuipers, Bart M.; Kollen, Boudewijn J.; Bots, Peter C. Kaijser; Burger, Bart J.; van Raay, Jos J. A. M.; Tulp, Niek J. A.; Verheyen, Cees C. P. M.

    2010-01-01

    The aim of this study was to determine the prognostic value of preoperative patellofemoral osteoarthritis, BMI and age for implant Survival of unicompartmental knee arthroplasty (UKA) performed in patients meeting strict admission criteria. The data and radiographs of 437 unilateral Oxford phase III

  14. Phase-based x-ray scattering—A possible method to detect cancer cells in a very early stage

    Energy Technology Data Exchange (ETDEWEB)

    Feye-Treimer, U., E-mail: feye-treimer@helmholtz-berlin.de; Treimer, W. [Department of Mathematics, Physics and Chemistry, University of Applied Sciences, D-13353 Berlin, Germany and Joint Department G-GTOMO, Helmholtz Zentrum fuer Materialien und Energie Berlin, D-14109 Berlin (Germany)

    2014-05-15

    Purpose: This theoretical work contains a detailed investigation of the potential and sensitivity of phase-based x-ray scattering for cancer detection in biopsies if cancer is in a very early stage of development. Methods: Cancer cells in their early stage of development differ from healthy ones mainly due to their faster growing cell nuclei and the enlargement of their densities. This growth is accompanied by an altered nucleus–plasma relation for the benefit of the cell nuclei, that changes the physical properties especially the index of refraction of the cell and the one of the cell nuclei. Interaction of radiation with matter is known to be highly sensitive to small changes of the index of refraction of matter; therefore a detection of such changes of volume and density of cell nuclei by means of high angular resolved phase-based scattering of x rays might provide a technique to distinguish malignant cells from healthy ones ifthe cell–cell nucleus system is considered as a coherent phase shifting object. Then one can observe from a thin biopsy which represents a monolayer of cells (no multiple scattering) that phase-based x-ray scattering curves from healthy cells differ from those of cancer cells in their early stage of development. Results: Detailed calculations of x-ray scattering patterns from healthy and cancer cell nuclei yield graphs and numbers with which one can distinguish healthy cells from cancer ones, taking into account that both kinds of cells occur in a tissue within a range of size and density. One important result is the role and the influence of the (lateral) coherence width of the radiation on the scattering curves and the sensitivity of phase-based scattering for cancer detection. A major result is that a larger coherence width yields a larger sensitivity for cancer detection. Further import results are calculated limits for critical sizes and densities of cell nuclei in order to attribute the investigated tissue to be healthy or

  15. Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Aboagye, Eric O.; Kenny, Laura M.; Myers, Melvyn [Imperial College London, Department of Surgery and Cancer, Faculty of Medicine, London (United Kingdom); Gilbert, Fiona J. [University of Cambridge, Radiology Department, Cambridge (United Kingdom); Fleming, Ian N. [University of Aberdeen, NCRI PET Research Network, Aberdeen Bioimaging Centre, Aberdeen (United Kingdom); Beer, Ambros J. [Technische Universitaet Munchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany); Cunningham, Vincent J. [University of Aberdeen, Institute of Medical Sciences, Aberdeen (United Kingdom); Marsden, Paul K. [St. Thomas' Hospital, Division of Imaging Sciences, PET Imaging Centre, London (United Kingdom); Visvikis, Dimitris [INSERM National Institute of Health and Clinical Sciences LaTIM, CHU Morvan, Brest (France); Gee, Antony D. [St. Thomas' Hospital, Division of Imaging Sciences, The Rayne Institute, London (United Kingdom); Groves, Ashley M. [University College London, University College Hospital, Institute of Nuclear Medicine, London (United Kingdom); Cook, Gary J. [St. Thomas' Hospital, KCL Division of Imaging, Sciences and Biomedical Engineering, PET Imaging Centre, London (United Kingdom); Kinahan, Paul E. [University of Washington, 222 Old Fisheries Center (FIS), Box 357987, Seattle, WA (United States); Clarke, Larry [Cancer Imaging Program, Imaging Technology Development Branch, Rockville, MD (United States)

    2012-07-15

    The evaluation of drug pharmacodynamics and early tumour response are integral to current clinical trials of novel cancer therapeutics to explain or predict long term clinical benefit or to confirm dose selection. Tumour vascularity assessment by positron emission tomography could be viewed as a generic pharmacodynamic endpoint or tool for monitoring response to treatment. This review discusses methods for semi-quantitative and quantitative assessment of tumour vascularity. The radioligands and radiotracers range from direct physiological functional tracers like [{sup 15}O]-water to macromolecular probes targeting integrin receptors expressed on neovasculature. Finally we make recommendations on ways to incorporate such measurements of tumour vascularity into early clinical trials of novel therapeutics. (orig.)

  16. Assessment of early warning system performance and improvements since it is in operational phase in Romania

    Science.gov (United States)

    Ionescu, Constantin; Marmureanu, Alexandru; Marmureanu, Gheorghe; Ortansa Cioflan, Carmen

    2017-04-01

    Earthquake represents a major natural disaster for Romanian territory. The main goal following the occurrence of a strong earthquake is to minimize the total number of fatalities. A rapid early warning system (REWS) was developed in Romania in order to provide 25-35 seconds warning time to Bucharest facilities for the earthquakes with M>5.0. The system consists of four components: a network of strong motion sensors installed in the epicentral area, a redundant communication network, an automatic analyzing system located in the Romanian Data Centre and an alert distribution system. The detection algorithm is based on the magnitude computation using strong motion data and rapid evaluation and scaling relation between the maximum P-wave acceleration measured in the epicentral area and the higher ground motion amplitude recorded in Bucharest. In order to reduce the damages caused by earthquakes, the exploitation of the up to date technology is very important. The information is the key point in the disaster management, and the internet is one of the most used instrument, implying also low costs. The Rapid Early Warning System was expanded to cover all countries affected by major earthquakes originating in the Vrancea seismic area and reduce their impact on existing installations of national interest in neighbouring Romania and elsewhere. REWS provides an efficient instrument for prevention and reaction based on the integrated system for seismic detection in South-Eastern Europe. REWS has been operational since 2013 and sends alert the authorities, hazardous facilities in Romania and Bulgaria (NPP, emergency response agencies etc.) and to public via twitter and some smartphone applications developed in the house. Also, NIEP is part of the UNESCO initiative case on developing a platform on earthquake early warning systems (IP-MEP) that aims to promote and strengthen the development of earthquake early warning systems in earthquake-prone regions of the world by sharing

  17. Effect of cortisol on neurophysin I/oxytocin and peptidyl glycine-alpha-amidating mono-oxygenase mRNA expression in bovine luteal and granulosa cells.

    Science.gov (United States)

    Ziolkowska, A; Mlynarczuk, J; Kotwica, J

    2013-01-01

    Cortisol stimulates the synthesis and secretion of oxytocin (OT) from bovine granulosa and luteal cells, but the molecular mechanisms of cortisol action remain unknown. In this study, granulosa cells or luteal cells from days 1-5 and 11-15 of the oestrous cycle were incubated for 4 or 8 h with cortisol (1 x 10(-5), 1 x 10(-7) M). After testing cell viability and hormone secretion (OT, progesterone, estradiol), we studied the effect of cortisol on mRNA expression for precursor of OT (NP-I/OT) and peptidyl glycine-alpha-amidating mono-oxygenase (PGA). The influence of RU 486 (1 x 10(-5) M), a progesterone receptor blocker and inhibitor of the glucocorticosteroid receptor (GR), on the expression for both genes was tested. Cortisol increased the mRNA expression for NP-I/OT and PGA in granulosa cells and stimulated the expression for NP-I/OT mRNA in luteal cells obtained from days 1-5 and days 11-15 of the oestrous cycle. Expression for PGA mRNA was increased only in luteal cells from days 11-15 of the oestrous cycle. In addition, RU 486 blocked the cortisol-stimulated mRNA expression for NP-I/OT and PGA in both types of cells. These data suggest that cortisol affects OT synthesis and secretion in bovine ovarian cells, by acting on the expression of key genes, that may impair ovary

  18. Administration of Zinc plus Cyclo-(His-Pro) Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes

    Science.gov (United States)

    Choi, Bo Young; Kim, In Yeol; Kim, Jin Hee; Lee, Bo Eun; Lee, Song Hee; Kho, A Ra; Sohn, Min; Suh, Sang Won

    2017-01-01

    The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro) (ZC) on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ)-induced diabetes. ZC (27 mg/kg) was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase) or 45 (late phase) days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs) and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes. PMID:28045430

  19. Administration of Zinc plus Cyclo-(His-Pro Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2017-01-01

    Full Text Available The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro (ZC on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ-induced diabetes. ZC (27 mg/kg was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase or 45 (late phase days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes.

  20. Early Detection of Amyloid Plaque in Alzheimer’s Disease Via X-ray Phase CT

    Science.gov (United States)

    2015-06-01

    to two reasons – (i) the fabrication/optimization of x-ray gratings were much more complicated and challenging than we initially anticipated and ( ii...Primarily due to two reasons – (i) the fabrication/optimization of x-ray gratings were much more complicated and challenging than we initially...re-optimization – Phase de-wrapping: Since x-ray grating fabrication is a complicated process, there inevitably exists imperfection in either grating

  1. [Increased urinary sodium excretion in the early phase of aneurysmal subarachnoid hemorrhage as a predictor of cerebral salt wasting syndrome].

    Science.gov (United States)

    Nakagawa, Ichiro; Kurokawa, Shinichiro; Takayama, Katsutoshi; Wada, Takeshi; Nakase, Hiroyuki

    2009-12-01

    Cerebral salt wasting syndrome (CSWS) in patients with aneurysmal subarachnoid hemorrhage (SAH) is considered to correlate with delayed ischemic neurological deficits (DIND) induced by cerebral vasospasm; however, its exact mechanism is still not well-known. The purpose of the present study is to evaluate the relationship between hyponatremia caused by CSWS and the increase of the urinary sodium excretion in early phase following SAH. Fifty-four patients with SAH were divided into 2 groups, normonatremia group and hyponatremia group which suffered hyponatremia after SAH. The hyponatremia group comprise 14 patients (26%) in whom the hyponatremia developed of the SAH. In this group, the serum level of sodium significantly decreased 7 days after SAH and then gradually normalised. Further, excretion of sodium in the urine tended to increase 3 days after SAH and significantly increased 7 days after SAH. In conclusion, the increased urinary sodium excretion in the early phase of SAH would serve as a predictive factor for CSWS after SAH. We consider that it is important to start sodium and fluid supplementation and inhibit natriuresis by fludrocortisone acetate administration before hyponatremia occurs in order to prevention delayed ischemic neurological deficits in SAH patients.

  2. Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism explaining rapidly spreading plague epizootics

    Science.gov (United States)

    Eisen, Rebecca J.; Bearden, Scott W.; Wilder, Aryn P.; Montenieri, John A.; Antolin, Michael F.; Gage, Kenneth L.

    2006-01-01

    Plague is a highly virulent disease believed to have killed millions during three historic human pandemics. Worldwide, it remains a threat to humans and is a potential agent of bioterrorism. Dissemination of Yersinia pestis, the etiological agent of plague, by blocked fleas has been the accepted paradigm for flea-borne transmission. However, this mechanism, which requires a lengthy extrinsic incubation period before a short infectious window often followed by death of the flea, cannot sufficiently explain the rapid rate of spread that typifies plague epidemics and epizootics. Inconsistencies between the expected rate of spread by blocked rat fleas and that observed during the Black Death has even caused speculation that plague was not the cause of this medieval pandemic. We used the primary vector to humans in North America, Oropsylla montana, which rarely becomes blocked, as a model for studying alternative flea-borne transmission mechanisms. Our data revealed that, in contrast to the classical blocked flea model, O. montana is immediately infectious, transmits efficiently for at least 4 d postinfection (early phase) and may remain infectious for a long time because the fleas do not suffer block-induced mortality. These factors match the criteria required to drive plague epizootics as defined by recently published mathematical models. The scenario of efficient early-phase transmission by unblocked fleas described in our study calls for a paradigm shift in concepts of how Y. pestis is transmitted during rapidly spreading epizootics and epidemics, including, perhaps, the Black Death. PMID:17032761

  3. Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism explaining rapidly spreading plague epizootics.

    Science.gov (United States)

    Eisen, Rebecca J; Bearden, Scott W; Wilder, Aryn P; Montenieri, John A; Antolin, Michael F; Gage, Kenneth L

    2006-10-17

    Plague is a highly virulent disease believed to have killed millions during three historic human pandemics. Worldwide, it remains a threat to humans and is a potential agent of bioterrorism. Dissemination of Yersinia pestis, the etiological agent of plague, by blocked fleas has been the accepted paradigm for flea-borne transmission. However, this mechanism, which requires a lengthy extrinsic incubation period before a short infectious window often followed by death of the flea, cannot sufficiently explain the rapid rate of spread that typifies plague epidemics and epizootics. Inconsistencies between the expected rate of spread by blocked rat fleas and that observed during the Black Death has even caused speculation that plague was not the cause of this medieval pandemic. We used the primary vector to humans in North America, Oropsylla montana, which rarely becomes blocked, as a model for studying alternative flea-borne transmission mechanisms. Our data revealed that, in contrast to the classical blocked flea model, O. montana is immediately infectious, transmits efficiently for at least 4 d postinfection (early phase) and may remain infectious for a long time because the fleas do not suffer block-induced mortality. These factors match the criteria required to drive plague epizootics as defined by recently published mathematical models. The scenario of efficient early-phase transmission by unblocked fleas described in our study calls for a paradigm shift in concepts of how Y. pestis is transmitted during rapidly spreading epizootics and epidemics, including, perhaps, the Black Death.

  4. Up-regulation of tumor necrosis factor superfamily genes in early phases of photoreceptor degeneration.

    Directory of Open Access Journals (Sweden)

    Sem Genini

    Full Text Available We used quantitative real-time PCR to examine the expression of 112 genes related to retinal function and/or belonging to known pro-apoptotic, cell survival, and autophagy pathways during photoreceptor degeneration in three early-onset canine models of human photoreceptor degeneration, rod cone dysplasia 1 (rcd1, X-linked progressive retinal atrophy 2 (xlpra2, and early retinal degeneration (erd, caused respectively, by mutations in PDE6B, RPGRORF15, and STK38L. Notably, we found that expression and timing of differentially expressed (DE genes correlated with the cell death kinetics. Gene expression profiles of rcd1 and xlpra2 were similar; however rcd1 was more severe as demonstrated by the results of the TUNEL and ONL thickness analyses, a greater number of genes that were DE, and the identification of altered expression that occurred at earlier time points. Both diseases differed from erd, where a smaller number of genes were DE. Our studies did not highlight the potential involvement of mitochondrial or autophagy pathways, but all three diseases were accompanied by the down-regulation of photoreceptor genes, and up-regulation of several genes that belong to the TNF superfamily, the extrinsic apoptotic pathway, and pro-survival pathways. These proteins were expressed by different retinal cells, including horizontal, amacrine, ON bipolar, and Müller cells, and suggest an interplay between the dying photoreceptors and inner retinal cells. Western blot and immunohistochemistry results supported the transcriptional regulation for selected proteins. This study highlights a potential role for signaling through the extrinsic apoptotic pathway in early cell death events and suggests that retinal cells other than photoreceptors might play a primary or bystander role in the degenerative process.

  5. Implant Stability Changes during Early Phase of Healing:A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    A. Mesgarzadeh

    2009-06-01

    Full Text Available Objective: To assess the stability changes as a reflection of early healing around roughened-surface implants in human by resonance frequency analysis (RFA.Materials and Methods: One hundred and fifty one ITI SLA implants were placed in either maxilla or mandible of 68 patients. Bone type was classified into 4 groups according to Lekholm and Zarb index. RFA was used for direct implant stability measurement on theday of implant placement, and at 14, 30 and 60 days after placement. Student t-test and ANOVA served for statistical analysis.Results: No early failure occurred. The highest and lowest primary stability was measured in type 1 and type 4 bone, respectively. Implant stability increased over time in types 3 and 4 bone but continuously decreased in type 1 bone during the first 60 days of healing.In type 2 a small decrease in stability was observed until 30 days, and after that the stability increased. The difference between implant stability in type 2 and type 4 bone at eachtime point was highly significant (P0.05. The effect of implant length and diameter on stability at different times was tested with mixed model ANOVA, and no significant difference among groups was observed (P>0.05Conclusion: The present study demonstrated that the pattern of stability changes was different among various bone types. With regard to primary stability and pattern of stability changes in types 2 and 3 bone, immediate and early loading protocols can be recommended in these two bone types, respectively.

  6. Phase Transitions in the Early Universe with Negatively Induced Supergravity Cosmological Constant

    Institute of Scientific and Technical Information of China (English)

    EL-NABULSI Ahmad Rami

    2006-01-01

    @@ We consider that the observable cosmological constant is the sum of the vacuum (Avac) and the induced term (Aind - 3m2/4) with m being the ultra-light masses (≈ Hubble parameter) implemented in the theory from supergravities arguments and non-minimal coupling. In the absence of a scalar buildup of matter fields, we study its effects on spontaneous symmetry breaking with a Higgs potential and show how the presence of the ultra-light masses yields some important consequences for the early universe and new constraints on the Higgs and electroweak gauge bosons masses.

  7. Ultra-Structural Changes of the Early Childhood Caries Starting Phases of Development

    Directory of Open Access Journals (Sweden)

    Kokoceva-Ivanovska Olga

    2014-03-01

    Full Text Available In the recent 20 years, besides dramatic reduction of caries in many countries where complex programme of prevention is carried out, prevalence of Early Childhood Caries (ECC has expressed continual growth trend. The aim of our research was to determine precisely ultra-structural changes in the enamel substance at the initial lesion of the ECC (white spot lesion, as initial change of great importance for its preventive aspect. Therefore, we directed our experiment to evaluate ultra-structural changes of the teeth enamel in primary teeth with circular caries in its opening stages of development: initial caries lesion and superficial form.

  8. Control of Early Age Cracking in Concrete. Phase 4 and 5: Material Modelling, Continuum Approach

    DEFF Research Database (Denmark)

    Hauggaard-Nielsen, Anders Boe; Damkilde, Lars; Hansen, Per Freiesleben

    1997-01-01

    This report deals with numerical modelling of early age concrete. The hydration process giving the strength and stiffness development after casting is discussed. Several factors influence the progress of hydration such as the temperature level and the moisture activity. The factors are coupled...... and a material model is proposed which includes some of the couplings. It is shown how more factors may be incorporated. The model is illustrated through analysis of measured creep response both at a varying load history and at a varying temperature history....

  9. Review of hardware cost estimation methods, models and tools applied to early phases of space mission planning

    Science.gov (United States)

    Trivailo, O.; Sippel, M.; Şekercioğlu, Y. A.

    2012-08-01

    The primary purpose of this paper is to review currently existing cost estimation methods, models, tools and resources applicable to the space sector. While key space sector methods are outlined, a specific focus is placed on hardware cost estimation on a system level, particularly for early mission phases during which specifications and requirements are not yet crystallised, and information is limited. For the space industry, cost engineering within the systems engineering framework is an integral discipline. The cost of any space program now constitutes a stringent design criterion, which must be considered and carefully controlled during the entire program life cycle. A first step to any program budget is a representative cost estimate which usually hinges on a particular estimation approach, or methodology. Therefore appropriate selection of specific cost models, methods and tools is paramount, a difficult task given the highly variable nature, scope as well as scientific and technical requirements applicable to each program. Numerous methods, models and tools exist. However new ways are needed to address very early, pre-Phase 0 cost estimation during the initial program research and establishment phase when system specifications are limited, but the available research budget needs to be established and defined. Due to their specificity, for vehicles such as reusable launchers with a manned capability, a lack of historical data implies that using either the classic heuristic approach such as parametric cost estimation based on underlying CERs, or the analogy approach, is therefore, by definition, limited. This review identifies prominent cost estimation models applied to the space sector, and their underlying cost driving parameters and factors. Strengths, weaknesses, and suitability to specific mission types and classes are also highlighted. Current approaches which strategically amalgamate various cost estimation strategies both for formulation and validation

  10. Neurocognitive Functioning in Schizophrenia and during the Early Phases of Psychosis: Targeting Cognitive Remediation Interventions

    Directory of Open Access Journals (Sweden)

    Yulia Zaytseva

    2013-01-01

    Full Text Available Recent interest in the early course of schizophrenia accentuated altered cognition prior to the onset. Ultrahigh risk (UHR individuals with attenuated positive symptoms and transient psychotic episodes demonstrate neurocognitive deficits across multiple domains such as memory, executive functioning, and processing speed which are consistent with similar disturbances identified in patients with a first episode of schizophrenia. Cognitive remediation (CR approaches representing a broad set of activities are aimed to restore or improve cognitive functioning. CR proved to be effective in modulating the cognitive dysfunction in schizophrenia but is rarely used in ultrahigh risk individuals. From the clinical prospective, a better understanding of cognitive functioning in at-risk states is essential for the development of optimal early intervention models. In the review, we highlight the intervention targets, notably the specific cognitive deficits in at risk individuals which preceed the transition to psychosis and emphasize the need of the additional studies using CR approaches in UHR group aiming to enhance cognition and therefore mediate functional improvement.

  11. Hypokalemia during the early phase of refeeding in patients with cancer

    Science.gov (United States)

    Grasso, Simona; Ferro, Yvelise; Migliaccio, Valeria; Mazza, Elisa; Rotundo, Stefania; Pujia, Arturo; Montalcini, Tiziana

    2013-01-01

    OBJECTIVE: Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding. METHODS: In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed. RESULTS: Significant weight loss (∼20%) was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p = 0.03 for potassium and 0.02 for protein, respectively). Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day). CONCLUSION: Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding. PMID:24270952

  12. Hypokalemia during the early phase of refeeding in patients with cancer

    Directory of Open Access Journals (Sweden)

    Simona Grasso

    2013-11-01

    Full Text Available OBJECTIVE: Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding. METHODS: In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed. RESULTS: Significant weight loss (∼20% was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p = 0.03 for potassium and 0.02 for protein, respectively. Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day. CONCLUSION: Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding.

  13. Changes in ovaries and uterus after aglepristone administration in the third week of luteal phase of non-pregnant bitches.

    Science.gov (United States)

    Kacprzak, Kamil; Jurka, Piotr; Dolka, Izabella; Czopowicz, Michał; Ruszczak, Anna; Duszewska, Anna

    2015-01-01

    The mechanism of aglepristone action in the placentation time in the bitch remains unclear. The aim of this study was to describe the mechanism by which aglepristone influences ovaries and uterus and to measure the levels of steroid sex hormones in non-pregnant bitches. Fourteen bitches assigned to a study (n=9) and control (n=5) group were given aglepristone and saline solution, respectively, on the 19th and 20th day after LH peak. On the 26th day after LH peak an ovariohysterectomy was performed. Blood samples were screened for estradiol and progesterone concentrations. Ovaries and uterine horns and bodies were isolated for histological and morphometrical diagnosis and immunohistochemistry analysis of α-estrogen and progesterone receptor expression. A decrease of progesterone (pbody (pbody of study bitches were significantly thicker than in the control group (pbody was thicker than myometrium of horns (pbody (pbody within groups. To the knowledge of the authors this is the first study, which describes the inflammatory effect developing in uterus in response to aglepristone administration, and attempts to elucidate its mechanisms.

  14. Double cloprostenol administration during mid luteal phase of oestrous cycle does not modify the interoestrous interval in gilts

    Directory of Open Access Journals (Sweden)

    Claudio Mazzoni

    2014-07-01

    Full Text Available The present study was undertaken to test the effect of two vulva injections of D-cloprostenol on day 7, 9 and 10 of oestrous cycle on the duration of the interestrous interval in gilts. Following a pre-treatment oestrous cycle, 87 gilts were assigned to receive vulva injections of 75 μg D-cloprostenol at 08:00 and 14:00 h on day 7 (D7; n=30, day 9 (D9; n=29 or day 10 (D10; n=28 of their second observed oestrous cycle. Across the treatments, the duration of the oestrous cycle with D-cloprostenol treatment (19.1±0.1 d was not different from that of the previous oestrous cycle (20.1±0.4 days. Plasma progesterone concentrations were evaluated 6 h before and 24 and 72 h after D-cloprostenol treatment in the D9 group. Compared to pretreatment levels (9.6±0.4 ng/mL, plasma progesterone concentrations were reduced (P<0.05 at 24 h (6.3±1.0 ng/mL and 72 h after treatment but complete luteolysis did not occur. These data indicate that in gilts double vulva administration of D-cloprostenol is not able to induce a complete luteolisys and hence the duration of the oestrous cycle is not modified.

  15. Studies of high temperature ternary phases in mixed-metal-rich early transition metal sulfide and phosphide systems

    Energy Technology Data Exchange (ETDEWEB)

    Marking, G.A.

    1994-01-04

    Investigations of ternary mixed early transition metal-rich sulfide and phosphide systems resulted in the discovery of new structures and new phases. A new series of Zr and Hf - group V transition metal - sulfur K-phases was synthesized and crystallographically characterized. When the group V transition metal was Nb or Ta, the unit cell volume was larger than any previously reported K-phase. The presence of adventitious oxygen was determined in two K-phases through a combination of neutron scattering and X-ray diffraction experiments. A compound Hf{sub 10}Ta{sub 3}S{sub 3} was found to crystallize in a new-structure type similar to the known gamma brasses. This structure is unique in that it is the only reported {open_quotes}stuffed{close_quotes} gamma-brass type structure. The metal components, Hf and Ta, are larger in size and more electropositive than the metals found in normal gamma brasses (e.g. Cu and Zn) and because of the larger metallic radii, sulfur can be incorporated into the structure where it plays an integral role in stabilizing this phase relative to others. X-ray single-crystal, X-ray powder and neutron powder refinements were performed on this structure. A new structure was found in the ternary Nb-Zr-P system which has characteristics in common with many known early transition metal-rich sulfides, selenides, and phosphides. This structure has the simplest known interconnection of the basic building blocks known for this structural class. Anomalous scattering was a powerful tool for differentiating between Zr and Nb when using Mo K{alpha} X-radiation. The compounds ZrNbP and HfNbP formed in the space group Prima with the simple Co{sub 2}Si structure which is among the most common structures found for crystalline solid materials. Solid solution compounds in the Ta-Nb-P, Ta-Zr-P, Nb-Zr-P, Hf-Nb-P, and Hf-Zr-S systems were crystallographically characterized. The structural information corroborated ideas about bonding in metal-rich compounds.

  16. 6S RNA regulation of relA alters ppGpp levels in early stationary phase.

    Science.gov (United States)

    Cavanagh, Amy T; Chandrangsu, Pete; Wassarman, Karen M

    2010-12-01

    6S RNA is a small, non-coding RNA that interacts directly with σ(70)-RNA polymerase and regulates transcription at many σ(70)-dependent promoters. Here, we demonstrate that 6S RNA regulates transcription of relA, which encodes a ppGpp synthase. The 6S RNA-dependent regulation of relA expression results in increased ppGpp levels during early stationary phase in cells lacking 6S RNA. These changes in ppGpp levels, although modest, are sufficient to result in altered regulation of transcription from σ(70)-dependent promoters sensitive to ppGpp, including those promoting expression of genes involved in amino acid biosynthesis and rRNA. These data place 6S RNA as another player in maintaining appropriate gene expression as cells transition into stationary phase. Independent of this ppGpp-mediated 6S RNA-dependent regulation, we also demonstrate that in later stationary phase, 6S RNA continues to downregulate transcription in general, and specifically at a subset of the amino acid promoters, but through a mechanism that is independent of ppGpp and which we hypothesize is through direct regulation. In addition, 6S RNA-dependent regulation of σ(S) activity is not mediated through observed changes in ppGpp levels. We suggest a role for 6S RNA in modulating transcription of several global regulators directly, including relA, to downregulate expression of key pathways in response to changing environmental conditions.

  17. 帕金森病运动前期研究进展%Premotor Phase of Early Parkinson Disease (review)

    Institute of Scientific and Technical Information of China (English)

    焦淑军; 袁红

    2011-01-01

    Clinical, neuroimaging, and pathologic studies suggested that a variety of nonmotor symptoms, such as olfactory dysfunction, dysautonomia, and mood and sleep disorders, can precede the typic motor features of Parkinson disease (PD) by years and, perhaps, even decades.The period when these symptoms arise can be referred as the premotor phase of the disease.This paper reviewed the conception, clinical manifestation, pathology, diogose of the premotor phase of early Parkinson disease.%临床症状学及神经影像学、病理学的资料均提示各种帕金森病(PD)非运动症状(NMS),如嗅觉障碍、自主神经机能异常、情感障碍、睡眠紊乱等,先于运动症状出现数年至十数年,这段时期称为运动前期(premotor phase).本文对帕金森病运动前期概念、临床表现、病理基础、诊断的研究进展做一综述.

  18. MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Zivadinov, R.; De Masi, R.; Nasuelli, D.; Monti Bragadin, L.; Cazzato, G.; Zorzon, M. [Neurological Clinic, Cattinara Hospital, Trieste (Italy); Ukmar, M.; Pozzi-Mucelli, R.S. [Dept. of Radiology, University of Trieste (Italy); Grop, A. [Dept. of Electrical, Electronics and Computer Science, University of Trieste (Italy)

    2001-04-01

    Correlation studies between various conventional and non-conventional MRI parameters and cognitive impairment in the early stages of multiple sclerosis (MS) are lacking, although it is known that a number of patients with early MS have mild cognitive impairment. Our aim was to explore whether this cognitive impairment is dependent on the extent and severity of the burden of disease, diffuse microscopic brain damage or both. We studied 63 patients with clinically definite relapsing-remitting (RR) MS, duration of disease 1-10 years and Expanded disability status scale scores {<=} 5.0. Mean age was 35.4 years, mean duration of disease 5.8 years and median EDSS score 1.5. Neuropsychological performance, psychological function, neurological impairment and disability were assessed. The patients also underwent MRI, including magnetisation-transfer (MT) studies. We quantified the lesion load on T2- and T1-weighted images, the magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT) and the brain parenchymal fraction (BPF). No significant difference was found between lesion loads in patients with and without cognitive impairment. In 15 patients (23.8 %) with overall cognitive impairment, median BPF and average NABT MTR were significantly lower than those in patients without cognitive impairment (0.868 vs 0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively). Multiple regression analysis models demonstrated that the only variables independently correlated with cognitive impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R = 0.76, P = 0.012). Our findings support the hypothesis that, cognitive decline in patients with MS, a low disability score and short duration of disease is directly associated with the extent and severity of diffuse brain damage. The loss of brain parenchyma did not correlate with the severity of microscopic damage in the NABT, indicating that the two processes could be distinct in the early stages of the disease. (orig.)

  19. The self-coherent camera-phasing sensor : from numerical simulations to early experiments

    Science.gov (United States)

    Janin-Potiron, P.; Martinez, P.; Baudoz, P.; Carbillet, M.; Gouvret, C.; Spang, A.

    2016-07-01

    Extremely Large Telescopes (ELTs) are the next technological step when considering astrophysical observation. They will provide unprecedented angular resolution, thus improving the imaging capability and hopefully allow the imaging of the first Earth-like exoplanet. For technological and mechanical reasons, the primary mirror of these instruments will have to be segmented. To reach the image quality needed for the most demanding observational programs, the segments must be kept aligned below tens of nm RMS. The development of cophasing technics is of prime importance for the next generation of space- and ground-based segmented telescopes. We propose to describe in this paper a new focal plane cophasing sensor that exploits the scientific image of a coronagraphic instrument to retrieve simultaneously piston and tip-tilt misalignments. It is based on the self- coherent camera (SCC) principle and provides a non-invasive system and an efficient phasing sensor from the image domain. Numerical simulations have successfully demonstrated the proper functioning of this system and its algorithms. Along this, work to implement and test the self-coherent camera - phasing sensor (SCC-PS) is currently ongoing and a first look at the cophasing stage of the Segmented Pupil Experiment for Exoplanet Detection (SPEED) will be proposed.

  20. Toxicities and early outcomes in a phase 1 trial of photodynamic therapy for premalignant and early stage head and neck tumors.

    Science.gov (United States)

    Ahn, Peter H; Quon, Harry; O'Malley, Bert W; Weinstein, Gregory; Chalian, Ara; Malloy, Kelly; Atkins, Joshua H; Sollecito, Thomas; Greenberg, Martin; McNulty, Sally; Lin, Alexander; Zhu, Timothy C; Finlay, Jarod C; Cengel, Keith; Livolsi, Virginia; Feldman, Michael; Mick, Rosemarie; Busch, Theresa M

    2016-04-01

    Management of early superficial lesions in the head and neck remains complex. We performed a phase 1 trial for high-grade premalignant and early superficial lesions of the head and neck using photodynamic therapy (PDT) with Levulan (ALA). Thirty-five subjects with high grade dysplasia, carcinoma in situ, or microinvasive (⩽1.5mm depth) squamous cell carcinoma were enrolled. Cohorts of 3-6 patients were given escalating intraoperative light doses of 50-200J/cm(2) 4-6h after oral administration of 60mg/kg ALA. Light at 629-635nm was delivered in a continuous (unfractionated) or fractionated (two-part) schema. PDT was delivered to 30/35 subjects, with 29 evaluable. There was one death possibly due to the treatment. The regimen was otherwise tolerable, with a 52% rate of grade 3 mucositis which healed within several weeks. Other toxicities were generally grade 1 or 2, including odynophagia (one grade 4), voice alteration (one grade 3), and photosensitivity reactions. One patient developed grade 5 sepsis. With a median follow-up of 42months, 10 patients (34%) developed local recurrence; 4 of these received 50J/cm(2) and two each received 100, 150, and 200J/cm(2). Ten (34%) patients developed recurrence adjacent to the treated field. There was a 69% complete response rate at 3months. ALA-PDT is well tolerated. Maximum Tolerated Dose appears to be higher than the highest dose used in this study. Longer followup is required to analyze effect of light dose on local recurrence. High marginal recurrence rates suggest use of larger treatment fields. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Toxicities and early outcomes in a phase 1 trial of photodynamic therapy for premalignant and early stage head and neck tumors

    Science.gov (United States)

    Ahn, Peter H.; Quon, Harry; O'Malley, Bert W.; Weinstein, Gregory; Chalian, Ara; Malloy, Kelly; Atkins, Joshua H.; Sollecito, Thomas; Greenberg, Martin; McNulty, Sally; Lin, Alexander; Zhu, Timothy C.; Finlay, Jarod C.; Cengel, Keith; Livolsi, Virginia; Feldman, Michael; Mick, Rosemarie; Busch, Theresa M.

    2016-01-01

    SUMMARY Objectives Management of early superficial lesions in the head and neck remains complex. We performed a phase 1 trial for high-grade premalignant and early superficial lesions of the head and neck using photodynamic therapy (PDT) with Levulan (ALA). Materials and methods Thirty-five subjects with high grade dysplasia, carcinoma in situ, or microinvasive (≤1.5 mm depth) squamous cell carcinoma were enrolled. Cohorts of 3–6 patients were given escalating intraoperative light doses of 50–200 J/cm2 4–6 h after oral administration of 60 mg/kg ALA. Light at 629–635 nm was delivered in a continuous (unfractionated) or fractionated (two-part) schema. Results PDT was delivered to 30/35 subjects, with 29 evaluable. There was one death possibly due to the treatment. The regimen was otherwise tolerable, with a 52% rate of grade 3 mucositis which healed within several weeks. Other toxicities were generally grade 1 or 2, including odynophagia (one grade 4), voice alteration (one grade 3), and photosensitivity reactions. One patient developed grade 5 sepsis. With a median follow-up of 42 months, 10 patients (34%) developed local recurrence; 4 of these received 50 J/cm2 and two each received 100, 150, and 200 J/cm2. Ten (34%) patients developed recurrence adjacent to the treated field. There was a 69% complete response rate at 3 months. Conclusions ALA-PDT is well tolerated. Maximum Tolerated Dose appears to be higher than the highest dose used in this study. Longer followup is required to analyze effect of light dose on local recurrence. High marginal recurrence rates suggest use of larger treatment fields. PMID:26865261

  2. Glucose balance and muscle glycogen during TPN in the early post-operative phase

    DEFF Research Database (Denmark)

    Henneberg, S; Stjernström, H; Essén-Gustavsson, B

    1985-01-01

    In order to study how muscle glycogen is influenced by different nutritional regimens in the early post-operative period we took muscle biopsies from 20 patients preoperatively and on the fourth post-operative day after abdominal aortic surgery. Ten patients received 93% of non-protein energy......-production) were performed and from these data glucose balance was calculated as the difference between glucose intake and glucose expenditure. Muscle biopsies were analysed for glycogen, adenosine triphosphate, glucose-6-phosphate, lactate and citrate. We found that it was possible to maintain muscle...... glycogen stores at pre-operative levels with a glucose-insulin regimen. With the fat regimen there was a 31% decrease in muscle glycogen and two patients had a negative glucose balance despite the fact that 150 g of glucose were given. Average glucose balance throughout the study correlated positively...

  3. [Use of pronouns: formal and functional aspects in the early phases of language development].

    Science.gov (United States)

    Reimann, B; Budwig, N

    1992-01-01

    This article presents findings from empirical studies of the development of the use of pronouns in early child language. This presentation includes discussion of 1) when personal, reflexive, possessive, and indefinite pronominal forms appear in child-initiated contexts, 2) which errors emerge, and 3) which communicative functions utterances with pronouns have in dialogue. A first comparison of German-speaking and (American-)English-speaking children's usage is offered, focussing in particular on the use of the pronominal forms I/ich, you/du, and my/mein. This crosslinguistic comparison reveals differences in the age of first use, but simultaneously suggests similarities in functional characteristics of such usage. The findings are discussed in connection with the question of the development of children's communicative competence.

  4. Glucose balance and muscle glycogen during TPN in the early post-operative phase

    DEFF Research Database (Denmark)

    Henneberg, S; Stjernström, H; Essén-Gustavsson, B;

    1985-01-01

    In order to study how muscle glycogen is influenced by different nutritional regimens in the early post-operative period we took muscle biopsies from 20 patients preoperatively and on the fourth post-operative day after abdominal aortic surgery. Ten patients received 93% of non-protein energy...... as glucose, 7% as fat (Intralipid) and insulin was given to keep the blood glucose below 10 mmol/l. The remaining patients had 80% of non-protein energy as fat (Intralipid). Amino acids constituting 12 g of nitrogen daily were given to both groups. Daily measurements of gas exchange (oxygen uptake, CO2...... glycogen stores at pre-operative levels with a glucose-insulin regimen. With the fat regimen there was a 31% decrease in muscle glycogen and two patients had a negative glucose balance despite the fact that 150 g of glucose were given. Average glucose balance throughout the study correlated positively...

  5. Electron-phonon coupling and structural phase transitions in early transition metal oxides and chalcogenides

    Science.gov (United States)

    Farley, Katie Elizabeth

    Pronounced nonlinear variation of electrical transport characteristics as a function of applied voltage, temperature, magnetic field, strain, or photo-excitation is usually underpinned by electronic instabilities that originate from the complex interplay of spin, orbital, and lattice degrees of freedom. This dissertation focuses on two canonical materials that show pronounced discontinuities in their temperature-dependent resistivity as a result of electron---phonon and electron---electron correlations: orthorhombic TaS3 and monoclinic VO2. Strong electron-phonon interactions in transition metal oxides and chalcogenides results in interesting structural and electronic phase transitions. The properties of the material can be changed drastically in response to external stimuli such as temperature, voltage, or light. Understanding the influence these interactions have on the electronic structure and ultimately transport characteristics is of utmost importance in order to take these materials from a fundamental aspect to prospective applications such as low-energy interconnects, steep-slope transistors, and synaptic neural networks. This dissertation describes synthetic routes to nanoscale TaS3 and VO2, develops mechanistic understanding of their electronic instabilities, and in the case of the latter system explores modulation of the electronic and structural phase transition via the incorporation of substitutional dopant atoms. We start in chapter 2 with a detailed study of the synthesis and electronic transport properties of TaS3, which undergoes a Peierls' distortion to form a charge density wave. Scaling this material down to the nanometer-sized regime allows for interrogation of single or discrete phase coherent domains. Using electrical transport and broad band noise measurements, the dynamics of pinning/depinning of the charge density wave is investigated. Chapter 3 provides a novel synthetic approach to produce high-edge-density MoS2 nanorods. MoS2 is a

  6. In vivo intra-luteal implants of prostaglandin (PG) E1 or E2 (PGE1, PGE2) prevent luteolysis in cows. II: mRNA for PGF2α, EP1, EP2, EP3 (A-D), EP3A, EP3B, EP3C, EP3D, and EP4 prostanoid receptors in luteal tissue.

    Science.gov (United States)

    Weems, Yoshie S; Bridges, Phillip J; Jeoung, Myoungkun; Arreguin-Arevalo, J Alejandro; Nett, Torrance M; Vann, Rhonda C; Ford, Stephen P; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2012-01-01

    Previously, it was reported that chronic intra-uterine infusion of PGE(1) or PGE(2) every 4h inhibited luteolysis in ewes by altering luteal mRNA for luteinizing hormone (LH) receptors and unoccupied and occupied luteal LH receptors. However, estradiol-17β or PGE(2) given intra-uterine every 8h did not inhibit luteolysis in cows, but infusion of estradiol+PGE(2) inhibited luteolysis. In contrast, intra-luteal implants containing PGE(1) or PGE(2) in Angus or Brahman cows also inhibited the decline in circulating progesterone, mRNA for LH receptors, and loss of unoccupied and occupied receptors for LH to prevent luteolysis. The objective of this experiment was to determine how intra-luteal implants of PGE(1) or PGE(2) alter mRNA for prostanoid receptors and how this could influence luteolysis in Brahman or Angus cows. On day-13 Angus cows received no intra-luteal implant and corpora lutea were retrieved or Angus and Brahman cows received intra-luteal silastic implants containing Vehicle, PGE(1), or PGE(2) and corpora lutea were retrieved on day-19. Corpora lutea slices were analyzed for mRNA for prostanoid receptors (FP, EP1, EP2, EP3 (A-D), EP3A, EP3B, EP3C, EP3D, and EP4) by RT-PCR. Day-13 Angus cow luteal tissue served as pre-luteolytic controls. mRNA for FP receptors decreased in day-19 Vehicle controls compared to day-13 Vehicle controls regardless of breed. PGE(1) and PGE(2) up-regulated FP gene expression on day-19 compared to day-19 Vehicle controls regardless of breed. EP1 mRNA was not altered by any treatment. PGE(1) and PGE(2) down-regulated EP2 and EP4 mRNA compared to day-19 Vehicle controls regardless of breed. PGE(1) or PGE(2) up-regulated mRNA EP3B receptor subtype compared to day-19 Vehicle control cows regardless of breed. The similarities in relative gene expression profiles induced by PGE(1) and PGE(2) support their agonistic effects. We conclude that both PGE(1) and PGE(2) may prevent luteolysis by altering expression of mRNA for prostanoid

  7. Functional limitations in the phase of clinically suspect arthralgia are as serious as in early clinical arthritis; a longitudinal study.

    Science.gov (United States)

    Ten Brinck, Robin M; van Steenbergen, Hanna W; Mangnus, Lukas; Burgers, Leonie E; Reijnierse, Monique; Huizinga, Tom Wj; van der Helm-van Mil, Annette Hm

    2017-01-01

    A phase of arthralgia may precede the emergence of rheumatoid arthritis (RA). Although several studies have focused on biomarkers, the relevance of this phase for patients is less studied. It is unknown if patients already have functional limitations and if this is correlated to the extent of subclinical inflammation. Therefore, we assessed functional disability in patients with clinically suspect arthralgia (CSA), its association with MRI-detected subclinical inflammation and its course during progression to clinical arthritis. From April 2012 to March 2015, 241 patients had arthralgia for <1 year and were, based on clinical presentation, considered at risk for RA by their rheumatologists. At baseline, Health Assessment Questionnaire (HAQ) scores were determined and unilateral 1.5 T MRI of metacarpophalangeal, wrist and metatarsophalangeal joints were made. Presence of MRI-detected subclinical inflammation was assessed by summing synovitis, tenosynovitis and bone marrow oedema scores (range 0-189). Patients were followed on arthritis development and HAQ scores were repeated when clinical arthritis had developed. The median HAQ score at presentation with CSA was 0.50. Higher MRI-inflammation scores were associated with higher HAQ scores (β=0.017, 95% CI=0.004 to 0.030). During median 103 weeks follow-up, 44 patients progressed to clinical arthritis. HAQ scores ≥1.0 were associated with arthritis development (HR=2.50, 95% CI=1.03 to 6.10). Within converters, median HAQ scores did not increase from presentation with CSA to arthritis development (0.88 and 0.75, p=0.36). HAQ scores ≥1.0 at presentation were associated with the development of clinical arthritis. Functional limitations in the prearthritis phase of CSA were as serious as in the early clinical phase, demonstrating the relevance of CSA from patients' perspectives.

  8. Early treatment with intravenous metoprolol for suspected acute myocardial infarction: a phase IV United States trial. Phase IV Metoprolol in Myocardial Infarction Study Group.

    Science.gov (United States)

    Antman, E M; Dupont, W D; Bonalsky, J; Califf, R M; Corwin, S; Fink, L; Hansen, D E; Kawanishi, D T; Kronenberg, M W; McKay, C R

    1989-05-01

    Recent randomized clinical trials have shown that total mortality and cardiovascular mortality are reduced by the early intravenous administration of beta-blockers to patients suspected of suffering from acute myocardial infarction. These trials were conducted on patients meeting strict entry criteria. In order to assess this therapy when applied to a broader range of myocardial infarction patients, we performed a Phase IV study of metoprolol in acute myocardial infarction. The study was designed to test whether early (less than 8 hours from onset of chest pain) intervention by practicing physicians with open label intravenous metoprolol for cases of suspected acute myocardial infarction achieved mortality results similar to those obtained in large randomized clinical trials. We studied 3824 patients treated by 741 physicians representing a broad spectrum of clinical practice in the United States. Seventy-two percent of the patients entered into the study had confirmed myocardial infarction (39% anterior, 39% inferior, 22% other locations) and 85% of all individuals treated tolerated the full intravenous dose of 15 mg of metoprolol. The 15 day total mortality and cardiovascular mortality rates were 4.9% and 4.5%; 90 day mortality rates were 6.9 and 5.9%. Patients with anterior infarctions had a significantly greater cumulative mortality rate than patients with other types of infarctions. Marked bradycardia (heart rate less than 45 beats per minute) in the first 8 hours post treatment occurred in 4.7% cases and hypotension (systolic blood pressure less than 90 mm Hg) occurred in 9.8% of cases. When compared with the results of the Göteborg and MIAMI trials of metoprolol, it appears that there is no appreciable increase in mortality or morbidity when metoprolol is used in the community practice of acute coronary care.

  9. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

    Science.gov (United States)

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

  10. Practical Guidance for Implementing Predictive Biomarkers into Early Phase Clinical Studies

    Directory of Open Access Journals (Sweden)

    Matthew J. Marton

    2013-01-01

    Full Text Available The recent U.S. Food and Drug Administration (FDA coapprovals of several therapeutic compounds and their companion diagnostic devices (FDA News Release, 2011, 2013 to identify patients who would benefit from treatment have led to considerable interest in incorporating predictive biomarkers in clinical studies. Yet, the translation of predictive biomarkers poses unique technical, logistic, and regulatory challenges that need to be addressed by a multidisciplinary team including discovery scientists, clinicians, biomarker experts, regulatory personnel, and assay developers. These issues can be placed into four broad categories: sample collection, assay validation, sample analysis, and regulatory requirements. In this paper, we provide a primer for drug development teams who are eager to implement a predictive patient segmentation marker into an early clinical trial in a way that facilitates subsequent development of a companion diagnostic. Using examples of nucleic acid-based assays, we briefly review common issues encountered when translating a biomarker to the clinic but focus primarily on key practical issues that should be considered by clinical teams when planning to use a biomarker to balance arms of a study or to determine eligibility for a clinical study.

  11. Stable isotope evidence for an amphibious phase in early proboscidean evolution.

    Science.gov (United States)

    Liu, Alexander G S C; Seiffert, Erik R; Simons, Elwyn L

    2008-04-15

    The order Proboscidea includes extant elephants and their extinct relatives and is closely related to the aquatic sirenians (manatees and dugongs) and terrestrial hyracoids (hyraxes). Some analyses of embryological, morphological, and paleontological data suggest that proboscideans and sirenians shared an aquatic or semiaquatic common ancestor, but independent tests of this hypothesis have proven elusive. Here we test the hypothesis of an aquatic ancestry for advanced proboscideans by measuring delta(18)O in tooth enamel of two late Eocene proboscidean genera, Barytherium and Moeritherium, which are sister taxa of Oligocene-to-Recent proboscideans. The combination of low delta(18)O values and low delta(18)O standard deviations in Barytherium and Moeritherium matches the isotopic pattern seen in aquatic and semiaquatic mammals, and differs from that of terrestrial mammals. delta(13)C values of these early proboscideans suggest that both genera are likely to have consumed freshwater plants, although a component of C(3) terrestrial vegetation cannot be ruled out. The simplest explanation for the combined evidence from isotopes, dental functional morphology, and depositional environments is that Barytherium and Moeritherium were at least semiaquatic and lived in freshwater swamp or riverine environments, where they grazed on freshwater vegetation. These results lend new support to the hypothesis that Oligocene-to-Recent proboscideans are derived from amphibious ancestors.

  12. Local and systemic proteomic changes in medicago truncatula at an early phase of Sinorhizobium meliloti infection.

    Science.gov (United States)

    Molesini, Barbara; Cecconi, Daniela; Pii, Youry; Pandolfini, Tiziana

    2014-02-07

    A symbiotic association with N-fixing bacteria facilitates the growth of leguminous plants under nitrogen-limiting conditions. The establishment of the symbiosis requires signal exchange between the host and the bacterium, which leads to the formation of root nodules, inside which bacteria are hosted. The formation of nodules is controlled through local and systemic mechanisms, which involves root-shoot communication. Our study was aimed at investigating the proteomic changes occurring in shoots and concomitantly in roots of Medicago truncatula at an early stage of Sinorhizobium meliloti infection. The principal systemic effects consisted in alteration of chloroplast proteins, induction of proteins responsive to biotic stress, and changes in proteins involved in hormonal signaling and metabolism. The most relevant local effect was the induction of proteins involved in the utilization of photosynthates and C-consuming processes (such as sucrose synthase and fructose-bisphosphate aldolase). In addition, some redox enzymes such as peroxiredoxin and ascorbate peroxidase showed an altered abundance. The analysis of local and systemic proteome changes suggests the occurrence of a stress response in the shoots and the precocious alteration of energy metabolism in roots and shoots. Furthermore, our data indicate the possibility that ABA and ethylene participate in the communicative network between root and shoot in the control of rhizobial infection.

  13. Early Phases Of Galaxy Assembly Revealed By Young Star-Forming Dwarfs At Z 3

    Science.gov (United States)

    Amorín, Ricardo; VUDS Collaboration

    2017-06-01

    Studying lower-redshift analogs of the first galaxies is essential to scrutinize the details of galaxy formation and cosmic reionization, paving the way for a better interpretation of observations of primeval galaxies with the James Webb Space Telescope. In this talk I will present a thorough study of a recently discovered population of small, sub-L* star-forming galaxies at redshift z 2-4 that exhibit all the rest-frame properties expected for early galaxies in their first epoch of assembling and chemical enrichment. Selected by their strong nebular emission in the UV (including emission lines such as CIII]1908, CIV1550 and OIII]1664) from thousands of galaxies in the VIMOS Ultra Deep Survey, these young low mass systems are extremely metal-deficient galaxies that are likely experiencing their first significant starburst episode. I will discuss their rest-frame properties, hard radiations fields, strong Lyman-alpha emission, HST morphologies and strongly sub-solar chemical abundances. Finally, I will compare their properties with that of galaxies observed at the edge of the reionization epoch, which pose interesting prospects for JWST studies.

  14. A combination treatment of entecavir and early-phase corticosteroid in severe exacerbation of chronic hepatitis B

    Science.gov (United States)

    Matsumoto, Kazuyuki; Miyake, Yasuhiro; Miyatake, Hirokazu; Takahara, Masahiro; Imada, Takayuki; Yagi, Satoru; Toyokawa, Tatsuya; Nakatsu, Morihito; Ando, Masaharu; Hirohata, Mamoru

    2009-01-01

    Of patients with severe exacerbation of chronic hepatitis B accompanied by jaundice and coagulopathy, 20%-30% have a fatal outcome. In this report, we describe 2 cases of severe exacerbation of chronic hepatitis B with jaundice and coagulopathy who were successfully treated with a combination of entecavir and corticosteroid. In both cases, rapid reductions in serum hepatitis B virus (HBV)-DNA levels were observed, and corticosteroid was stopped after serum HBV-DNA levels became undetectable. Entecavir treatment was continued. Generally, entecavir treatment reduced serum HBV-DNA levels rapidly, although the improvement in liver function was delayed by a few weeks. During this time lag, liver cell injury continued and the disease progressed. Corticosteroid suppressed the excessive host immune response and was useful for stopping progressive deterioration. A combination of entecavir and early-phase corticosteroid may be a useful treatment in severe exacerbation of chronic hepatitis B. PMID:19340912

  15. Factors associated with a positive attitude towards change among employees during the early phase of a downsizing process.

    Science.gov (United States)

    Svensen, Erling; Neset, Gunnar; Eriksen, Hege R

    2007-04-01

    Most research on organizational changes in working life, including downsizing, focuses on the negative attitudes and negative consequences of the change. The aim of this study was to evaluate if the employee's previous learning experience and characteristics of the working environment were associated with positive attitudes towards organizational change. The 467 employees (73.5% males) working in a global oil company in the early phases of a downsizing process were asked to answer a questionnaire with demographic variables, perception of the working environment, and attitude to change (93% response rate). Corporate social responsibility (CSR), involvement and participation, team leadership and team effectiveness were important factors related to positive attitudes towards organizational change. Non-leaders and older employees were positive to change. We conclude that employees' perceptions of their psychosocial working environment, in particular the CSR, were highly related to their attitude to organizational change.

  16. [Experience in using xeomin in the treatment of arm and hand spasticity in the early rehabilitation phase of stroke].

    Science.gov (United States)

    Kostenko, E V; Petrova, L V; Ganzhula, P A; Lisenker, L N; Otcheskaia, O V; Khozova, A A; Boĭko, A N

    2012-01-01

    To reduce arm and hand spasticity, 28 patients in the early rehabilitation phase of ischemic hemisphere stroke received injections of the botulinum toxin A preparation xeomin in the content of complex rehabilitation programs. The following muscles: m. biceps brachii, m. flexor digitorum profundus, m. flexor digitorum superficialis, m. flexor carpi ulnaris, m. flexor carpi radialis were injected according to standard scheme. The total dose of drug was 200U in moderate (2-3 scores on the Ashworth scale) and 300U in marked (3-4 scores on the Ashworth scale) spasticity. Efficacy and safety of treatment was assessed at baseline and 2, 4, 8, 12, 16 weeks after injections. Xeomin significantly (prehabilitation efficiency. The treatment with xeomin was safe, no serious side-effects were found.

  17. Activity of toluene-degrading Pseudomonas putida in the early growth phase of a biofilm for waste gas treatment

    DEFF Research Database (Denmark)

    Pedersen, A.R.; Møller, S.; Molin, S.

    1997-01-01

    A biological trickling filter for treatment of toluene-containing waste gas was studied. The overall kinetics of the biofilm growth was followed in the early growth phase. A rapid initial colonization took place during the first three days. The biofilm thickness increased exponentially, whereas...... the increase of active biomass and polymers was linear. In order to investigate the toluene degradation, various toluene degraders from the multispecies biofilm were isolated, and a Pseudomonas putida was chosen as a representative of the toluene-degrading population. A specific rRNA oligonucleotide probe...... was used to follow the toluene-degrading P. putida in the multispecies biofilm in the filter by means of number and cellular rRNA content. P. putida appeared to detach from the biofilm during the first three days of growth, after which P. putida was found at a constant level of 10% of the active biomass...

  18. A combination treatment of entecavir and early-phase corticosteroid in severe exacerbation of chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Kazuyuki Matsumoto; Yasuhiro Miyake; Hirokazu Miyatake; Masahiro Takahara; Takayuki Imada; Satoru Yagi; Tatsuya Toyokawa; Morihito Nakatsu; Masaharu Ando; Mamoru Hirohata

    2009-01-01

    Of patients with severe exacerbation of chronic hepatitis B accompanied by jaundice and coagulopathy, 20%-30% have a fatal outcome. In this report, we describe 2 cases of severe exacerbation of chronic hepatitis B with jaundice and coagulopathy who were successfully treated with a combination of entecavir and corticosteroid. In both cases, rapid reductions in serum hepatitis B virus (HBV)-DNA levels were observed, and corticosteroid was stopped after serum HBV-DNA levels became undetectable. Entecavir treatment was continued. Generally, entecavir treatment reduced serum HBV-DNA levels rapidly, although the improvement in liver function was delayed by a few weeks. During this time lag, liver cell injury continued and the disease progressed. Corticosteroid suppressed the excessive host immune response and was useful for stopping progressive deterioration. A combination of entecavir and early-phase corticosteroid may be a useful treatment in severe exacerbation of chronic hepatitis B.

  19. Survival and progression rates of large European silver eel Anguilla anguilla in late freshwater and early marine phases

    DEFF Research Database (Denmark)

    Aarestrup, Kim; Thorstad, Eva B.; Koed, Anders;

    2010-01-01

    The population of European silver eel Anguilla anguilla has declined tremendously in the last decades. The cause of this decline is unknown, and it is necessary to investigate the migratory behaviour and survival rates of silver eels during the reproductive migration in order to understand...... was high in fresh water. However, 60% of eels were lost in the inner and outer fjord, supporting the hypothesis that mortality is large in the early phase of the marine migration and that fishing may be a major cause of mortality of silver eels. There was no indication that the slowest......-migrating individuals were more prone to fishing mortality than the faster-migrating individuals. Progression rate increased as the eels proceeded downriver and out of the fjord. The migration was predominantly nocturnal, both in the river and fjord. Based on the available evidence, a considerable increase in eel...

  20. Early-phase adaptations to intrahospital training in strength and functional mobility of children with leukemia.

    Science.gov (United States)

    San Juan, Alejandro F; Fleck, Steven J; Chamorro-Viña, Carolina; Maté-Muñoz, José L; Moral, Susana; García-Castro, Javier; Ramírez, Manuel; Madero, Luis; Lucia, Alejandro

    2007-02-01

    Improvements in chemotherapy and radiotherapy have contributed to the high survival rate (approximately 70%) of childhood acute lymphoblastic leukemia (ALL). However, during treatment, lack of physical activity and treatment cause various short- to long-term side effects, such as muscle atrophy and physical deconditioning. The purpose of this study was to determine the effects of an intrahospital, short-duration (8 weeks) exercise training program on muscle strength and endurance and functional mobility of children with ALL. Seven children (4 boys and 3 girls; 4-7 years of age) who were in the maintenance phase of treatment for ALL were selected as subjects. Three training sessions of 90- to 120-minute duration were performed each week. Each session included 11 different strength exercises engaging the major muscle groups and aerobic training. Gains in strength and endurance were assessed with a 6 repetition maximum test for upper (seated bench press and seated lateral row) and lower extremities (leg press). Gains in functional mobility were assessed with the time up and go test (TUG) and the timed up and down stairs test (TUDS). Performance was significantly improved after the training program in all strength tests (p children receiving treatment against ALL (i.e., improved functional mobility and muscle strength). Although more research is needed in the area of exercise training and pediatric cancer, exercise sciences can play a beneficial role in assisting both oncologists in treating cancer and improving children's quality of life during and after treatment.

  1. Operational limits on WEST inertial divertor sector during the early phase experiment

    Science.gov (United States)

    Firdaouss, M.; Corre, Y.; Languille, P.; Greuner, H.; Autissier, E.; Desgranges, C.; Guilhem, D.; Gunn, J. P.; Lipa, M.; Missirlian, M.; Pascal, J.-Y.; Pocheau, C.; Richou, M.; Tsitrone, E.

    2016-02-01

    The primary goal of the WEST project is to be a test bed to characterize the fatigue and lifetime of ITER-like W divertor components subjected to relevant thermal loads. During the first phase of exploitation (S2 2016), these components (W monoblock plasma facing unit—W-PFU) will be installed in conjunction with graphite components (G-PFU). Since the G-PFU will not be actively cooled, it is necessary to ensure the expected pulse duration allows the W-PFU to reach its steady state without overheating the G-PFU assembly structure or the embedded stainless-steel diagnostics. High heat flux tests were performed at the GLADIS facility to assess the thermal behavior of the G-PFU. Some operational limits based on plasma parameters were determined. It was found that it is possible to operate at an injected power such that the maximal incident heat flux on the lower divertor is 10 MW m-2 for the required pulse length.

  2. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    Science.gov (United States)

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (Ppreeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  3. Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

    Directory of Open Access Journals (Sweden)

    Dietlind L. Wahner-Roedler

    2011-01-01

    Full Text Available Most patients with fibromyalgia use complementary and alternative medicine (CAM. Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ and the Center for Epidemiologic Studies Depression Scale (CES-D at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02 and by 18% in the placebo group (P < .001. The difference in change in scores between the groups was not significant (P = .16. With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004 and in the placebo group by 15% (P = .05. The change in scores was similar in the groups (P = .83. Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

  4. Simplified spacecraft vulnerability assessments at component level in early design phase at the European Space Agency's Concurrent Design Facility

    Science.gov (United States)

    Kempf, Scott; Schäfer, Frank K.; Cardone, Tiziana; Ferreira, Ivo; Gerené, Sam; Destefanis, Roberto; Grassi, Lilith

    2016-12-01

    During recent years, the state-of-the-art risk assessment of the threat posed to spacecraft by micrometeoroids and space debris has been expanded to the analysis of failure modes of internal spacecraft components. This method can now be used to perform risk analyses for satellites to assess various failure levels - from failure of specific sub-systems to catastrophic break-up. This new assessment methodology is based on triple-wall ballistic limit equations (BLEs), specifically the Schäfer-Ryan-Lambert (SRL) BLE, which is applicable for describing failure threshold levels for satellite components following a hypervelocity impact. The methodology is implemented in the form of the software tool Particle Impact Risk and vulnerability Analysis Tool (PIRAT). During a recent European Space Agency (ESA) funded study, the PIRAT functionality was expanded in order to provide an interface to ESA's Concurrent Design Facility (CDF). The additions include a geometry importer and an OCDT (Open Concurrent Design Tool) interface. The new interface provides both the expanded geometrical flexibility, which is provided by external computer aided design (CAD) modelling, and an ease of import of existing data without the need for extensive preparation of the model. The reduced effort required to perform vulnerability analyses makes it feasible for application during early design phase, at which point modifications to satellite design can be undertaken with relatively little extra effort. The integration of PIRAT in the CDF represents the first time that vulnerability analyses can be performed in-session in ESA's CDF and the first time that comprehensive vulnerability studies can be applied cost-effectively in early design phase in general.

  5. Does radiation prevent 5-fluorouracil-induced colitis in the early phase of radiochemotherapy? A case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Rischke, H.C.; Momm, F.; Henke, M.; Frommhold, H. [University Hospital Freiburg (Germany). Dept. of Radiotherapy; Wiech, T. [University Hospital Freiburg (Germany). Dept. of General Pathology and Pathologic Anatomy

    2007-08-15

    Case Report: A 43-year-old man with T3 N2 M0 adenocarcinoma of the lower rectum was admitted for preoperative radiochemotherapy (RCT). Daily fractions of 1.8 Gy (planned total dose: 50.4 Gy) and concomitant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, and mitomycin C (MMC) were administered. On day 10, the patient developed abdominal pain and massive diarrhea. Computed tomography, endoscopy, histopathologic and serologic tests revealed severe colitis confined to the upper abdomen and most probably related to 5-FU. Unexpectedly, the bowel inflammation was restricted to areas not irradiated. 4 months later, during the course of disease, relapse with pulmonary metastases occurred. A palliative chemotherapy with 5-FU, oxaliplatin, and leucovorin was started. Again, the patient suffered from severe diarrhea and dose reduction was necessary. Discussion: It was speculated that in the early phase of RCT the well-known anti-inflammatory nature of low-dose radiation prevented exacerbation of colitis. To the authors' knowledge, this observation has not been published before. With respect to the current literature and the clinical findings it is discussed that both increased leukocyte/endothelial cell adhesion and altered release of reactive oxygen species or inducible nitric oxide synthase (iNOS) may play a role in 5-FU-induced colitis. Conclusion: This observation led to the hypothesis that the anti-inflammatory effect of low-dose irradiation may attenuate 5-FU-induced colitis in the very early phase of RCT. It appears worthwhile to separate side effects of RCT into radiation- and chemotherapy-induced effects, which requires a detailed diagnostic work-up. This differentiation has an impact on planning individual therapy: the authors did not saw conclusive evidence of an increased radiosensitivity but chemosensitivity in their patient and therefore continued radiotherapy. This assumption was confirmed when the patient received palliative 5-FU

  6. Effects of type I collagen degradation on the durability of three adhesive systems in the early phase of dentin bonding.

    Directory of Open Access Journals (Sweden)

    Lin Hu

    Full Text Available This study was designed to evaluate the effects of type I collagen degradation on the durability of three adhesive systems in the early phase of dentin bonding.Bonded dentin specimens were prepared using three different types of adhesive systems. Micro-tensile bond strength and degradation of collagen were tested before, and after 1 month or 4 months of aging in artificial saliva. The relationship between micro-tensile bond strength and collagen degradation was analyzed by calculating their Pearson's correlation coefficient.Aging induced time-dependent reduction in micro-tensile bond strengths for all the tested adhesive systems, although such reduction for the single-step self-etching adhesive G-Bond (GB was not statistically significant. The bond strength of the two-step self-etching primer adhesive system Clearfil SE Bond (SEB was similar to that of the two-step etch-and-rinse self-priming adhesive system Single Bond 2 (SB, and they were both significantly reduced after one or four months of aging. A negative correlation was found between the degree of collagen degradation and magnitude of micro-tensile bond strength (r = -0.65, p = 0.003. The Pearson's correlation coefficient was 0.426, indicating that 42.6% of the aging-induced reduction in bond strength can be explained by the degradation of collagen.In the early phase of dentin bonding, there was a negative correlation between the degree of collagen degradation and the magnitude of micro-tensile bond strength. The reduction of bond strength was accompanied by the degradation of collagen. These results provide evidence for the causative relationship between the degradation of collagen and the deterioration of dentin-adhesive interface.

  7. Granulocytic Myeloid-Derived Suppressor Cells Increased in Early Phases of Primary HIV Infection Depending on TRAIL Plasma Level.

    Science.gov (United States)

    Tumino, Nicola; Bilotta, Maria T; Pinnetti, Carmela; Ammassari, Adriana; Antinori, Andrea; Turchi, Federica; Agrati, Chiara; Casetti, Rita; Bordoni, Veronica; Cimini, Eleonora; Abbate, Isabella; Capobianchi, Maria R; Martini, Federico; Sacchi, Alessandra

    2017-04-15

    It has been demonstrated that myeloid-derived suppressor cells (MDSC) are expanded in HIV-1-infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study, we evaluated the frequency of MDSC in patients during primary HIV infection (PHI) and factors involved in MDSC control. Patients with PHI and chronic HIV infection (CHI) were enrolled. PHI staging was performed according to Fiebig classification, and circulating MDSC frequency and function were evaluated by flow cytometry. Cytokine levels were evaluated by Luminex technology. We found that granulocytic MDSC (Gr-MDSC) frequency was higher in patients with PHI compared with healthy donors, but lower than that in patients with CHI. Interestingly, Gr-MDSC expansion was observed in the early phases of HIV infection (Fiebig II/III), but it was not associated with HIV viral load and CD4 T-cell count. Interestingly, in PHI, Gr-MDSC frequency was inversely correlated with plasmatic level of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), although a direct correlation was observed in CHI. Furthermore, lower level of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) was observed in PHI compared with that in CHI. In vitro experiments demonstrated that, differently from CHI, recombinant TRAIL-induced apoptosis of Gr-MDSC from PHI, an effect that can be abrogated by GM-CSF. We found that Gr-MDSC are expanded early during PHI and may be regulated by TRAIL and GM-CSF levels. These findings shed light on the fine mechanisms regulating the immune system during HIV infection and open new perspectives for immune-based strategies.

  8. Main corrective measures in an early phase of nuclear power plants’ preparation for safe long term operation

    Energy Technology Data Exchange (ETDEWEB)

    Krivanek, Robert, E-mail: r.krivanek@iaea.org [International Atomic Energy Agency (IAEA), Department of Nuclear Safety and Security, Operational Safety Section, Vienna 1400 (Austria); Fiedler, Jan, E-mail: fiedler@fme.vutbr.cz [University of Technology Brno, Faculty of Mechanical Engineering, Energy Institute, Technická 2896/2, 616 69 Brno (Czech Republic)

    2017-05-15

    Highlights: • Results of SALTO missions provide the most important issues for safe long term operation (LTO) of nuclear power plants. • The most important technical corrective measures in an early phase of preparation for safe LTO are described. • Their satisfactory resolution creates a basis for further activities to demonstrate preparedness for safe LTO. - Abstract: This paper presents the analysis of main technical deficiencies of nuclear power plants (NPPs) in preparedness for safe long term operation (LTO) and the main corrective measures in an early phase of preparation for safe LTO of NPPs. It focuses on technical aspects connected with management of physical ageing of NPP structures, systems and components (SSCs). It uses as a basis results of IAEA SALTO missions performed between 2005 and 2016 (see also paper NED8805 in Nuclear Engineering and Design in May 2016) and the personal experiences of the authors with preparation of NPPs for safe LTO. This paper does not discuss other important aspects of safe LTO of NPPs, e.g. national nuclear energy policies, compliance of NPPs with the latest international requirements on design, obsolescence, environmental impact and economic aspects of LTO. Chapter 1 provides a brief introduction of the current status of the NPP’ fleet in connection with LTO. Chapter 2 provides an overview of SALTO peer review service results with a focus on deficiencies related to physical ageing of safety SSCs and a demonstration that SSCs will perform their safety function during the intended period of LTO. Chapter 3 discusses the main corrective measures which NPPs typically face during the preparation for demonstration of safe LTO. Chapter 4 summarizes the current status of the NPP’ fleet in connection with LTO and outlines further steps needed in preparation for safe LTO.

  9. Global Warming Potential from early phase decomposition of soil organic matter amendments

    Science.gov (United States)

    Mayer, A.; Silver, W. L.

    2015-12-01

    Organic matter amendments to soil are widely used as a method of enhancing nutrient availability for crops or grassland. Amendments such as composted manure or greenwaste also have the co-benefits of potentially increasing soil carbon (C) stocks (DeLonge et al., 2013) and diverting organic waste from landfills or manure lagoons. However, application of organic matter amendments can also stimulate emissions of greenhouse gases (GHGs). In this study we determined how the chemical quality of organic matter amendments affected soil C and N content and GHG emissions during early stage decomposition. California grassland soils were amended with six different amendments of varying C and N content including three composts and three feedstocks (goat and horse bedding and cattle manure). Amendments and soils were incubated in the laboratory for 7 weeks; GHG fluxes were measured weekly. The three feedstocks emitted significantly more GHGs than the composted materials. With the exception of cow manure, N content of the amendment was linearly correlated with global warming potential emitted (R2= 0.66, P mineral soil, as expected. However, greenwaste compost also surprisingly resulted in net C losses, while goat bedding, horse bedding, and the other compost were either C neutral or a slight net C sink at the end of the incubation. Ongoing analyses are examining the fate of the C incorporated from the amendment to the soil as occluded or free light fraction, as well as N mineralization rates. Our data suggest that N content of organic matter amendments is a good predictor of initial GHG emissions. The study also indicates that composting greenwaste with N-rich bedding and manure can result in lower GHG emissions and C sequestration compared to the individual uncomposted components.

  10. Early phase tendon transfers in radial and ulnar nerve injuries: internal splinting

    Directory of Open Access Journals (Sweden)

    Nilgün Markal Ertaş

    2010-06-01

    Full Text Available Objectives: Internal splinting is defined as early tendon transfer performed during or just after nerve repair followingnerve injury and is a controversial issue. The objectivesof internal splinting are avoiding the use of long term external splinting, avoiding permanent hand deformities until the injured nerve is reinnervated and supporting sensorial recovery. In this paper we present our clinical cases of internal splinting and discuss the results in terms of indications, timing, advantages, and disadvantages of internal splinting.Materials and Methods: We applied internal splinting in 11 patients, 3 patients with radial nerve injury and 8 patients with ulnar nerve injury. Internal splinting was performed contemporarily with the nerve repair in 5 patients,in 2 weeks following nerve repair in 1 patient and in 4 weeks following nerve repair in 5 patients. Pronator teres was transferred to extensor carpi radialis brevis and flexor carpi radialis was transferred to extensor digitorum communis in radial nerve injuries. Omer’s superficial Y technique and its modification were used for ulnar nerve injuries.Results: Patients were followed up for at least 1 year with physical examination and electroneuromyelography and recovery of sensorial and motor functions were achieved in all of them.Conclusion: We concluded that internal splinting is usefulfor avoiding external splint usage and preventing the establishment of hand deformity until recovery of the nerve. The contribution of internal splinting to sensorial recovery was noteworthy as stated in the literature but the lack of control group and the small number of our cases was limited to come to a definite conclusion. We did not experience any disadvantage of internal splinting.

  11. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

    Science.gov (United States)

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2014-12-01

    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P Brahman cows when compared w Day-13 or Day-19 Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P Brahman cows when compared with Day-19 Brahman controls. ANG-2 was increased (P 0.05) of PGE1 or PGE2 on ANG-2 in Brahman cows. PGE1 or PGE2 may alter cow luteal FGF-2, ANG-1, or ANG-2 but not VEGF to prevent luteolysis; however, species or breed differences may exist. Published by Elsevier Inc.

  12. Early-phase photometry and spectroscopy of transitional Type Ia SN 2012ht: Direct constraint on the rise time

    CERN Document Server

    Yamanaka, Masayuki; Kawabata, Miho; Tanaka, Masaomi; Takaki, Katsutoshi; Ueno, Issei; Masumoto, Kazunari; Kawabata, Koji S; Itoh, Ryosuke; Moritani, Yuki; Akitaya, Hiroshi; Arai, Akira; Honda, Satoshi; Nishiyama, Koichi; Kabashima, Fumio; Matsumoto, Katsura; Nogami, Daisaku; Yoshida, Michitoshi

    2014-01-01

    We report photometric and spectroscopic observations of the nearby Type Ia Supernova (SN Ia) 2012ht from $-15.8$ days to $+49.1$ days after $B$-band maximum. The decline rate of the light curve is $\\Delta m_{15}$($B$)$=1.39~\\pm~0.05$ mag, which is intermediate between normal and subluminous SNe Ia, and similar to that of the `transitional' Type Ia SN 2004eo. The spectral line profiles also closely resemble those of SN 2004eo. We were able to observe SN 2012ht at very early phase, when it was still rising and was about three magnitudes fainter than at the peak. The rise time to the $B$-band maximum is estimated to be $17.6 \\pm 0.5$ days and the time of the explosion is MJD $56277.98 \\pm 0.13$. SN 2012ht is the first transitional SN Ia whose rise time is directly measured without using light curve templates, and the fifth SN Ia overall. This rise time is consistent with those of the other four SNe within the measurement error, even including the extremely early detection of SN 2013dy. The rising part of the lig...

  13. Tracking the distribution of $^{26}$Al and $^{60}$Fe during the early phases of star and disk evolution

    CERN Document Server

    Kuffmeier, Michael; Haugboelle, Troels; Bizzarro, Martin; Nordlund, Aake

    2016-01-01

    The short-lived $^{26}$Al and $^{60}$Fe radionuclides are synthesized and expelled in the interstellar medium by core-collapse supernova events. The solar system's first solids, calcium-aluminium refractory inclusions (CAIs), contain evidence for the former presence of the $^{26}$ Al nuclide defining the canonical $^{26}$Al/$^{27}$ Al ratio of $\\sim5 \\times10^{-5}$. A different class of objects temporally related to canonical CAIs are CAIs with fractionation and unidentified nuclear effects (FUN CAIs), which record a low initial $^{26}$Al/$^{27}$Al of $10^{-6}$. The contrasting level of $^{26}$Al between these objects is often interpreted as reflecting the admixing of the $^{26}$Al nuclide during the early formative phase of the Sun. We use giant molecular cloud (GMC) scale adaptive mesh-refinement numerical simulations to trace the abundance of $^{26}$Al and $^{60}$Fe in star-forming gas during the early stages of accretion of individual low mass protostars. We find that the $^{26}$Al/$^{27}$Al and $^{60}$Fe...

  14. IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection.

    Directory of Open Access Journals (Sweden)

    Andreas Grahnert

    Full Text Available Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised people. Previously we showed that mice succumb to intranasal infection by induction of pulmonary interleukin (IL-4Rα-dependent type 2 immune responses, whereas IL-12-dependent type 1 responses confer resistance. In the experiments presented here, IL-4Rα⁻/⁻ mice unexpectedly show decreased fungal control early upon infection with C. neoformans, whereas wild-type mice are able to control fungal growth accompanied by enhanced macrophage and dendritic cell recruitment to the site of infection. Lower pulmonary recruitment of macrophages and dendritic cells in IL-4Rα⁻/⁻ mice is associated with reduced pulmonary expression of CCL2 and CCL20 chemokines. Moreover, IFN-γ and nitric oxide production are diminished in IL-4Rα⁻/⁻ mice compared to wild-type mice. To directly study the potential mechanism(s responsible for reduced production of IFN-γ, conventional dendritic cells were stimulated with C. neoformans in the presence of IL-4 which results in increased IL-12 production and reduced IL-10 production. Together, a beneficial role of early IL-4Rα signaling is demonstrated in pulmonary cryptococcosis, which contrasts with the well-known IL-4Rα-mediated detrimental effects in the late phase.

  15. Kadar dan Daya Luteolitik PGF2? Produksi Sel Monolayer Vesikula Seminalis dan Endometrium Sapi Bali (PROSTAGLANDIN F2? CONCENTRATIONS OF BALI CATTLE ENDOMETRIAL AND SEMINAL VESICLE MONOLAYER CELLS CULTURE PRODUCTS AND ITS IN VITRO TEST ON LUTEAL MONOLAYER

    National Research Council Canada - National Science Library

    Tjok Gde Oka Pemayun; I Gusti Ngurah Bagus Trilaksana; Laba Mahaputra

    2012-01-01

    The aims of this research were to determine PGF2? concentration the produced by bali cattlesendometrial and seminal vesicle monolayer cell culture and in vitro luteolytic ability on luteal monolayercell culture...

  16. An association between low-dose hyper-radiosensitivity and the early G2-phase checkpoint in normal fibroblasts of cancer patients.

    Science.gov (United States)

    Słonina, Dorota; Gasińska, Anna; Biesaga, Beata; Janecka, Anna; Kabat, Damian

    2016-03-01

    In our previous study, low-dose hyper-radiosensitivity (HRS) effect was demonstrated for normal fibroblasts (asynchronous and G2-phase enriched) of 4 of the 25 cancer patients investigated. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, the study indicated that G2-phase enrichment had no influence on HRS identification. The conclusion contradicts that reported for human tumor cells, and suggests different mechanism of HRS in normal human cells. In the present paper we report, for the first time, the activity of early G2-phase checkpoint after low-dose irradiation in normal fibroblasts of these 4 HRS-positive patients and 4 HRS-negative patients and answer the question regarding the role of this checkpoint in normal human cells. The response of the early G2-phase checkpoint was determined by assessment of the progression of irradiated cells into mitosis using the mitotic marker, phosphorylated histone H3. We found evident differences in the activity of the early G2-phase checkpoint between HRS-positive and HRS-negative fibroblasts. In HRS-positive fibroblasts the checkpoint was not triggered and DNA damage was not recognized after doses lower than 0.2Gy resulting in HRS response. On the contrary, in HRS-negative fibroblasts the early G2-phase checkpoint was activated regardless of the dose in the range 0.1-2Gy. In conclusion, although cell cycle phase has no effect on the presence of HRS effect in normal human fibroblasts, the data reported here indicate that HRS response in these cells is associated with the functioning of early G2-phase checkpoint in a threshold-dose dependent manner, similarly as it takes place in most of human tumor and other cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Contralateral limb deficit after ACL-reconstruction: an analysis of early and late phase of rate of force development.

    Science.gov (United States)

    Mirkov, Dragan M; Knezevic, Olivera M; Maffiuletti, Nicola A; Kadija, Marko; Nedeljkovic, Aleksandar; Jaric, Slobodan

    2017-03-01

    The aim of this study was to assess the effect of a unilateral anterior cruciate ligament reconstruction (ACLR) on maximum voluntary contraction (MVC) and explosive strength of both the involved limb and the uninvolved limb. Nineteen male athletes completed a standard isometric testing protocol 4 months post-ACLR, while 16 healthy participants served as a control group (CG). The explosive strength of the knee extensors and flexors was assessed as RFD obtained from the slope of the force-time curves over various time intervals. Both muscle groups of the involved limb had significantly lower MVC compared to the uninvolved. The involved limb also had significantly lower RFD in the late phase of contraction (140-250 ms) for both knee extensors and flexors (P < 0.05). There was no difference in MVC between the uninvolved limb and the CG. However, RFD of the uninvolved limb was lower compared to CG for both knee extensors (0-180 ms; P < 0.01) and flexors (0-150 ms; P < 0.05). ACLR leads to lower MVC and explosive strength of the involved limb. As a consequence of potential crossover (presumably neural-mediated) effects, explosive strength deficits could be bilateral, particularly in the early phase of the contraction (<100 ms).

  18. Early Phase Detection and Coverage of Extragalactic and Galactic Black Hole X-ray Transients with the SKA

    CERN Document Server

    Yu, Wenfei; Yan, Zhen; Zhang, Wenda

    2015-01-01

    SKA's large field of view and high sensitivity at low frequencies will provide almost a complete coverage of the very early rising phase of extragalactic and Galactic transients which undergo a flare or outburst due to an abrupt accretion onto either supermassive (such as tidal disruption events, TDEs) or stellar mass black hole transients (such as black hole LMXB) , when their broadband emission is supposed to be jet-dominated at low luminosities, allowing SKA to be the first facility to make source discoveries and to send out alerts for follow-up ground or space observations as compared with the sensitivity of future X-ray wide-field-view monitoring. On the other hand, due to extremely large rate-of-change in the mass accretion rate during the rising phase of TDE flares or transient outbursts, SKA will be able to cover an extremely large range of the mass accretion rate as well as its rate-of-change not accessible with observations in persistent black hole systems, which will shape our understanding of disk...

  19. Bridging the Faraoni and Selli oceanic anoxic events: late Hauterivian to early Aptian dysaerobic to anaerobic phases in the Tethys

    Directory of Open Access Journals (Sweden)

    K. B. Föllmi

    2012-01-01

    Full Text Available A detailed geochemical analysis was performed on the upper part of the Maiolica Formation in the Breggia (southern Switzerland and Capriolo sections (northern Italy. The analysed sediments consist of well-bedded, partly siliceous, pelagic carbonate, which lodges numerous thin, dark and organic-rich layers. Stable-isotope, phosphorus, organic-carbon and a suite of redox-sensitive trace-element contents (RSTE: Mo, U, Co, V and As were measured. The RSTE pattern and Corg:Ptot ratios indicate that most organic-rich layers were deposited under dysaerobic rather than anaerobic conditions and that latter conditions were likely restricted to short intervals in the latest Hauterivian, the early Barremian and the pre-Selli early Aptian.

    Correlations are both possible with organic-rich intervals in central Italy (the Gorgo a Cerbara section and the Boreal Lower Saxony Basin, as well as with the facies and drowning pattern in the Helvetic segment of the northern Tethyan carbonate platform. Our data and correlations suggest that the latest Hauterivian witnessed the progressive installation of dysaerobic conditions in the Tethys, which went along with the onset in sediment condensation, phosphogenesis and platform drowning on the northern Tethyan margin, and which culminated in the Faraoni anoxic episode. This episode is followed by further episodes of dysaerobic conditions in the Tethys and the Lower Saxony Basin, which became more frequent and progressively stronger in the late early Barremian. Platform drowning persisted and did not halt before the latest early Barremian. The late Barremian witnessed diminishing frequencies and intensities in dysaerobic conditions, which went along with the progressive installation of the Urgonian carbonate platform. Near the Barremian-Aptian boundary, the increasing density in dysaerobic episodes in the Tethyan and Lower Saxony Basins is paralleled by a change towards heterozoan carbonate

  20. A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection

    DEFF Research Database (Denmark)

    Bergh, Christina; Lindenberg, Svend; Skouby, Sven Olaf

    2012-01-01

    SUMMARY QUESTION: Is vaginal progesterone gel equivalent to vaginal micronized progesterone tablets concerning ongoing pregnancy rate and superior concerning patient convenience when used for luteal support after IVF/ICSI? SUMMARY ANSWER: Equivalence of treatments in terms of ongoing live...... intrauterine pregnancy rate has not been demonstrated; the 95% confidence interval (CI) for the difference in ongoing pregnancy rate (-8.2 to 0.1%) did not lie entirely within the pre-specified equivalence interval -7 to 7%. WHAT IS KNOWN ALREADY: No significant differences in clinical pregnancy rates have....... PARTICIPANTS AND SETTING: A total of 2057 women ≤ 40 years of age were included and down-regulated, using the long agonist protocol and rFSH for stimulation. Luteal support was given for 19 days after embryo transfer or until a negative pregnancy test Day 14 after embryo transfer. Patient convenience...

  1. Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells.

    Science.gov (United States)

    Liu, Jianqi; Kuulasmaa, Tiina; Kosma, Veli-Matti; Bützow, Ralf; Vänttinen, Teemu; Hydén-Granskog, Christel; Voutilainen, Raimo

    2003-10-01

    Activins and inhibins are often antagonistic in the regulation of ovarian function. TGFbeta type III receptor, betaglycan, has been identified as a coreceptor to enhance the binding of inhibins to activin type II receptor and thus to prevent the binding of activins to their receptor. In this study we characterized the expression and regulation pattern of betaglycan gene in normal ovaries and sex cord-stromal tumors and in cultured human granulosa-luteal cells from women undergoing in vitro fertilization. Expression of betaglycan mRNA was detected by RT-PCR or Northern blotting in normal ovarian granulosa, thecal, and stroma cells as well as in granulosa-luteal cells. Immunohistochemical analysis revealed positive staining for betaglycan in antral and preovulatory follicular granulosa and thecal cells and in corpora lutea of normal ovaries. Furthermore, betaglycan expression was detected in the vast majority of granulosa cell tumors, thecomas, and fibromas, with weaker staining in granulosa cell tumors compared with fibrothecomas. In cultured granulosa-luteal cells, FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA, as did the protein kinase A activator dibutyryl cAMP and the protein kinase C inhibitor staurosporine. In contrast, the protein kinase C activator 12-O-tetradecanoyl phorbol 13-acetate had no significant effect on betaglycan mRNA levels. Treatment with prostaglandin E(2) and with its receptor EP2 subtype agonist butaprost increased betaglycan mRNA accumulation and progesterone secretion dose- and time-dependently. In summary, betaglycan gene is expressed in normal human ovarian steroidogenic cells and sex cord-stromal ovarian tumors. The accumulation of its mRNA in cultured granulosa-luteal cells is up-regulated by gonadotropins and prostaglandin E(2), probably via the protein kinase A pathway. The specific expression and regulation pattern of betaglycan gene may be related to the functional antagonism of inhibins to

  2. The accelerating effect of chitosan-silica hybrid dressing materials on the early phase of wound healing.

    Science.gov (United States)

    Park, Ji-Ung; Jung, Hyun-Do; Song, Eun-Ho; Choi, Tae-Hyun; Kim, Hyoun-Ee; Song, Juha; Kim, Sukwha

    2017-10-01

    Commercialized dressing materials with or without silver have played a passive role in early-phase wound healing, protecting the skin defects from infections, absorbing exudate, and preventing dehydration. Chitosan (CTS)-based sponges have been developed in pure or hybrid forms for accelerating wound healing, but their wound-healing capabilities have not been extensively compared with widely used commercial dressing materials, providing limited information in a practical aspect. In this study, we have developed CTS-silica (CTS-Si) hybrid sponges with water absorption, flexibility, and mechanical behavior similar to those of CTS sponges. In vitro and in vivo tests were performed to compare the CTS-Si sponges with three commercial dressing materials [gauze, polyurethane (PU), and silver-containing hydrofiber (HF-Ag)] in addition to CTS sponges. Both in vitro and in vivo tests showed that CTS-Si sponges promoted fibroblast proliferation, leading to accelerated collagen synthesis, whereas the CTS sponges did not exhibit significant differences in fibroblast proliferation and collagen synthesis from gauze, PU, and HF-Ag sponges. In case of CTS-Si, the inflammatory cells were actively recruited to the wound by the influence of the released silicon ions from CTS-Si sponges, which, in return, led to an enhanced secretion of growth factors, particularly TGF-β during the early stage. The higher level of TGF-β likely improved the proliferation of fibroblasts, and as a result, collagen synthesis by fibroblasts became remarkably productive, thereby increasing collagen density at the wound site. Therefore, the CTS-Si hybrid sponges have considerable potential as a wound-dressing material for accelerating wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1828-1839, 2017. © 2016 Wiley Periodicals, Inc.

  3. EARLY-PHASE PHOTOMETRY AND SPECTROSCOPY OF TRANSITIONAL TYPE Ia SN 2012ht: DIRECT CONSTRAINT ON THE RISE TIME

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, Masayuki; Nogami, Daisaku [Kwasan Observatory, Kyoto University, 17-1 Kitakazan-ohmine-cho, Yamashina-ku, Kyoto 607-8471 (Japan); Maeda, Keiichi [Department of Astronomy, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kawabata, Miho; Masumoto, Kazunari; Matsumoto, Katsura [Astronomical Institute, Osaka Kyoiku University, Asahigaoka, Kashiwara, Osaka 582-8582 (Japan); Tanaka, Masaomi [National Astronomical Observatory of Japan, Osawa, Mitaka, Tokyo 181-8588 (Japan); Takaki, Katsutoshi; Ueno, Issei; Itoh, Ryosuke [Department of Physical Science, Hiroshima University, Kagamiyama 1-3-1, Higashi-Hiroshima 739-8526 (Japan); Kawabata, Koji S.; Moritani, Yuki; Akitaya, Hiroshi; Yoshida, Michitoshi [Hiroshima Astrophysical Science Center, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526 (Japan); Arai, Akira; Honda, Satoshi [Center for Astronomy, University of Hyogo, 407-2 Nishigaichi, Sayo-cho, Sayo, Hyogo 679-5313 (Japan); Nishiyama, Koichi [Kurume, Fukuoka-ken (Japan); Kabashima, Fujio, E-mail: yamanaka@kwasan.kyoto-u.ac.jp [Miyaki-cho, Saga-ken (Japan)

    2014-02-20

    We report photometric and spectroscopic observations of the nearby Type Ia Supernova (SN Ia) 2012ht from –15.8 days to +49.1 days after B-band maximum. The decline rate of the light curve is Δm {sub 15}(B) = 1.39 ± 0.05 mag, which is intermediate between normal and subluminous SNe Ia, and similar to that of the ''transitional'' Type Ia SN 2004eo. The spectral line profiles also closely resemble those of SN 2004eo. We were able to observe SN 2012ht at a very early phase, when it was still rising and was about three magnitudes fainter than at the peak. The rise time to the B-band maximum is estimated to be 17.6 ± 0.5 days and the time of the explosion is MJD 56277.98 ± 0.13. SN 2012ht is the first transitional SN Ia whose rise time is directly measured without using light curve templates, and the fifth SN Ia overall. This rise time is consistent with those of the other four SNe within the measurement error, even including the extremely early detection of SN 2013dy. The rising part of the light curve can be fitted by a quadratic function, and shows no sign of a shock-heating component due to the interaction of the ejecta with a companion star. The rise time is significantly longer than that inferred for subluminous SNe such as SN 1991bg, which suggests that a progenitor and/or explosion mechanism of transitional SNe Ia are more similar to normal SNe Ia rather than to subluminous SNe Ia.

  4. Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance.

    Science.gov (United States)

    Nakano, Takashi; Okumura, Akihisa; Tanabe, Takuya; Niwa, Shimpei; Fukushima, Masato; Yonemochi, Rie; Eda, Hisano; Tsutsumi, Hiroyuki

    2013-06-01

    Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir early, based on post-marketing experiences. Spontaneous safety reports collected in the early post-marketing phase vigilance were analyzed. Adverse events of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious events were intensively reviewed by the Safety Evaluation Committee. Abnormal behavior/delirium was a frequently reported event. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.

  5. Changes in diurnal rhythms of free cortisol secretion during different phases of menstrual cycle%月经周期不同阶段游离皮质醇昼夜节律的变化

    Institute of Scientific and Technical Information of China (English)

    包爱民; 刘荣玉; Eus J.W.Van Someren; Michel A.Hofman; 周江宁

    2003-01-01

    The effect of the menstrual cycle on the diurnal cortisol rhythm was investigated in 15 normally cyclic healthy women during reproductive life. Salivary cortisol was measured by radioimmunoassay in samples collected every 2 h for 24 h during the four phases of the menstrual cycle: menstrual phase, late follicular/peri-ovulation phase, early to mid luteal phase and late luteal phase, respectively. Distinct diurnal rhythms of free cortisol were found throughout the menstrual cycle by using a nonlinear periodic regression model. The model was characterized by an asymmetrically peaked diurnal cycle and ultradian harmonics. There was a trend to higher troughs and significantly shorter peak-width in phase Ⅱ and phase Ⅳ compared to phase Ⅰ . The ultradian amplitude in phase Ⅳ was significantly lower compared with phase I and showed a trend of decrease compared with phase Ⅱ. The results suggest that the daily cortisol secretion is modulated by the phase of the menstrual cycle.%为了研究皮质醇分泌的昼夜节律在月经周期中的变化,实验对15位月经周期正常的育龄期健康妇女,在月经周期的不同阶段分别于24 h内每隔两小时采样,检测唾液昼夜游离皮质醇水平.采用非线性回归分析模型分析皮质醇昼夜节律.结果显示,皮质醇昼夜节律在整个月经周期都具有复杂的明显受到亚节律(ultradian)影响的分泌形式;与月经期相比,围排卵期和黄体晚期昼夜节律波峰宽度(peak-width)明显减低(P=0.005与0.031),而昼夜节律波谷(trough)有抬高趋势(P=0.0622与0.066);黄体晚期的亚节律波幅(ultradian amplitude)与月经期相比显著减低(P=0.002)而与围排卵期相比有减低趋势(P=0.05).这些结果提示月经周期的不同阶段对皮质醇分泌的昼夜节律有影响.

  6. Analyses of the pathways involved in early- and late-phase induction of IFN-beta during C. muridarum infection of oviduct epithelial cells.

    Directory of Open Access Journals (Sweden)

    Sishun Hu

    Full Text Available We previously reported that the IFN-β secreted by Chlamydia muridarum-infected murine oviduct epithelial cells (OE cells was mostly dependent on the TLR3 signaling pathway. To further characterize the mechanisms of IFN-β synthesis during Chlamydia infection of OE cells in vitro, we utilized specific inhibitory drugs to clarify the roles of IRF3 and NF-κB on both early- and late-phase C. muridarum infections. Our results showed that the pathways involved in the early-phase of IFN-β production were distinct from that in the late-phase of IFN-β production. Disruption of IRF3 activation using an inhibitor of TBK-1 at early-phase Chlamydia infection had a significant impact on the overall synthesis of IFN-β; however, disruption of IRF3 activation at late times during infection had no effect. Interestingly, inhibition of NF-κB early during Chlamydia infection also had a negative effect on IFN-β production; however, its impact was not significant. Our data show that the transcription factor IRF7 was induced late during Chlamydia infection, which is indicative of a positive feedback mechanism of IFN-β synthesis late during infection. In contrast, IRF7 appears to play little or no role in the early synthesis of IFN-β during Chlamydia infection. Finally, we demonstrate that antibiotics that target chlamydial DNA replication are much more effective at reducing IFN-β synthesis during infection versus antibiotics that target chlamydial transcription. These results provide evidence that early- and late-phase IFN-β production have distinct signaling pathways in Chlamydia-infected OE cells, and suggest that Chlamydia DNA replication might provide a link to the currently unknown chlamydial PAMP for TLR3.

  7. Differential modulation of motor cortical plasticity and excitability in early and late phases of human motor learning.

    Science.gov (United States)

    Rosenkranz, Karin; Kacar, Aleksandra; Rothwell, John C

    2007-10-31

    Different phases of motor skill learning appear to involve different physiological processes, with long-term potentiation (LTP) occurring at existing synapses in early and cortical reorganization involving synaptogenesis in later phases. Here, we test the evolution of skill learning-dependent changes in motor plasticity and excitability in six subjects trained to perform rapid thumb abductions over 5 d. Plasticity was examined using paired-associative stimulation (PAS) of the median nerve and motor cortex to induce LTP-like "PAS given with an interstimulus interval of 25 ms (PAS25)" or long-term depression (LTD)-like "PAS given with an interstimulus interval of 10 ms (PAS10)" plasticity. Excitability was tested by measuring recruitment of motor-evoked-potentials "input-output (IO) curve" and of short-latency intracortical inhibition (SICI curve), and sensorimotor organization (SMO). Task performance improved continuously over 5 d. After practice on day 1, the PAS25 effect reversed from facilitation to inhibition whereas the slope of the IO curve increased and the level of SICI decreased. These effects on IO curve and SICI were still present or even enhanced before the last practice on day 5, and were not changed by it. The effect of proprioceptive input from the trained muscle on SMO was also strengthened before practice on day 5. In contrast, PAS-induced plasticity was not influenced by motor practice on day 5, and had returned to prepractice values. The interference with PAS-induced plasticity suggests that the initial performance improvement relies on increasing the efficacy of existing synaptic connections. However, the long-lasting changes in the IO curve, SICI curve, and SMO suggest that continued practice enhances performance by changing Motor cortical organization. We hypothesize that new synaptic connections might have formed that allow LTP/LTD-susceptibility to be restored without reducing synaptic strength and performance skill.

  8. OBJECTIVE EVALUATION OF CARDIAC AUTONOMIC ACTIVITY IN DIFFERENT PHASES OF MENSTRUAL CYCLE

    Directory of Open Access Journals (Sweden)

    Srujana

    2015-01-01

    Full Text Available A wide spectrum of biological function is regulated by the cyclic changes in estrogen and progesterone levels during regular menstrual cycle. However limited literature is available concerning the relationship of these hormones and cardiac autonomic activity. In the present study, we hypothesize that there would be heart rate variability during different phases of menstrual cycle, which can be attributed to the effect of ovarian steroids on cardiovascular function in women. The aim of the study is to compare the c ardiac autonomic activity in the different phases of menstrual cycle ( M enstrual, follicular and luteal phases using heart rate variability. The objective is to establish a physiological correlation between the cardiac autonomic activity and different phas es of menstrual cycle. The study was conducted in 48 regularly menstruating young female, of age group 18 - 30yrs, in the Upgraded Department of Physiology, Osmania medical college, from December 2011 to August 2013, using LABCHART software provided by ADLAB S. The power spectral analysis of HRV was used to calculate low frequency(LF , high frequency (HF component and their ratio (LF/HF during menstrual (2±1 days, follicular(11±1 day and luteal phases (20±1day from the first day of bleeding. Results showe d a significant increase was noted in low frequency component in luteal phase compared to follicular phase (p=0.000, whereas, a tendency for increase in high frequency component was observed in follicular phase (p=0.004. Furthermore, LF/HF was significan tly higher in luteal phase than in the follicular phase (p=0.000 indicating an increased sympathetic activity. The conclusion is regulation of autonomic tone is modified during menstrual cycle. The alteration in the balance of ovarian hormones might be re sponsible for these changes.

  9. Multi-Dimensional Simulations for Early Phase Spectra of Aspherical Hypernovae: SN 1998bw and Off-Axis Hypernovae

    CERN Document Server

    Tanaka, Masaomi; Mazzali, Paolo A; Nomoto, Ken'ichi

    2007-01-01

    Early phase optical spectra of aspherical jet-like supernovae (SNe) are presented. We focus on energetic core-collapse SNe, or hypernovae. Based on hydrodynamic and nucleosynthetic models, radiative transfer in SN atmosphere is solved with a multi-dimensional Monte-Carlo radiative transfer code, SAMURAI. Since the luminosity is boosted in the jet direction, the temperature there is higher than in the equatorial plane by ~ 2,000 K. This causes anisotropic ionization in the ejecta. Emergent spectra are different depending on viewing angle, reflecting both aspherical abundance distribution and anisotropic ionization. Spectra computed with an aspherical explosion model with kinetic energy 20 x 10^{51} ergs are compatible with those of the Type Ic SN 1998bw if ~ 10-20% of the synthesized metals are mixed out to higher velocities. The simulations enable us to predict the properties of off-axis hypernovae. Even if an aspherical hypernova explosion is observed from the side, it should show hypernova-like spectra but ...

  10. An investigation of low ergonomics risk awareness, among staffs at early product development phase in Malaysia automotive industries

    Science.gov (United States)

    Aziz, Fazilah Abdul; Razali, Noraini; Najmiyah Jaafar, Nur

    2016-02-01

    Currently there are many automotive companies still unable to effectively prevent consequences of poor ergonomics in their manufacturing processes. This study purpose is to determine the surrounding factors that influence low ergonomics risk awareness among staffs at early product development phase in Malaysia automotive industry. In this study there are four variables, low ergonomic risk awareness, inappropriate method and tools, tight development schedule and lack of management support. The survey data were gathered from 245 respondents of local automotive companies in Malaysia. The data was analysed through multiple regression and moderated regression using the IBM SPSS software. Study results revealed that low ergonomic risk awareness has influenced by inappropriate method and tool, and tight development schedule. There were positive linear relationships between low ergonomic risk awareness and inappropriate method and tools, and tight development schedule. The more inappropriate method and tools applied; the lower their ergonomic risk awareness. The more tight development schedule is the lower ergonomic risk awareness. The relationship between low ergonomic risk awareness and inappropriate method and tools depends on staff's age, and education level. Furthermore the relationship between low ergonomic risk awareness and tight development schedule depends on staff's working experience and number of project involvement. The main contribution of this paper was identified the number of factors of low ergonomics risk awareness and offers better understanding on ergonomics among researchers and automotive manufacturer's employees during product development process.

  11. Trace elements in early phase type 2 diabetes mellitus-A population-based study. The HUNT study in Norway.

    Science.gov (United States)

    Hansen, Ailin Falkmo; Simić, Anica; Åsvold, Bjørn Olav; Romundstad, Pål Richard; Midthjell, Kristian; Syversen, Tore; Flaten, Trond Peder

    2017-03-01

    Differences in trace elements levels between individuals with type 2 diabetes and controls have been reported in several studies in various body fluids and tissues, but results have been inconsistent. In order to examine trace element levels in the early phase of type 2 diabetes, we investigated the association between whole blood levels of 26 trace elements and the prevalence of previously undiagnosed, screening-detected type 2 diabetes. The study was conducted as a case-control study nested within the third survey of the population-based Nord-Trøndelag Health Study (HUNT3 Survey). Among participants without previously known diabetes, 128 cases of type 2 diabetes were diagnosed in people with a high diabetes risk score (FINDRISC≥15), and frequency-matched for age and sex with 755 controls. Blood samples were analyzed by high resolution inductively coupled plasma mass spectrometry. Associations between trace element levels and the prevalence of previously undiagnosed type 2 diabetes were evaluated with multivariable conditional logistic regression controlling for age, sex, body mass index, waist-to-hip ratio, education, income, smoking and family history of diabetes. The prevalence of previously undiagnosed type 2 diabetes increased across tertiles/quartiles for cadmium, chromium, iron, nickel, silver and zinc, and decreased with increasing quartiles of bromine (Ptrendzinc in the development of type 2 diabetes.

  12. The Silicon and Calcium High-Velocity Features in Type Ia Supernovae from Early to Maximum Phases

    CERN Document Server

    Zhao, Xulin; Maeda, Keiichi; Sai, Hanna; Zhang, Tianmeng; Zhang, Jujia; Huang, Fang; Rui, Liming; Zhou, Qi; Mo, Jun

    2015-01-01

    The high-velocity features (HVFs) in optical spectra of type Ia supernovae (SNe Ia) are examined with a large sample including very early-time spectra (e.g., t < -7 days). Multiple Gaussian fits are applied to examine the HVFs and their evolutions, using constraints on expansion velocities for the same species (i.e., SiII 5972 and SiII 6355). We find that strong HVFs tend to appear in SNe Ia with smaller decline rates (e.g., dm15(B)<1.4 mag), clarifying that the finding by Childress et al. (2014) for the Ca-HVFs in near-maximum-light spectra applies both to the Si-HVFs and Ca-HVFs in the earlier phase. The Si-HVFs seem to be more common in fast-expanding SNe Ia, which is different from the earlier result that the Ca-HVFs are associated with SNe Ia having slower SiII 6355 velocities at maximum light (i.e., Vsi). This difference can be due to that the HVFs in fast-expanding SNe Ia usually disappear more rapidly and are easily blended with the photospheric components when approaching the maximum light. Mor...

  13. Enzymatic characterization of germination-specific cysteine protease-1 expressed transiently in cotyledons during the early phase of germination.

    Science.gov (United States)

    Tsuji, Akihiko; Tsukamoto, Kana; Iwamoto, Keiko; Ito, Yuka; Yuasa, Keizo

    2013-01-01

    Papain-like cysteine protease activity that shows a unique transient expression profile in cotyledons of daikon radish during germination was detected. The enzyme showed a distinct elution pattern on DEAE-cellulose compared with cathepsin B-like and Responsive to dessication-21 cysteine protease. Although this activity was not detected in seed prior to imbibition, the activity increased markedly and reached a maximum at 2 days after imbibition and then decreased rapidly and completely disappeared after 5 days. Using cystatin-Sepharose, the 26 kDa cysteine protease (DRCP26) was isolated from cotyledons at 2 days after imbibition. The deduced amino acid sequence from the cDNA nucleotide sequence indicated that DRCP26 is an orthologue of Arabidopsis unidentified protein, germination-specific cysteine protease-1, belonging to the C1 family of cysteine protease predicted from genetic information. In an effort to characterize the enzymatic properties of DRCP26, the enzyme was purified to homogeneity from cotyledons at 48 h after imbibition. The best synthetic substrate for the enzyme was carbobenzoxy-Phe-Arg-4-methylcoumaryl-7-amide. All model peptides were digested to small peptides by the enzyme, suggesting that DRCP26 possesses broad cleavage specificity. These results indicated that DRCP26 plays a role in the mobilization of storage proteins in the early phase of seed germination.

  14. GIGANTEA and EARLY FLOWERING 4 in Arabidopsis Exhibit Differential Phase-Specific Genetic Influences over a Diurnal Cycle

    Institute of Scientific and Technical Information of China (English)

    Yumi Kim; Miji Yeom; Hyunmin Kim; Junhyun Lim; HeeJung Koo; Daehee Hwang; David Somers; Hong Gil Nam

    2012-01-01

    The endogenous circadian clock regulates many physiological processes related to plant survival and adaptability.GIGANTEA (GI),a clock-associated protein,contributes to the maintenance of circadian period length and amplitude,and also regulates flowering time and hypocotyl growth in response to day length.Similarly,EARLY FLOWERING 4 (ELF4),another clock regulator,also contributes to these processes.However,little is known about either the genetic or molecular interactions between GI and ELF4 in Arabidopsis.In this study,we investigated the genetic interactions between GI and ELF4 in the regulation of circadian clock-controlled outputs.Our mutant analysis shows that GI is epistatic to ELF4 in flowering time determination,while ELF4 is epistatic to GI in hypocotyl growth regulation.Moreover,GI and ELF4 have a synergistic or additive effect on endogenous clock regulation.Gene expression profiling of gi,elf4,and gi elf4 mutants further established that Gland ELF4 have differentially dominant influences on circadian physiological outputs at dusk and dawn,respectively.This phasing of GI and ELF4 influences provides a potential means to achieve diversity in the regulation of circadian physiological outputs,including flowering time and hypocotyl growth.

  15. Psychotropic and Anticonvulsant Drug Usage in Early Childhood Special Education Programs I. Phase One: A Preliminary Report: Prevalence, Attitude, Training, and Problems.

    Science.gov (United States)

    Gadow, Kenneth D.

    As part of a three phase study designed to survey the teachers and parents of children receiving psychotropic and anticonvulsant drugs, 208 teachers of preschool special education children on medication were mailed questionnaires. The Early Childhood Medication Questionnaire used in the survey included items relating to teacher, program, and…

  16. Properties and geoeffectiveness of magnetic clouds in the rising, maximum and early declining phases of solar cycle 23

    Directory of Open Access Journals (Sweden)

    K. E. J. Huttunen

    2005-02-01

    Full Text Available The magnetic structure and geomagnetic response of 73 magnetic clouds (MC observed by the WIND and ACE satellites in solar cycle 23 are examined. The results have been compared with the surveys from the previous solar cycles. The preselected candidate MC events were investigated using the minimum variance analysis to determine if they have a flux-rope structure and to obtain the estimation for the axial orientation (θC, φC. Depending on the calculated inclination relative to the ecliptic we divided MCs into "bipolar" (θC<45° and "unipolar" (θC>45°. The number of observed MCs was largest in the early rising phase, although the halo CME rate was still low. It is likely that near solar maximum we did not identify all MCs at 1AU, as they were crossed far from the axis or they had interacted strongly with the ambient solar wind or with other CMEs. The occurrence rate of MCs at 1AU is also modified by the migration of the filament sites on the Sun towards the poles near solar maximum and by the deflection of CMEs towards the equator due to the fast solar wind flow from large polar coronal holes near solar minimum. In the rising phase nearly all bipolar MCs were associated with the rotation of the magnetic field from the south at the leading edge to the north at the trailing edge. The results for solar cycles 21-22 showed that the direction of the magnetic field in the leading portion of the MC starts to reverse at solar maximum. At solar maximum and in the declining phase (2000-2003 we observed several MCs with the rotation from the north to the south. We observed unipolar (i.e. highly inclined MCs frequently during the whole investigated period. For solar cycles 21-22 the majority of MCs identified in the rising phase were bipolar while in the declining phase most MCs were unipolar. The geomagnetic response of a given MC depends greatly on its magnetic structure and the orientation of the sheath

  17. A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vasculitis: a histological study

    Science.gov (United States)

    Vinen, Catherine S; Turner, David R; Oliveira, David B G

    2004-01-01

    Administration of mercuric chloride (HgCl2) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl2 and then spontaneously resolve. If animals are re-challenged with HgCl2 6 weeks after initial exposure, they are resistant to autoimmunity, developing only attenuated disease. Recently, a separate phase of early caecal vasculitis was described beginning 24 h after initiating HgCl2 and prior to caecal entry of T cells. Previous work suggested this early vasculitis was αβ T-cell independent and implied a role for mast cells. We further tested this hypothesis by performing a histological study during the first 93 h following HgCl2 challenge defining the precise relationship between gut mast cell degranulation and appearing caecal vasculitis. We also studied whether early caecal vasculitis enters a resistant phase upon re-challenge with HgCl2. We show a direct correlation between mast cell degranulation and early caecal vasculitis following initial HgCl2 challenge. We demonstrate resistance to re-challenge in this phase of injury, with results at re-challenge also showing a correlation between mast cell degranulation and early caecal injury. PMID:15255970

  18. Effect of synchronization of donor cells in early G1-phase using shake-off method on developmental potential of somatic cell nuclear transfer embryos in cattle.

    Science.gov (United States)

    Goto, Yuji; Hirayama, Muneyuki; Takeda, Kazuya; Tukamoto, Nobuyuki; Sakata, Osamu; Kaeriyama, Hiroshi; Geshi, Masaya

    2013-08-01

    In this study, we compared the developmental ability of somatic cell nuclear transfer (SCNT) embryos reconstructed with three bovine somatic cells that had been synchronized in G0-phase (G0-SCNT group) or early G1-phase (eG1-SCNT group). Furthermore, we investigated the production efficiency of cloned offspring for NT embryos derived from these donor cells. The G0-phase and eG1-phase cells were synchronized, respectively, using serum starvation and antimitotic reagent treatment combined with shaking of the plate containing the cells (shake-off method). The fusion rate in the G0-SCNT groups (64.2 ± 1.8%) was significantly higher than that of eG1-SCNT groups (39.2 ± 1.9%) (P cells in eG1-phase using the shake-off method improved the overall production efficiency of the clone offspring per transferred embryo.

  19. Migration as a turning point in food habits: the early phase of dietary acculturation among women from South Asian, African, and Middle Eastern Countries living in Norway.

    Science.gov (United States)

    Terragni, Laura; Garnweidner, Lisa M; Pettersen, Kjell Sverre; Mosdøl, Annhild

    2014-01-01

    This article explores the early phase of dietary acculturation after migration. South Asian, African and Middle Eastern women (N = 21) living in Norway were interviewed about their early experiences with food in a new context. The findings pointed to abrupt changes in food habits in the first period after migration. To various degrees, women reported unfamiliarity with foods in shops, uncertainty about meal formats and food preparation and fear of eating food prohibited by their religion. Their food consumption tended to be restricted to food items perceived as familiar or safe. Our findings indicate that the first period after migration represents a specific phase in the process of dietary acculturation. Early initiatives aimed at enhancing confidence in food and familiarity with the new food culture are recommended.

  20. Phase evolution during early stages of mechanical alloying of Cu–13 wt.% Al powder mixtures in a high-energy ball mill

    Energy Technology Data Exchange (ETDEWEB)

    Dudina, Dina V.; Lomovsky, Oleg I. [Institute of Solid State Chemistry and Mechanochemistry SB RAS, Kutateladze str. 18, Novosibirsk 630128 (Russian Federation); Valeev, Konstantin R.; Tikhov, Serguey F.; Boldyreva, Natalya N. [Boreskov Institute of Catalysis SB RAS, pr. Lavrentieva 5, Novosibirsk 630090 (Russian Federation); Salanov, Aleksey N.; Cherepanova, Svetlana V.; Zaikovskii, Vladimir I. [Boreskov Institute of Catalysis SB RAS, pr. Lavrentieva 5, Novosibirsk 630090 (Russian Federation); Novosibirsk State University (NSU), Pirogova str. 2, Novosibirsk 630090 (Russian Federation); Andreev, Andrey S. [Boreskov Institute of Catalysis SB RAS, pr. Lavrentieva 5, Novosibirsk 630090 (Russian Federation); Novosibirsk State University (NSU), Pirogova str. 2, Novosibirsk 630090 (Russian Federation); Soft Matter Sciences and Engineering Laboratory, UMR 7615 CNRS UPMC, ESPCI ParisTech, 10 rue Vauquelin, Paris 75005 (France); Lapina, Olga B.; Sadykov, Vladislav A. [Boreskov Institute of Catalysis SB RAS, pr. Lavrentieva 5, Novosibirsk 630090 (Russian Federation); Novosibirsk State University (NSU), Pirogova str. 2, Novosibirsk 630090 (Russian Federation)

    2015-04-25

    Highlights: • Phase formation during early stages of Cu–Al mechanical alloying was studied. • The products of mechanical alloying are of highly non-equilibrium character. • X-ray amorphous phases are present in the products of mechanical alloying. • An Al-rich X-ray amorphous phase is distributed between the crystallites. - Abstract: We report the phase and microstructure evolution of the Cu–13 wt.% Al mixture during treatment in a high-energy planetary ball mill with a particular focus on the early stages of mechanical alloying. Several characterization techniques, including X-ray diffraction phase analysis, nuclear magnetic resonance spectroscopy, differential dissolution, thermal analysis, and electron microscopy/elemental analysis, have been combined to study the evolution of the phase composition of the mechanically alloyed powders and describe the microstructure of the multi-phase products of mechanical alloying at different length scales. The following reaction sequence has been confirmed: Cu + Al → CuAl{sub 2}(+Cu) → Cu{sub 9}Al{sub 4} + (Cu) → Cu(Al). The phase evolution was accompanied by the microstructure changes, the layered structure of the powder agglomerates disappearing with milling time. This scheme is further complicated by the processes of copper oxidation, reduction of copper oxides by metallic aluminum, and by variation of the stoichiometry of Cu(Al) solid solutions with milling time. Substantial amounts of X-ray amorphous phases were detected as well. Differential dissolution technique has revealed that a high content of aluminum in the Cu(Al) solid solution-based powders is due to the presence of Al-rich phases distributed between the Cu(Al) crystallites.

  1. 78 FR 73555 - Deepwater Horizon Oil Spill; Draft Programmatic and Phase III Early Restoration Plan and Draft...

    Science.gov (United States)

    2013-12-06

    ... Environmental Impact Statement (Draft Phase III ERP/PEIS). The Draft Phase III ERP/PEIS considers programmatic... programmatic restoration alternatives. The Draft Phase III ERP/PEIS evaluates these restoration alternatives... the Framework Agreement. The Draft Phase III ERP/PEIS also evaluates the environmental consequences...

  2. [Combined cataract-glaucoma surgery with deep sclerectomy. An alternative to gonio-trephination in the intra- and early postoperative phases].

    Science.gov (United States)

    Mohr, A; Rais, M; Eckardt, C

    2001-03-01

    We examined the value of deep sclerectomy combined with phacoemulsification as a surgical technique in the peri- and postoperative phases. Deep sclerectomy with phacoemulsification was carried out in 18 patients. Mean postoperative follow-up was 7.5 weeks. Deep sclerectomy was more difficult to perform than goniotrephination. We observed neither fibrin reaction nor hypotonic dysregulation (intraocular pressure, IOP, < 8 mmHg). Five patients required additional pressure-lowering drugs during postoperative IOP regulation. We consider the low inflammatory response in the early postoperative phase to outweigh the greater surgical difficulty and prolonged surgery time. Further studies must verify whether higher IOP during the early postoperative phase is sufficient for good long-term IOP regulation.

  3. Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

    Science.gov (United States)

    Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

    2017-02-01

    Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD.

  4. Differential expression profiles of Streptococcus mutans ftf, gtf and vicR genes in the presence of dietary carbohydrates at early and late exponential growth phases.

    Science.gov (United States)

    Shemesh, Moshe; Tam, Avshalom; Feldman, Mark; Steinberg, Doron

    2006-09-04

    Dental caries is one of the most common infectious diseases that affects humans. Streptococcus mutans, the main pathogenic bacterium associated with dental caries, produces a number of extracellular sucrose-metabolizing enzymes, such as glucosyltransferases (GTFB, GTFC and GTFD) and fructosyltransferase (FTF). The cooperative action of these enzymes is essential for sucrose-dependent cellular adhesion and biofilm formation. A global response regulator (vicR) plays important roles in S. mutans ftf and gtf expression in response to a variety of stimuli. A real-time reverse-transcription polymerase chain-reaction was used to quantify the relative levels of ftf, gtfB, gtfC, gtfD and vicR transcription of S. mutans in the presence of various dietary carbohydrates: sucrose, D-glucose, D-fructose, D-glucitol (D-sorbitol), D-mannitol and xylitol. Ftf was highly expressed at late exponential phase in the presence of sorbitol and mannitol. GtfB was highly expressed in the presence of all the above carbohydrates except for xylitol at early exponential growth phase and glucose and fructose at late exponential growth phase. Similar to gtfB, the expression of gtfC was also induced with the presence of all the tested carbohydrates except for xylitol at early growth and glucose and fructose at late exponential phase. In addition, no effect of mannitol on gtfC expression at early exponential phase was observed. GtfD was less influenced compared to the gtfB and gtfC, demonstrating enhanced expression especially in the presence of sorbitol, glucose, mannitol and xylitol at early exponential phase and mannitol at late exponential phase. VicR expression was induced only at the presence of xylitol at late exponential phase, and a decrease in expression was recorded at early exponential phase. Our findings show that dietary carbohydrates have a major influence on the transcription of ftf, gtfB, gtfC and gtfD, but less on vicR. Sorbitol and mannitol, which are considered as noncariogenic

  5. Dynamical mechanisms of phase-2 early afterdepolarizations in human ventricular myocytes: insights from bifurcation analyses of two mathematical models.

    Science.gov (United States)

    Kurata, Yasutaka; Tsumoto, Kunichika; Hayashi, Kenshi; Hisatome, Ichiro; Tanida, Mamoru; Kuda, Yuhichi; Shibamoto, Toshishige

    2017-01-01

    Early afterdepolarization (EAD) is known as a cause of ventricular arrhythmias in long QT syndromes. We theoretically investigated how the rapid (IKr) and slow (IKs) components of delayed-rectifier K(+) channel currents, L-type Ca(2+) channel current (ICaL), Na(+)/Ca(2+) exchanger current (INCX), Na(+)-K(+) pump current (INaK), intracellular Ca(2+) (Cai) handling via sarcoplasmic reticulum (SR), and intracellular Na(+) concentration (Nai) contribute to initiation, termination, and modulation of phase-2 EADs, using two human ventricular myocyte models. Bifurcation structures of dynamical behaviors in model cells were explored by calculating equilibrium points, limit cycles (LCs), and bifurcation points as functions of parameters. EADs were reproduced by numerical simulations. The results are summarized as follows: 1) decreasing IKs and/or IKr or increasing ICaL led to EAD generation, to which mid-myocardial cell models were especially susceptible; the parameter regions of EADs overlapped the regions of stable LCs. 2) Two types of EADs (termination mechanisms), IKs activation-dependent and ICaL inactivation-dependent EADs, were detected; IKs was not necessarily required for EAD formation. 3) Inhibiting INCX suppressed EADs via facilitating Ca(2+)-dependent ICaL inactivation. 4) Cai dynamics (SR Ca(2+) handling) and Nai strongly affected bifurcations and EAD generation in model cells via modulating ICaL, INCX, and INaK Parameter regions of EADs, often overlapping those of stable LCs, shifted depending on Cai and Nai in stationary and dynamic states. 5) Bradycardia-related induction of EADs was mainly due to decreases in Nai at lower pacing rates. This study demonstrates that bifurcation analysis allows us to understand the dynamical mechanisms of EAD formation more profoundly.

  6. An interesterified palm olein test meal decreases early-phase postprandial lipemia compared to palm olein: a randomized controlled trial.

    Science.gov (United States)

    Hall, Wendy L; Brito, Marcela Fiuza; Huang, Junlan; Wood, Lucy V; Filippou, Androulla; Sanders, Thomas A B; Berry, Sarah E E

    2014-09-01

    Palm oil that has been interesterified to produce a higher proportion of palmitic acid (16:0) in the sn-2 position reduces postprandial lipemia in young, normolipidemic men and women, but effects in older subjects with higher fasting triacylglycerol (TAG) concentrations are unknown. We tested the hypothesis that high-fat meals rich in interesterified palm olein (IPO) decrease lipemia and alter plasma lipoprotein fraction composition compared to native palm olein (NPO) in men aged 40-70 years with fasting TAG concentrations ≥1.2 mmol/L. Postprandial changes in plasma lipids following meals containing 75 g fat (NPO and IPO) were compared using a randomized, double-blind crossover design (n = 11). Although there were no significant differences in plasma TAG concentrations between meals over the total 6-h postprandial measurement period, IPO resulted in a decreased plasma TAG response during the first 4 h of the postprandial period (iAUC 1.65 mmol/L h, 95% CI 1.01-2.29) compared to NPO (iAUC 2.33 mmol/L h, 95% CI 1.58-3.07); meal effect P = 0.024. Chylomicron fraction TAG concentrations at 4-6 h were slightly reduced following IPO compared to NPO [NPO-IPO mean difference 0.29 mmol/L (95% CI -0.01-0.59), P = 0.055]. There were no differences in IDL fraction TAG, cholesterol or apolipoprotein B48 concentrations following IPO compared with NPO. In conclusion, consuming a meal containing palm olein with a higher proportion of 16:0 in the sn-2 position decreases postprandial lipemia compared to native palm olein during the early phase of the postprandial period in men with higher than optimal fasting triacylglycerol concentrations.

  7. Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

    Science.gov (United States)

    Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N

    2017-07-03

    Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

  8. GnRHa trigger for final oocyte maturation: is HCG trigger history?

    DEFF Research Database (Denmark)

    Humaidan, Peter; Alsbjerg, Birgit

    2014-01-01

    gonadotrophin (HCG) trigger. Early trials showed a severe luteal phase insufficiency after GnRHa trigger despite the application of standard luteal phase support protocols. Subsequent research has led to modifications of the luteal phase support, resulting in reproductive outcome comparable to that seen after...... HCG trigger in normal- and high-responders. GnRHa trigger facilitates a tailored approach to subsequent luteal phase support, taking into account the ovarian response to stimulation. In the future, GnRHa is likely to be used for trigger in all women co-treated with GnRH antagonists....

  9. Slit2/Robo4 Signaling: Potential Role of a VEGF-Antagonist Pathway to Regulate Luteal Permeability

    Science.gov (United States)

    Bekes, I.; Haunerdinger, V.; Sauter, R.; Holzheu, I.; Janni, W.; Wöckel, A.; Wulff, C.

    2017-01-01

    Introduction The corpus luteum (CL) is dependent on luteal vascular permeability, which is controlled by human chorionic gonadotropin (hCG) via vascular endothelial growth factor (VEGF). In this study we investigated the role of a potential VEGF antagonist pathway – Slit2/Robo4 – and its influence on endothelial cell adhesion. Materials and Methods Luteinized granulosa cells (LGCs) were stimulated with hCG in the absence or presence of a VEGF inhibitor. The expression of VEGF and Slit2 were measured. Human umbilical vein endothelial cells (HUVECs) were stimulated with Slit2 or VEGF, and gene expressions of cadherin 5 (CDH5) and claudin 5 (CLDN5) were measured. Following Robo4 knockdown, CDH5, CLDN5 and endothelial permeability were measured. Results Stimulation of human LGCs with hCG significantly increased VEGF while Slit2 expression was significantly suppressed. Inhibition of VEGF action after hCG stimulation did not change Slit2 suppression. Slit2 knockdown did not affect VEGF expression. While VEGF stimulation of HUVECs significantly suppressed CDH5 and CLDN5 gene expression, stimulation of HUVECs with Slit2 resulted in a significant increase in CDH5 and CLDN5. Robo4 knockdown was done, leading to downregulation of CDH5 and CLDN5 which resulted in significantly increased permeability. Conclusions Our results indicate the existence of a VEGF-antagonist pathway in the CL that decreases vascular permeability. During the functional life of the CL the pathway is suppressed by hCG. It is possible that stimulation of this pathway could be used to treat ovarian hyperstimulation syndrome. PMID:28190892

  10. Prostaglandin F2 alpha stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells

    Energy Technology Data Exchange (ETDEWEB)

    Davis, J.S.; Weakland, L.L.; Weiland, D.A.; Farese, R.V.; West, L.A.

    1987-06-01

    The present studies were conducted to determine whether prostaglandin F2 alpha (PGF2 alpha) stimulates the production of ''second messengers'' derived from inositol phospholipid hydrolysis and increases intracellular free Ca2+ ((Ca2+)i) in isolated bovine luteal cells. PGF2 alpha provoked rapid (10 sec) and sustained (up to 60 min) increases in the levels of inositol mono-, bis-, and trisphosphates (InsP, InsP2, and InsP3, respectively). InsP3 was formed more rapidly than InsP2 or InsP after PGF2 alpha treatment. In addition, PGF2 alpha increased inositol phospholipid turnover, as evidenced by increased /sup 32/PO/sub 4/ incorporation into phosphatidic acid and phosphatidylinositol. LiCl (1-20 mM) enhanced inositol phosphate accumulation in response to PGF2 alpha. Maximal increases in InsP3 occurred at 1 microM PGF2 alpha, with half-maximal stimulation occurring at 36 nM. The acute effects of PGF2 alpha on InsP3 levels were independent of reductions in extracellular calcium. Prostaglandins E1 and E2 also stimulated increases in inositol phosphate levels, albeit to a lesser extent. PGF2 alpha also induced rapid and concentration-dependent increases in (Ca2+)i as measured by quin-2 fluorescence. The PGF2 alpha-induced increases in (Ca2+)i were maximal within 30 sec (approximately 2- to 3-fold), and (Ca2+)i remained elevated for 8-10 min. The PGF2 alpha-induced increases in (Ca2+)i were also independent of extracellular calcium. These findings demonstrate that the action of PGF2 alpha is coupled to the phospholipase C-InsP3 and diacylglycerol second messenger system in the corpus luteum.

  11. PRognostic factor of Early Death In phase II Trials or the end of 'sufficient life expectancy' as an inclusion criterion? (PREDIT model).

    Science.gov (United States)

    Grellety, Thomas; Cousin, Sophie; Letinier, Louis; Bosco-Lévy, Pauline; Hoppe, Stéphanie; Joly, Damien; Penel, Nicolas; Mathoulin-Pelissier, Simone; Italiano, Antoine

    2016-10-04

    Optimizing patient selection is a necessary step to design better clinical trials. 'Life expectancy' is a frequent inclusion criterion in phase II trial protocols, a measure that is subjective and often difficult to estimate. The aim of this study was to identify factors associated with early death in patients included in phase II studies. We retrospectively collected medical records of patients with advanced solid tumors included in phase II trials in two French Comprehensive Cancer Centers (Bordeaux, Center 1 set; Lille, Center 2 set). We analyzed patients' baseline characteristics. Predictive factors associated with early death (mortality at 3 months) were identified by logistic regression. We built a model (PREDIT, PRognostic factor of Early Death In phase II Trials) based on prognostic factors isolated from the final multivariate model. Center 1 and 2 sets included 303 and 227 patients, respectively. Patients from Center 1 and 2 sets differed in tumor site, urological (26 % vs 15 %) and gastrointestinal (18 % vs 28 %) and in lung metastasis incidence (10 % vs 49 %). Overall survival (OS) at 3 months was 88 % (95 % CI [83.5; 91.0], Center 1 set) and 91 % (95 % CI [86.7; 94.2], Center 2 set). Presence of a 'life expectancy' inclusion criterion did not improve the 3-month OS (HR 0.6, 95 % CI [0.2; 1.2], p = 0.2325). Independent factors of early death were an ECOG score of 2 (OR 13.3, 95%CI [4.1; 43.4]), hyperleukocytosis (OR 5.5, 95 % CI [1.9; 16.3]) and anemia (OR 2.8, 95 % CI [1.1; 7.1]). Same predictive factors but with different association levels were found in the Center 2 set. Using the Center 1 set, ROC analysis shows a good discrimination to predict early death (AUC: 0.89 at 3 months and 0.86 at 6 months). Risk modeling in two independent cancer populations based on simple clinical parameters showed that baseline ECOG of 2, hyperleukocytosis and anemia are strong early-death predictive factors. This model allows identifying patients who may

  12. Luteal 3beta-hydroxysteroid dehydrogenase and 20alpha-hydroxysteroid dehydrogenase activities in the rat corpus luteum of pseudopregnancy: Effect of the deciduoma reaction

    Directory of Open Access Journals (Sweden)

    Telleria Carlos M

    2004-05-01

    Full Text Available Abstract Background In the rat, the maintenance of gestation is dependent on progesterone production from the corpora lutea (CL, which are under the control of pituitary, decidual and placental hormones. The luteal metabolism of progesterone during gestation has been amply studied. However, the regulation of progesterone synthesis and degradation during pseudopregnancy (PSP, in which the CL are mainly under the control of pituitary prolactin (PRL, is not well known. The objectives of this investigation were: i to study the luteal metabolism of progesterone during PSP by measuring the activities of the enzymes 3beta-hydroxysteroid dehydrogenase (3betaHSD, involved in progesterone biosynthesis, and that of 20alpha-hydroxysteroid dehydrogenase (20alphaHSD, involved in progesterone catabolism; and ii to determine the role of decidualization on progesterone metabolism in PSP. Methods PSP was induced mechanically at 10:00 h on the estrus of 4-day cycling Wistar rats, and the stimulus for decidualization was provided by scratching the uterus on day 4 of PSP. 3betaHSD and 20alphaHSD activities were measured in the CL isolated from ovaries of PSP rats using a spectrophotometric method. Serum concentrations of progesterone, PRL, androstenedione, and estradiol were measured by radioimmunoassay (RIA. Results The PSP stage induced mechanically in cycling rats lasted 11.3 ± 0.09 days (n = 14. Serum progesterone concentration was high until day 10 of PSP, and declined thereafter. Serum PRL concentration was high on the first days of PSP but decreased significantly from days 6 to 9, having minimal values on days 10 and 11. Luteal 3betaHSD activities were elevated until day 6 of PSP, after which they progressively declined, reaching minimal values at the end of PSP. Luteal 20alphaHSD activities were very low until day 9, but abruptly increased at the end of PSP. When the deciduoma was induced by scratching the uterus of pseudopregnant animals on day 4 (PSP

  13. Alterations in luteal production of androstenedione, testosterone, and estrone, but not estradiol, during mid- and late pregnancy in pigs: effects of androgen deficiency.

    Science.gov (United States)

    Grzesiak, Malgorzata; Knapczyk-Stwora, Katarzyna; Ciereszko, Renata E; Wieciech, Iwona; Slomczynska, Maria

    2014-09-15

    Recently, we have found that flutamide-induced androgen deficiency altered progesterone production in the porcine corpus luteum (CL) during mid- and late pregnancy. Herein, we tested whether flutamide administration subsequently influences androgen and estrogen metabolism in the CL of pregnancy. Pregnant gilts were treated with flutamide between Days 43 and 49 (GD50F), 83 and 89 (GD90F), or 101 and 107 (GD108F) of gestation. Corpora lutea (CLs) were collected from treated and nontreated (control) pigs. The concentrations of androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) together with the levels of expression of mRNAs and proteins for cytochrome P450 17α-hydroxylase/c17-20 lyase (CYP17A1), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), cytochrome P450 aromatase (CYP19A1), and 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) were measured in the CL of control and flutamide-treated animals. Steroidogenic enzymes were also immunolocalized in luteal tissues. The luteal concentrations of A4 and T were higher in the GD50F (P = 0.006, P = 0.03) and GD108F (P = 0.005, P = 0.035) groups, but lower in the GD90F (P = 0.004, P = 0.014) group. The E1 level was greater only in the GD90F (P = 0.03) and GD108F (P = 0.035) groups, whereas E2 concentration was not affected by flutamide treatment. Increased luteal CYP17A1 mRNA and protein expression was found in the GD50F (P = 0.002, P = 0.03) and GD108F (P = 0.0026, P = 0.03) groups, but reduced in the GD90F (P = 0.002, P = 0.03) group. mRNA of 17β-HSD1 was upregulated in the GD50F (P = 0.0005) group, but downregulated in the GD90F (P = 0.002) and GD108F (P = 0.0005) groups. In contrast, 17β-HSD1 protein expression was higher in the GD50F and GD108F (P = 0.03) groups, but lower in the GD90F (P = 0.03) group. Both CYP19A1 mRNA and protein levels were greater in the GD90F (P = 0.001, P = 0.028) and GD108F (P = 0.005, P = 0.03) groups. Neither 17β-HSD7 mRNA nor protein level were affected by

  14. Menstrual cycle phase effects in the gender dimorphic stress cue reactivity of smokers.

    Science.gov (United States)

    Saladin, Michael E; Wray, Jennifer M; Carpenter, Matthew J; McClure, Erin A; LaRowe, Steven D; Upadhyaya, Himanshu P; Gray, Kevin M

    2015-05-01

    We previously reported that female smokers evidence greater subjective craving and stress/emotional reactivity to personalized stress cues than males. The present study employed the same dataset to assess whether females in the follicular versus luteal phase of the menstrual cycle accounted for the gender differences. Two objective criteria, onset of menses and luteinizing hormone surge (evaluated via home testing kits), were used to determine whether female smokers were in either the follicular (n = 22) or the luteal (n = 15) phase of their menstrual cycle, respectively. The females and a sample of male smokers (n = 53) were then administered a laboratory-based cue reactivity paradigm that involved assessment of craving, stress, and emotional reactivity in response to counterbalanced presentations of both a personalized stress script and neutral/relaxed script. While there were no significant differences between females in the follicular versus luteal phase on any outcome measure, females in the luteal menstrual phase reported greater craving than males whereas females in the follicular phase reported greater stress and arousal than males and perceived the stress cues as more emotionally aversive than males. This preliminary investigation suggests that gender differences in craving versus affective responding to stress cues may, in part, be explained variation by menstrual cycle phase. Study limitations and implications of the findings for future research and treatment are briefly discussed. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Impact of Buserelin Acetate or hCG Administration on the Day of First Artificial Insemination on Subsequent Luteal Profile and Conception Rate in Murrah Buffalo (Bubalus bubalis).

    Science.gov (United States)

    Pandey, A K; Ghuman, Sps; Dhaliwal, G S; Agarwal, S K; Phogat, J B

    2016-08-01

    This study was designed to investigate the impact of buserelin acetate (BA) or human chorionic gonadotropin (hCG) administration on the day of first artificial insemination (AI) on subsequent luteal profile (diameter of corpus luteum (CL) and plasma progesterone) and conception rate in Murrah buffalo. The present experiment was carried out at two locations in 117 buffalo that were oestrus-synchronized using cloprostenol (500 μg) administered (i.m.) 11 days apart followed by AI during standing oestrus. Based on treatment (i.m.) at the time of AI, buffalo were randomly categorized (n = 39 in each group) into control (isotonic saline solution, 5 ml), dAI-BA (buserelin acetate, 20 μg) and dAI-hCG (hCG, 3000 IU) group. Out of these, 14 buffalo of each group were subjected to ovarian ultrasonography on the day of oestrus to monitor the preovulatory follicle and on days 5, 12, 16 and 21 post-ovulation to monitor CL diameter. On the day of each sonography, jugular vein blood samples were collected for the estimation of progesterone concentrations. All the buffalo (n = 117) were confirmed for pregnancy on day 40 post-ovulation. The conception rate was better (p hCG (66.7%) groups as compared to their control counterparts (30.8%). Furthermore, the buffalo of dAI-hCG group had improved (p  0.05) to exhibit stimulatory impact of treatment on luteal profile when compared to control group. In brief, buserelin acetate or hCG treatment on the day of first AI leads to an increase in conception rate; however, an appreciable impact on post-ovulation luteal profile was observed only in hCG-treated Murrah buffalo. © 2016 Blackwell Verlag GmbH.

  16. Different types of postpartum luteal activity affected by the exposure of heat stress and subsequent reproductive performance in Holstein lactating cows.

    Science.gov (United States)

    Kornmatitsuk, B; Chantaraprateep, P; Kornmatitsuk, S; Kindahl, H

    2008-10-01

    The aim of the present study was to determine the effect of heat stress on postpartum (PP) luteal activity and subsequent reproductive performance in lactating cows. Thirty Holstein-Friesian (HF, >or=75%) cows (hot season, n = 15 and cool season, n = 15) were studied over 60 days after calving. The changes of temperature-humidity index (THI) were monitored within both seasons. Body condition scores (BCS), uterine involution and the ovarian structures were recorded. Plasma samples were obtained three times a week for the analysis of progesterone (P4) and prostaglandin F(2 alpha) metabolite (PG metabolite). Subsequent reproductive performance of the cows, calved within the same period was also evaluated. The means of THI for hot and cool seasons varied between 84-87 and 78-83 respectively. A drop of the mean BCS was recorded at 5 weeks PP in the cows during hot season (p cows with normal PP ovarian cyclicity during hot and cool seasons were 4/15 (26.7%) and 9/15 (60.0%) respectively. A higher percentage of abnormal luteal activity was found in the cows during hot season (p = 0.07) and delayed luteal cyclicity/anovulation was the most pronounced atypical P4 profile. The levels of PG metabolite were not different between groups and the relationship between the levels of PG metabolite and the time of uterine involution was not evident (p > 0.05). The heat detection rates and the pregnancy rates were higher in the cows during cool season (p heat stress conditions had negative effects on BCS and altered a normal process of ovarian resumption PP, consequently resulted in lower reproductive performance in a tropical dairy herd.

  17. Soluble Flt-1 and PlGF: new markers of early pregnancy loss?

    LENUS (Irish Health Repository)

    Muttukrishna, Shanthi

    2012-01-31

    Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6-10 weeks from women presenting with TM (n = 40), from asymptomatic controls (n = 32) and from non- pregnant women in their luteal phase (n = 14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P<0.001) and PlGF (44%, P<0.001) compared to those with a normal pregnancy outcome. Asymptomatic control pregnant women had similar MS levels of sFlt-1 and PlGF compared to the TM patients with a normal outcome. The mean MS sFlt-1 (>10 fold) and MS PlGF ( approximately 2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage ( approximately 25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these

  18. Soluble Flt-1 and PlGF: new markers of early pregnancy loss?

    LENUS (Irish Health Repository)

    Muttukrishna, Shanthi

    2011-01-01

    Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6-10 weeks from women presenting with TM (n = 40), from asymptomatic controls (n = 32) and from non- pregnant women in their luteal phase (n = 14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P<0.001) and PlGF (44%, P<0.001) compared to those with a normal pregnancy outcome. Asymptomatic control pregnant women had similar MS levels of sFlt-1 and PlGF compared to the TM patients with a normal outcome. The mean MS sFlt-1 (>10 fold) and MS PlGF (∼2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage (∼25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are

  19. Good practices for the operational safety management in the early recovery phase of a seismic event using GPR

    Science.gov (United States)

    Bianchini Ciampoli, Luca; Giulia Brancadoro, Maria; Benedetto, Andrea; D'Amico, Fabrizio; Calvi, Alessandro; Alani, Amir M.; Tosti, Fabio

    2017-04-01

    This study deals with a case report about the planning and the performance of GPR surveys carried out in the town of Amatrice, in the district of Rieti, Italy. As sadly known, the town has been hit by a 6.9 magnitude earthquake in the nighttime of August 24th 2016. The strength of the seism, along with the age and the deterioration rate of the structural asset, have caused the razing to the ground and the critical damaging of the majority of the buildings within the "red zone area", corresponding to the historical town center. In the early recovery phase taking place afterwards, the strong seismic swarm subsequent the main shake has sensitively slowed down the rescue and rehabilitation operations. Moreover, the main issue was related to the unsafety operational conditions of volunteers and firemen. To this effect, the geotechnical stability of the roads and the large operational areas represented critical issues, as up to 40 tons crane trucks were needed to put in safety the highest buildings, such as three-floor buildings and historical towers. In this framework, ground-penetrating radar (GPR) provided a valuable help in preliminary assessing the stability of the areas where the crane trucks were planned to operate as well as to be parked over. The main objective of the GPR tests was to verify the absence of possible cavities beneath the ground surface that could undermine the strength of the surface under heavy loadings. To that effect, a multi-frequency ground-coupled GPR system was used. This radar system can simultaneously collect data at both the frequencies of 600 MHz and 1600 MHz. Four different sites were surveyed, namely, two sections of the main road passed on by the cranes, and two machinery depot areas down by the towers. In the former case, the surveys were performed by parallel longitudinal scans, due to the significant longitudinal length of the sections, whereas in the latter, two grids with differing sizes were realized and scanned for producing

  20. [Producing a sequence of movements in response to a sequence of visual stimuli. Inter-individual differences in early phase of sequence learning].

    Science.gov (United States)

    Kurganskiĭ, A V; Grigal, P P

    2009-01-01

    In this work, we studied the inter-individual variants at the early stage of serial learning in the sequence reproduction task where subjects were asked to produce a sequence of movements whose serial order was given by the sequence of visual stimuli. A total of 20 adults participated in the experiment where, besides the sequence reproduction task, each subject also performed the simple visuomotor reaction time task, the choice reaction time task and the serial reaction time task. It was found that individual latencies vs. trial number plots (learning curves) were characterized by one distinctive feature: the latency reduction, if any, took a form of either an abrupt decline down to a stationary level (fast phase) or a gradual approximately linear leveling off over the entire block of 60 trials (slow phase). The diversity of the individual learning curves were limited to the following four types: a flat curve, a curve with the fast phase only, a curve with the slow phase only, and a curve that combined both phases with the leading fast phase followed by the slow phase. All the subjects were subdivided into four groups according to the subject's type of learning curve. We analyzed the correlation pattern between temporal indices (latencies and inter-response intervals) and compared these indices to simple visuomotor reaction time, choice reaction time and the amount of learning in the serial reaction time task. The significant between-group differences found in this analysis suggest that there are some essential functional differences related to the group break up. It was suggested that inter-individual variants in the character of the early stage of sequence learning are determined mainly by the functional and structural complexity of the internal representation of the sequence and by the way the working memory operates in order to recognize the driving sequence of visual stimuli and to translate the internal representation of a sequence into motor commands.

  1. Comparison of the effects of high- and low-frequency repetitive transcranial magnetic stimulation on upper limb hemiparesis in the early phase of stroke.

    Science.gov (United States)

    Sasaki, Nobuyuki; Mizutani, Saneyuki; Kakuda, Wataru; Abo, Masahiro

    2013-05-01

    Recently, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and low-frequency rTMS (LF-rTMS) are reported to improve motor function significantly in chronic hemiparetic stroke patients. However, few studies have investigated the safety and efficacy of these rTMS modalities introduced during the early phase of stroke. The purpose of this study was to clarify the rTMS modality that is more beneficial for upper limb hemiparesis in the early phase of stroke using a randomized controlled trial. Twenty-nine patients with a hemispheric stroke lesion in the early phase of stroke were examined. Patients were randomly assigned into 3 groups: the HF-rTMS group (10 Hz rTMS to the lesional hemisphere [n = 9]), the LF-rTMS group (1 Hz rTMS to the nonlesional hemisphere [n = 11]), and the sham stimulation group [n = 9]). Patients received sessions for 5 consecutive days. Grip strength and tapping frequency were assessed before and after the intervention. Motor improvement of the affected upper limb after intervention was compared among the 3 groups. All patients completed the 5-day protocol. Both the HF-rTMS and LF-rTMS groups had significant increases in both grip strength and tapping frequency. Comparison of the extent of improvement showed a more significant increase in grip strength and tapping frequency in the HF-rTMS group compared to the sham stimulation group (each P stimulation group. HF-rTMS applied to the lesional hemisphere in the early phase of stroke was more beneficial for motor improvement of the affected upper limb than LF-rTMS. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. The integration of Mathematics, Science and Technology in early childhood education and the foundation phase: The role of the formation of the professional identities of beginner teachers

    OpenAIRE

    2015-01-01

    This article focuses on the professional identity formation of six beginner teachers (three in early childhood education and three in the foundation phase), involved in the teaching of Mathematics, Science and Technology (MST). Attention is in particular being paid to the role of professional identity in how they applied innovative teaching methods such as enquiry-based teaching. The study is based on the personal narratives of the six teachers, regarding their own learning experiences in MST...

  3. Comparison of methods for measuring viable E. coli cells during cultivation: great differences in the early and late exponential growth phases.

    Science.gov (United States)

    Wang, Hengwei; Cheng, Hairong; Wei, Dongzhi; Wang, Fengqing

    2011-01-01

    Four methods, namely enumeration of colony-forming units (CFU), aerobic respiration, MTT reduction capacity and succinate dehydrogenase activity were compared to determine the viability of E. coli cells at the early and late exponential growth phases. Our results revealed that great differences in cell viability existed between these methods and that the choice of method to determine cell viability must be made with caution.

  4. Plasma volume and water/sodium balance differences due to sex and menstrual phase after 4 hours of head-down bed rest (HDBR).

    Science.gov (United States)

    Edgell, Heather; Grinberg, Anna; Beavers, Keith; Gagne, Nathalie; Totosy de Zepetnek, Julia; Greaves, Danielle; Hughson, Richard L.

    In both sexes, orthostatic responses are impaired by spaceflight or head-down bed-rest (HDBR), with a greater impact in women. Decreased plasma volume (PV) could contribute to reductions in cardiac output and blood pressure upon an orthostatic challenge. We hypothesized that a greater decrease in PV in women might lead to poorer orthostatic responses. We further hypothesized that the responses in women would differ throughout the menstrual cycle. We studied the responses of men (n=6) and women (n= 6) to 4-hr HDBR and 4-hr seated control (SEAT). Furthermore, we studied women in both the follicular (Day 8-11) and luteal (Day 18-24) phases of menstruation in a repeated measures design. After 4-hr HDBR, PV decreased in men (-175.1 ± 56.8 mL; vs. SEAT: P=0.076) and in the follicular phase, but did not change in the luteal phase (Luteal: -55.0 ± 54.6 mL; Follicular: -226.4 ± 88.2 mL (Interaction effect: P=0.01)). After 4-hr HDBR, only men appear to exhibit increased urine volume (Men, difference from SEAT: +298.3 ± 105.5 mL; Luteal, difference from SEAT: +59.4 ± 34.3 mL; Follicular, difference from SEAT: +43.7 ± 190.0 mL; P=0.16). No changes in urinary sodium after 4-hr HDBR were observed in any group (Men, difference from SEAT: -16.5 ± 13.5 µmol; Luteal, difference from SEAT: -8.0 ± 8.8 µmol; Follicular, difference from SEAT: +28.2 ± 29.5 µmol; P=0.264). No changes in urinary osmolarity were observed after 4-hr HDBR in any group (Men, difference from SEAT: -38.8 ± 126.2 mmol/kg; Luteal, difference from SEAT: -85.1 ± 66.9 mmol/kg; Follicular, difference from SEAT: -99.1 ± 98.5 mmol/kg; P=0.906). The changes in plasma volume do not appear to be a result of urinary water and sodium loss. Perhaps actions of atrial natriuretic peptide, urodilatin, the RAAS pathway, and/or capillary filtration are involved. From these observed changes in plasma volume, we surmise that women in the follicular phase of the menstrual cycle may exhibit lower cardiac output and thus

  5. Early life exposure to farm animals and symptoms of asthma, rhinoconjunctivitis and eczema: an ISAAC Phase Three Study

    NARCIS (Netherlands)

    Brunekreef, B.; von Mutius, E.; Wong, G.; Odhiambo, J.; Clayton, T.O.

    2012-01-01

    BACKGROUND: Associations between early life exposure to farm animals and respiratory symptoms and allergy in children have been reported in developed countries, but little is known about such associations in developing countries. OBJECTIVE: To study the association between early life exposure to far

  6. Supercritical fluid chromatography and steady-state recycling: phase appropriate technologies for the resolutions of pharmaceutical intermediates in the early drug development stage.

    Science.gov (United States)

    Yan, Tony Q; Orihuela, Carlos; Preston, Jay P; Xia, Fang

    2010-11-01

    The use of phase appropriate technologies is critical for efficiently moving drug candidates forward in the early stages of drug discovery and development. Phase appropriate purification technology develops the analytical method and subsequently scales up the method and turns the sample around quickly (Kennedy et al., J Chromatogr A 2004; 1046:55). In this article, separation results and conditions from supercritical fluid chromatography (SFC), high-performance liquid chromatography (HPLC), and steady-state recycling (SSR) for the resolutions of three pharmaceutical intermediates in the early stage of the drug development are discussed. The first study used SFC and SSR to separate an impurity for a Good Manufacturing Practice (GMP) campaign. The analytical method development and scale-up conditions are discussed. Productivity, solvent usage, and sample solubility under SFC and SSR conditions are also compared. The second study compared SFC to batch HPLC in separating a diastereomer. Due to higher separation efficiency, SFC was able to resolute multiple peaks. The third study involved the addition of dichloromethane as a co-solvent in SFC purification--improving sample selectivity and solubility. From the separation results of these purifications, SFC and SSR are clearly phase appropriate technologies in the early drug development stage.

  7. Early gonadotropin-releasing hormone antagonist start improves follicular synchronization and pregnancy outcome as compared to the conventional antagonist protocol.

    Science.gov (United States)

    Park, Chan Woo; Hwang, Yu Im; Koo, Hwa Seon; Kang, Inn Soo; Yang, Kwang Moon; Song, In Ok

    2014-12-01

    To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR). A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol. The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%). The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials.

  8. Pharmacokinetics of omeprazole and its metabolites in three phases of menstrual cycle.

    Science.gov (United States)

    Nazir, Shabnam; Iqbal, Zafar; Ahmad, Lateef; Shah, Yasar; Nasir, Fazli

    2015-03-01

    Omeprazole (OMP) is effective in the treatment of gastric hyperacidity and is metabolized by CYP2C19 and CYP3A4. These enzymes are modulated by estrogen and progesterone which regulate the menstrual cycle. The variations in the pharmacokinetics (PK) of many drugs like amphetamine, benzodiazepines and caffeine have been reported during menstrual cycle. In present study, the PK of the omeprazole and its metabolites was investigated during various phases of the menstrual cycle. A single oral dose, open-label, non-controlled, pharmacokinetic study of omeprazole was conducted in healthy young/premenopausal females (n = 16). The PK of omeprazole, 5-hydroxy-omeprazole and omeprazole sulphone was evaluated in three phases of menstrual cycle. The blood samples were analyzed using reversed-phase HPLC coupled with UV detector and the PK data were evaluated. The activities of CYP2C19 and CYP3A4 were determined as AUC(OH-OMP)/AUC(OMP) and AUC(OMP-SUL)/AUC(OMP), respectively. Omeprazole showed significantly (p menstrual phases, respectively. The [Formula: see text] of 5-hydroxy omeprazole was also significantly (p < 0.05) higher in follicular phase. The metabolic ratios (MR) of 5-hydroxy omeprazole and omeprazole sulphone were lower in follicular phase compared with the luteal phase. The present study suggests that high estrogen levels of follicular phase may result in increased absorption of omeprazole. The lower MR for 5-hydroxy omeprazole and omeprazole sulphone in follicular phase as compared to luteal phase suggests that metabolism of omeprazole is low in follicular phase as compared to luteal phase, which is progesterone-dominant phase. However, the clinical significance for these findings needs to be determined.

  9. Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers.

    Science.gov (United States)

    Rozera, G; Abbate, I; Vlassi, C; Giombini, E; Lionetti, R; Selleri, M; Zaccaro, P; Bartolini, B; Corpolongo, A; D'Offizi, G; Baiocchini, A; Del Nonno, F; Ippolito, G; Capobianchi, M R

    2014-03-01

    HIV quasispecies was analysed in plasma and proviral genomes hosted by duodenal mucosa and peripheral blood cells (PBMC) from patients with early or chronic infection, with respect to viral heterogeneity, tropism compartmentalization and extent of immune activation. Seventeen HIV-1-infected combined antiretroviral therapy naive patients were enrolled (11 early infection and six chronic infection). V3 and nef genomic regions were analysed by ultra-deep pyrosequencing. Sequences were used to infer co-receptor usage and to construct phylogenetic trees. As markers of immune activation, plasma sCD14 and soluble tumour necrosis factor receptor II (sTNFRII) levels were measured. Median diversity of HIV RNA was lower in patients with early infection versus chronic infection patients. Overall, direct correlation was observed between V3 diversity and X4 frequency; V3 diversity of HIV RNA was inversely correlated with CD4 T-cell count; median sCD14 and sTNFRII values were similar in early and chronic patients, but X4 frequency of HIV RNA was directly correlated with plasma sCD14. The proportion of patients harbouring X4 variants and median intra-patient X4 frequency of proviral genomes tended to be higher in chronic infection than early infection patients. More pronounced compartmentalization of proviral quasispecies in gut compared with PBMC samples was observed in patients with early infection compared with chronic patients. The loss of gut/PBMC compartmentalization in more advanced stages of HIV infection was confirmed by longitudinal observation. More studies are needed to understand the pathogenetic significance of early HIV quasispecies compartmentalization and progressive intermixing of viral variants in subsequent phases of the infection, as well as the role of immune activation in tropism switch.

  10. Evidence Based Evaluation of Traditional Chinese Medicine Treatment of Luteal Insufficiency%中医治疗黄体功能不足循证评价

    Institute of Scientific and Technical Information of China (English)

    吴鹏飞

    2015-01-01

    Objective To evaluate and analysis the system by using the scientific method of chinese medicine treatment of luteal insufficiency treatment effect.MethodsTo collect and TCM Treatment on luteal insufficiency related documents in the database bycomputer,and to screen. The analysis and evaluation of the retrieval result using metaanalysis software.Results A total of 23 literatures related to the acquisition,corpus luteum insufficiency with infertility and 15 articles,on luteal insufficiency leads todysfunctional uterine bleeding,menstrual disorders,abortion and the 1,other symptoms 5. Based on the analysis of available in the treatment of infertility,other symptoms of traditional chinese medicine, the total effective rate,pregnancy rate is higher than that of western medicine treatment. In the treatment of dysfunctionaluterine bleeding, menstrual disorders and abortion symptoms,not much difference between chinese and western medicine treatment effect.ConclusionChinese medicine treatment of inadequate luteal function have a more significant effect,especially in the treatment of corpus luteum insufficiency lead to infertility and other diseases,the effect is better than western medicine,safety is guaranteed. This studypossible influencing factors of different degree,there is some risk of bias,and thus influence the evaluation result is reliable,only to provide some reference for chinese medicine treatment of luteal insufficiency.%目的对中医治疗黄体功能不足的治疗效果利用科学方法进行系统评价与分析。方法利用计算机在数据库中收集与中医药治疗黄体功能不足相关的文献,并进行筛选。利用Meta分析软件对检索结果进行分析评价。结果共采集相关文献23篇,有关黄体功能不足性不孕的有15篇,有关黄体功能不足导致的功能失调性子宫出血、经期紊乱、流产的各1篇,其他症状5篇。根据分析可得在不孕症、其他症状的治疗中,中药的总有

  11. A phase II study of combination chemotherapy in early relapsed epithelial ovarian cancer using gemcitabine and pegylated liposomal doxorubicin

    DEFF Research Database (Denmark)

    Mirza, Mansoor Raza; Lund, Bente; Lindegaard, Jacob Christian

    2010-01-01

    Treatment of epithelial ovarian cancer patients relapsing with a short treatment-free interval (TFI) after prior chemotherapy is unsatisfactory. This phase II trial evaluated the activity and feasibility of pegylated liposomal doxorubicin (PLD) plus gemcitabine in this setting.......Treatment of epithelial ovarian cancer patients relapsing with a short treatment-free interval (TFI) after prior chemotherapy is unsatisfactory. This phase II trial evaluated the activity and feasibility of pegylated liposomal doxorubicin (PLD) plus gemcitabine in this setting....

  12. Gravitational waves from first order phase transitions as a probe of an early matter domination era and its inverse problem

    Energy Technology Data Exchange (ETDEWEB)

    Barenboim, Gabriela, E-mail: Gabriela.Barenboim@uv.es; Park, Wan-Il, E-mail: Wanil.Park@uv.es

    2016-08-10

    We investigate the gravitational wave background from a first order phase transition in a matter-dominated universe, and show that it has a unique feature from which important information about the properties of the phase transition and thermal history of the universe can be easily extracted. Also, we discuss the inverse problem of such a gravitational wave background in view of the degeneracy among macroscopic parameters governing the signal.

  13. Rapamycin ameliorates inflammation and fibrosis in the early phase of cirrhotic portal hypertension in rats through inhibition of mTORC1 but not mTORC2.

    Directory of Open Access Journals (Sweden)

    Weijie Wang

    Full Text Available OBJECTIVE: Hepatic stellate cells (HSCs transdifferentiation and subsequent inflammation are important pathological processes involved in the formation of cirrhotic portal hypertension. This study characterizes the pathogenetic mechanisms leading to cholestatic liver fibrosis and portal hypertension, and focuses on mammalian target of rapamycin (mTOR pathway as a potential modulator in the early phase of cirrhotic portal hypertension. METHODS: Early cirrhotic portal hypertension was induced by bile duct ligation (BDL for three weeks. One week after operation, sham-operated (SHAM and BDL rats received rapamycin (2 mg/kg/day by intraperitoneal injection for fourteen days. Vehicle-treated SHAM and BDL rats served as controls. Fibrosis, inflammation, and portal pressure were evaluated by histology, morphometry, and hemodynamics. Expressions of pro-fibrogenic and pro-inflammatory genes in liver were measured by RT-PCR; alpha smooth muscle actin (α-SMA and antigen Ki67 were detected by immunohistochemistry; expressions of AKT/mTOR signaling molecules, extracellular-signal-regulated kinase 1/2 (ERK1/2, p-ERK1/2, and interleukin-1 beta (IL-1β were assessed by western blot. RESULTS: The AKT/mTOR signaling pathway was markedly activated in the early phase of cirrhotic portal hypertension induced by BDL in rats. mTOR blockade by rapamycin profoundly improved liver function by limiting inflammation, fibrosis and portal pressure. Rapamycin significantly inhibited the expressions of phosphorylated 70KD ribosomal protein S6 kinase (p-P70S6K and phosphorylated ribosomal protein S6 (p-S6 but not p-AKT Ser473 relative to their total proteins in BDL-Ra rats. Those results suggested that mTOR Complex 1 (mTORC1 rather than mTORC2 was inhibited by rapamycin. Interestingly, we also found that the level of p-ERK1/2 to ERK1/2 was significantly increased in BDL rats, which was little affected by rapamycin. CONCLUSIONS: The AKT/mTOR signaling pathway played an important

  14. Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth--Three Phases in Early Lactation and Progressive Individual Differences.

    Science.gov (United States)

    Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I Kati; Watson, David G; Kennedy, Malcolm W

    2015-01-01

    Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1-6 (Phase 1), days 7-20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth.

  15. Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca with Time after Birth--Three Phases in Early Lactation and Progressive Individual Differences.

    Directory of Open Access Journals (Sweden)

    Tong Zhang

    Full Text Available Ursids (bears in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1-6 (Phase 1, days 7-20 (Phase 2, and beyond day 20 (Phase 3. While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth.

  16. On the Chemical Evolution of Upper Mantle of the Early Earth—An Experimental Study on Melting of the Silicate Phase in Jilin Chondrite at High Pressures

    Institute of Scientific and Technical Information of China (English)

    谢鸿森; 方虹; 等

    1989-01-01

    Relatively old ages of chondrites(normally around 4.5Ga)suggest that their parent bodies did not experience any mely-fractionation under high temperature and high pressure conditions pertaining to the interior of terrestrial plaets.Therefore,it is reasonable to take chondrites as starting materials in the study of the chemical evolution of the early earth.The sillicate phase in the Jilin chondrite (H5)was chosen for this purpose because it possesses a chemical composition similar to that of the primitive mantle.The melting experiment was carried out at 20-30 k bar and has rsulted in a product which contains1-5% melts in addition to solid cryustal phase.The chemical composition of the melt phases and the partitioning of various elements between the coexisting silicate melts are geochemically similar to those of anatectic rocks on the earth.This can thus serve as the basis for discussing the chemical evolution of the early upper mantle.

  17. SU-E-I-91: Quantitative Assessment of Early Hepatocellular Carcinoma and Cavernous Hemangioma of Live Using In-Line Phase-Contrast X-Ray Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Duan, J [Department of Radiation Oncology, Shandong Tumor Hospital, Jinan (China)

    2015-06-15

    Purpose: To investigate the potential utility of in-line phase-contrast imaging (ILPCI) technique with synchrotron radiation in detecting early hepatocellular carcinoma and cavernous hemangioma of live using in vitro model system. Methods: Without contrast agents, three typical early hepatocellular carcinoma specimens and three typical cavernous hemangioma of live specimens were imaged using ILPCI. To quantitatively discriminate early hepatocellular carcinoma tissues and cavernous hemangioma tissues, the projection images texture feature based on gray level co-occurrence matrix (GLCM) were extracted. The texture parameters of energy, inertia, entropy, correlation, sum average, sum entropy, difference average, difference entropy and inverse difference moment, were obtained respectively. Results: In the ILPCI planar images of early hepatocellular carcinoma specimens, vessel trees were clearly visualized on the micrometer scale. Obvious distortion deformation was presented, and the vessel mostly appeared as a ‘dry stick’. Liver textures appeared not regularly. In the ILPCI planar images of cavernous hemangioma of live specimens, typical vessels had not been found compared with the early hepatocellular carcinoma planar images. The planar images of cavernous hemangioma of live specimens clearly displayed the dilated hepatic sinusoids with the diameter of less than 100 microns, but all of them were overlapped with each other. The texture parameters of energy, inertia, entropy, correlation, sum average, sum entropy, and difference average, showed a statistically significant between the two types specimens image (P<0.01), except the texture parameters of difference entropy and inverse difference moment(P>0.01). Conclusion: The results indicate that there are obvious changes in morphological levels including vessel structures and liver textures. The study proves that this imaging technique has a potential value in evaluating early hepatocellular carcinoma and cavernous

  18. Quantitative phase-filtered wavelength-modulated differential photoacoustic radar tumor hypoxia imaging toward early cancer detection.

    Science.gov (United States)

    Dovlo, Edem; Lashkari, Bahman; Soo Sean Choi, Sung; Mandelis, Andreas; Shi, Wei; Liu, Fei-Fei

    2016-10-19

    Overcoming the limitations of conventional linear spectroscopy used in multispectral photoacoustic imaging, wherein a linear relationship is assumed between the absorbed optical energy and the absorption spectra of the chromophore at a specific location, is crucial for obtaining accurate spatially-resolved quantitative functional information by exploiting known chromophore-specific spectral characteristics. This study introduces a non-invasive phase-filtered differential photoacoustic technique, wavelength-modulated differential photoacoustic radar (WM-DPAR) imaging that addresses this issue by eliminating the effect of the unknown wavelength-dependent fluence. It employs two laser wavelengths modulated out-of-phase to significantly suppress background absorption while amplifying the difference between the two photoacoustic signals. This facilitates pre-malignant tumor identification and hypoxia monitoring, as minute changes in total hemoglobin concentration and hemoglobin oxygenation are detectable. The system can be tuned for specific applications such as cancer screening and SO2 quantification by regulating the amplitude ratio and phase shift of the signal. The WM-DPAR imaging of a head and neck carcinoma tumor grown in the thigh of a nude rat demonstrates the functional PA imaging of small animals in vivo. The PA appearance of the tumor in relation to tumor vascularity is investigated by immunohistochemistry. Phase-filtered WM-DPAR imaging is also illustrated, maximizing quantitative SO2 imaging fidelity of tissues. Oxygenation levels within a tumor grown in the thigh of a nude rat using the two-wavelength phase-filtered differential PAR method.

  19. Neuroprotective effects of riluzole in early phase Parkinson's disease on clinically relevant parameters in the marmoset MPTP model

    NARCIS (Netherlands)

    Verhave, P.S.; Jongsma, M.J.; Berg, R.M. van den; Vanwersch, R.A.P.; Smit, A.B.; Philippens, I.H.C.H.M.

    2012-01-01

    The present study evaluates neuroprotection in a marmoset MPTP (1-methyl-1,2,3,6-tetrahydropyridine) model representing early Parkinson's disease (PD). The anti-glutamatergic compound riluzole is used as a model compound for neuroprotection. The compound is one of the few protective compounds used i

  20. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia

    NARCIS (Netherlands)

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, SV; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-01-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the

  1. Early Identification of Delinquency Prone Youth. The Eau Claire County Youth Study, Phase IV, 1969-1972.

    Science.gov (United States)

    Feldhusen, John F.; And Others

    Procedures for early identification of delinquency-prone youth in Eau Claire County, Wisconsin, are described in this report of a 1961-1972 study designed to delineate the problems of aggressive and disruptive classroom behavior as related to delinquency. Data collection began in 1961, when each 3rd-, 6th-, and 9th-grade teacher in Eau Claire…

  2. Biomechanical and neuromuscular adaptations during the landing phase of a stepping-down task in patients with early or established knee osteoarthritis.

    Science.gov (United States)

    Sanchez-Ramirez, Diana C; Malfait, Bart; Baert, Isabel; van der Leeden, Marike; van Dieën, Jaap; Lems, Willem F; Dekker, Joost; Luyten, Frank P; Verschueren, Sabine

    2016-06-01

    To compare the knee joint kinematics, kinetics and EMG activity patterns during a stepping-down task in patients with knee osteoarthritis (OA) with control subjects. 33 women with knee OA (early OA, n=14; established OA n=19) and 14 female control subjects performed a stepping-down task from a 20cm step. Knee joint kinematics, kinetics and EMG activity were recorded on the stepping-down leg during the loading phase. During the stepping-down task patients with established knee OA showed greater normalized medial hamstrings activity (p=0.034) and greater vastus lateralis-medial hamstrings co-contraction (p=0.012) than controls. Greater vastus medialis-medial hamstrings co-contraction was found in patients with established OA compared to control subjects (p=0.040) and to patients with early OA (p=0.023). Self-reported knee instability was reported in 7% and 32% of the patients with early and established OA, respectively. The greater EMG co-activity found in established OA might suggest a less efficient use of knee muscles or an attempt to compensate for greater knee laxity usually present in patients with established OA. In the early stage of the disease, the biomechanical and neuromuscular control of stepping-down is not altered compared to healthy controls. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Qualitative methods in early-phase drug trials: broadening the scope of data and methods from an RCT of N-acetylcysteine in schizophrenia.

    Science.gov (United States)

    Berk, Michael; Munib, Ahmed; Dean, Olivia; Malhi, Gin S; Kohlmann, Kristy; Schapkaitz, Ian; Jeavons, Sue; Katz, Fiona; Anderson-Hunt, Murray; Conus, Philippe; Hanna, Barbara; Otmar, Renée; Ng, Felicity; Copolov, David L; Bush, Ashley I

    2011-07-01

    The pharmacokinetic profile of a drug often gives little indication of its potential therapeutic application, with many therapeutic uses of drugs being discovered serendipitously while being studied for different indications. As hypothesis-driven, quantitative research methodology is exclusively used in early-phase trials, unexpected but important phenomena may escape detection. In this context, this study aimed to examine the potential for integrating qualitative research methods with quantitative methods in early-phase drug trials. To our knowledge, this mixed methodology has not previously been applied to blinded psychopharmacologic trials. We undertook qualitative data analysis of clinical observations on the dataset of a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) in patients with DSM-IV-TR-diagnosed schizophrenia (N = 140). Textual data on all participants, deliberately collected for this purpose, were coded using NVivo 2, and emergent themes were analyzed in a blinded manner in the NAC and placebo groups. The trial was conducted from November 2002 to July 2005. The principal findings of the published trial could be replicated using a qualitative methodology. In addition, significant differences between NAC- and placebo-treated participants emerged for positive and affective symptoms, which had not been captured by the rating scales utilized in the quantitative trial. Qualitative data in this study subsequently led to a positive trial of NAC in bipolar disorder. The use of qualitative methods may yield broader data and has the potential to complement traditional quantitative methods and detect unexpected efficacy and safety signals, thereby maximizing the findings of early-phase clinical trial research. www.anzctr.org.au Identifier: ACTRN12605000363684. © Copyright 2011 Physicians Postgraduate Press, Inc.

  4. Inflammatory cytokines imbalance in the very early phase of acute coronary syndrome: correlations with angiographic findings and in-hospital events.

    Science.gov (United States)

    Brunetti, Natale Daniele; Munno, Irene; Pellegrino, Pier Luigi; Ruggero, Vincenzo; Correale, Michele; De Gennaro, Luisa; Cuculo, Andrea; Campanale, Erasmo Giulio; Di Biase, Matteo

    2011-02-01

    The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-α, and IFN-γ) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p < 0.001; TNF-α and IFN-γ, p < 0.05) and more often incurred early complications (IL-2, p < 0.05; IFN-γ, p < 0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r = 0.47; lactate dehydrogenase, r = 0.54; troponin I, r = 0.58; p < 0.05). TNF-α levels were associated with a worse prognosis at follow-up (Log rank, p < 0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.

  5. Genomics-based early-phase clinical trials in oncology: recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies.

    Science.gov (United States)

    Liu, Stephen V; Miller, Vincent A; Lobbezoo, Marinus W; Giaccone, Giuseppe

    2014-11-01

    The Methodology for the Development of Innovative Cancer Therapies (MDICT) task force discussed incorporation of genomic profiling into early (Phase I and II) clinical trials in oncology. The task force reviewed the challenges of standardising genomics data in a manner conducive to conducting clinical trials. Current barriers to successful and efficient implementation were identified and discussed, as well as the methods of genomic analysis, the proper setting for study and strategies to facilitate timely completion of genomics-based studies. The importance of properly capturing and cataloguing outcomes was also discussed. Several recommendations regarding the use of genomics in these trials are provided.

  6. Evaluation and prognostic significance of left ventricular diastolic function assessed by Doppler echocardiography in the early phase of a first acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Jensen, S E; Gøtzsche, O

    1997-01-01

    deceleration time development of congestive heart failure during the first week following a first acute myocardial infarction. CONCLUSION: Assessment of left ventricular diastolic function complements measurements of systolic function......AIM: To study the prognostic significance of left ventricular diastolic function evaluated by transmitral and pulmonary venous flow velocities obtained in the early phase of a first acute myocardial infarction in relation to later development of congestive heart failure. METHODS: Pulsed Doppler...... echocardiography of transmitral and pulmonary venous flow was assessed in 65 consecutive patients with a first myocardial infarction within 1 h of arrival in the coronary care unit. RESULTS: A univariate regression analysis identified age, left ventricular ejection fraction

  7. Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

    Science.gov (United States)

    Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

    2017-08-30

    Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

  8. Relationships among leaf functional traits, litter traits, and mass loss during early phases of leaf litter decomposition in 12 woody plant species.

    Science.gov (United States)

    Zukswert, Jenna M; Prescott, Cindy E

    2017-09-08

    Litter 'quality' or decomposability has historically been estimated through measuring chemical attributes, such as concentrations of nitrogen or 'lignin'. More recently, foliar functional traits, which may incorporate indications of the physical structures of tissues, have been found to correlate with litter mass loss rates. However, these traits may not be adequate to predict early rates of mass loss, in which two factors are crucial: the amount of material quickly lost through leaching, and the ease of access of decomposer organisms to the more labile tissues in the interior of the litter. We investigated relationships among physical and chemical traits in foliage and litter of 12 species native to British Columbia and then observed how these traits related to mass loss during the first 3 months (Phase I) and between 3 and 12 months (Phase II). Novel traits measured in this study include cuticle thickness, litter leaching loss, and litter water uptake. Foliar and litter traits both co-varied along spectra, but several chemical traits, such as nitrogen concentration, changed from foliage to litter, i.e., during senescence. Phase I mass loss was best predicted by leaching loss and traits relating to leaching, such as cuticle thickness and specific leaf area. Phase II mass loss was predicted by traits that may relate to decomposer access and activity, such as leaf dry matter content and foliar nitrogen. Physical traits predicted mass loss as well or better than chemical traits, suggesting that physical characteristics of litter are important in determining early rates of decomposition.

  9. Whole breast irradiation vs. APBI using multicatheter brachytherapy in early breast cancer – simulation of treatment costs based on phase 3 trial data

    Science.gov (United States)

    Harat, Maciej; Makarewicz, Roman

    2016-01-01

    Purpose A recent large phase 3 trial demonstrated that the efficacy of accelerated partial-breast irradiation (APBI) in the treatment of early breast cancer is non-inferior to that of whole breast irradiation (WBI) commonly used in this indication. The aim of this study was to compare the costs of treatment with APBI and WBI in a population of patients after conserving surgery for early breast cancer, and to verify if the use of APBI can result in direct savings of a public payer. Material and methods The hereby presented cost analysis was based on the results of GEC-ESTRO trial. Expenditures for identified cost centers were estimated on the basis of reimbursement data for the public payer. After determining the average cost of early breast cancer treatment with APBI and WBI over a 5-year period, the variance in this parameter resulting from fluctuations in the price per single procedure was examined on univariate sensitivity analysis. Then, incremental cost-effectiveness ratio (ICER) was calculated to verify the cost against clinical outcome. Finally, a simulation of public payer’s expenditures for the treatment of early breast cancer with APBI and WBI in 2013 and 2025 has been conducted. Results The average cost of treatment with APBI is lower than for WBI, even assuming a potential increase in the unit price of the former procedure. There was no additional health benefit of WBI and the calculation of cost-effectiveness was based on the absolute difference in overall local control rate. However, this difference (0.92% vs. 1.44%) was fairly minimal and was not identified as statistically significant during 5 years. Conclusions The use of APBI as an alternative to WBI in the treatment of early breast cancer would substantially reduce healthcare expenditures in both 2013 and 2025, even assuming an increase in the price per single APBI procedure.

  10. The effects of menstrual cycle phase on physical performance in female soccer players

    Science.gov (United States)

    Julian, Ross; Hecksteden, Anne; Fullagar, Hugh H. K.; Meyer, Tim

    2017-01-01

    Background Female soccer has grown extensively in recent years, however differences in gender-specific physiology have rarely been considered. The female reproductive hormones which rise and fall throughout the menstrual cycle, are known to affect numerous cardiovascular, respiratory, thermoregulatory and metabolic parameters, which in turn, may have implications on exercise physiology and soccer performance. Therefore, the main aim of the present study was to investigate potential effects of menstrual cycle phase on performance in soccer specific tests. Methods Nine sub elite female soccer players, all of whom have menstrual cycles of physiological length; performed a series of physical performance tests (Yo-Yo Intermittent endurance test (Yo-Yo IET), counter movement jump (CMJ) and 3x30 m sprints). These were conducted at distinct time points during two main phases of the menstrual cycle (early follicular phase (FP) and mid luteal phase (LP)) where hormones contrasted at their greatest magnitude. Results Yo-Yo IET performance was considerably lower during the mid LP (2833±896 m) as compared to the early FP (3288±800 m). A trend towards significance was observed (p = 0.07) and the magnitude based inferences suggested probabilities of 0/61/39 for superiority/equality/inferiority of performance during the mid LP, leading to the inference of a possibly harmful effect. For CMJ (early FP, 20.0±3.9 cm; mid LP 29.6±3.0 cm, p = 0.33) and sprint (early FP, 4.7±0.1 s; mid LP, 4.7±0.1 s, p = 0.96) performances the results were unclear (8/24/68, 48/0/52, respectively). Conclusion The results of this study are in support of a reduction in maximal endurance performance during the mid LP of the menstrual cycle. However, the same effect was not observed for jumping and sprint performance. Therefore, consideration of cycle phase when monitoring a player’s endurance capacity may be worthwhile. PMID:28288203

  11. Very Early Phases of Massive Star Formation: An SMA Follow-up of Herschel Hi-Gal Survey Cores

    Science.gov (United States)

    Smith, Howard Alan; Zhang, Q.; Jimenez-Serra, I. M.; Beltran, M.; Cesaroni, R.; Finn, S.; Foster, J.; Jackson, J.; Molinari, S.; Viti, S.

    2011-01-01

    We used the Submillimeter Array (SMA) to observe eight cold, massive ( 1000Msol) dense cores in dark clouds discovered in the Herschel HiGal survey. In contrast to numerous studies of hot molecular cores, very little is known about objects prior to the hot core phase. The SMA results allow us to study systematically the physical and chemical evolution of these dense cores. These protostellar objects were selected because the Hershel SEDs of the dust have temperatures spanning the range between about 10K and 20K, suggestive of different evolutionary phases of very young stars, because the objects were comparatively bright at 250 microns ( 10Jy) and distinct in all five FIR HiGal bands, and because they seemed to be morphologically simple. Only one of the sources is bright enough to be detected at MIPS24; this source, the most mature one, already shows a small outflow in CO. The SMA was used in both compact and very extended configurations, with the 230GHz band. The SMA molecular line maps will be compared with chemical modelling (including dust grain and gas phase reactions) to constrain the physical conditions in these young cores, and their evolutionary stages.

  12. Schistogram changes after administration of antischistosomal drugs in mice at the early phase of Schistosoma mansoni infection

    Directory of Open Access Journals (Sweden)

    Andrea Cassia Simoes Vimieiro

    2013-11-01

    Full Text Available Mice infected with Schistosoma mansoni were treated with oxamniquine, praziquantel, artesunate at the pre-patent phase, aiming at observing schistogram alterations. Half of the animals were perfused five days post-treatment for counting and classification of immature worms, based on pre-established morphological criteria (schistogram; the remaining animals were evaluated 42 or 100 days after infection and perfusion of the portal-system was performed for collection and counting of adult worms and oogram. It was observed that oxamniquine and artesunate treatment administered at the pre-postural phase causes significant reduction in the number of immature and adult worms. However, there was little reduction with praziquantel when used at the dose of 400 mg/kg for treatments administered 14, 15, 21 or 23 days post-infection. Artesunate was responsible for significant alterations in development of young worms, as well as for a higher number of worms presenting intestinal damages. Immature adult worms were detected in mice treated with artesunate or oxamniquine at the pre-patent phase of infection and recovered by perfusion 100 days after infection. Schistogram proved to be a very useful tool for experimental evaluation of the activity of antischistosomal drugs and a good model to identify the most sensitive stages to drugs.

  13. Sound shell model for acoustic gravitational wave production at a first-order phase transition in the early Universe

    CERN Document Server

    Hindmarsh, Mark

    2016-01-01

    A model for the acoustic production of gravitational waves at a first order phase transition is presented. The source of gravitational radiation is the sound waves generated by the explosive growth of b