BIRD’S-EYE VIEW OF GnRH ANALOG USE IN A PEDIATRIC ENDOCRINOLOGY REFERRAL CENTER

PubMed Central

Watson, Sara E.; Greene, Ariana; Lewis, Katherine; Eugster, Erica A.

2017-01-01

Objective Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center. Methods We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without. Results A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at ≥8 years of age in 62 (39%). Conclusion Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP. PMID:25667370

Oral contraceptive therapy for polycystic ovary disease after chronic gonadotropin-releasing agonist administration. Predictors of continued ovarian suppression.

PubMed

Elkind-Hirsch, K E; Anania, C; Malinak, R

1996-09-01

To study the beneficial effects of oral contraceptive (OC) therapy following gonadotropin-releasing hormone agonist (GnRH-a) administration in women with polycystic ovary disease (PCOD). Twenty-three hyperandrogenic women (aged 15-39) were randomized into two groups; GnRH-a (depot every 28 days) for six months or combination therapy (GnRH-a plus OC "addback") for six months. Following six months of treatment with either therapy, all patients received OC therapy for at least six months. The hormonal state was evaluated at three-month intervals. Hormone levels of luteinizing hormone (LH), testosterone (T) and free T remained suppressed within the normal range in 11 of 17 patients (65%) during the six months of OC only therapy, while the other six patients showed "escape" from suppression, with the LH, T and free T concentrations rising to pre-GnRH-a treatment levels. Use of OC addback therapy did not potentiate the long-acting therapeutic effect of GnRH-a pretreatment; three of six patients in the escape group were pretreated with combination therapy and three with GnRH-a only. In the majority of women with PCOD, OC therapy following GnRH-a administration was effective in maintaining ovarian androgen suppression. Failure to maintain ovarian suppression in this patient population was associated with higher elevations of baseline free T concentrations.

GnRH agonist trigger for the induction of oocyte maturation in GnRH antagonist IVF cycles: a SWOT analysis.

PubMed

Engmann, Lawrence; Benadiva, Claudio; Humaidan, Peter

2016-03-01

Gonadotrophin releasing hormone agonist (GnRHa) trigger is effective in the induction of oocyte maturation and prevention of ovarian hyperstimulation syndrome during IVF treatment. This trigger concept, however, results in early corpora lutea demise and consequently luteal phase dysfunction and impaired endometrial receptivity. The aim of this strenghths, weaknesses, opportunities and threats analysis was to summarize the progress made over the past 15 years to optimize ongoing pregnancy rates after GnRHa trigger. The advantages and potential drawbacks of this type of triggering are reviewed. The current approach to the management of GnRHa trigger in autologous cycles is based on the peak serum oestradiol level or follicle number and aims at a fresh embryo transfer or a segmentation approach with elective cryopreservation policy. We recommend intensive luteal support with transdermal oestradiol and intramuscular progesterone alone if peak serum oestradiol is 4000 or more pg/ml after GnRHa trigger or dual trigger with GnRHa and HCG 1000 IU if peak serum oestradiol is less than 4000 pg/mL. On the contrary, we recommend HCG 1500 IU 35 h after GnRHa trigger if there are less than 25 follicles, or freeze all oocytes or embryos if there are over 25 follicles. Copyright © 2015. Published by Elsevier Ltd.

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

PubMed Central

2013-01-01

Background 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. Methods 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. Results 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. Conclusions 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. PMID:24369069

Role of cortactin in dynamic actin remodeling events in gonadotrope cells.

PubMed

Navratil, Amy M; Dozier, Melissa G; Whitesell, Jennifer D; Clay, Colin M; Roberson, Mark S

2014-02-01

GnRH induces marked activation of the actin cytoskeleton in gonadotropes; however, the physiological consequences and cellular mechanisms responsible have yet to be fully elucidated. The current studies focus on the actin scaffolding protein cortactin. Using the gonadotrope-derived αT3-1 cell line, we found that cortactin is phosphorylated at Y(421), S(405), and S(418) in a time-dependent manner in response to the GnRH agonist buserelin (GnRHa). GnRHa induced translocation of cortactin to the leading edge of the plasma membrane where it colocalizes with actin and actin-related protein 3 (Arp3). Incubation of αT3-1 cells with the c-src inhibitor phosphoprotein phosphatase 1, blocked tyrosine phosphorylation of cortactin, reduced cortactin association with Arp3, and blunted actin reorganization in response to GnRHa. Additionally, we used RNA silencing strategies to knock down cortactin in αT3-1 cells. Knockdown of cortactin blocked the ability of αT3-1 cells to generate filopodia, lamellipodia, and membrane ruffles in response to GnRHa. We show that lamellipodia and filopodia are capable of LHβ mobilization in primary pituitary culture after GnRHa treatment, and disruption of these structures using jasplakinolide reduces LH secretion. Collectively, our findings suggest that after GnRHa activation, src activity leads to tyrosine phosphorylation of cortactin, which facilitates its association with Arp3 to engage the actin cytoskeleton. The reorganization of actin by cortactin potentially underlies GnRHa-induced secretory events within αT3-1 cells.

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

PubMed

Humaidan, Peter; Papanikolaou, E G; Kyrou, D; Alsbjerg, B; Polyzos, N P; Devroey, P; Fatemi, Human M

2012-02-01

In stimulated IVF/intracytoplasmic sperm injection cycles, the luteal phase is disrupted, necessitating luteal-phase supplementation. The most plausible reason behind this is the ovarian multifollicular development obtained after ovarian stimulation, resulting in supraphysiological steroid concentrations and consecutive inhibition of LH secretion by the pituitary via negative feedback at the level of the hypothalamic-pituitary axis. With the introduction of the gonadotrophin-releasing hormone-(GnRH) antagonist, an alternative to human chorionic gonadotrophin triggering of final oocyte maturation 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 insufficiency seen after GnRHa triggering and the various trials that have been performed to assess the most optimal luteal support in relation to GnRHa triggering. Although more research is needed, GnRHa triggering is now an alternative to HCG triggering, combining a significant reduction in OHSS with high ongoing pregnancy rates. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Time- and dose-related effects of a gonadotropin-releasing hormone agonist and dopamine antagonist on reproduction in the Northern leopard frog (Lithobates pipiens).

PubMed

Vu, Maria; Weiler, Bradley; Trudeau, Vance L

2017-12-01

Gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone release to control ovulation and spermiation in vertebrates. Dopamine (DA) has a clear inhibitory role in the control of reproduction in numerous teleosts, and emerging evidence suggests that similar mechanisms may exist in amphibians. The interactions between GnRH and DA on spawning success and pituitary gene expression in the Northern leopard frog (Lithobates pipiens) were therefore investigated. Frogs were injected during the natural breeding season with a GnRH agonist [GnRH-A; (Des-Gly 10 , D-Ala 6 , Pro-NHEt 9 )-LHRH; 0.1μg/g and 0.4μg/g] alone and in combination with the dopamine receptor D2 antagonist metoclopramide (MET; 5μg/g and 10μg/g). Injected animals were allowed to breed in outdoor mesocosms. Time to amplexus and oviposition were assessed, and egg mass release, incidences of amplexus, egg mass weight, total egg numbers and fertilization rates were measured. To examine gene expression, female pituitaries were sampled at 12, 24 and 36h following injection of GnRH-A (0.4μg/g) alone and in combination with MET (10μg/g). The mRNA levels of the genes lhb, fshb, gpha, drd2 and gnrhr1 were measured using quantitative real-time PCR. Data were analyzed by a two-way ANOVA. Both GnRH-A doses increased amplexus, oviposition and fertilization alone. Co-injection of MET with GnRH-A did not further enhance spawning success. Injection of GnRH-A alone time-dependently increased expression of lhb, fshb, gpha and gnrhr1. The major effect of MET alone was to decrease expression of drd2. Importantly, the stimulatory effects of GnRH-A on lhb, gpha and gnrhr1 were potentiated by the co-injection of MET at 36h. At this time, expression of fshb was increased only in animals injected with both GnRH-A and MET. Spawning success was primarily driven by the actions of GnRH-A. The hypothesized inhibitory action of DA was supported by pituitary gene expression analysis. The results from this study provide a fundamental framework for future time- and dose-response investigations to improve current spawning methods in amphibians. Copyright © 2017. Published by Elsevier Inc.

Puberty suppression in gender identity disorder: the Amsterdam experience.

PubMed

Kreukels, Baudewijntje P C; Cohen-Kettenis, Peggy T

2011-05-17

The use of gonadotropin-releasing hormone analogs (GnRHa) to suppress puberty in adolescents with gender dysphoria is a fairly new intervention in the field of gender identity disorders or transsexualism. GnRHa are used to give adolescents time to make balanced decisions on any further treatment steps, and to obtain improved results in the physical appearance of those who opt to continue with sex reassignment. The effects of GnRHa are reversible. However, concerns have been raised about the risk of making the wrong treatment decisions, as gender identity could fluctuate during adolescence, adolescents in general might have poor decision-making abilities, and there are potential adverse effects on health and on psychological and psychosexual functioning. Proponents of puberty suppression emphasize the beneficial effects of GnRHa on the adolescents' mental health, quality of life and of having a physical appearance that makes it possible for the patients to live unobtrusively in their desired gender role. In this Review, we discuss the evidence pertaining to the debate on the effects of GnRHa treatment. From the studies that have been published thus far, it seems that the benefits outweigh the risks. However, more systematic research in this area is needed to determine the safety of this approach.

Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatin-induced toxicity: a controlled experimental animal study

PubMed Central

2013-01-01

Background With the continuous improvement of surgery and chemotherapeutic treatments, many tumour patients increasingly achieve long-term survival and can even be completely cured. However, platinum-containing drugs, which are widely used to treat a variety of types of cancer, cause menstrual disorders and ovarian failure, which in turn lead to infertility. Thus far, gonadotropin releasing hormone (GnRH) agonist (GnRHa) and antagonist (GnRHant) are reported to act as protective agents of the ovary in chemotherapy through the inhibition of the female gonadal axis. Nevertheless, they both have disadvantages that limit their use. GnRHa causes a flare-up effect during the first week after administration, and no long-acting GnRHant agent is available. GnRHa combined with GnRHant may prevent the flare-up effect of GnRHa and rapidly inhibit the female gonadal axis. Several clinical studies with small sample sizes have reported controversial conclusions. In this strictly controlled animal study, we investigated the advantages of combination treatment with GnRHa and GnRHant. Methods Rats aged 12 weeks were divided into six groups: Control, cisplatin (CDDP), GnRHa, GnRHant, Combination (sht, short-term) and Combination (lng, long-term) of GnRHa and GnRHant. The last four groups received Triptorelin (1 mg/kg·d, for 14 days), Cetrorelix (0.5 mg/kg·d, for 10 days), a combination of Triptorelin (1 mg/kg·d, for 10 days) and Cetrorelix (0.5 mg/kg·d, for 10 days) in the long-term group and for 3 days in the short-term group. The Control and CDDP groups received saline (1 ml/kg·d, for 10 day). Then, all groups apart from the Control group received cisplatin (1 mg/kg·d, for 10 days), and the Control group received another 10 days of saline as described above. Blood samples were collected to detect the serum levels of E2, LH and FSH. Observation of oestrous cyclicity was also performed after drug administration. Finally, bilateral ovaries were collected for histological study and follicle counting. Results We observed a flare-up effect in rats treated with GnRHa, but not in any of the combination groups. The percentage of normal cyclicity increased from 0% in the CDDP group to 25.0%, 33.3%, 66.7% and 41.7%, in the GnRHa, GnRHant, combination (lng) and combination (sht) groups, respectively. Pretreatment with GnRHa, GnRHant and combination (lng) significantly protected the primordial follicles from destruction by preserving 57.6%, 63.4%, 87.1% and 60.4% of the follicles, respectively. Conclusions The combination of a GnRH agonist with antagonist completely prevented the flare-up effect and enhanced the protective effect of the ovary from cisplatin-induced gonadotoxicity in rats. PMID:23452939

Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty.

PubMed

Poomthavorn, Preamrudee; Khlairit, Patcharin; Mahachoklertwattana, Pat

2009-01-01

A test involving 100 microg of intravenous gonadotropin-releasing hormone (GnRH) is a gold standard for confirming the diagnosis of central precocious puberty (CPP). However, intravenous GnRH for testing is commercially limited. To develop subcutaneous GnRH agonist (GnRH-A) testing and define a peak luteinizing hormone (LH) cutoff value in diagnosing CPP. A retrospective study of 101 girls with sexual precocity was undertaken. All girls underwent 100 microg subcutaneous GnRH-A (triptorelin) testing. Blood samples before and 30, 60, 90 and 120 min after GnRH-A injection were analyzed for LH and follicle-stimulating hormone levels. Criteria for diagnosing CPP include accelerated height, advanced bone age and pubertal-sized uterus and ovaries. Fifty-five girls were documented as having CPP. The remaining 46 girls were diagnosed with premature thelarche (PT). Peak LH concentration in the CPP group was significantly greater than that of the PT group with a median (range) of 10.0 IU/l (2.93-65.39) and 3.04 IU/l (0.19-8.82), respectively. Peak LH was achieved within 60 min following GnRH-A injection. Peak LH of 6 IU/l provided the most appropriate cutoff level in diagnosing CPP with a sensitivity of 89.1% and a specificity of 91.3%. Subcutaneous GnRH-A can be used as an alternative to confirm the diagnosis of CPP. Copyright 2009 S. Karger AG, Basel.

A single sample GnRHa stimulation test in the diagnosis of precocious puberty

USDA-ARS?s Scientific Manuscript database

Gonadotropin-releasing hormone (GnRH) has been the standard test for diagnosing central precocious puberty. Because GnRH is no longer available, GnRH analogues (GnRHa) are now used. Random LH concentration, measured by the third-generation immunochemiluminometric assay, is a useful screening tool ...

Comparison between two forms of vaginally administered progesterone for luteal phase support in assisted reproduction cycles.

PubMed

Geber, Selmo; Moreira, Ana Carolina Ferreira; de Paula, Sálua Oliveira Calil; Sampaio, Marcos

2007-02-01

The use of progesterone for luteal phase support has been demonstrated to be beneficial in assisted reproduction cycles using gonadotrophin-releasing hormone analogues (GnRHa). Two micronized progesterone preparations are available for vaginal administration: capsules and gel. The objective of this study was to compare the efficacy of these two forms for luteal phase support in assisted reproduction cycles. A total of 244 couples undergoing IVF/intracytoplasmic sperm injection cycles were included in the study and were randomly allocated (sealed envelopes) into two groups: group 1 (122) received vaginal capsules of 200 mg of micronized progesterone (Utrogestan), 3 times daily, and group 2 (122) received micronized progesterone in gel (Crinone 8%), once daily. Both groups received progesterone for 13 days beginning day 1 after oocyte retrieval, continuing until the pregnancy test was performed and until 12 weeks of pregnancy. Groups were compared by clinical data and assisted reproduction results and had similar ages and causes of infertility. Although the pregnancy rate was higher for those receiving progesterone gel than capsules (44.26 and 36.06% respectively), this difference was not statistically significant. The study showed that vaginal progesterone gel and capsules used for luteal phase support in assisted reproduction cycles with long protocol GnRHa result in similar pregnancy rates.

Embryo banking between induction and consolidation chemotherapy in women with leukemia.

PubMed

Rossi, Brooke V; Ashby, Rachel K; Srouji, Serene S

2011-12-01

To report the results of controlled ovarian hyperstimulation (COH) after long-acting GnRH agonist (GnRH-a) and chemotherapy for the purposes of embryo cryopreservation. Case report. University medical center. Two premenopausal women with acute myelogenous leukemia with recent treatment with GnRH-a and induction chemotherapy for hematopoietic cell transplantation (HCT). COH with embryo cryopreservation. Numbers of oocytes and embryos cryopreserved. Both patients responded to gonadotropin stimulation and cryopreserved embryos. Women who have received recent long-acting GnRH-a and chemotherapy may respond to gonadotropin stimulation. The option of embryo banking can be offered to leukemia patients who are preparing for HCT. Copyright © 2011. Published by Elsevier Inc.

Comparison of ovulation induction and pregnacy outcomes in IVF patients with normal ovarian reserve who underwent long protocol with recombinant-FSH and highly purified-hMG.

PubMed

Celik, Cem; Sofuoğlu, Kenan; Selçuk, Selçuk; Asoğlu, Mehmet Reşit; Abalı, Remzi; Cetingöz, Elçin; Baykal, Bahar; Uludoğan, Mehmet

2011-01-01

Gonadotropins used in controlled ovarian stimulation have been increasing in number. Beside the recombinant preparations such as rec-FSH, rec-LH and h-hMG human-derived preparations have entered the market. We decided to compare the effects of rec-FSH and HP-hMG with GnRHa on embryo quality and pregnancy outcome in women undergoing an IVF cycle. In this study, data of 87 patients who had applied to our center from 2007 to 2008 and who had met all inclusion criteria, were analyzed. The patients underwent controlled ovarian hyperstimulation with HP-hMG, rec-FSH following down-regulation with a GnRHa in a long protocol, selected according to determined criteria and acquired embryo via IVF transfer. Of the 87 patients, 44 were stimulated with rec-FSH and 43 with HP-hMG. Distribution of infertility causes was similar between the groups. Duration of gonadotropin administration (p=0.677, Student's t-test) and the total dose of gonadotropin received (p=0.392, Student's t-test) were similar between the two groups. The fertilization rate of the rec-FSH group was significantly higher than the HP-hMG group (p=0.001, Mann-Whitney U test). No significant differences were observed between the study groups in biochemical, clinical and ongoing pregnancy parameters. The higher oocyte yield with rec-FSH does not result in higher quality embryos. LH activity in combination with FSH activity positively affected the oocyte and embryo maturation. Therefore, when we consider the clinical and ongoing pregnancy rates there is no inferiority of HP-hMG in controlled ovarian stimulation.

Comparison of ovulation induction and pregnacy outcomes in IVF patients with normal ovarian reserve who underwent long protocol with recombinant-FSH and highly purified-hMG

PubMed Central

Çelik, Cem; Sofuoğlu, Kenan; Selçuk, Selçuk; Asoğlu, Mehmet Reşit; Abalı, Remzi; Çetingöz, Elçin; Baykal, Bahar; Uludoğan, Mehmet

2011-01-01

Objective Gonadotropins used in controlled ovarian stimulation have been increasing in number. Beside the recombinant preparations such as rec-FSH, rec-LH and h-hMG human-derived preparations have entered the market. We decided to compare the effects of rec-FSH and HP-hMG with GnRHa on embryo quality and pregnancy outcome in women undergoing an IVF cycle. Material and Methods In this study, data of 87 patients who had applied to our center from 2007 to 2008 and who had met all inclusion criteria, were analyzed. The patients underwent controlled ovarian hyperstimulation with HP-hMG, rec-FSH following down-regulation with a GnRHa in a long protocol, selected according to determined criteria and acquired embryo via IVF transfer. Results Of the 87 patients, 44 were stimulated with rec-FSH and 43 with HP-hMG. Distribution of infertility causes was similar between the groups. Duration of gonadotropin administration (p=0.677, Student’s t-test) and the total dose of gonadotropin received (p=0.392, Student’s t-test) were similar between the two groups. The fertilization rate of the rec-FSH group was significantly higher than the HP-hMG group (p=0.001, Mann-Whitney U test). No significant differences were observed between the study groups in biochemical, clinical and ongoing pregnancy parameters. Conclusion The higher oocyte yield with rec-FSH does not result in higher quality embryos. LH activity in combination with FSH activity positively affected the oocyte and embryo maturation. Therefore, when we consider the clinical and ongoing pregnancy rates there is no inferiority of HP-hMG in controlled ovarian stimulation. PMID:24591951

Feasibility of corifollitropin alfa/GnRH antagonist protocol combined with GnRH agonist triggering and freeze-all strategy in polycystic ovary syndrome patients.

PubMed

Hwang, Jiann-Loung; Chen, Shee-Uan; Chen, Hen-Ju; Chen, Hsin-Fu; Yang, Yu-Shih; Chang, Chin-Hao; Seow, Kok-Min; Tzeng, Chii-Ruey; Lin, Yu-Hung

2018-06-01

The long-acting corifollitropin alfa is comparable to FSH in terms of pregnancy outcomes in normal responders and poor responders. Corifollitropin alfa has never been studied in polycystic ovary syndrome (PCOS) patients because of concerns of excessive ovarian stimulation and ovarian hyperstimulation syndrome (OHSS). The purpose of the study was to evaluate if corifollitropin alfa can be used in PCOS patients. Forty PCOS patients who were going to undergo in vitro fertilization were enrolled in this study. A single injection of corifollitropin alfa was administered on cycle day 2 or day 3. From stimulation day 8 onwards, daily FSH was administered until the day of final oocyte maturation. Cetrorelix was administered from stimulation day 5 to prevent premature LH surge. Final oocyte maturation was triggered by: acetate. All embryos were cryopreserved and replaced in subsequent cycles. All 40 patients were subjected to oocyte retrieval, and none developed moderate or severe ovarian hyperstimulation syndrome (0%, 95% CI 0-0.088). For each patient, an average of 23.4 (±7.4; 95% CI 21.0-25.7) oocytes were retrieved and a mean of 11.7 (±6.4; 95% CI 9.6-13.8) embryos were frozen. Mean serum estradiol level on the day of GnRHa triggering was 7829.9 pg/ml (±3297; 95% CI 6775-8885). The cumulated ongoing pregnancy rate after 3 frozen-thawed embryo transfers was 75.0% (95% CI 61.6%-88.4%). The results suggest that corifollitropin alfa/GnRH antagonist protocol can be used in PCOS patients, in combination with GnRHa triggering and embryo cryopreservation. Copyright © 2017. Published by Elsevier B.V.

The benefit of individualized low-dose hCG support for high responders in GnRHa-triggered IVF/ICSI cycles.

PubMed

Huang, Chen-Yu; Shieh, Miawh-Lirng; Li, Hsin-Yang

2016-07-01

To assess the pregnancy outcome and ovarian hyperstimulation syndrome (OHSS) incidence in high responders receiving gonadotropin-releasing hormone agonist (GnRHa) trigger plus individualized support of low-dose human chorionic gonadotropin (hCG). Such support includes 500-1000 IU hCG given at trigger and, if serum estradiol (E2) dropped to below 800 pg/mL before the 6(th) day after oocyte retrieval, an additional rescue dose of 300 IU hCG. This was a retrospective study of potential high responders aged from 28 years to 40 years at a tertiary fertility center in Taiwan. By means of chart review, we assessed the pregnancy outcome and OHSS incidence in high responders receiving GnRHa trigger plus individualized low-dose hCG support. The main outcomes were measured by ongoing pregnancy rate and OHSS incidence (SPSS), in which statistical significance was determined by Chi-square test. Moderate to severe OHSS did not develop in any patient receiving GnRHa trigger plus individualized low-dose hCG support. In fact, a satisfactory ongoing pregnancy rate (46.9%) was noted in patients receiving GnRHa trigger plus individualized low-dose hCG support. Our study suggested that GnRHa trigger combined with individualized low-dose hCG support appears to be a safe approach with a satisfactory pregnancy outcome. Copyright © 2016. Published by Elsevier Taiwan LLC.

A Study on Dietary Habits and Lifestyle of Girls with Precocious Puberty

PubMed Central

Heo, Jae-Seong; Moon, Hyeok-Soo

2016-01-01

Purpose This study was conducted to analyze the change in the obesity index in girls receiving a gonadotropin-releasing hormone agonist (GnRHa), based on treatment duration, and to aid in nutritional counseling by investigating dietary habits and lifestyle. Methods Anthropometric examinations were conducted on 62 girls treated with GnRHa from January 2010 through July 2014. Parents were asked to fill out questionnaires on patient dietary habits and lifestyle. Results The group taking GnRHa for over 1 year had a higher rate of obesity increase than the group taking GnRHa for less than 1 year, but they had common habits related to obesity, which should be corrected. In addition, 69.2% of the normal weight group taking GnRHa for over 1 year gained weight, and needed more intensive programs, which include physical exercise and nutritional education. Although girls with precocious puberty showed a decrease in the intake of high-calorie foods with nutritional intervention regardless of treatment duration, they still had problems that needed improvement, such as shorter meals and lack of exercise. Conclusion Girls with precocious puberty and their parents should emphasize maintenance of proper body weight, especially when treatment for over 1 year is anticipated. Consistent education in nutrition, ways to increase intensity and duration of physical activity, and the need to slow down mealtimes are important in managing obesity; doctors need to perform regular checkups and provide nutritional counseling. PMID:27437190

Follicle Size on Day of Trigger Most Likely to Yield a Mature Oocyte.

PubMed

Abbara, Ali; Vuong, Lan N; Ho, Vu N A; Clarke, Sophie A; Jeffers, Lisa; Comninos, Alexander N; Salim, Rehan; Ho, Tuong M; Kelsey, Tom W; Trew, Geoffrey H; Humaidan, Peter; Dhillo, Waljit S

2018-01-01

To identify follicle sizes on the day of trigger most likely to yield a mature oocyte following hCG, GnRH agonist (GnRHa), or kisspeptin during IVF treatment. Retrospective analysis to determine the size of follicles on day of trigger contributing most to the number of mature oocytes retrieved using generalized linear regression and random forest models applied to data from IVF cycles (2014-2017) in which either hCG, GnRHa, or kisspeptin trigger was used. HCG and GnRHa data were collected at My Duc Hospital, Ho Chi Minh City, Vietnam, and kisspeptin data were collected at Hammersmith Hospital, London, UK. Four hundred and forty nine women aged 18-38 years with antral follicle counts 4-87 were triggered with hCG ( n  = 161), GnRHa ( n  = 165), or kisspeptin ( n  = 173). Follicle sizes on the day of trigger most likely to yield a mature oocyte. Follicles 12-19 mm on the day of trigger contributed the most to the number of oocytes and mature oocytes retrieved. Comparing the tertile of patients with the highest proportion of follicles on the day of trigger 12-19 mm, with the tertile of patients with the lowest proportion within this size range, revealed increases of 4.7 mature oocytes for hCG ( P  < 0.0001) and 4.9 mature oocytes for GnRHa triggering ( P  < 0.01). Using simulated follicle size profiles of patients with 20 follicles on the day of trigger, our model predicts that the number of oocytes retrieved would increase from a mean 9.8 (95% prediction limit 9.3-10.3) to 14.8 (95% prediction limit 13.3-16.3) oocytes due to the difference in follicle size profile alone. Follicles 12-19 mm on the morning of trigger administration were most likely to yield a mature oocyte following hCG, GnRHa, or kisspeptin.

Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty.

PubMed

Park, Jina; Kim, Jae Hyun

2017-03-01

Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP. Patient group included 83 girls (aged 7.0-8.9 years) with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI]) were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment. No statistical difference in BMI z -score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all P <0.001). In normal-weight subjects in the patient group, BMI z -score was significantly increased during GnRHa treatment (-0.1±0.7 vs. 0.1±0.8, P <0.001), whereas HOMA-IR and QUICKI exhibited no differences. In overweight subjects in the patient group; BMI z -score and HOMA-IR were not significantly different, whereas QUICKI was significantly decreased during GnRHa treatment (0.35±0.03 vs. 0.33±0.02, P =0.044). Girls with CPP exhibited increased insulin resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z -scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z -scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI.

PubMed

Mohsen, Iman Abdel; El Din, Rasha Ezz

2013-02-01

To compare the IVF outcomes of letrozole/antagonist and microdose GnRH agonist flare up protocols in poor ovarian responders undergoing intracytoplasmic sperm injection. A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which four or less oocytes were retrieved when the gonadotrophin starting dose was at least 300 IU/day. Sixty patients were randomized by computer-generated list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a protocol (microdose flare) n = 30. Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used gonadotropins and the number of stimulation days were significantly lower in the letrozole/antagonist protocol. The peak E2 level on the day of hCG, the endometrial thickness, the retrieved oocytes, the number of fertilized oocytes, the number of transferred embryos and the cancellation rate were statistically similar in both groups. The letrozole/antagonist protocol is a cost-effective and patient-friendly protocol that may be used in poor ovarian responders for IVF/ICSI.

Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival.

PubMed

Zhang, Ying; Ji, Yajie; Li, Jianwei; Lei, Li; Wu, Siyu; Zuo, Wenjia; Jia, Xiaoqing; Wang, Yujie; Mo, Miao; Zhang, Na; Shen, Zhenzhou; Wu, Jiong; Shao, Zhimin; Liu, Guangyu

2018-04-01

To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints. The median follow-up time was 56.9 months (IQR 49.5-72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups. For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation and survival outcomes that were no worse than simultaneous use. The application of GnRHa can probably be delayed until menstruation resumption after chemotherapy.

No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial.

PubMed

Demeestere, Isabelle; Brice, Pauline; Peccatori, Fedro A; Kentos, Alain; Dupuis, Jehan; Zachee, Pierre; Casasnovas, Olivier; Van Den Neste, Eric; Dechene, Julie; De Maertelaer, Viviane; Bron, Dominique; Englert, Yvon

2016-08-01

We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up. A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up. Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467). To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma. © 2016 by American Society of Clinical Oncology.

Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women.

PubMed

Zhou, Huimei; Cao, Dongyan; Yang, Jiaxin; Shen, Keng; Lang, Jinghe

2017-07-01

The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH). We performed a retrospective analysis including the clinical characteristics of 29 patients younger than 45 years with early well-differentiated endometrioid adenocarcinoma of the uterus (EC) or CAH who were treated at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2012 to April 2016. Eighteen patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with the levonorgestrel intrauterine hormonal system (Mirena® Bayer Health Care Pharmaceutical Inc, Wayne, NY) was inserted. Eleven patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with oral letrozole 2.5 mg daily. The patients underwent follow-up with endometrial sampling by hysteroscopy and curettage for endometrial response every 3 months. After a median follow-up of 18.7 months (range, 5.6-54.9 months), 15 women (88.2%) in the EC group and 12 women (100%) in the CAH group had complete response (CR) after GnRHa combination treatment. Among the women who achieved CR, 1 woman (8.3%) with CAH and 1 woman (5.9%) with EC had recurrence after CR, and they finally underwent a hysterectomy. Time to CR was similar in the 2 groups (4.5 ± 1.9 months in the CAH group vs 5.0 ± 2.9 months in the EC group). Ten women (34.5%) had CR after the first 3 months, 8 women (27.6%) had CR after 6 months, and 9 women (31.0%) had CR after 9 months. Both GnRHa with the levonorgestrel-releasing intrauterine system and GnRHa with letrozole are alternative treatments for women with CAH and EC who desire fertility preservation. A larger multicenter trial of the fertility-preserving treatment is warranted.

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones.

PubMed

Malik, Minnie; Britten, Joy; Cox, Jeris; Patel, Amrita; Catherino, William H

2016-01-01

To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Laboratory study. University research laboratory. Women undergoing hysterectomy for symptomatic leiomyomas. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy. Published by Elsevier Inc.

GnRH agonist for triggering of final oocyte maturation: time for a change of practice?

PubMed

Humaidan, P; Kol, S; Papanikolaou, E G

2011-01-01

GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering. This narrative review is based on expert presentations and subsequent group discussions supplemented with publications from literature searches and the authors' knowledge. Moreover, randomized controlled trials (RCTs) were identified and analysed either in fresh IVF cycles with embryo transfer (ET), oocyte donation cycles or cycles without ET; risk differences were calculated regarding pregnancy rate and OHSS rate. In fresh IVF cycles with ET (9 RCTs) no OHSS was reported after GnRHa triggering [0% incidence in the GnRHa group: risk difference 5% (with 95% CI: -0.07 to 0.02)]. Importantly, the delivery rate improved significantly after modified luteal support [6% risk difference in favour of the HCG group (95% CI: -0.14 to 0.2)] when compared with initial studies with conventional luteal support [18% risk difference (95% CI: -0.36 to 0.01)]. In oocyte donation cycles (4 RCTs) the OHSS incidence is 0% [10% risk difference (95% CI: 0.02-0.40)]. GnRHa triggering is a valid alternative to hCG triggering, resulting in an elimination of OHSS. After modified luteal support there is now a non-significant difference of 6% in delivery rate in favour of hCG triggering.

Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

PubMed

Liu, S; Liu, Q; Cheng, X; Luo, Y; Wen, Y

2016-10-01

This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP). Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin-releasing hormone analogue (GnRHa) therapy and GnRHa plus growth hormone (GH) combination therapy to treat ICPP girls. A total of six RCTs (162 patients) and six CCTs (247 patients) were included. Compared to the GnRHa therapy group, the combination therapy group achieved taller final height (mean difference, MD = 2.81 cm, 95 % CI 1.76-3.87, four CCTs; MD = 4.30 cm, 95 % CI 0.59-8.01, one RCT); greater progression of final height compared with target height (MD = 3.92 cm, 95 % CI 3.12-4.73, four CCTs; MD = 4.00 cm, 95 % CI 1.93-6.07, One RCT) and larger height gains (MD = 3.49 cm, 95 % CI 0.97-6.01, four CCTs; MD = 3.88 cm, 95 % CI 0.15-7.61, one RCT). No severe adverse effects of treatment were reported. For ICPP girls, the GnRHa and GH combination therapy had advantages over GnRHa alone on final height and no severe adverse effects were reported. We recommend comprehensive assessment of the individual growth rate, patient compliance, the clinical effects, the height expectations of individual patients and the treatment cost to the family in order to identify the best therapy for individual patients.

Use of a potent, long acting agonist of gonadotropin-releasing hormone in the treatment of precocious puberty.

PubMed

Boepple, P A; Mansfield, M J; Wierman, M E; Rudlin, C R; Bode, H H; Crigler, J F; Crawford, J D; Crowley, W F

1986-02-01

Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with CPP have been treated during the last 5 yr with the potent GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of duration of the GnRH agonists in the luteal phase in the outcome of assisted reproduction cycles.

PubMed

Geber, Selmo; Sampaio, Marcos

2013-06-01

The effect of long-acting GnRHa, in the luteal phase, during ART cycles varies from one patient to another. The aim of this study was to evaluate whether the effect of long-acting GnRHa in the luteal phase, in ART cycles, affects pregnancy rates according to the duration of its action in such phase. This is a retrospective study of 367 patients submitted to ovulation induction for in vitro fertilization/intracytoplasmic sperm injection procedures that used long-acting depot GnRHa for pituitary suppression. Patients were stratified according to the period of action of the agonist in the luteal phase: group 1, ≤ 6 days; group 2, 7 to 12 days; and group 3, >12 days. The following variables were analyzed: ovarian response, age, infertility causes and pregnancy rates. Group 1 (n = 53) had a mean age of 33.8 ± 4.55 years (23-44 years) and a pregnancy rate of 45.2%. In group 2 (n = 118), mean age was 33.7 ± 4.5 years (24-44 years) and the pregnancy rate was 38.9%. In group 3 (n = 196), mean age was 33.7 ± 4.4 years (23-43 years) and the pregnancy rate was 47.4%. Regardless of the duration of depot GnRHa action in the luteal phase, no significant association with pregnancy rates was found.

Comparison between a single dose of goserelin (depot) and multiple daily doses of leuprolide acetate for pituitary suppression in IVF treatment: a clinical endocrinological study of the ovarian response.

PubMed

Geber, Selmo; Sales, Liana; Sampaio, Marcos A C

2002-07-01

Compare the efficacy and safety of two different GnRHa, used for pituitary suppression in IVF cycles. A total of 292 patients using depot goserelin (Group 1) and 167 using daily leuprolide acetate (Group 2) were compared. Days required to achieve pituitary function suppression, duration of ovarian stimulation, total dose of HMG, number of aspirated follicles, number of oocytes retrieved, and presence of functional ovarian cyst were analyzed. The time taken to achieve downregulation was similar. The mean number of ampoules used for superovulation was higher in Group 1; however, this difference was observed only for patients >40 years old that started GnRHa in the follicular phase. There was no difference between the two groups in the duration of superovulation, in the number of follicles aspirated, and the number of oocytes retrieved. In the group of patients with >40 years the incidence of ovarian cysts was higher in Group 2. Both routes of GnRHa have similar effects for pituitary suppression and ovulation induction in assisted reproductive technology. Therefore the long-acting GnRHa is an excellent option, as only a single subcutaneous dose is necessary, decreasing the risk of the patient to forget its use and, most important, it does not interfere in the patient's quality of life.

[Medical treatment for the management of painful endometriosis without infertility: CNGOF-HAS Endometriosis Guidelines].

PubMed

Sauvan, M; Chabbert-Buffet, N; Canis, M; Collinet, P; Fritel, X; Geoffron, S; Legendre, G; Wattier, J-M; Fernandez, H

2018-03-01

To provide clinical practice guidelines for the management of painful endometriosis in women without infertility. Systematic review of the literature literature since 2006, level of evidence rating, external proofreading and grading of the recommendation grade by an expert group according to HAS methodology. Combined hormonal contraceptives (COP) and the levonorgestrel-releasing intra-uterin system (LNG-IUS) are recommended as first-line hormonal therapies for the treatment of painful endometriosis (grade B). Second-line therapy relies on oral desogestrel microprogestative, etonogestrel-releasing implant, GnRH analogs (GnRHa) and dienogest (grade C). It is recommended to use add-back therapy containing estrogen in association with GnRHa (grade B). After endometriosis surgery, hormonal treatment relying on COP or LNG-IUS is recommended to prevent pain recurrence (grade B). COP is recommended to reduce the risk of endometrioma recurrence after surgery (grade B) but the prescription of GnRHa is not recommended (grade C). Continuous COP is recommended in case of dysmenorrhea (grade B). GnRHa is not recommended as first line endometriosis treatment for adolescent girl because of the risk of bone demineralization (grade B). The management of endometriosis-induced chronic pain requires an interdisciplinary evaluation. Physical therapies improving the quality of life such as yoga, relaxation or osteopathy can be proposed (expert agreement). Promising medical alternatives are currently under preclinical and clinical evaluation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression✩,✩✩

PubMed Central

Joshi, R.N.; Safadi, F.F.; Barbe, M.F.; Carpio-Cano, Fe Del; Popoff, S.N.; Yingling, V.R.

2013-01-01

Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n=10), GnRH-a group (n=10), and Energy Restriction (ER, n=12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals’ intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of nutritional stress the increased vertebral bone volume may be an adaptive mechanism to store mineral which differs from suppressed estradiol resulting from hypothalamic suppression. PMID:21807131

The Effects of Gonadotropin-Releasing Hormone Agonist Combined with Add-Back Therapy on Quality of Life for Adolescents with Endometriosis: A Randomized Controlled Trial.

PubMed

Sadler Gallagher, Jenny; Feldman, Henry A; Stokes, Natalie A; Laufer, Marc R; Hornstein, Mark D; Gordon, Catherine M; DiVasta, Amy D

2017-04-01

Use of gonadotropin-releasing hormone agonists (GnRHa) to treat endometriosis can cause mood and vasomotor side effects. "Add-back therapy," the combination of low-dose hormones, limits side effects but research is limited to adults. We sought to characterize quality of life (QOL) before treatment and to compare an add-back regimen of norethindrone acetate (NA) with conjugated estrogens (CEE) to NA alone for preventing side effects of GnRHa therapy in female adolescents with endometriosis. Twelve-month double-blind, placebo-controlled trial. Pediatric Gynecology clinic in Boston, Massachusetts. Fifty female adolescents (aged 15-22 years) with surgically confirmed endometriosis initiating treatment with GnRHa. Subjects were randomized to: NA (5 mg/d) with CEE (0.625 mg/d) or NA (5 mg/d) with placebo. All subjects received leuprolide acetate depot every 3 months. The Short Form-36 v2 Health Survey, Beck Depression Inventory II, and Menopause Rating Scale were completed at repeated intervals. At baseline, subjects reported impaired physical health-related QOL compared with national norms (all P < .0001). Over 12 months, these Short Form-36 v2 scores improved (all P < .05). Subjects receiving NA with CEE showed greater improvements in the pain, vitality, and physical health subscales (P between groups < .05) than those receiving NA alone, as well as better physical functioning (P < .05). There were no changes in depression or menopause-like symptoms in either group. Female adolescents with endometriosis initiating GnRHa therapy have impaired QOL. Treatment with GnRHa combined with add-back therapy led to improved QOL, with no worsening of mood or menopausal side effects. NA with CEE was superior to NA alone for improving physical health-related QOL. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

The serum level of C-reactive protein in patients undergoing GnRH agonist protocols for in vitro fertilization cycle.

PubMed

Liu, B; Zhang, L; Guo, R W; Wang, W J; Duan, X Q; Liu, Y W

2014-01-01

The synchronization of the uterus and mature eggs at the molecular level is the key factor in embryo transfer, and the regulation of synchronization depends on a variety of cytokines. C-reactive protein (CRP), as the first acute phase reaction protein, is involved in the entire process of embryo transfer. The study is designed to investigate the correlation among CRP, sex hormone, controlled ovarian hyperstimulation (COH) cycle, and pregnancy outcome. Ninety-two patients who accepted in vitro fertilization (IVF) treatment cycles because of tubal factor were included in the study. Seventy treated cases were included to complete final analysis with the full set of results. Respectively on the second day of the menstruation (Day-2) in gonadotropin-releasing hormone agonist (GnRH-a) short program treatment, on the morning in human chorionic gonadotropin (hCG) treatment (Day-hCG) and the embryo transplant day (Day-ET), plasma CRP level was tested by enzyme-linked immunosorbent assay (ELISA). The correlativity among CRP level, sex hormone, COH, and pregnancy outcome was analyzed by statistical methods. In the short program GnRH-a of 70 cases, there was no relationship between serum CRP level and the infertility age, gonadotropin (Gn) dosage, number of oocytes retrieved, the number of normal fertilization, and sex hormone. In the short program of GnRH-a, the change of serum CRP levels in Day-2, Day-hCG, Day-ET: serum CRP in Day-2 < Day-hCG < Day-ET and the level of serum CRP gradually increased in Day-2, Day-hCG, and Day-ET in both the pregnant group and non-pregnant group. In non-pregnant group, the ratio of hCG/D2 and ET/hCG-day were significantly higher than the pregnant group. The area under receiver operating characteristic (ROC) curve was 0.806, indicating the accuracy of diagnostic tests is medium, the authors chose the point which presents the ratio of CRP in Day-ET to Day-hCG which was less than 1.752 as a predictor of treatment outcome, the sensitivity of the experiment was 77.8%, and the specificity 75%. CRP as a sensitive inflammatory marker, CRP ratio of Day-ET/Day-hCG could be a predictor of treatment outcome by ROC curve analysis in COH program.

Efficient induction of spawning of northern leopard frogs (Lithobates pipiens) during and outside the natural breeding season.

PubMed

Trudeau, Vance L; Schueler, Frederick W; Navarro-Martin, Laia; Hamilton, Christine K; Bulaeva, Elizabeth; Bennett, Amanda; Fletcher, William; Taylor, Lisa

2013-02-25

Amphibian declines are now recognized globally. It is also well known that many anurans do not reproduce easily in captivity, especially when held over long periods, or if they require hibernation before breeding. A simple method to induce spawning and subsequent development of large numbers of healthy tadpoles is therefore required to meet research and conservation goals. The method is based on simultaneous injection of both female and male leopard frogs, Lithobates pipiens (formerly called Rana pipiens) with a cocktail of a gonadotropin-releasing hormone agonist (GnRH-A) and a dopamine antagonist. We call this the AMPHIPLEX method, which is derived from the combination of the words amphibian and amplexus. Following injection, the animals are thereby induced, and perform amplexus and natural fertilization under captive conditions. We tested combinations of a GnRH agonist with 2 different dopamine antagonists in L. pipiens in the breeding season. The combination of des-Gly(10), D-Ala(6), Pro-NHEt(9)-GnRH (0.4 micrograms/g body weight; GnRH-A) with metoclopramide hydrochloride (10 micrograms/g body weight; MET) or domperidone (DOM) were equally effective, producing 89% and 88% successful spawning, respectively. This yielded more than 44,000 eggs for the 16/18 females that ovulated in the GnRH-A+MET group, and more than 39,000 eggs for the 15/17 females that ovulated in the GnRH-A+DOM group. We further tested the GnRH-A+MET in frogs collected in the wild in late autumn and hibernated for a short period under laboratory conditions, and report a low spawning success (43%). However, GnRH-A priming 24 hours prior to injections of the GnRH-A+MET cocktail in animals hibernated for 5-6 weeks produced out-of-season spawning (89%) and fertilization (85%) comparable to those we observed for in-season spawning. Assessment of age and weight at metamorphosis indicated that L. pipiens tadpoles resulting from out-of-season spawning grew normally and metamorphosed successfully. We provide evidence for successful captive breeding of the leopard frog, L. pipiens. This simple protocol can be used to obtain large numbers of eggs in a predictable, timed manner.

Adverse Effects of Induced Hot Flashes on Objectively Recorded and Subjectively Reported Sleep: Results of a Gonadotropin-Releasing Hormone Agonist Experimental Protocol

PubMed Central

Joffe, Hadine; White, David P.; Crawford, Sybil L.; McCurnin, Kristin E.; Economou, Nicole; Connors, Stephanie; Hall, Janet E.

2013-01-01

Objectives The impact of hot flashes on sleep is of great clinical interest, but results are inconsistent, especially when both hot flashes and sleep are measured objectively. Using objective and subjective measurements, we examined the impact of hot flashes on sleep by inducing hot flashes with a gonadotropin-releasing hormone agonist (GnRHa). Methods The GnRHa leuprolide was administered to 20 healthy premenopausal volunteers without hot flashes or sleep disturbances. Induced hot flashes were assessed objectively (skin-conductance monitor) and subjectively (daily diary) during one-month follow-up. Changes from baseline in objective (actigraphy) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were compared between women who did and did not develop objective hot flashes, and, in parallel analyses, subjective hot flashes. Results New-onset hot flashes were recorded in 14 (70%) and reported by 14 (70%) women (80% concordance). Estradiol was universally suppressed. Objective sleep efficiency worsened in women with objective hot flashes and improved in women without objective hot flashes (median decrease 2.6%, increase 4.2%, p=0.005). Subjective sleep quality worsened more in those with than without subjective hot flashes (median increase PSQI 2.5 vs. 1.0, p=0.03). Objective hot flashes were not associated with subjective sleep quality, nor were subjective symptoms linked to objective sleep measures. Conclusions This experimental model of induced hot flashes demonstrates a causal relationship between hot flashes and poor sleep quality. Objective hot flashes result in worse objective sleep efficiency, while subjective hot flashes worsen perceived sleep quality. PMID:23481119

Orthotopic Transplantation of Cryopreserved Mouse Ovaries and Gonadotrophin Releasing Hormone Analogues in the Restoration of Function following Chemotherapy-Induced Ovarian Damage

PubMed Central

Li, Qing; Szatmary, Peter; Liu, Yanyang; Ding, Zhenyu; Zhou, Jin; Sun, Yi; Luo, Feng

2015-01-01

Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients’ quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I); cyclophosphamide only (group II); cyclophosphamide plus GnRHa (group III); cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV). Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide. PMID:25811681

Pelvic adhesion and gonadotropin-releasing hormone analogue: effects of triptorelin acetate depot on coagulation and fibrinolytic activities.

PubMed

Di Nardo, Maria Antonietta; Annunziata, Maria Laura; Ammirabile, Massimiliano; Di Minno, Matteo Nicola Dario; Ruocco, Anna Lilia; De Falco, Marianna; Di Lieto, Andrea

2012-06-01

The study investigated the impact of gonadotropin-releasing hormone analogue (GnRH-a) on coagulation and fibrinolytic activities and its effectiveness in the prevention of pelvic adhesion after myomectomy. Thirty-two infertile women underwent myomectomy followed by adhesion evaluation surgery with a second-look laparoscopy. Before myomectomy, 15 women were treated with triptorelin acetate for 3 months and 17 received no treatment. Plasminogen activator inhibitor (PAI), thrombin activatable fibrinolysis inhibitor (TAFI), protein C (PC), plasminogen, α2-antiplasmin were determined by enzyme-linked immunosorbent assays and the activity of coagulation factors V and VIII by coagulometric methods. Patients treated with GnRH-a showed significant decrease in PAI, TAFI, factors V, and VIII (P < .05) and increased PC (P < .05), but no significant change in plasminogen and α2-antiplasmin levels compared with control group. The incidence, extent, and severity of adhesions were significantly lower in GnRH-a-treated patients compared with control group (P < .05), suggesting a possible critical role of the GnRH-a therapy in preventing postoperative adhesion development.

GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro.

PubMed

Bildik, Gamze; Akin, Nazlı; Senbabaoglu, Filiz; Sahin, Gizem Nur; Karahuseyinoglu, Sercin; Ince, Umit; Taskiran, Cagatay; Selek, Ugur; Yakin, Kayhan; Guzel, Yilmaz; Ayhan, Cem; Alper, Ebru; Cetiner, Mustafa; Balaban, Basak; Mandel, Nil Molinas; Esen, Tarık; Iwase, Akira; Urman, Bulent; Oktem, Ozgur

2015-12-01

Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of peripubertal gonadotropin-releasing hormone agonist on brain development in sheep--a magnetic resonance imaging study.

PubMed

Nuruddin, Syed; Bruchhage, Muriel; Ropstad, Erik; Krogenæs, Anette; Evans, Neil P; Robinson, Jane E; Endestad, Tor; Westlye, Lars T; Madison, Cindee; Haraldsen, Ira Ronit Hebold

2013-10-01

In many species sexual dimorphisms in brain structures and functions have been documented. In ovine model, we have previously demonstrated that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) action increased sex-differences of executive emotional behavior. The structural substrate of this behavioral alteration however is unknown. In this magnetic resonance image (MRI) study on the same animals, we investigated the effects of GnRH agonist (GnRHa) treatment on the volume of total brain, hippocampus and amygdala. In total 41 brains (17 treated; 10 females and 7 males, and 24 controls; 11 females and 13 males) were included in the MRI study. Image acquisition was performed with 3-T MRI scanner. Segmentation of the amygdala and the hippocampus was done by manual tracing and total gray and white matter volumes were estimated by means of automated brain volume segmentation of the individual T2-weighted MRI volumes. Statistical comparisons were performed with general linear models. Highly significant GnRHa treatment effects were found on the volume of left and right amygdala, indicating larger amygdalae in treated animals. Significant sex differences were found for total gray matter and right amygdala, indicating larger volumes in male compared to female animals. Additionally, we observed a significant interaction between sex and treatment on left amygdala volume, indicating stronger effects of treatment in female compared to male animals. The effects of GnRHa treatment on amygdala volumes indicate that increasing GnRH concentration during puberty may have an important impact on normal brain development in mammals. These novel findings substantiate the need for further studies investigating potential neurobiological side effects of GnRHa treatment on the brains of young animals and humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Critical Appraisal of the Effect of Gonadotropin-Releasing Hormon Analog Treatment on Adult Height of Girls with Central Precocious Puberty

PubMed Central

Bereket, Abdullah

2017-01-01

Central precocious puberty (CPP) is a diagnosis that pediatric endocrinologists worldwide increasingly make in girls of age 6-8 years and is mostly idiopathic. Part of the reason for increasing referral and diagnosis is the perception among the doctors as well as the patients that treatment of CPP with long-acting gonadotropin-releasing hormon analogues (GnRHa) promote height of the child. Although, the timing and the tempo of puberty does influence statural growth and achieved adult height, the extent of this effect is variable depending on several factors and is modest in most cases. Studies investigating GnRHa treatment in girls with idiopathic CPP demonstrate that treatment is able to restore adult height compromised by precocious puberty. However, reports on untreated girls with precocious puberty demonstrate that some of these girls achieve their target height without treatment as well, thus, blurring the net effect of GnRHa treatment on height in girls with CPP. Clinical studies on treatment of girls with idiopathic CPP on adult stature suffers from the solid evidence-base due mainly to the lack of well-designed randomized controlled studies and our insufficiencies of predicting adult height of a child with narrow precision. This is particularly true for girls in whom age of pubertal onset is close to physiological age of puberty, which are the majority of cases treated with GnRHa nowadays. Heterogeneous nature of pubertal tempo (progressive vs. nonprogressive) leading to different height outcomes also complicates the interpretation of the results in both treated and untreated cases. This review will attemp to summarize and critically appraise available data in the field. PMID:29280737

Does endometrial integrin expression in endometriosis patients predict enhanced in vitro fertilization cycle outcomes after prolonged GnRH agonist therapy?

PubMed

Surrey, Eric S; Lietz, Annette K; Gustofson, Robert L; Minjarez, Debra A; Schoolcraft, William B

2010-02-01

To determine whether endometrial expression of the integrin alpha(v)beta(3) vitronectin can predict which endometriosis patient subgroup will benefit from pre-IVF cycle prolonged GnRH agonist (GnRHa) therapy. Prospective randomized institutional review board approved pilot trial. Private assisted reproductive technology program. IVF candidates with regular menses, surgically confirmed endometriosis, and normal ovarian reserve. All patients underwent endometrial biopsy 9 to 11 days post-LH surge to evaluate alpha(v)beta(3) integrin expression. Patients were randomized either to receive depot leuprolide acetate 3.75 mg every 28 days for three doses before controlled ovarian hyperstimulation (COH) or to proceed directly to COH and IVF. Group 1: integrin-positive controls (N = 12); group 2: integrin-positive administered prolonged GnRHa (N = 8). Group A: integrin-negative controls (N = 7); group B: integrin-negative administered prolonged GnRHa (N = 9). COH responses, ongoing pregnancy and implantation rates. There were no significant effects of GnRH agonist treatment in either of the integrin expression strata regarding ongoing pregnancy or implantation rates, although these outcomes were more frequent in group 2 vs. 1 (62.5% vs. 41.6% and 35% vs. 20.6%, respectively). This effect may have because of limited sample size. The value of a negative integrin biopsy in predicting an ongoing pregnancy after prolonged GnRH agonist therapy was only 44.4%. Endometrial alpha(v)beta(3) integrin expression did not predict which endometriosis patients would benefit from prolonged GnRHa therapy before IVF. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Evaluation of an accelerated 3D SPACE sequence with compressed sensing and free-stop scan mode for imaging of the knee.

PubMed

Henninger, B; Raithel, E; Kranewitter, C; Steurer, M; Jaschke, W; Kremser, C

2018-05-01

To prospectively evaluate a prototypical 3D turbo-spin-echo proton-density-weighted sequence with compressed sensing and free-stop scan mode for preventing motion artefacts (3D-PD-CS-SPACE free-stop) for knee imaging in a clinical setting. 80 patients underwent 3T magnetic resonance imaging (MRI) of the knee with our 2D routine protocol and with 3D-PD-CS-SPACE free-stop. In case of a scan-stop caused by motion (images are calculated nevertheless) the sequence was repeated without free-stop mode. All scans were evaluated by 2 radiologists concerning image quality of the 3D-PD-CS-SPACE (with and without free-stop). Important knee structures were further assessed in a lesion based analysis and compared to our reference 2D-PD-fs sequences. Image quality of the 3D-PD-CS-SPACE free-stop was found optimal in 47/80, slightly compromised in 21/80, moderately in 10/80 and severely in 2/80. In 29/80, the free-stop scan mode stopped the 3D-PD-CS-SPACE due to subject motion with a slight increase of image quality at longer effective acquisition times. Compared to the 3D-PD-CS-SPACE with free-stop, the image quality of the acquired 3D-PD-CS-SPACE without free-stop was found equal in 6/29, slightly improved in 13/29, improved with equal contours in 8/29, and improved with sharper contours in 2/29. The lesion based analysis showed a high agreement between the results from the 3D-PD-CS-SPACE free-stop and our 2D-PD-fs routine protocol (overall agreement 96.25%-100%, Cohen's Kappa 0.883-1, p < 0.001). 3D-PD-CS-SPACE free-stop is a reliable alternative for standard 2D-PD-fs protocols with acceptable acquisition times. Copyright © 2018 Elsevier B.V. All rights reserved.

Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep.

PubMed

Nuruddin, Syed; Krogenæs, Anette; Brynildsrud, Ola Brønstad; Verhaegen, Steven; Evans, Neil P; Robinson, Jane E; Haraldsen, Ira Ronit Hebold; Ropstad, Erik

2013-12-01

The nature of hormonal involvement in pubertal brain development has attracted wide interest. Structural changes within the brain that occur during pubertal development appear mainly in regions closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors, results in exaggerated sex-differences in cognitive executive function and emotional control, as well as sex and hemisphere specific patterns of expression of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explored effects of this treatment regime on the gene expression profile of the ovine amygdala. The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until approximately 50 weeks of age. Gene expression profiles of the left and right amygdala were measured using 8×15 K Agilent ovine microarrays. Differential expression of selected genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for Annotation, Visualization and integrated Discovery) version 6.7 software packages, respectively. GnRHa treatment was associated with significant sex- and hemisphere-specific differential patterns of gene expression. GnRHa treatment was associated with differential expression of 432 (|logFC|>0.3, adj. p value <0.05) and 46 (p value <0.0.5) genes in the left and right amygdala, respectively, of female animals, relative to the reference sample which consisted of all a pooled sample from control and treated animals of both sexes. No genes were found to be differentially expressed as a result of GnRHa treatment in the male animals. The results indicated that GnRH may, directly and/or indirectly, be involved in the regulation of sex- and hemisphere-specific differential expression of genes in the amygdala. This finding should be considered when long-term peri-pubertal GnRHa treatment is used in children. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gonadotrophin-releasing hormone agonist combined with high-intensity focused ultrasound ablation for adenomyosis: a clinical study.

PubMed

Guo, Y; Duan, H; Cheng, J; Zhang, Y

2017-08-01

This study was to investigate the clinical efficacy of a gonadotrophin-releasing hormone agonist (GnRH-a) combined with high-intensity focused ultrasound (HIFU) ablation treatment for adenomyosis. A non-randomized prospective study. Gynaecological Minimally Invasive Centre in a single hospital. Patients with adenomyosis. Seventy-nine patients with adenomyosis were enrolled, including 55 patients in the control group treated with only HIFU and 24 patients in the study group treated with GnRH-a combined with HIFU. All the patients follow up 6 months after the HIFU procedure. The related parameters in the two groups were assessed before and 3 months as well as 6 months after treatment including serum levels of tumor marker and cytokine, volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrheal scores. Differences between the group treated with HIFU alone and the group treated with GnRH-a combined with HIFU. Before HIFU treatment, no significant difference was observed in serum levels of CA125, CA19-9, and interleukin-6 (IL-6), the volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrhea scores between the two groups. (P > 0.05). The serum CA125 levels significantly decreased in both groups after HIFU, but the serum CA125 levels in the study group were still significantly lower than those in the control group (P < 0.05). The volume of uterine and adenomyotic lesion significantly decreased in both groups after HIFU procedure, and decreased even more in the study group 3 and 6 months after treatment (P < 0.05). Dysmenorrhea scores and menstruation volumes significantly decreased in both groups after HIFU treatment. Moreover in the study group were significantly lower than those in the control group after 3 and 6 months (P < 0.05). No significant difference was observed in the rate of adverse effects between the two groups. The short-term follow-up results indicate that the combination of GnRH-a and HIFU treatment significantly decreased serum CA125 levels, volumes of uterine, adenomyotic lesion and menstrual blood, as well as dysmenorrhea scores, and improved the clinical outcomes compared with the HIFU ablation alone in patients with adenomyosis. However, the further follow-up is needed to explore the long-term effects. A combination of GnRH-a with HIFU in the treatment of adenomyosis significantly decreased serum CA125 levels, uterine and adenomyotic lesion volumes, dysmenorrhea scores, and menstrual blood volumes. © 2017 Royal College of Obstetricians and Gynaecologists.

Infertility – prevention and management

PubMed Central

Somers, Emily C; Marder, Wendy

2017-01-01

Summary Women with autoimmune diseases are more at risk for infertility and subfertility, menstrual irregularities and decreased parity due to multiple possible etiologies, including underlying inflammatory disease, gonadotoxic medications, and psychosocial issues related to living with chronic disease. An awareness of these issues, and the validation and support of patients going through fertility related issues, is important for providing comprehensive care to this patient population. In particular, an understanding of the expanding options for fertility preservation strategies during gonadotoxic medications is essential, including gonadotropin releasing hormone analogues (GnRH-a) co-therapy and oocyte cryopreservation. Referral to a reproductive endocrinology clinic is indicated in this patient population, in part to help manage symptoms of hypoestrogenism that may result from GnRH-a therapy. PMID:28390569

Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity.

PubMed

Pereira, Nigel; Elias, Rony T; Neri, Queenie V; Gerber, Rachel S; Lekovich, Jovana P; Palermo, Gianpiero D; Rosenwaks, Zev

2016-11-01

This study investigates whether an adjuvant gonadotrophin-releasing hormone agonist (GnRHa) trigger with human chorionic gonadotrophin (HCG) improves fresh intracytoplasmic sperm injection (ICSI) cycle outcomes in patients with poor fertilization history after standard HCG trigger alone. This study compared 156 patients with <40% fertilization rate in a prior ICSI cycle with standard HCG trigger who underwent another ICSI cycle with a combined 2 mg GnRHa and 1500 IU HCG ovulatory trigger. There was no difference in the baseline demographics, ovarian stimulation outcomes or sperm parameters of the groups. More mature oocytes were retrieved in the combined trigger group compared with the HCG trigger group: 12 (9-14) versus 10 (7-12); P = 0.01. The fertilization rate in the combined trigger group (59.2%) was higher than the HCG group (35.3%); P = 0.01. The odds of clinical pregnancy and live birth were 1.8 and 1.7 times higher, respectively, when comparing the former group to the latter; P = 0.03. The results suggest that combined GnRHa and HCG trigger in ICSI cycles is a reasonable approach to increase oocyte maturity, specifically ooplasmic maturity, thereby increasing fertilization and improving ICSI cycle outcomes in patients with a history of poor fertilization after standard HCG trigger alone. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A case of diffuse uterine leiomyomatosis who had two successful pregnancies after medical management.

PubMed

Purohit, Ramkrishna; Sharma, Jay Gopal; Singh, Sarabjeet

2011-06-01

To describe a case report of diffuse uterine leiomyomatosis who had successful pregnancy twice following conservative management. Retrospective report. Private general hospital. A nulliparous woman 25 years of age presented with menorrhagia and infertility. She had innumerable small fibroids of 4-42 mm size throughout the myometrium. Size of the symmetrically enlarged uterus was 131×80×60 mm, clinically corresponding to that of 12 weeks of gestation. She received a GnRH analogue (GnRHa; leuprolide acetate) 3.75 mg per month for 6 months. Reduction of uterus size, menstrual amount, conception, pregnancy outcome. Enlarged uterus reduced to almost normal size after 3 doses of GnRHa. She did not experience heavy bleeding during menstruation. She conceived spontaneously in the first cycle after discontinuation of GnRHa. Antenatal course was uneventful. A healthy male baby of 2.5 kg was delivered by cesarean section at 39 weeks. The placenta weighed 330 g. There was no postpartum hemorrhage. She conceived spontaneously for the second time in the first cycle after resumption of menses. Antenatal, intranatal (cesarean section), and postnatal courses of the second pregnancy were uneventful. The second neonate weighed 3.0 kg and the placenta 400 g. Conservative treatment may help to achieve successful pregnancy in case of diffuse uterine leiomyomatosis. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis†.

PubMed

Khan, Khaleque Newaz; Fujishita, Akira; Kitajima, Michio; Hiraki, Koichi; Nakashima, Masahiro; Masuzaki, Hideaki

2014-11-01

Is there any risk of intra-uterine bacterial colonization and concurrent occurrence of endometritis in women with endometriosis? An increase in intra-uterine microbial colonization and concurrent endometritis occurred in women with endometriosis that was further increased after GnRH agonist (GnRHa) treatment. Higher bacterial contamination of menstrual blood and increased endotoxin level in menstrual and peritoneal fluids have been found in women with endometriosis than in control women. However, information on intra-uterine microbial colonization across the phases of the menstrual cycle and possible occurrence of endometritis in women with endometriosis is still lacking. This is a case-controlled study with prospective collection of vaginal smears/endometrial samples from women with and without endometriosis and retrospective evaluation. Vaginal smears and endometrial smears were collected from 73 women with endometriosis and 55 control women. Twenty of the women with endometriosis and 19 controls had received GnRHa therapy for a period of 4-6 months. Vaginal pH was measured by intra-vaginal insertion of a pH paper strip. The bacterial vaginosis (BV) score was analyzed by Gram-staining of vaginal smears and based on a modified Nugent-BV scoring system. A panel of bacteria was analyzed by culture of endometrial samples from women treated with GnRHa or not treated. Immunohistochemcial analysis was performed using antibody against Syndecan-1 (CD138) and myeloperoxidase in endometrial biopsy specimens from women with and without endometriosis. A significant shifting of intra-vaginal pH to ≥4.5 was observed in women with endometriosis compared with control women (79.3 versus 58.4%, P < 0.03). Compared with untreated women, use of GnRHa therapy also shifted vaginal pH to ≥4.5 in both control women (P = 0.004) and in women with endometriosis (P = 0.03). A higher risk of increasing intermediate flora (total score, 4-6) (P = 0.05) was observed in women with endometriosis who had GnRHa treatment versus untreated women. The number of colony forming units (CFU/ml) of Gardnerella, α-Streptococcus, Enterococci and Escherichia coli was significantly higher in endometrial samples from women with endometriosis than control women (P < 0.05 for each bacteria). GnRHa-treated women also showed significantly higher colony formation for some of these bacteria in endometrial samples than in untreated women (Gardnerella and E. coli for controls; Gardnerella, Enterococci and E. coli for women with endometriosis, P < 0.05 for all). Although there was no significant difference in the occurrence of acute endometritis between women with and without endometriosis, both GnRHa-treated controls and women with endometriosis had a significantly higher occurrence of acute endometritis (P = 0.003 for controls, P = 0.001 for endometriosis versus untreated women). Multiple analysis of covariance analysis revealed that an intra-vaginal pH of ≥4.5 (P = 0.03) and use of GnRHa (P = 0.04) were potential factors that were significantly and independently associated with intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis. These findings indicated the occurrence of sub-clinical uterine infection and endometritis in women with endometriosis after GnRHa treatment. We cannot exclude the introduction of bias from unknown previous treatment with immunosuppressing or anti-microbial agents. We have studied a limited range of bacterial species and used only culture-based methods. More sensitive molecular approaches would further delineate the similarities/differences between the vaginal cavity and uterine environment. Our current findings may have epidemiological and biological implications and help in understanding the pathogenesis of endometriosis and related disease burden. The worsening of intra-uterine microbial colonization and higher occurrence of endometritis in women with endometriosis who were treated with GnRHa identifies some future therapeutic avenues for the management, as well as prevention of recurrence, of endometriosis. Further studies are needed to examine intra-uterine colonization of a broad range of common bacteria as well as different viruses and their role in the occurrence of endometritis. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study. Not applicable. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?

PubMed

Berkkanoglu, Murat; Ozgur, Kemal

2010-07-01

To find out the optimum maximal dosage of recombinant follicle stimulating hormone (rFSH) in microdose gonadotropin-releasing hormone analog (GnRH-a) flare cycles in poor responders. Prospective randomized study. Private infertility clinic. A total of 119 women were taken into the study. The study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration. On the third day of GnRH-a administration, 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH (group A, n = 38), or 450 IU of rFSH (group B, n = 39), or 600 IU of rFSH (group C, n = 42). Peak E(2) levels, days of stimulation with rFSH, total rFSH dosage, total number of oocytes retrieved, M2 oocytes retrieved, total number of embryos, number of embryos transferred, number of Grade-1 embryos transferred, clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer. Clinical pregnancy rates were 13.1%, 15.3%, and 16.1% for group A, group B, and group C, respectively. There were no significant differences in the age, peak serum E(2) concentration, days of stimulation with rFSH, total number of M2 oocytes retrieved, number of embryos transferred, clinical pregnancy rates, and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage. There is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles. In addition, because the duration of stimulation does not differ between the groups, the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages, and this would obviously cost less money to the patients. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist.

PubMed

Yun, Bo Seong; Seong, Seok Ju; Cha, Dong Hyun; Kim, Ji Yeon; Kim, Mi-La; Shim, Jeong Yun; Park, Ji Eun

2015-08-01

To evaluate changes in proliferating and apoptotic markers of myoma tissue from patients treated with a selective progesterone receptor modulator (SPRM) or GnRH agonist by measuring expression of PDGF-A mRNA, IGF-1 mRNA, bcl-2 mRNA, and PCNA and caspase-3 protein. Between December 2013 and July 2014, women with symptomatic leiomyoma were divided into control (no treatment before surgery), SPRM (treatment with ulipristal acetate [SPRM] for 3 months before surgery), and GnRHa (treatment with leuprolide acetate [GnRH agonist] for 3 months before surgery) groups. Tissue specimens were collected from the myoma core and normal myometrium of all patients. The expression of mRNA and protein was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot. A total of 38 patients were enrolled (control group, n=14; SPRM group, n=13; GnRHa group, n=11). PDGF-A mRNA expression was lower in both the myoma core and normal myometrium tissues of the SPRM compared with the control group, but there was no difference between the control and GnRHa group. There were also no group differences in bcl-2 mRNA or IGF-1 mRNA expression. Both PCNA and caspase-3 protein expression were higher in the leiomyoma tissue of the SPRM compared with the control group, but there was no difference between the control and GnRHa groups in the expression of either protein. Both proliferation and apoptosis were increased in the leiomyoma of patients after SPRM treatment, but there was no change following GnRH agonist treatment, in vivo. However, PDGF-A mRNA was decreased after SPRM treatment, indicating a dual effect of progesterone on the regulation of growth factors. Furthermore, there was an increase in caspase-3 protein, but not bcl-2 mRNA, expression in the SPRM group suggesting that SPRM may exert its effects in pathways other than the bcl-2 apoptotic pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The management of menstrual suppression and uterine bleeding: a survey of current practices in the Pediatric Blood and Marrow Transplant Consortium.

PubMed

Adegite, Enitan A; Goyal, Rakesh K; Murray, Pamela J; Marshal, Mike; Sucato, Gina S

2012-09-01

Current guidelines recommend the use of combined hormonal contraceptive pills for menstrual suppression in pediatric blood and marrow transplant (BMT) recipients but recent research reveals that provider practice varies. This study was designed to describe the current practice for managing menstrual issues, that is, menstrual suppression and uterine bleeding, in pediatric BMT patients and to better understand health care providers' practices in the use of gonadotropin-releasing hormone agonists (GnRHa). A cross sectional survey consisting of 53 questions was distributed via email to principal investigators in the Pediatric Blood and Marrow Transplant Consortium (PBMTC). Responses were collected using www.surveymonkey.com. Menstrual suppression and uterine bleeding in pediatric BMT patients are primarily managed by pediatric oncologists (97%). The most frequently reported hormonal method used for induction of therapeutic amenorrhea was GnRHa (41%). The top three reasons for choosing a method were greater likelihood of amenorrhea, concerns about side effects, and possible gonadal protection. Continuous combined hormonal contraceptive pills were the most commonly used method for the management of clinically significant uterine bleeding regardless of primary method used for menstrual suppression. Despite the 2002 PBMTC guidelines, wide variation in menstrual suppression management practices still exists. Our data show that use of GnRHa is more common than previously reported. Additional research is needed to develop evidence-based practice guidelines in pediatric BMT patients. Copyright © 2012 Wiley Periodicals, Inc.

Ultrasound guided high-intensity focused ultrasound combined with gonadotropin releasing hormone analogue (GnRHa) ablating uterine leiomyoma with homogeneous hyperintensity on T2 weighted MR imaging.

PubMed

Yang, Shenghua; Kong, Fanjing; Hou, Ruijie; Rong, Fengmei; Ma, Nana; Li, Shaoping; Yang, Jun

2017-05-01

The study aimed to evaluate the safety and efficiency of ultrasound-guided high-intensity focused ultrasound (USgHIFU) combined with gonadotropin-releasing hormone analogue (GnRHa)-ablating symptomatic uterine leiomyoma with homogeneous hyperintensity on T 2 weighted MRI prospectively. A total of 34 patients with 42 symptomatic uterine leiomyomas with homogeneous hyperintensity on T 2 weighted MRI were enrolled in our study. In the patient who had multiple uterine leiomyomas, only one dominant leiomyoma was treated. According to the principles of voluntariness, 18 patients underwent a 3-month therapy of GnRHa (once a month) before the high-intensity focused ultrasound (HIFU) treatment, while 16 patients received only HIFU treatment. Enhanced MRI was performed before and after GnRHa and HIFU treatment. Evaluation of the main indicators included treatment time, sonication time, treatment efficiency, non-perfused volume (NPV) (indicative of successful ablation) ratio and energy effect ratio; adverse events were also recorded. The treatment time and sonication time of the combination group were 102.0 min (55.8-152.2 min) and 25.4 min (12.2-34.1 min); however, they were 149.0 min (87.0-210.0 min) and 38.9 min (14.0-46.7 min) in the simple USgHIFU group. The treatment and sonication time for the combination group was significantly shorter than that for the simple USgHIFU group. Treatment efficiency, NPV ratio and energy effect ratio were 46.7 mm 3  s -1 (28.5-95.8 mm 3  s -1 ), 69.2 ± 29.8% (35.5-97.4%) and 9.9 KJ mm -3 (4.5-15.7 KJ mm -3 ) in the combination group, respectively; but, the lowest treatment efficiency, lowest NPV ratio and more energy effect ratio were observed in the simple HIFU group, which were 16.8 mm 3  s -1 (8.9-32.9 mm 3  s -1 ), 50.2 ± 27.3% (0-78.6%) and 23.8 KJ mm -3 (12.4-46.2 KJ mm -3 ), respectively. Pain scores in the combination group were 3.0 ± 0.5 points (2-4 points)-significantly less than the simple USgHIFU group. There were no significant adverse reactions in either group. Our data suggest that USgHIFU combined with GnRHa may be performed to ablate symptomatic uterine leiomyoma with homogeneous hyperintensity on T 2 weighted MRI. Advances in knowledge: The conclusions indicate that GnRHa can improve the effectiveness of the USgHIFU treatment of a homogeneous hyperintense leiomyoma on T 2 weighted MRI, and combination treatment could be a promising alternative treatment for the uterine leiomyoma.

Triptorelin for the treatment of endometriosis.

PubMed

Leone Roberti Maggiore, Umberto; Scala, Carolina; Remorgida, Valentino; Venturini, Pier Luigi; Del Deo, Fabio; Torella, Marco; Colacurci, Nicola; Salvatore, Stefano; Ferrari, Stefano; Papaleo, Enrico; Candiani, Massimo; Ferrero, Simone

2014-06-01

Over the past 30 years, gonadotropin-releasing hormone agonists (GnRH-a) have been used to induce a hypoestrogenic status in women with endometriosis with the aim to cause an improvement in pain symptoms similar to that observed after menopause. Triptorelin is one of the most commonly used GnRH-a. This review offers an explanation of the mechanism of action, of the pharmacokinetics and pharmacodynamics of triptorelin and gives the readers a complete overview of the studies on the clinical efficacy, tolerability and safety of this agent in patients with endometriosis. The studies reviewed in the current manuscript demonstrate the efficacy of triptorelin in improving pain symptoms caused by endometriosis. Further, this effect is confirmed by the reduction in the volume of the endometriotic nodules during treatment. Future research should evaluate whether the pre-operative administration of triptorelin prior to surgical excision of endometriomas may be useful in preserving the ovarian reserve.

A protocol for isolating insect mitochondrial genomes: a case study of NUMT in Melipona flavolineata (Hymenoptera: Apidae).

PubMed

Françoso, Elaine; Gomes, Fernando; Arias, Maria Cristina

2016-07-01

Nuclear mitochondrial DNA insertions (NUMTs) are mitochondrial DNA sequences that have been transferred into the nucleus and are recognized by the presence of indels and stop codons. Although NUMTs have been identified in a diverse range of species, their discovery was frequently accidental. Here, our initial goal was to develop and standardize a simple method for isolating NUMTs from the nuclear genome of a single bee. Subsequently, we tested our new protocol by determining whether the indels and stop codons of the cytochrome c oxidase subunit I (COI) sequence of Melipona flavolineata are of nuclear origin. The new protocol successfully demonstrated the presence of a COI NUMT. In addition to NUMT investigations, the protocol described here will also be very useful for studying mitochondrial mutations related to diseases and for sequencing complete mitochondrial genomes with high read coverage by Next-Generation technology.

Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward.

PubMed

Macoveanu, Julian; Henningsson, Susanne; Pinborg, Anja; Jensen, Peter; Knudsen, Gitte M; Frokjaer, Vibe G; Siebner, Hartwig R

2016-03-01

Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex-steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women.

[Effect of luteal-phase gonadotropin-releasing hormone agonist administration on pregnancy outcome in IVF/ICSI cycles: a systematic review and Meta-analysis].

PubMed

Yu, L P; Liu, N; Liu, Y

2016-11-25

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 WanFang database to collect randomized controlled trial (RCT) involving GnRH-a administration in the luteal-phase on IVF/ICSI cycles in ART. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality according to the Cochrane Handbook. Then, Meta-analysis was performed using Stata 13.0. Results: A total of 3 406 patients, 3 280 IVF/ICSI cycles from 11 RCT were subjected to Meta-analysis. All cycles presented statistically significantly higher rates of live birth/ongoing pregnancy ( RR= 1.29, 95% CI: 1.11-1.51), clinical pregnancy ( RR= 1.24, 95% CI: 1.08-1.43) and multiple pregnancy ( RR= 1.95, 95% CI: 1.21-3.14) in patients who received luteal-phase GnRH-a administration compared with those who did not. Conclusions: These findings demonstrate that the luteal-phase GnRH-a administration could increase birth/ongoing pregnancy rate, clinical pregnancy rate and multiple pregnancy rate in all cycles, so it may be an ideal choice for luteal phase support in patients undergoing IVF/ICSI therapy.

Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia.

PubMed

Quintos, J B; Vogiatzi, M G; Harbison, M D; New, M I

2001-04-01

Short stature in the adult patient with congenital adrenal hyperplasia (CAH) is commonly seen, even among patients in excellent adrenal control during childhood and puberty. In this study we examine the effect of GH therapy on height prediction in children with both CAH and compromised height prediction. Leuprolide acetate, a GnRH analog (GnRHa), was given to patients with evidence of early puberty. GH (n = 12) or the combination of GH and GnRHa (n = 8) was administered to 20 patients with CAH while they continued therapy with glucocorticoids. Each patient in the treatment group was matched according to age, sex, bone age, puberty, and type of CAH with another CAH patient treated only with glucocorticoid replacement. The match was made at the start of GH treatment. Of the 20 patients, 12 have completed 2 yr of therapy. After 1 yr of GH or combination GH and GnRHa therapy, the mean growth rate increased from 5 +/- 1.9 to 7.8 +/- 1.6 cm/yr vs. 5.4 +/- 1.7 to 5 +/- 2 cm/yr in the group not receiving GH (P < 0.0001). During the second year of treatment, the mean growth rate was 6 +/- 1.6 vs. 4.2 +/- 2.1 cm/yr in the group not receiving GH (P < 0.001). The height SD score for chronological age in the treatment group at the end of 1 and 2 yr of treatment improved significantly more than the nontreatment group (P < 0.01). A similar improvement in the height SD score for bone age was found in the treatment group after 1 (-1.4 +/- 0.9 vs. -1.7 +/- 0.9; P < 0.0001) and 2 yr of therapy (-0.67 +/- 0.68 vs. -1.7 +/- 1.2; P < 0.0004). The mean predicted adult height improved from 159 +/- 11 (baseline) to 170 +/- 7.5 cm (after 2 yr of therapy) closely approximating target height (173 +/- 8 cm). All patients continued the hydrocortisone treatment. In patients with CAH and compromised height prediction, treatment with GH or the combination of GH and GnRHa results in an improvement of growth rate and height prediction and a reduction in height deficit for bone age.

Simulating fail-stop in asynchronous distributed systems

NASA Technical Reports Server (NTRS)

Sabel, Laura; Marzullo, Keith

1994-01-01

The fail-stop failure model appears frequently in the distributed systems literature. However, in an asynchronous distributed system, the fail-stop model cannot be implemented. In particular, it is impossible to reliably detect crash failures in an asynchronous system. In this paper, we show that it is possible to specify and implement a failure model that is indistinguishable from the fail-stop model from the point of view of any process within an asynchronous system. We give necessary conditions for a failure model to be indistinguishable from the fail-stop model, and derive lower bounds on the amount of process replication needed to implement such a failure model. We present a simple one-round protocol for implementing one such failure model, which we call simulated fail-stop.

Proposed test protocol for video imaging detection at intersection stop lines.

DOT National Transportation Integrated Search

2010-08-01

Test protocols for non-loop detectors have often required comparing the performance : attributes of these detectors with those of loops or other point detectors, or to manual counts. : However, that comparison is not always appropriate for a variety ...

Ultrasound guided high-intensity focused ultrasound combined with gonadotropin releasing hormone analogue (GnRHa) ablating uterine leiomyoma with homogeneous hyperintensity on T2 weighted MR imaging

PubMed Central

Yang, Shenghua; Kong, Fanjing; Hou, Ruijie; Rong, Fengmei; Ma, Nana; Li, Shaoping

2017-01-01

Objective: The study aimed to evaluate the safety and efficiency of ultrasound-guided high-intensity focused ultrasound (USgHIFU) combined with gonadotropin-releasing hormone analogue (GnRHa)-ablating symptomatic uterine leiomyoma with homogeneous hyperintensity on T2 weighted MRI prospectively. Methods: A total of 34 patients with 42 symptomatic uterine leiomyomas with homogeneous hyperintensity on T2 weighted MRI were enrolled in our study. In the patient who had multiple uterine leiomyomas, only one dominant leiomyoma was treated. According to the principles of voluntariness, 18 patients underwent a 3-month therapy of GnRHa (once a month) before the high-intensity focused ultrasound (HIFU) treatment, while 16 patients received only HIFU treatment. Enhanced MRI was performed before and after GnRHa and HIFU treatment. Evaluation of the main indicators included treatment time, sonication time, treatment efficiency, non-perfused volume (NPV) (indicative of successful ablation) ratio and energy effect ratio; adverse events were also recorded. Results: The treatment time and sonication time of the combination group were 102.0 min (55.8–152.2 min) and 25.4 min (12.2–34.1 min); however, they were 149.0 min (87.0–210.0 min) and 38.9 min (14.0–46.7 min) in the simple USgHIFU group. The treatment and sonication time for the combination group was significantly shorter than that for the simple USgHIFU group. Treatment efficiency, NPV ratio and energy effect ratio were 46.7 mm3 s-1 (28.5–95.8 mm3 s-1), 69.2 ± 29.8% (35.5–97.4%) and 9.9 KJ mm−3 (4.5–15.7 KJ mm−3) in the combination group, respectively; but, the lowest treatment efficiency, lowest NPV ratio and more energy effect ratio were observed in the simple HIFU group, which were 16.8 mm3 s−1 (8.9–32.9 mm3 s−1), 50.2 ± 27.3% (0–78.6%) and 23.8 KJ mm−3 (12.4–46.2 KJ mm−3), respectively. Pain scores in the combination group were 3.0 ± 0.5 points (2–4 points)—significantly less than the simple USgHIFU group. There were no significant adverse reactions in either group. Conclusion: Our data suggest that USgHIFU combined with GnRHa may be performed to ablate symptomatic uterine leiomyoma with homogeneous hyperintensity on T2 weighted MRI. Advances in knowledge: The conclusions indicate that GnRHa can improve the effectiveness of the USgHIFU treatment of a homogeneous hyperintense leiomyoma on T2 weighted MRI, and combination treatment could be a promising alternative treatment for the uterine leiomyoma. PMID:28256923

Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty

ClinicalTrials.gov

2014-01-08

Precocious; Leuprolide Acetate; Luteinizing Hormone (LH); Gonadotrophin-releasing Hormone Agonist (GnRHa); Tanner Staging; Depot Formulation; Suppression of LH; Central Precocious Puberty (CPP); Gonadotrophin-releasing Hormone (GnRH); Lupron; GnRH Analog; Pediatrics Central Precocious Puberty

Comparison of the effects of ovarian cauterization and gonadotropin-releasing hormone agonist and oral contraceptive therapy combination on endocrine changes in women with polycystic ovary disease.

PubMed

Taskin, O; Yalcinoglu, A I; Kafkasli, A; Burak, F; Ozekici, U

1996-06-01

To study the effects of laparoscopic ovarian cauterization and combination of long-acting GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy on endocrine changes in women with clomiphene citrate (CC)- resistant polycystic ovary disease (PCOD). Prospective, randomized. University-based infertility clinic. Seventeen women with CC-resistant PCOD were included randomly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months. Serum concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin (SHBG) were determined before each therapeutic approach and during the follicular phase of first menstrual cycle after the cessation of each treatment. The mean serum concentrations and the clinical profiles were similar in both groups. Both groups showed significant changes in LH, FSH, A, T, and SHBG compared with pretreatment levels. There were no significant differences in the final concentrations of LH, FSH, and A between the two study groups after each treatment, whereas T and SHBG levels were significantly different in the goserelin and OC group. The decrease in LH and increase in SHBG serum concentrations were greater in the goserelin and OC-treated women [-59% and + 5.9% versus - 70% and + 13.5%, respectively]. Although the SHBG concentration increased in both groups, the serum SHBG concentration of the goserelin and OC group was significantly higher than the other group. Both therapeutic modalities revealed similar effects on the endocrine profiles in women with CC-resistant PCOD. Considering the invasiveness, cost, and potential complications of laparoscopic ovarian cauterization, noninvasive medical treatment with GnRH-a and OC combination may be more effective in restoring the optimal follicular environment in women with PCOD.

Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone responsiveness, to estradiol negative feedback in the female.

PubMed

Sarma, Hirendra N; Manikkam, Mohan; Herkimer, Carol; Dell'Orco, James; Welch, Kathleen B; Foster, Douglas L; Padmanabhan, Vasantha

2005-10-01

Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal hypergonadotropism manifest as a selective increase in LH. This hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30-90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 microg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH pulsatility, reduced FSH by approximately 25%, and E2 production diminished to near detection limit of assay at both ages in both groups. Prenatal T treatment produced a precocious and selective reduction in responsiveness of LH but not FSH to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse frequency. Collectively, these findings support the hypothesis that prenatal exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback of LH/GnRH secretion to contribute to the development of hypergonadotropism.

Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea.

PubMed

Berardelli, Rita; Gianotti, Laura; Karamouzis, Ioannis; Picu, Andreea; Giordano, Roberta; D'Angelo, Valentina; Zinnà, Domenico; Lanfranco, Fabio; Ghigo, Ezio; Arvat, Emanuela

2011-10-01

Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility. We studied the effects of a GnRHa, cetrorelix (CTX 3.0 mg), in six women with HA (age 30.7 ± 3.2 years; BMI 21.5 ± 1.7 kg/m(2)) and six control subjects (CS, 28.2 ± 0.6 years; 22.6 ± 0.9 kg/m(2)) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4 h (08.00-12.00 am) before, +24 h and +96 h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72 h after CTX. CS: CTX reduced (p < 0.05) LH, FSH, and oestradiol (nadir at +12 h, +24 h, and +24 h); LH rebounded at +96 h, FSH and oestradiol recovered at +48 h and +72 h. The 4-h evaluation showed LH and FSH reduction (p < 0.05) at +24 h, with LH rebound at +96 h. HA: CTX reduced (p < 0.05) LH, FSH, and oestradiol, (nadir at +24 h, +48 h, and +48 h, recovery at +48 h, +72 h, and +96 h). The 4-h evaluation showed gonadotropin reduction (p < 0.05) 24 h after CTX, without any rebound effect. One single CTX dose still modulates gonadotropin secretion in HA. Its 'paradoxical' stimulatory effect on gonadotropins needs to be verified after prolonged administration.

Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection.

PubMed

Hamlyn, Elizabeth; Ewings, Fiona M; Porter, Kholoud; Cooper, David A; Tambussi, Giuseppe; Schechter, Mauro; Pedersen, Court; Okulicz, Jason F; McClure, Myra; Babiker, Abdel; Weber, Jonathan; Fidler, Sarah

2012-01-01

The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV infection (CHI). Two populations with protocol-indicated ART cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450) trials. Time for pVL to reach pre-ART levels after stopping ART was assessed in PHI using survival analysis. Differences in pVL between PHI and CHI populations 4 weeks after stopping ART were examined using linear and logistic regression. Differences in pVL slopes up to 48 weeks were examined using linear mixed models and viral burden was estimated through a time-averaged area-under-pVL curve. CHI participants were categorised by nadir CD4 at ART stop. Of 171 PHI participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95% CI 48-51) weeks after stopping ART. Four weeks after stopping treatment, although the proportion with pVL ≥ 400 copies/ml was similar (78% PHI versus 79% CHI), levels were 0.45 (95% CI 0.26-0.64) log(10) copies/ml lower for PHI versus CHI, and remained lower up to 48 weeks. Lower CD4 nadir in CHI was associated with higher pVL after ART stop. Rebound for CHI participants with CD4 nadir >500 cells/mm(3) was comparable to that experienced by PHI participants. Stopping ART initiated in PHI and CHI was associated with viral rebound to levels conferring increased transmission risk, although the level of rebound was significantly lower and sustained in PHI compared to CHI.

[Management of painful endometriosis in adolescents: CNGOF-HAS Endometriosis Guidelines].

PubMed

Sauvan, M; Chabbert-Buffet, N; Geoffron, S; Legendre, G; Wattier, J-M; Fernandez, H

2018-03-01

To analyse the literature on the treatment of adolescent painful endometriosis. This work is based on a Review of the literature between January 2006 and December 2017. The Medline (Pubmed) and Cochrane database were searched for meta-analyzes, randomized trials, literature reviews, controlled, not controlled and retrospective studies published on the subject. Studies concerning adolescent's dysmenorrhea without endometriosis were excluded. Study quality is heterogeneous. Dienogest and GnRH agonists (GnRHa) are the only treatments specifically evaluated for the treatment of adolescent endometriosis. They reduce the pain associated with endometriosis. Combined oral contraceptives have not been studied in the context of endometriosis but they are effective on dysmenorrhea. Add back therapy, containing estrogens improves bone mineral density and quality of life for young women treated with GnRHa. Medical treatment of endometriosis in adolescent is associated with risks related to the young age. The therapeutic strategy should take into account the adverse effects of each treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effectiveness of oxaliplatin desensitization protocols.

PubMed

Cortijo-Cascajares, Susana; Nacle-López, Inmaculada; García-Escobar, Ignacio; Aguilella-Vizcaíno, María José; Herreros-de-Tejada, Alberto; Cortés-Funes Castro, Hernán; Calleja-Hernández, Miguel-Ángel

2013-03-01

Hypersensitivity reaction (HSR) to antineoplastic drugs can force doctors to stop treatment and seek other alternatives. These alternatives may be less effective, not as well tolerated and/or more expensive. Another option is to use desensitization protocols that induce a temporary state of tolerance by gradually administering small quantities of the antineoplastic drug until the therapeutic dosage is reached. The aim of this study is to assess the effectiveness of oxaliplatin desensitization protocols. A retrospective observational study was carried out between January 2006 and May 2011. The inclusion criteria were patients undergoing chemotherapy treatment with oxaliplatin who had developed an HSR to the drug and who were candidates for continuing the treatment using a desensitization protocol. The patients' clinical records were reviewed and variables were gathered relating to the patient, the treatment, the HSR, and the desensitization protocol administered. The data were analysed using version 18.0 of the statistics program SPSS. A total of 53 desensitization protocols were administered to 21 patients. In 89 % of these cases, no new reactions occurred while the drug was being administered. New reactions of mild severity only occurred in 11 % of cases, and none of these reactions were severe enough for treatment to be stopped. All patients were able to complete the desensitization protocol. This study confirms that oxaliplatin desensitization protocols are safe and effective and allow patients to continue with the treatment that initially caused an HSR.

The stability of locus equation slopes across stop consonant voicing/aspiration

NASA Astrophysics Data System (ADS)

Sussman, Harvey M.; Modarresi, Golnaz

2004-05-01

The consistency of locus equation slopes as phonetic descriptors of stop place in CV sequences across voiced and voiceless aspirated stops was explored in the speech of five male speakers of American English and two male speakers of Persian. Using traditional locus equation measurement sites for F2 onsets, voiceless labial and coronal stops had significantly lower locus equation slopes relative to their voiced counterparts, whereas velars failed to show voicing differences. When locus equations were derived using F2 onsets for voiced stops that were measured closer to the stop release burst, comparable to the protocol for measuring voiceless aspirated stops, no significant effects of voicing/aspiration on locus equation slopes were observed. This methodological factor, rather than an underlying phonetic-based explanation, provides a reasonable account for the observed flatter locus equation slopes of voiceless labial and coronal stops relative to voiced cognates reported in previous studies [Molis et al., J. Acoust. Soc. Am. 95, 2925 (1994); O. Engstrand and B. Lindblom, PHONUM 4, 101-104]. [Work supported by NIH.

Two Different Fatigue Protocols and Lower Extremity Motion Patterns During a Stop-Jump Task

PubMed Central

Quammen, David; Cortes, Nelson; Van Lunen, Bonnie L.; Lucci, Shawn; Ringleb, Stacie I.; Onate, James

2012-01-01

Context: Altered neuromuscular control strategies during fatigue probably contribute to the increased incidence of non-contact anterior cruciate ligament injuries in female athletes. Objective: To determine biomechanical differences between 2 fatigue protocols (slow linear oxidative fatigue protocol [SLO-FP] and functional agility short-term fatigue protocol [FAST-FP]) when performing a running-stop-jump task. Design: Controlled laboratory study. Setting: Laboratory. Patients or Other Participants: A convenience sample of 15 female soccer players (age = 19.2 ±0.8 years, height = 1.67±0.05m, mass = 61.7 + 8.1 kg) without injury participated. Intervention(s): Five successful trials of a running–stop-jump task were obtained prefatigue and postfatigue during the 2 protocols. For the SLO-FP, a peak oxygen consumption (V˙o2peak) test was conducted before the fatigue protocol. Five minutes after the conclusion of the V˙o2peak test, participants started the fatigue protocol by performing a 30-minute interval run. The FAST-FP consisted of 4 sets of a functional circuit. Repeated 2 (fatigue protocol) × 2 (time) analyses of variance were conducted to assess differences between the 2 protocols and time (prefatigue, postfatigue). Main Outcome Measure(s): Kinematic and kinetic measures of the hip and knee were obtained at different times while participants performed both protocols during prefatigue and postfatigue. Results: Internal adduction moment at initial contact (IC) was greater during FAST-FP (0.064 ±0.09 Nm/kgm) than SLO-FP (0.024±0.06 Nm/kgm) (F1,14 = 5.610, P=.03). At IC, participants had less hip flexion postfatigue (44.7°±8.1°) than prefatigue (50.1°±9.5°) (F1,14 = 16.229, P=.001). At peak vertical ground reaction force, participants had less hip flexion postfatigue (44.7°±8.4°) than prefatigue (50.4°±10.3°) (F1,14 = 17.026, P=.001). At peak vertical ground reaction force, participants had less knee flexion postfatigue (−35.9°±6.5°) than prefatigue (−38.8°±5.03°) (F1,14 = 11.537, P=.001). Conclusions: Our results demonstrated a more erect landing posture due to a decrease in hip and knee flexion angles in the postfatigue condition. The changes were similar between protocols; however, the FAST-FP was a clinically applicable 5-minute protocol, whereas the SLO-FP lasted approximately 45 minutes. PMID:22488228

Ovarian Damage During Chemotherapy in Autoimmune Diseases: Broad Health Implications beyond Fertility

PubMed Central

Marder, Wendy; Fisseha, Senait; Ganser, Martha A.; Somers, Emily C.

2012-01-01

Women with autoimmune diseases such as lupus, scleroderma, and vasculitis receiving cyclophosphamide for severe disease manifestations risk primary ovarian insufficiency (POI) due to gonadotoxicity of this therapy. In addition to loss of reproductive potential, POI is associated with increased risk of morbidity and mortality. Practitioners caring for women requiring gonadotoxic therapies should be familiar with long-term health implications of POI and strategies for ovarian preservation. Accumulating evidence supports the effectiveness of adjunctive gonadotropin releasing hormone analog (GnRH-a) for ovarian protection during gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly and invasive than assisted reproductive technologies used for achievement of future pregnancies, but is not Food and Drug Administration approved for ovarian preservation. This review focuses on POI comorbidities and strategies for mitigation of related sequelae, which can accumulate over decades of hypoesteogenism. These issues are arguably more pronounced for women with chronic autoimmune diseases, in whom superimposed POI further heightens risks of cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is not desired, ovarian protection during gonadotoxic therapy should be a major goal of disease management. PMID:23970822

Expression of three gonadotropin subunits and gonadotropin receptor mRNA during male-to-female sex change in the cinnamon clownfish, Amphiprion melanopus.

PubMed

An, Kwang Wook; Lee, Jehee; Choi, Cheol Young

2010-08-01

To quantify the sex-change progression from male to female in the cinnamon clownfish, Amphiprion melanopus, we divided gonadal development into three stages (I, mature male; II, male at 90 days after removal of the female; and III, mature female), and the expression of GTH subunits and GTH receptors during each of these stages was investigated. The mRNA of the three GTH subunits and their receptors increased with progression from male to female. To understand the effect of gonadotropin-releasing hormone (GnRH) on this progression, we examined expression of genes encoding the GTH subunit mRNA in the pituitary and the GTH-receptor mRNA in the gonads in addition to investigating changes in plasma E(2) levels after GnRH analogue (GnRHa) injection. GnRHa treatment increased mRNA expression levels of these genes, as well as plasma E(2) levels, indicating that GnRH plays an important regulatory role in the brain-pituitary-gonad axis of immature cinnamon clownfish. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Transdermal testosterone pretreatment in poor responders undergoing ICSI: a randomized clinical trial.

PubMed

Bosdou, J K; Venetis, C A; Dafopoulos, K; Zepiridis, L; Chatzimeletiou, K; Anifandis, G; Mitsoli, A; Makedos, A; Messinis, I E; Tarlatzis, B C; Kolibianakis, E M

2016-05-01

Does pretreatment with transdermal testosterone increase the number of cumulus-oocyte complexes (COCs) retrieved by more than 1.5 in poor responders undergoing intracytoplasmic sperm injection (ICSI), using recombinant follicle stimulating hormone (FSH) and gonadotrophin releasing hormone agonists (GnRHa)? Testosterone pretreatment failed to increase the number of COCs by more than 1.5 as compared with no pretreatment in poor responders undergoing ICSI (difference between medians: 0.0, 95% CI: -1.0 to +1.0). Androgens are thought to play an important role in early follicular development by enhancing ovarian sensitivity to FSH. In a recent meta-analysis, testosterone pretreatment resulted in an increase of 1.5 COCs as compared with no pretreatment. However, this effect was based on the analysis of only two randomized controlled trials (RCTs) including 163 patients. Evidently, there is a need for additional RCTs that will allow firmer conclusions to be drawn. The present RCT was designed to detect a difference of 1.5 COCs (sample size required = 48 patients). From 02/2014 until 04/2015, 50 poor responders fulfilling the Bologna criteria have been randomized (using a randomization list) to either testosterone pretreatment for 21 days ( ITALIC! n = 26) or no pretreatment ( ITALIC! n = 24). All patients underwent a long follicular GnRHa protocol. Recombinant FSH stimulation was started on Day 22 following GnRHa initiation. In the testosterone pretreatment group, a daily dose of 10 mg of testosterone gel was applied transdermally for 21 days starting from GnRHa initiation. Results are expressed as median (interquartile range). No differences in baseline characteristics were observed between the two groups compared. Testosterone levels [median (interquartile range)] were significantly higher in the testosterone pretreatment on the day of initiation of FSH stimulation [114 (99.5) ng/dl versus 20 (20) ng/dl, respectively, ITALIC! P < 0.001]. Duration of FSH stimulation [median (interquartile range)] was similar between the groups compared [12.5 (3.0) days versus 12 (3.0) days, respectively, ITALIC! P = 0.52]. The number of COCs retrieved [median (interquartile range)] was not different between the testosterone pretreatment and the no pretreatment groups [3.5 (4.0) versus 3.0 (3.0), 95% CI for the median: 2.0-5.0 versus 2.7-4.3, respectively; difference between medians: 0.0, 95% CI: +1.0 to -1.0). Similarly no differences were observed regarding fertilization rates [median (interquartile range)] [66.7% (32.5) versus 66.7% (42.9), respectively, ITALIC! P = 0.97] and live birth rates per randomized patient (7.7% versus 8.3%, respectively, rate difference: -0.6%, 95% CI: -19.0 to +16.9). The study was not powered to detect differences less than 1.5 COCs, although it is doubtful whether these differences would be clinically relevant. Moreover, due to sample size restrictions, no conclusions can be drawn regarding the probability of live birth. The results of this randomized clinical trial, suggesting that pretreatment with 10 mg of transdermal testosterone for 21 days does not improve ovarian response by more than 1.5 oocytes, could be used to more accurately consult patients with poor ovarian response. However, an improvement in IVF outcome using a higher dose of testosterone or a longer pretreatment period cannot be excluded. The study was partially funded by a Scholarship from the Academy of Athens. C.A.V. reports personal fees and non-financial support from Merck, Sharp and Dome, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from IPSEN Hellas S.A., outside the submitted work. B.C.T. reports grants from Merck Serono, grants from Merck Sharp & Dohme, personal fees from Merck Serono, personal fees from Merck Sharp & Dohme, personal fees from IBSA & Ferring, outside the submitted work. NCT01961336. 10 October 2013. 02/2014. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress Puberty in Gender Dysphoric Adolescents.

PubMed

Schagen, Sebastian E E; Cohen-Kettenis, Peggy T; Delemarre-van de Waal, Henriette A; Hannema, Sabine E

2016-07-01

Puberty suppression using gonadotropin-releasing hormone agonists (GnRHas) is recommended by current guidelines as the treatment of choice for gender dysphoric adolescents. Although GnRHas have long been used to treat precocious puberty, there are few data on the efficacy and safety in gender dysphoric adolescents. Therefore, the Endocrine Society guideline recommends frequent monitoring of gonadotropins, sex steroids, and renal and liver function. To evaluate the efficacy and safety of GnRHa treatment to suppress puberty in gender dysphoric adolescents. Forty-nine male-to-female and 67 female-to-male gender dysphoric adolescents treated with triptorelin were included in the analysis. Physical examination, including assessment of Tanner stage, took place every 3 months and blood samples were drawn at 0, 3, and 6 months and then every 6 months. Body composition was evaluated using dual energy x-ray absorptiometry. GnRHa treatment caused a decrease in testicular volume in 43 of 49 male-to-female subjects. In one of four female-to-male subjects who presented at Tanner breast stage 2, breast development completely regressed. Gonadotropins and sex steroid levels were suppressed within 3 months. Treatment did not have to be adjusted because of insufficient suppression in any subject. No sustained abnormalities of liver enzymes or creatinine were encountered. Alkaline phosphatase decreased, probably related to a slower growth velocity, because height SD score decreased in boys and girls. Lean body mass percentage significantly decreased during the first year of treatment in girls and boys, whereas fat percentage significantly increased. Triptorelin effectively suppresses puberty in gender dysphoric adolescents. These data suggest routine monitoring of gonadotropins, sex steroids, creatinine, and liver function is not necessary during treatment with triptorelin. Further studies should evaluate the extent to which changes in height SD score and body composition that occur during GnRHa treatment can be reversed during subsequent cross-sex hormone treatment. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Training response inhibition to reduce food consumption: Mechanisms, stimulus specificity and appropriate training protocols.

PubMed

Adams, Rachel C; Lawrence, Natalia S; Verbruggen, Frederick; Chambers, Christopher D

2017-02-01

Training individuals to inhibit their responses towards unhealthy foods has been shown to reduce food intake relative to a control group. Here we aimed to further explore these effects by investigating the role of stimulus devaluation, training protocol, and choice of control group. Restrained eaters received either inhibition or control training using a modified version of either the stop-signal or go/no-go task. Following training we measured implicit attitudes towards food (Study 1) and food consumption (Studies 1 and 2). In Study 1 we used a modified stop-signal training task with increased demands on top-down control (using a tracking procedure and feedback to maintain competition between the stop and go processes). With this task, we found no evidence for an effect of training on implicit attitudes or food consumption, with Bayesian inferential analyses revealing substantial evidence for the null hypothesis. In Study 2 we removed the feedback in the stop-signal training to increase the rate of successful inhibition and revealed a significant effect of both stop-signal and go/no-go training on food intake (compared to double-response and go training, respectively) with a greater difference in consumption in the go/no-go task, compared with the stop-signal task. However, results from an additional passive control group suggest that training effects could be partly caused by increased consumption in the go control group whereas evidence for reduced consumption in the inhibition groups was inconclusive. Our findings therefore support evidence that inhibition training tasks with higher rates of inhibition accuracy are more effective, but prompt caution for interpreting the efficacy of laboratory-based inhibition training as an intervention for behaviour change. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Absence of luteal phase defect and spontaneous pregnancy in IVF patients despite GnRH-agonist trigger and "freeze all policy" without luteal phase support: a report of four cases.

PubMed

Gurbuz, Ali Sami; Deveer, Ruya; Ozcimen, Necati; Ozcimen, Emel Ebru; Lawrenz, Barbara; Banker, Manish; Garcia-Velasco, Juan Antonio; Fatemi, Human Mousavi

2016-01-01

Human chorionic gonadotropin (hCG) is commonly used for final oocyte maturation in "in vitro fertilization" (IVF)-treatment cycles, however, the main important risk is development of severe ovarian hyperstimulation syndrome (OHSS). OHSS can almost be avoided by using gonadotrophin-releasing-hormone agonist for final oocyte maturation in an antagonist protocol. However, primarily this approach lead to a very poor reproductive outcome, despite the use of a standard luteal phase support. The reason seems to be severe luteolysis. Obviously, luteolysis post-gonadotropin-releasing-hormone-agonist (post-GnRH-a) trigger is individual specific, and not all patients will develop a complete luteolysis, as expected previously. Luteolysis can been reverted by the administration of hCG. Unprotected intercourse around the time of ovulation induction and oocyte retrieval can lead to a spontaneous conception in IVF treatment and, endogenous hCG, produced by the trophoblast, will rescue the corpora lutea. Therefore, one should not rely on complete luteolysis after GnRH-a triggering and, especially patients for egg donation and pre-implantation-genetic diagnosis for single gene disorder, have to be counselled to avoid unprotected intercourse.

Effective dose of salmon GnRha for induction of ovulation in channel catfish, Ictalurus punctatus

USDA-ARS?s Scientific Manuscript database

The present study was conducted to determine the minimum effective salmon Gonadotropin Releasing Hormone analog (sGnRHa) dose to stimulate ovulation in channel catfish. Four doses of sGnRHa (0, 5, 10 and 25 µg /Kg) were compared with commonly used 100 µg mammalian Luteinizing Hormone Releasing Hor...

[Clinical study of high intensity focused ultrasound ablation combined with GnRH-a and LNG-IUS for the treatment of adenomyosis].

PubMed

Ye, M Z; Deng, X L; Zhu, X G; Xue, M

2016-09-25

Objective: To investigate the clinical effect of dysmenorrhea in patients with adenomyosis treated by high intensity focused ultrasound(HIFU)ablation combined with gonadotropin-releasing hormone agonist(GnRH-a)and levonorgestrel-releasing intrauterine system(LNG-IUS). Methods: From April 2012 to December 2015, 477 cases of adenomyosis patients with dysmenorrhea were treated by HIFU in the Third Xiangya Hospital. Among them, some patients were treated with HIFU alone, some of them were treated with HIFU combined with GnRH-a and(or)LNG-IUS, thus were classified as H group, H+G group, H+M group and H+G+M group. The improvements of clinical results were compared among the four groups and the influencing factors of HIFU treatment for adenomyosis were also analyzed. Results: During the follow-up period, the overall effective rates of the treatment decreased with time, 3 months 89.4%(345/386), 12 months 84.0%(221/263), 24 months 74.2%(98/132), and the overall recurrence rate was 12.9%(39/303). The significant difference in the curative at 3 months[H group 83.7%(170/203), H+M group 95.0%(95/100), H+G group 100.0%(43/43), H+G+M group 96.8%(30/31)], 12 months[H group 79.4%(123/155), H+M group 93.2%(69/74), H+G group 11/12, H+G+M group 15/17], and 24 months[H group 68.0%(51/75), H+M group 96.4%(27/28), H+G group 6/12, H+G+M group 15/15]after HIFU treatment and recurrence rate[H group 19.0%(29/153), H+M group 3.3%(3/90), H+G group 19.4%(6/31), H+G+M group 4.5%(1/22)]were observed among the four groups( P <0.05). Pairwise comparison further showed that, in 3 months after the treatment, the effect of H group was significantly lower than those of H+M group and H+G group( P = 0.003, P =0.005); in 12 months after the treatment, the effect of H group was significantly lower than that of H+M group( P =0.006); while in 24 months after treatment, the effect of H group was significantly lower than that of H+G+M group( P =0.005), and the effect of H+G group was lower than that of H+G+M group( P = 0.001); and the recurrence rate of H group was significantly higher than that of H+M group( P <0.008). In patients of group H, the effect of HIFU was related to uterine size, the effect of patients with large uterine volume was significantly higher than that of small volume of uterine of patients( P =0.017, OR =2.739, 95% CI : 1.200- 6.251); with increasing of age, the improvement of dysmenorrhea had a increasing trend( P <0.05). Conclusions: HIFU combined with GnRH-a and(or)LNG-IUS could improve the treatment effect in relief of dysmenorrhea. Based on our results, individual treatment protocol should be selected for different patients.

Ionization chamber dosimetry of small photon fields: a Monte Carlo study on stopping-power ratios for radiosurgery and IMRT beams.

PubMed

Sánchez-Doblado, F; Andreo, P; Capote, R; Leal, A; Perucha, M; Arráns, R; Núñez, L; Mainegra, E; Lagares, J I; Carrasco, E

2003-07-21

Absolute dosimetry with ionization chambers of the narrow photon fields used in stereotactic techniques and IMRT beamlets is constrained by lack of electron equilibrium in the radiation field. It is questionable that stopping-power ratio in dosimetry protocols, obtained for broad photon beams and quasi-electron equilibrium conditions, can be used in the dosimetry of narrow fields while keeping the uncertainty at the same level as for the broad beams used in accelerator calibrations. Monte Carlo simulations have been performed for two 6 MV clinical accelerators (Elekta SL-18 and Siemens Mevatron Primus), equipped with radiosurgery applicators and MLC. Narrow circular and Z-shaped on-axis and off-axis fields, as well as broad IMRT configured beams, have been simulated together with reference 10 x 10 cm2 beams. Phase-space data have been used to generate 3D dose distributions which have been compared satisfactorily with experimental profiles (ion chamber, diodes and film). Photon and electron spectra at various depths in water have been calculated, followed by Spencer-Attix (delta = 10 keV) stopping-power ratio calculations which have been compared to those used in the IAEA TRS-398 code of practice. For water/air and PMMA/air stopping-power ratios, agreements within 0.1% have been obtained for the 10 x 10 cm2 fields. For radiosurgery applicators and narrow MLC beams, the calculated s(w,air) values agree with the reference within +/-0.3%, well within the estimated standard uncertainty of the reference stopping-power ratios (0.5%). Ionization chamber dosimetry of narrow beams at the photon qualities used in this work (6 MV) can therefore be based on stopping-power ratios data in dosimetry protocols. For a modulated 6 MV broad beam used in clinical IMRT, s(w,air) agrees within 0.1% with the value for 10 x 10 cm2, confirming that at low energies IMRT absolute dosimetry can also be based on data for open reference fields. At higher energies (24 MV) the difference in s(w,air) was up to 1.1%, indicating that the use of protocol data for narrow beams in such cases is less accurate than at low energies, and detailed calculations of the dosimetry parameters involved should be performed if similar accuracy to that of 6 MV is sought.

Physician-Initiated Stop-Smoking Program for Patients Receiving Treatment for Early-Stage Cancer

ClinicalTrials.gov

2015-10-06

Bladder Cancer; Breast Cancer; Colorectal Cancer; Head and Neck Cancer; Lung Cancer; Lymphoma; Prostate Cancer; Testicular Germ Cell Tumor; Tobacco Use Disorder; Unspecified Adult Solid Tumor, Protocol Specific

Achilles Tendinosis Stopping the Progression to Disability.

PubMed

Chessin, Meta

2012-09-01

The purpose of this article is to differentiate between acute Achilles tendinitis and chronic Achilles tendinosis and to highlight a specific treatment protocol for mid-portion Achilles tendinosis. Tendinosis (degeneration of the tendon) results from chronic tissue injury and has long-term implications for a dancer's career. An eccentric heavy-load exercise protocol has been used successfully to treat tendinosis in athletes. A modified eccentric exercise protocol is proposed as one component of an effective rehabilitation program for dancers. This protocol facilitates tissue remodeling to build strength, flexibility, and adaptability of the Achilles tendon tissue, so that dancers can continue to dance without further complications of the injury.

Stopping-power and mass energy-absorption coefficient ratios for Solid Water.

PubMed

Ho, A K; Paliwal, B R

1986-01-01

The AAPM Task Group 21 protocol provides tables of ratios of average restricted stopping powers and ratios of mean energy-absorption coefficients for different materials. These values were based on the work of Cunningham and Schulz. We have calculated these quantities for Solid Water (manufactured by RMI), using the same x-ray spectra and method as that used by Cunningham and Schulz. These values should be useful to people who are using Solid Water for high-energy photon calibration.

Polyarteritis nodosa: MDCT as a 'One-Stop Shop' Modality for Whole-Body Arterial Evaluation

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

Tsai, W.-L.; Tsai, I-C.; Lee Tain, E-mail: s841082@ym.edu.t

Polyarteritis nodosa is a rare disease, which is characterized by aneurysm formation and occlusion in the arteries of multiple systems. Due to its extensive involvement, whole-body evaluation is necessary for diagnosis and treatment monitoring. We report a case of polyarteritis nodosa using multidetector-row computed tomography (MDCT) as a 'one-stop shop' modality for whole-body arterial evaluation. With precise protocol design, MDCT can be used as a reliable noninvasive modality providing comprehensive whole-body arterial evaluation.

Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: A Systematic Review and Meta-analysis.

PubMed

Ding, Nan; Liu, Xingchen; Jian, Qiliang; Liang, Zhongzhen; Wang, Fang

2017-11-01

Increasing evidence indicates that a dual trigger (a gonadotrophin-releasing hormone agonist [GnRH-a] with a human chorionic gonadotrophin [hCG] trigger) is the best choice for final oocyte maturation in the GnRH antagonist (GnRH-ant) cycle. However, this conclusion remains controversial. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of a GnRH-a combined with a standard hCG trigger in comparison with hCG alone for final oocyte maturation in the GnRH-ant cycle for in vitro fertilization. Complete electronic databases, including PubMed, Embase, The Cochrane Library, and Web of Science, were searched for relevant randomized controlled trials (RCT). The search was not restricted by language or publication time. Two reviewers selected trials and assessed trial quality independently by using the Cochrane Handbook 5.1.0. Four eligible RCT studies involving 527 women were included. The results of this meta-analysis indicated that the dual trigger group had a significantly higher pregnancy rate (relative risk [RR], 1.55; 95% confidence interval [CI], 1.17-2.06) than the hCG-only trigger group. No significant differences were found in the number of oocytes retrieved (weighted mean difference [WMD], 0.47; 95% CI, -0.42 to 1.37), number of mature oocytes retrieved (WMD, 0.41; 95% CI, -0.48 to 1.30), number of fertilized oocytes (WMD, 0.47; 95% CI, -0.32 to 1.26), number of good-quality embryos (WMD, 0.17; 95% CI, -0.29 to 0.64), or implantation rate (RR, 1.17; 95% CI, 0.69-2.00) between the two groups. GnRH-a and hCG as dual trigger was equivalent to hCG in triggering oocyte maturation and may be beneficial in improving reproductive outcomes. Further intensive randomized-controlled studies should be conducted to investigate the efficacy of the dual trigger. Copyright © 2017 Elsevier B.V. All rights reserved.

Perioperative management of trauma patients admitted on clopidogrel (Plavix). A survey of orthopaedic departments across the United Kingdom.

PubMed

Inman, Dominic S; Michla, Yusuf; Partington, Paul F

2007-05-01

Clopidogrel (Plavix) is an anti-platelet drug recommended as lifelong treatment by NICE for all patients following stroke, MI, and peripheral vascular disease. It is also indicated for short-term use following cardiac stent insertion. It irreversibly inhibits platelets for up to 7 days. Current recommendations are to stop treatment 7 days before elective surgery. Current evidence shows that delay to surgery more than 4 days in patients with hip fractures increases postoperative mortality. To determine current practice of orthopaedic surgeons in their management of patients taking clopidogrel admitted following a hip fracture to trauma units in the UK with respect to its peri-operative withdrawal and subsequent timing of surgery. To perform a review of the available literature and produce a suggested protocol for the peri-operative management of this rapidly increasing cohort of patients. National postal survey. Orthopaedic consultants representing each unit receiving trauma patients in the United Kingdom. There was a 57% response rate (139/244 UK trauma units). 41% (56) stop clopidogrel and operate immediately, 11% (15) stop clopidogrel for between 5 and 10 days pre-operatively, 10% (14) stop clopidogrel for 10 days preoperatively, 19% (26) continue clopidogrel and operate immediately, 19% (26) have another protocol. 15% (20) have written departmental guidelines. 2%(3) quoted published evidence for their practice. This study demonstrates that there are a wide variety of practices, largely based on anecdotal evidence. Most units (85%) have no formal guidelines. There is evidence in the cardiac literature of increased intra-operative bleeding in patients operated on while taking clopidogrel. There is likely to be an exponential rise in such patients presenting to trauma units and further research is required to guide best practice. Following review of the literature we propose an interim protocol for the withdrawal and resumption of clopidogrel peri-operatively in patients with hip fractures.

Process membership in asynchronous environments

NASA Technical Reports Server (NTRS)

Ricciardi, Aleta M.; Birman, Kenneth P.

1993-01-01

The development of reliable distributed software is simplified by the ability to assume a fail-stop failure model. The emulation of such a model in an asynchronous distributed environment is discussed. The solution proposed, called Strong-GMP, can be supported through a highly efficient protocol, and was implemented as part of a distributed systems software project at Cornell University. The precise definition of the problem, the protocol, correctness proofs, and an analysis of costs are addressed.

[Constraints on publication rights in industry-initiated clinical trials--secondary publication].

PubMed

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2006-06-19

In 22 of 44 industry-initiated clinical trial protocols from 1994-95, it was noted that the sponsor either owned the data or needed to approve the manuscript; another 18 protocols had other constraints. Furthermore, in 16 trials, the sponsor had access to accumulating data, and in an additional 16 trials the sponsor could stop the trial at any time, for any reason. These facts were not noted in any of the trial reports. We found similar constraints on publication rights in 44 protocols from 2004. This tight sponsor control over industry-initiated trials should be changed.

Fostering community understanding of sufficient benefit and early stopping for a phase 2B HIV prevention clinical trial in Africa.

PubMed

White, Rhonda; Chileshe, Modesta; Dawson, Liza; Donnell, Deborah; Hillier, Sharon; Morar, Neetha; Noguchi, Lisa; Dixon, Dennis

2011-02-01

Most trials of interventions are designed to address the traditional null hypothesis of no benefit. VOICE, a phase 2B HIV prevention trial funded by NIH and conducted in Africa, is designed to assess if the intervention will prevent a substantial fraction of infections. Planned interim analysis may provide conclusive evidence against the traditional null hypothesis without establishing substantial benefit. At this interim point, the Data and Safety Monitoring Board would then face the dilemma of knowing the product has some positive effect, but perhaps not as great an effect as the protocol has declared necessary. In March 2008, NIH program staff recommended that the VOICE protocol team discuss the stopping rules with stakeholders prior to initiating the protocol. The goals of the workshop were to inform community representatives about the potential ethical dilemma associated with stopping rules and engage in dialogue about these issues. We describe the resulting community consultation and summarize the outcomes. A 2-day workshop was convened with the goal of having a clear and transparent consultation with the stakeholders around the question, 'Given emerging evidence that a product could prevent some infections, would the community support a decision to continue accruing to the trial?' Participants included research staff and community stakeholders. Lectures with visual aids, discussions, and exercises using interactive learning tasks were used, with a focus on statistics and interpreting data from trials, particularly interim data. Results of oral and written evaluations by participants were reviewed. The feedback was mostly positive, with some residual confusion regarding statistical concepts. However, discussions with attendees later revealed that not all felt prepared to engage fully in the workshop. This was the presenters' first experience facilitating a formal discussion with an audience that had no advanced science, research, or mathematics training. Community representatives' concern regarding speaking for their communities without consulting them also created a challenge for the workshop. Open discussion around trial stopping rules requires that all discussants have an understanding of trial design concepts and feel a sense of empowerment to ask and answer questions. The VOICE CWG workshop was a first step toward the goal of open discussion regarding trial stopping rules and interim results for the study; however, ongoing education and dialogue must occur to ensure that all stakeholders fully participate in the process.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

2018-01-30

It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

Brain Maturation, Cognition and Voice Pattern in a Gender Dysphoria Case under Pubertal Suppression.

PubMed

Schneider, Maiko A; Spritzer, Poli M; Soll, Bianca Machado Borba; Fontanari, Anna M V; Carneiro, Marina; Tovar-Moll, Fernanda; Costa, Angelo B; da Silva, Dhiordan C; Schwarz, Karine; Anes, Maurício; Tramontina, Silza; Lobato, Maria I R

2017-01-01

Introduction: Gender dysphoria (GD) (DMS-5) is a condition marked by increasing psychological suffering that accompanies the incongruence between one's experienced or expressed gender and one's assigned gender. Manifestation of GD can be seen early on during childhood and adolescence. During this period, the development of undesirable sexual characteristics marks an acute suffering of being opposite to the sex of birth. Pubertal suppression with gonadotropin releasing hormone analogs (GnRHa) has been proposed for these individuals as a reversible treatment for postponing the pubertal development and attenuating psychological suffering. Recently, increased interest has been observed on the impact of this treatment on brain maturation, cognition and psychological performance. Objectives: The aim of this clinical report is to review the effects of puberty suppression on the brain white matter (WM) during adolescence. WM Fractional anisotropy, voice and cognitive functions were assessed before and during the treatment. MRI scans were acquired before, and after 22 and 28 months of hormonal suppression. Methods: We performed a longitudinal evaluation of a pubertal transgender girl undergoing hormonal treatment with GnRH analog. Three longitudinal magnetic resonance imaging (MRI) scans were performed for diffusion tensor imaging (DTI), regarding Fractional Anisotropy (FA) for regions of interest analysis. In parallel, voice samples for acoustic analysis as well as executive functioning with the Wechsler Intelligence Scale (WISC-IV) were performed. Results: During the follow-up, white matter fractional anisotropy did not increase, compared to normal male puberty effects on the brain. After 22 months of pubertal suppression, operational memory dropped 9 points and remained stable after 28 months of follow-up. The fundamental frequency of voice varied during the first year; however, it remained in the female range. Conclusion: Brain white matter fractional anisotropy remained unchanged in the GD girl during pubertal suppression with GnRHa for 28 months, which may be related to the reduced serum testosterone levels and/or to the patient's baseline low average cognitive performance.Global performance on the Weschler scale was slightly lower during pubertal suppression compared to baseline, predominantly due to a reduction in operational memory. Either a baseline of low average cognition or the hormonal status could play a role in cognitive performance during pubertal suppression. The voice pattern during the follow-up seemed to reflect testosterone levels under suppression by GnRHa treatment.

Brain Maturation, Cognition and Voice Pattern in a Gender Dysphoria Case under Pubertal Suppression

PubMed Central

Schneider, Maiko A.; Spritzer, Poli M.; Soll, Bianca Machado Borba; Fontanari, Anna M. V.; Carneiro, Marina; Tovar-Moll, Fernanda; Costa, Angelo B.; da Silva, Dhiordan C.; Schwarz, Karine; Anes, Maurício; Tramontina, Silza; Lobato, Maria I. R.

2017-01-01

Introduction: Gender dysphoria (GD) (DMS-5) is a condition marked by increasing psychological suffering that accompanies the incongruence between one's experienced or expressed gender and one's assigned gender. Manifestation of GD can be seen early on during childhood and adolescence. During this period, the development of undesirable sexual characteristics marks an acute suffering of being opposite to the sex of birth. Pubertal suppression with gonadotropin releasing hormone analogs (GnRHa) has been proposed for these individuals as a reversible treatment for postponing the pubertal development and attenuating psychological suffering. Recently, increased interest has been observed on the impact of this treatment on brain maturation, cognition and psychological performance. Objectives: The aim of this clinical report is to review the effects of puberty suppression on the brain white matter (WM) during adolescence. WM Fractional anisotropy, voice and cognitive functions were assessed before and during the treatment. MRI scans were acquired before, and after 22 and 28 months of hormonal suppression. Methods: We performed a longitudinal evaluation of a pubertal transgender girl undergoing hormonal treatment with GnRH analog. Three longitudinal magnetic resonance imaging (MRI) scans were performed for diffusion tensor imaging (DTI), regarding Fractional Anisotropy (FA) for regions of interest analysis. In parallel, voice samples for acoustic analysis as well as executive functioning with the Wechsler Intelligence Scale (WISC-IV) were performed. Results: During the follow-up, white matter fractional anisotropy did not increase, compared to normal male puberty effects on the brain. After 22 months of pubertal suppression, operational memory dropped 9 points and remained stable after 28 months of follow-up. The fundamental frequency of voice varied during the first year; however, it remained in the female range. Conclusion: Brain white matter fractional anisotropy remained unchanged in the GD girl during pubertal suppression with GnRHa for 28 months, which may be related to the reduced serum testosterone levels and/or to the patient's baseline low average cognitive performance.Global performance on the Weschler scale was slightly lower during pubertal suppression compared to baseline, predominantly due to a reduction in operational memory. Either a baseline of low average cognition or the hormonal status could play a role in cognitive performance during pubertal suppression. The voice pattern during the follow-up seemed to reflect testosterone levels under suppression by GnRHa treatment. PMID:29184488

A functional agility short-term fatigue protocol changes lower extremity mechanics

PubMed Central

Cortes, Nelson; Quammen, David; Lucci, Shawn; Greska, Eric; Onate, James

2012-01-01

The purpose of this study was to evaluate the effects of a functional agility fatigue protocol on lower extremity biomechanics between two unanticipated tasks (stop-jump and sidestep). The subjects consisted of fifteen female collegiate soccer athletes (19 ± 0.7 years, 1.67 ± 0.1 m, 61.7 ± 8 kg) free of lower extremity injury. Participants performed five trials of stop-jump and sidestep tasks. A functional short-term agility protocol was performed, and immediately following participants repeated the unanticipated running tasks. Lower extremity kinematic and kinetic values were obtained pre and post fatigue. Repeated measures analyses of variance were conducted for each dependent variable with an alpha level set at 0.05. Knee position post-fatigue had increased knee internal rotation (11.4 ± 7.5° vs. 7.9 ± 6.5° p = 0.011) than pre-fatigue, and a decreased knee flexion angle (−36.6 ± 6.2° vs.−40.0 ± 6.3°, p = 0.003), as well as hip position post-fatigue had decreased hip flexion angle (35.5 ± 8.7° vs. 43.2 ± 9.5°, p = 0.002). A quick functional fatigue protocol altered lower extremity mechanics of Division I collegiate soccer athletes during landing tasks. Proper mechanics should be emphasized from the beginning of practice/game to aid in potentially minimizing the effects of fatigue in lower extremity mechanics. PMID:22424559

An overview of treatments for endometriosis.

PubMed

Brown, Julie; Farquhar, Cynthia

2015-01-20

What treatments are associated with improved outcomes for women with endometriosis? The levonorgestrel-releasing intrauterine system (LNG-IUD), gonadotropin-releasing hormone analogues (GnRHa; nafarelin, leuprolide, buserelin, goserelin, triptorelin), laparoscopic ablation, and excision are associated with relief of pain due to endometriosis. Gonadotropin-releasing hormone analogues and laparoscopic ablation or excision are associated with increased clinical pregnancy rates in women with endometriosis. Gonadotropin-releasing hormone analogues, danazol, and depot progestagens are associated with a higher incidence of adverse events.

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

PubMed

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.

Bacterial contamination hypothesis: a new concept in endometriosis.

PubMed

Khan, Khaleque N; Fujishita, Akira; Hiraki, Koichi; Kitajima, Michio; Nakashima, Masahiro; Fushiki, Shinji; Kitawaki, Jo

2018-04-01

Endometriosis is a multifactorial disease that mainly affects women of reproductive age. The exact pathogenesis of this disease is still debatable. The role of bacterial endotoxin (lipopolysaccharide, LPS) and Toll-like receptor 4 (TLR4) in endometriosis were investigated and the possible source of endotoxin in the pelvic environment was examined. The limulus amoebocyte lysate test was used to measure the endotoxin levels in the menstrual fluid and peritoneal fluid and their potential role in the growth of endometriosis was investigated. Menstrual blood and endometrial samples were cultured for the presence of microbes. The effect of gonadotrophin-releasing hormone agonist (GnRHa) treatment on intrauterine microbial colonization (IUMC) and the occurrence of endometritis was investigated. Lipopolysaccharide regulates the pro-inflammatory response in the pelvis and growth of endometriosis via the LPS/TLR4 cascade. The menstrual blood was highly contaminated with Escherichea coli and the endometrial samples were colonized with other microbes. A cross-talk between inflammation and ovarian steroids or the stress reaction also was observed in the pelvis. Treatment with GnRHa further worsens intrauterine microbial colonization, with the consequent occurrence of endometritis in women with endometriosis. For the first time, a new concept called the "bacterial contamination hypothesis" is proposed in endometriosis. This study's findings of IUMC in women with endometriosis could hold new therapeutic potential in addition to the conventional estrogen-suppressing agent.

Effect of oxygen-breathing during a decompression-stop on bubble-induced platelet activation after an open-sea air dive: oxygen-stop decompression.

PubMed

Pontier, J-M; Lambrechts, K

2014-06-01

We highlighted a relationship between decompression-induced bubble formation and platelet micro-particle (PMP) release after a scuba air-dive. It is known that decompression protocol using oxygen-stop accelerates the washout of nitrogen loaded in tissues. The aim was to study the effect of oxygen deco-stop on bubble formation and cell-derived MP release. Healthy experienced divers performed two scuba-air dives to 30 msw for 30 min, one with an air deco-stop and a second with 100% oxygen deco-stop at 3 msw for 9 min. Bubble grades were monitored with ultrasound and converted to the Kisman integrated severity score (KISS). Blood samples for cell-derived micro-particle analysis (AnnexinV for PMP and CD31 for endothelial MP) were taken 1 h before and after each dive. Mean KISS bubble score was significantly lower after the dive with oxygen-decompression stop, compared to the dive with air-decompression stop (4.3 ± 7.3 vs. 32.7 ± 19.9, p < 0.001). After the dive with an air-breathing decompression stop, we observed an increase of the post-dive mean values of PMP (753 ± 245 vs. 381 ± 191 ng/μl, p = 0.003) but no significant change in the oxygen-stop decompression dive (329 ± 215 vs. 381 +/191 ng/μl, p = 0.2). For the post-dive mean values of endothelial MP, there was no significant difference between both the dives. The Oxygen breathing during decompression has a beneficial effect on bubble formation accelerating the washout of nitrogen loaded in tissues. Secondary oxygen-decompression stop could reduce bubble-induced platelet activation and the pro-coagulant activity of PMP release preventing the thrombotic event in the pathogenesis of decompression sickness.

Current protocols in the management of oral submucous fibrosis: An update.

PubMed

Arakeri, Gururaj; Rai, Kirthi Kumar; Boraks, George; Patil, Shekar Gowda; Aljabab, Abdulsalam S; Merkx, M A W; Carrozzo, Marco; Brennan, Peter A

2017-07-01

Oral submucous fibrosis (OSMF) is a debilitating condition of oral cavity which has significant potential for malignant transformation. In spite of over 20 years of research, the pathogenesis of the condition is still obscure and no single management modality is effective. Many OSMF treatment protocols have been proposed to alleviate the signs and symptoms of the disorder and there is overwhelming evidence that as areca nut is primary cause, stopping its use may have a considerable effect on symptoms rather than reversing pre-existing fibrosis. We present a review of the current protocols for managing OSMF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cycle regimens for frozen-thawed embryo transfer.

PubMed

Ghobara, Tarek; Gelbaya, Tarek A; Ayeleke, Reuben Olugbenga

2017-07-05

Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have historically been found to be lower than following embryo transfer undertaken two to five days following oocyte retrieval. Nevertheless, FET increases the cumulative pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh embryo transfer. FET is performed using different cycle regimens: spontaneous ovulatory (natural) cycles; cycles in which the endometrium is artificially prepared by oestrogen and progesterone hormones, commonly known as hormone therapy (HT) FET cycles; and cycles in which ovulation is induced by drugs (ovulation induction FET cycles). HT can be used with or without a gonadotrophin releasing hormone agonist (GnRHa). This is an update of a Cochrane review; the first version was published in 2008. To compare the effectiveness and safety of natural cycle FET, HT cycle FET and ovulation induction cycle FET, and compare subtypes of these regimens. On 13 December 2016 we searched databases including Cochrane Gynaecology and Fertility's Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. Other search sources were trials registers and reference lists of included studies. We included randomized controlled trials (RCTs) comparing the various cycle regimens and different methods used to prepare the endometrium during FET. We used standard methodological procedures recommended by Cochrane. Our primary outcomes were live birth rates and miscarriage. We included 18 RCTs comparing different cycle regimens for FET in 3815 women. The quality of the evidence was low or very low. The main limitations were failure to report important clinical outcomes, poor reporting of study methods and imprecision due to low event rates. We found no data specific to non-ovulatory women. 1. Natural cycle FET comparisons Natural cycle FET versus HT FETNo study reported live birth rates, miscarriage or ongoing pregnancy.There was no evidence of a difference in multiple pregnancy rates between women in natural cycles and those in HT FET cycle (odds ratio (OR) 2.48, 95% confidence interval (CI) 0.09 to 68.14, 1 RCT, n = 21, very low-quality evidence). Natural cycle FET versus HT plus GnRHa suppressionThere was no evidence of a difference in rates of live birth (OR 0.77, 95% CI 0.39 to 1.53, 1 RCT, n = 159, low-quality evidence) or multiple pregnancy (OR 0.58, 95% CI 0.13 to 2.50, 1 RCT, n = 159, low-quality evidence) between women who had natural cycle FET and those who had HT FET cycles with GnRHa suppression. No study reported miscarriage or ongoing pregnancy. Natural cycle FET versus modified natural cycle FET (human chorionic gonadotrophin (HCG) trigger)There was no evidence of a difference in rates of live birth (OR 0.55, 95% CI 0.16 to 1.93, 1 RCT, n = 60, very low-quality evidence) or miscarriage (OR 0.20, 95% CI 0.01 to 4.13, 1 RCT, n = 168, very low-quality evidence) between women in natural cycles and women in natural cycles with HCG trigger. However, very low-quality evidence suggested that women in natural cycles (without HCG trigger) may have higher ongoing pregnancy rates (OR 2.44, 95% CI 1.03 to 5.76, 1 RCT, n = 168). There were no data on multiple pregnancy. 2. Modified natural cycle FET comparisons Modified natural cycle FET (HCG trigger) versus HT FETThere was no evidence of a difference in rates of live birth (OR 1.34, 95% CI 0.88 to 2.05, 1 RCT, n = 959, low-quality evidence) or ongoing pregnancy (OR 1.21, 95% CI 0.80 to 1.83, 1 RCT, n = 959, low-quality evidence) between women in modified natural cycles and those who received HT. There were no data on miscarriage or multiple pregnancy. Modified natural cycle FET (HCG trigger) versus HT plus GnRHa suppressionThere was no evidence of a difference between the two groups in rates of live birth (OR 1.11, 95% CI 0.66 to 1.87, 1 RCT, n = 236, low-quality evidence) or miscarriage (OR 0.74, 95% CI 0.25 to 2.19, 1 RCT, n = 236, low-quality evidence) rates. There were no data on ongoing pregnancy or multiple pregnancy. 3. HT FET comparisons HT FET versus HT plus GnRHa suppressionHT alone was associated with a lower live birth rate than HT with GnRHa suppression (OR 0.10, 95% CI 0.04 to 0.30, 1 RCT, n = 75, low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 0.64, 95% CI 0.37 to 1.12, 6 RCTs, n = 991, I 2 = 0%, low-quality evidence) or ongoing pregnancy (OR 1.72, 95% CI 0.61 to 4.85, 1 RCT, n = 106, very low-quality evidence).There were no data on multiple pregnancy. 4. Comparison of subtypes of ovulation induction FET Human menopausal gonadotrophin(HMG) versus clomiphene plus HMG HMG alone was associated with a higher live birth rate than clomiphene combined with HMG (OR 2.49, 95% CI 1.07 to 5.80, 1 RCT, n = 209, very low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 1.33, 95% CI 0.35 to 5.09,1 RCT, n = 209, very low-quality evidence) or multiple pregnancy (OR 1.41, 95% CI 0.31 to 6.48, 1 RCT, n = 209, very low-quality evidence).There were no data on ongoing pregnancy. This review did not find sufficient evidence to support the use of one cycle regimen in preference to another in preparation for FET in subfertile women with regular ovulatory cycles. The most common modalities for FET are natural cycle with or without HCG trigger or endometrial preparation with HT, with or without GnRHa suppression. We identified only four direct comparisons of these two modalities and there was insufficient evidence to support the use of either one in preference to the other.

The Many Faces of the Economic Bulletin Board.

ERIC Educational Resources Information Center

Boettcher, Jennifer

1996-01-01

The Economic Bulletin Board (EBB), a one-stop site for economic statistics and government-sponsored business information, can be accessed on the World Wide Web, gopher, telnet, file transfer protocol, dial-up, and fax. Each access method has advantages and disadvantages related to connections, pricing, depth of access, retrieval, and system…

Quantifying the bias in the estimated treatment effect in randomized trials having interim analyses and a rule for early stopping for futility.

PubMed

Walter, S D; Han, H; Briel, M; Guyatt, G H

2017-04-30

In this paper, we consider the potential bias in the estimated treatment effect obtained from clinical trials, the protocols of which include the possibility of interim analyses and an early termination of the study for reasons of futility. In particular, by considering the conditional power at an interim analysis, we derive analytic expressions for various parameters of interest: (i) the underestimation or overestimation of the treatment effect in studies that stop for futility; (ii) the impact of the interim analyses on the estimation of treatment effect in studies that are completed, i.e. that do not stop for futility; (iii) the overall estimation bias in the estimated treatment effect in a single study with such a stopping rule; and (iv) the probability of stopping at an interim analysis. We evaluate these general expressions numerically for typical trial scenarios. Results show that the parameters of interest depend on a number of factors, including the true underlying treatment effect, the difference that the trial is designed to detect, the study power, the number of planned interim analyses and what assumption is made about future data to be observed after an interim analysis. Because the probability of stopping early is small for many practical situations, the overall bias is often small, but a more serious issue is the potential for substantial underestimation of the treatment effect in studies that actually stop for futility. We also consider these ideas using data from an illustrative trial that did stop for futility at an interim analysis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of a pilot walking school bus intervention on children's pedestrian safety behaviors: a pilot study.

PubMed

Mendoza, Jason A; Watson, Kathy; Chen, Tzu-An; Baranowski, Tom; Nicklas, Theresa A; Uscanga, Doris K; Hanfling, Marcus J

2012-01-01

Walking school buses (WSB) increased children's physical activity, but impact on pedestrian safety behaviors (PSB) is unknown. We tested the feasibility of a protocol evaluating changes to PSB during a WSB program. Outcomes were school-level street crossing PSB prior to (Time 1) and during weeks 4-5 (Time 2) of the WSB. The protocol collected 1252 observations at Time 1 and 2548 at Time 2. Mixed model analyses yielded: intervention schoolchildren had 5-fold higher odds (p<0.01) of crossing at the corner/crosswalk but 5-fold lower odds (p<0.01) of stopping at the curb. The protocol appears feasible for documenting changes to school-level PSB. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparison between the TRS-398 code of practice and the TG-51 dosimetry protocol for flattening filter free beams

NASA Astrophysics Data System (ADS)

Lye, J. E.; Butler, D. J.; Oliver, C. P.; Alves, A.; Lehmann, J.; Gibbons, F. P.; Williams, I. M.

2016-07-01

Dosimetry protocols for external beam radiotherapy currently in use, such as the IAEA TRS-398 and AAPM TG-51, were written for conventional linear accelerators. In these accelerators, a flattening filter is used to produce a beam which is uniform at water depths where the ionization chamber is used to measure the absorbed dose. Recently, clinical linacs have been implemented without the flattening filter, and published theoretical analysis suggested that with these beams a dosimetric error of order 0.6% could be expected for IAEA TRS-398, because the TPR20,10 beam quality index does not accurately predict the stopping power ratio (water to air) for the softer flattening-filter-free (FFF) beam spectra. We measured doses on eleven FFF linacs at 6 MV and 10 MV using both dosimetry protocols and found average differences of 0.2% or less. The expected shift due to stopping powers was not observed. We present Monte Carlo k Q calculations which show a much smaller difference between FFF and flattened beams than originally predicted. These results are explained by the inclusion of the added backscatter plates and build-up filters used in modern clinical FFF linacs, compared to a Monte Carlo model of an FFF linac in which the flattening filter is removed and no additional build-up or backscatter plate is added.

Timing and technique impact the effectiveness of road-based, mobile acoustic surveys of bats.

PubMed

D'Acunto, Laura E; Pauli, Benjamin P; Moy, Mikko; Johnson, Kiara; Abu-Omar, Jasmine; Zollner, Patrick A

2018-03-01

Mobile acoustic surveys are a common method of surveying bat communities. However, there is a paucity of empirical studies exploring different methods for conducting mobile road surveys of bats. During 2013, we conducted acoustic mobile surveys on three routes in north-central Indiana, U.S.A., using (1) a standard road survey, (2) a road survey where the vehicle stopped for 1 min at every half mile of the survey route (called a "start-stop method"), and (3) a road survey with an individual using a bicycle. Linear mixed models with multiple comparison procedures revealed that when all bat passes were analyzed, using a bike to conduct mobile surveys detected significantly more bat passes per unit time compared to other methods. However, incorporating genus-level comparisons revealed no advantage to using a bike over vehicle-based methods. We also found that survey method had a significant effect when analyses were limited to those bat passes that could be identified to genus, with the start-stop method generally detecting more identifiable passes than the standard protocol or bike survey. Additionally, we found that significantly more identifiable bat passes (particularly those of the Eptesicus and Lasiurus genera) were detected in surveys conducted immediately following sunset. As governing agencies, particularly in North America, implement vehicle-based bat monitoring programs, it is important for researchers to understand how variations on protocols influence the inference that can be gained from different monitoring schemes.

Enlightenment about the new Architect-i2000 estradiol (Abbott Laboratories) immunoassay during in vitro fertilization.

PubMed

Taieb, Joëlle; Mendez Lozano, Daniel H; Benattar, Clarisse; Messaoudi, Chérif; Poüs, Christian

2007-12-01

We assessed a new estradiol (E2) immunoassay on the Architect-i2000 (Abbott Laboratories) for monitoring ovulation stimulation for IVF-ET and re-establishing clinical cut-off points. The method has been modified to improve E2 measurements especially at normal and low concentrations. E2 was determined for 552 samples, from 83 women, presenting normal follicular status and undergoing 100 cycles of IVF treatment. We assessed the value of this assay for down-regulation of E2 concentration limit using gonadoliberin-releasing hormone agonist (GnRHa), and monitoring of the ovarian hyperstimulation, expected range of E2 per mature follicle prior to the administration of exogenous hCG and day 3 concentration limit. We compared results with our routine method (E2-6II Advia-Centaur; Siemens-Diagnostics) for which decision-making values were known. Considering E2 concentrations obtained with the new Architect-i2000 assay for patients treated with GnRHa for 2 weeks, the cutoff-point for ovarian down-regulation should be set down at 110 pmol/L to maintain 100% of sensitivity. Considering day 3 concentration limit determination, results were not significantly different from those obtained with our routine method. The mean E2 values per mature follicle fell into the range generally expected. E2 determination with the new E2 Architect-i2000 assay could be used to monitor ovulation, in patients undergoing IVF-ET, in combination with transvaginal ultrasound.

A randomized, controlled clinical trial comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status.

PubMed

Parsanezhad, Mohammad Ebrahim; Azmoon, Mina; Alborzi, Saeed; Rajaeefard, Abdoreza; Zarei, Afsun; Kazerooni, Talieh; Frank, Vivian; Schmidt, Ernst Hienrich

2010-01-01

To examine and compare the efficacy and safety of GnRH agonist (GnRHa) vs. aromatase inhibitor in premenopausal women with leiomyomas. Multicenter, randomized, controlled clinical trial. University hospitals. A total of 70 subjects with a single uterine myoma measuring >or=5 cm. Subjects were randomized into two groups with use of a random table. They were treated with aromatase inhibitor (group A) or GnRHa (group B). Group A received letrozole (2.5 mg/d) for 12 weeks. Group B received triptorelin (3.75 mg/mo) for 12 weeks. Measurement of myoma volume and E(2), FSH, LH, and T levels. Total myoma volume decreased by 45.6% in group A and 33.2% in group B. Reductions in myoma volume in the two groups were statistically significant. There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment. Uterine myoma volume was successfully reduced by use of an aromatase inhibitor. Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention, specifically women with unexplained infertility having uterine myoma. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

Expression of Fushi tarazu factor 1 homolog and Pit-1 genes in the pituitaries of pre-spawning chum and sockeye salmon.

PubMed

Higa, M; Ando, H; Urano, A

2001-06-01

Fushi tarazu factor-1 (FTZ-F1) and Pit-1 are major pituitary transcription factors, controlling expression of genes coding for gonadotropin (GTH) subunits and growth hormone/prolactin/somatolactin family hormone, respectively. As a first step to investigate physiological factors regulating gene expression of these transcription factors, we determined their mRNA levels in the pituitaries of chum salmon (Oncorhynchus keta) at different stages of sexual maturation. FTZ-F1 gene expression was increased in males at the stage before spermiation, where the levels of GTH alpha and IIbeta subunit mRNAs were elevated. Pit-1 mRNA showed maximum levels at the final stage of sexual maturation in both sexes, when expression of somatolactin gene peaked. To clarify whether gonadotropin-releasing hormone (GnRH) is involved in these increases in FTZ-F1 and Pit-1 gene expression, we examined effects of GnRH analog (GnRHa) administration on their gene expression in maturing sockeye salmon (Oncorhynchus nerka). GnRHa stimulated Pit-1 gene expression in females only, but failed to stimulate FTZ-F1 gene expression in both sexes. The up-regulated expression of FTZ-F1 and Pit-1 genes at the pre-spawning stages suggest that the two transcription factors have roles in sexual maturation of salmonids. Physiological factors regulating gene expression of FTZ-F1 and Pit-1 are discussed in this review.

Reduction in surgical antibiotic prophylaxis expenditure and the rate of surgical site infection by means of a protocol that controls the use of prophylaxis.

PubMed

Gomez, Marisa I; Acosta-Gnass, Silvia I; Mosqueda-Barboza, Luisa; Basualdo, Juan A

2006-12-01

To evaluate the effectiveness of an intervention based on training and the use of a protocol with an automatic stop of antimicrobial prophylaxis to improve hospital compliance with surgical antibiotic prophylaxis guidelines. An interventional study with a before-after trial was conducted in 3 stages: a 3-year initial stage (January 1999 to December 2001), during which a descriptive-prospective survey was performed to evaluate surgical antimicrobial prophylaxis and surgical site infections; a 6-month second stage (January to June 2002), during which an educational intervention was performed regarding the routine use of a surgical antimicrobial prophylaxis request form that included an automatic stop of prophylaxis (the "automatic-stop prophylaxis form"); and a 3-year final stage (July 2002 to June 2005), during which a descriptive-prospective survey of surgical antimicrobial prophylaxis and surgical site infections was again performed. An 88-bed teaching hospital in Entre Ríos, Argentina. A total of 3,496 patients who underwent surgery were included in the first stage of the study and 3,982 were included in the final stage. Comparison of the first stage of the study with the final stage revealed that antimicrobial prophylaxis was given at the appropriate time to 55% and 88% of patients, respectively (relative risk [RR], 0.27 [95% confidence interval {CI}, 0.25-0.30]; P<.01); the antimicrobial regimen was adequate in 74% and 87% of patients, respectively (RR, 0.50 [95% CI, 0.45-0.55]; P<.01); duration of the prophylaxis was adequate in 44% and 55% of patients, respectively (RR, 0.80 [95% CI, 0.77-0.84]; P<.01); and the surgical site infection rates were 3.2% and 1.9%, respectively (RR, 0.59 [95% CI, 0.44-0.79]; P<.01). Antimicrobial expenditure was 10,678.66 US$ per 1,000 patient-days during the first stage and 7,686.05 US$ per 1,000 patient-days during the final stage (RR, 0.87 [95% CI, 0.86-0.89]; P<.01). The intervention based on training and application of a protocol with an automatic stop of prophylaxis favored compliance with the hospital's current surgical antibiotic prophylaxis guidelines before the intervention, achieving significant reductions of surgical site infection rates and substantial savings for the healthcare system.

"CAN Stop"--implementation and evaluation of a secondary group prevention for adolescent and young adult cannabis users in various contexts--study protocol.

PubMed

Baldus, Christiane; Miranda, Alejandra; Weymann, Nina; Reis, Olaf; Moré, Kerstin; Thomasius, Rainer

2011-04-18

Current research shows that overall numbers for cannabis use among adolescents and young adults dropped in recent years. However, this trend is much less pronounced in continuous cannabis use. With regard to the heightened risk for detrimental health- and development-related outcomes, adolescents and young adults with continuous cannabis use need special attention. The health services structure for adolescents and young adults with substance related problems in Germany, is multifaceted, because different communal, medical and judicial agencies are involved. This results in a rather decentralized organizational structure of the help system. This and further system-inherent characteristics make the threshold for young cannabis users rather high. Because of this, there is a need to establish evidence-based low-threshold help options for young cannabis users, which can be easily disseminated. Therefore, a training programme for young cannabis users (age 14-21) was developed in the "CAN Stop" project. Within the project, we seek to implement and evaluate the training programme within different institutions of the help system. The evaluation is sensitive to the different help systems and their specific prerequisites. Moreover, within this study, we also test the practicability of a training provision through laypersons. The CAN Stop study is a four-armed randomized wait-list controlled trial. The four arms are needed for the different help system settings, in which the CAN Stop training programme is evaluated: (a) the drug addiction aid and youth welfare system, (b) the out-patient medical system, (c) the in-patient medical system and (d) prisons for juvenile offenders. Data are collected at three points, before and after the training or a treatment as usual, and six months after the end of either intervention. The CAN Stop study is expected to provide an evidence-based programme for young cannabis users seeking to reduce or quit their cannabis use. Moreover, we seek to gain knowledge about the programme's utility within different settings of the German help system for young cannabis users and information about the settings' specific clientele. The study protocol is discussed with regard to potential difficulties within the different settings. ISRCTN: ISRCTN57036983.

Throughput and Energy Efficiency of a Cooperative Hybrid ARQ Protocol for Underwater Acoustic Sensor Networks

PubMed Central

Ghosh, Arindam; Lee, Jae-Won; Cho, Ho-Shin

2013-01-01

Due to its efficiency, reliability and better channel and resource utilization, cooperative transmission technologies have been attractive options in underwater as well as terrestrial sensor networks. Their performance can be further improved if merged with forward error correction (FEC) techniques. In this paper, we propose and analyze a retransmission protocol named Cooperative-Hybrid Automatic Repeat reQuest (C-HARQ) for underwater acoustic sensor networks, which exploits both the reliability of cooperative ARQ (CARQ) and the efficiency of incremental redundancy-hybrid ARQ (IR-HARQ) using rate-compatible punctured convolution (RCPC) codes. Extensive Monte Carlo simulations are performed to investigate the performance of the protocol, in terms of both throughput and energy efficiency. The results clearly reveal the enhancement in performance achieved by the C-HARQ protocol, which outperforms both CARQ and conventional stop and wait ARQ (S&W ARQ). Further, using computer simulations, optimum values of various network parameters are estimated so as to extract the best performance out of the C-HARQ protocol. PMID:24217359

Non-Uniform Per-Packet Priority Marker for Use with Adaptive Protocols

DTIC Science & Technology

2014-01-07

through con­ gestion points that would totally stop traffic from a customer using the SLA shown in FIG. 5, though only some fraction of his traffic...assigning priori­ ties to TCP flows. PDQoS has potential to fill the need for a quality of service mechanism that is simple to configure and to

Energy Consumption Research of Mobile Data Collection Protocol for Underwater Nodes Using an USV.

PubMed

Lv, Zhichao; Zhang, Jie; Jin, Jiucai; Li, Qi; Gao, Baoru

2018-04-16

The Unmanned Surface Vehicle (USV) integrated with an acoustic modem is a novel mobile vehicle for data collection, which has an advantage in terms of mobility, efficiency, and collection cost. In the scenario of data collection, the USV is controlled autonomously along the planning trajectory and the data of underwater nodes are dynamically collected. In order to improve the efficiency of data collection and extend the life of the underwater nodes, a mobile data collection protocol for underwater nodes using the USV was proposed. In the protocol, the stop-and-wait ARQ transmission mechanism is adopted, where the duty cycle is designed considering the ratio between the sleep mode and the detection mode, and the transmission ratio is defined by the duty cycle, wake-up signal cycles, and USV’s speed. According to protocol, the evaluation index for energy consumption is constructed based on the duty cycle and the transmission ratio. The energy consumption of the protocol is simulated and analyzed using the mobile communication experiment data of USV, taking into consideration USV’s speed, data sequence length, and duty cycle. Optimized protocol parameters are identified, which in turn denotes the proposed protocol’s feasibility and effectiveness.

A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning.

PubMed

Isbister, Geoffrey K; Downes, Michael A; Mcnamara, Kylie; Berling, Ingrid; Whyte, Ian M; Page, Colin B

2016-01-01

The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15-60 min and frequently results in adverse reactions. We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion. A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4-9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 1000 U/L or abnormal ALT. 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15-98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31-39%): 173 (26.5%; 95% CI: 23-30%) only gastrointestinal, 50 (8%; 95% CI: 6-10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1-1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13-28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.

Modified natural cycle for embryo transfer using frozen-thawed blastocysts: A satisfactory option.

PubMed

Le, Quoc V; Abhari, Sina; Abuzeid, Omar M; DeAnna, Jennifer; Satti, Mohamed A; Abozaid, Tarek; Khan, Iqbal; Abuzeid, Mostafa I

2017-06-01

To describe pregnancy outcomes of frozen-thawed blastocysts cycles using modified natural cycle frozen embryo transfers (NC-FET) and down-regulated hormonally controlled frozen embryo transfers (HC-FET) protocols. This retrospective cohort study included all patients undergoing either modified NC-FET or down-regulated HC-FET using frozen-thawed day 5 embryos. Cycles with donor blastocysts were excluded. Four hundred twenty eight patients underwent a total of 493 FET cycles. Patients with regular menses and evidence of ovulation underwent modified NC-FET. These patients were given hCG 10,000 IU IM on the day of LH-surge. Vaginal progesterone (P4) was started two days later and blastocyst transfer was planned seven days after detecting the LH surge. Anovulatory patients and some ovulatory patients underwent down-regulated HC-FET. These patients were placed on medroxy-progesterone acetate (10mg) for 10days to bring on menses and were also given a half-dose of GnRH-agonist (GnRH-a) on the third day of medroxy-progesterone acetate. Exogenous estradiol was initiated on the third day of menses. Once serum E2 levels reached >500pg/mL and endometrial lining reached >8mm, intramuscular (IM) P4 in oil was administered. Blastocyst FET was planned 6days after initiating P4. The primary outcomes included clinical pregnancy and delivery rates. There were 197 patients in the modified NC-FET protocol and 181 in the down-regulated HC-FET protocol. Mean age (years), day-3 FSH levels (mIU/mL) and percentage of patients with male factor infertility were significantly higher and mean BMI (kg/m 2 ) was significantly lower in modified NC-FET compared to HC-FET, respectively. Analysis of the first cycle pregnancy outcomes revealed no significant differences in clinical pregnancy rate (54.3% vs. 52.5%) and delivery rate (47.2% vs. 43.6%) between modified NC-FET and HC-FET. Logistic regression analysis showed age (OR=0.939, 95% CI 0.894-0.989, p=0.011), number of blastocysts transferred (OR=1.414, 95% CI 1.046-1.909, p=0.024), and the year of FET (OR=1.127, 95% CI 1.029-1.234, p=0.010) were significant factors impacting clinical pregnancy. An age analysis within three age groups (≤35, 36-39, ≥40) was performed, but no significant difference in clinical pregnancy was observed. Our data suggests that modified NC-FET protocol has comparable pregnancy outcomes to down-regulated HC-FET when utilizing frozen-thawed day 5 embryos. Published by Elsevier B.V.

Hormonal profile and follicular dynamics concurrent with CIDR and insulin modified Ovsync TAI programs and their impacts on the fertility response in buffaloes.

PubMed

Ramoun, A A; Emara, A M; Heleil, B A; Darweish, S A; Abou-Ghait, H A

2017-12-01

Fifty one cyclic Egyptian buffaloes were used to study the hormonal profile and follicular dynamics concurrent with CIDR and insulin modified Ovsync TAI programs and their impacts on the consequent fertility responses. The buffaloes were randomly assigned into 3 ovulation synchronization protocols: Ovsync-alone (n = 13, control) CIDR-sync (n = 20) and Insulin-sync (n = 18). Ovsync-alone protocol consisted of two im injections of 20 μg bueserlin (GnRHa) on Day 0 (GnRH 1) and on Day 9 (GnRH 2) with an im injection of 500 μg of cloprostenol sodium (PGF 2 α) on Day 7. The CIDR-sync protocol consisted of the same treatment protocol as in Ovsync in addition to intra-vaginal insertion of CIDR (contains 1.38 gm of progesterone) on Day 0 followed by removal on Day 7. The Insulin-sync protocol consisted of the same treatment protocol as in Ovsync plus 3 sc injections of insulin at a dose of 0.25 i.u/1 kg, on Days 7, 8, and 9. Buffaloes in all groups were inseminated 16 h after GnRH2 by the same inseminator using frozen semen in straws. Blood samples were collected on Days 0, 3, 5 for serum progesterone assay and on Day 9 to measure serum concentrations of estradiol, insulin and IGF-1. Transrectal ultrasonographic scanning of the ovaries was conducted on Days 7, 8 and 9 to record the diameter of the largest follicle. Pregnancy diagnosis was conducted on Day 30 post-TAI by trans-rectal ultrasonographic scanning of the uterus to calculate conception rate. The serum progesterone concentration showed an increase (p < 0.01) in pregnant compared with non-pregnant buffaloes in both Ovsync-alone and Insulin-sync groups, but not in CIDR-sync group (p > 0.05) on Days 3 and 5. The serum estradiol concentration on Day 9 showed an increase (p < 0.01) in pregnant compared with the non-pregnant buffaloes in all of the treated groups. In Insulin-sync and Ovsync-alone groups, the diameter of the largest follicle (LF) was larger (p < 0.01) in pregnant compared with non-pregnant buffaloes, but in CIDR-sync, the diameter of the (LF) was larger (p < 0.01) in non-pregnant compared with pregnant buffaloes. Also, the results showed that the greatest diameter of LF was observed in pregnant buffaloes in Insulin-sync compared with either pregnant or non-pregnant buffaloes in all groups. It is concluded that modified CIDR-sync and Insulin-sync could improve fertility response through modulating hormonal profile and follicular dynamics in buffaloes during low breeding season. Copyright © 2017 Elsevier Inc. All rights reserved.

Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria.

PubMed

Costa, Rosalia; Dunsford, Michael; Skagerberg, Elin; Holt, Victoria; Carmichael, Polly; Colizzi, Marco

2015-11-01

Puberty suppression by gonadotropin-releasing hormone analogs (GnRHa) is prescribed to relieve the distress associated with pubertal development in adolescents with gender dysphoria (GD) and thereby to provide space for further exploration. However, there are limited longitudinal studies on puberty suppression outcome in GD. Also, studies on the effects of psychological support on its own on GD adolescents' well-being have not been reported. This study aimed to assess GD adolescents' global functioning after psychological support and puberty suppression. Two hundred one GD adolescents were included in this study. In a longitudinal design we evaluated adolescents' global functioning every 6 months from the first visit. All adolescents completed the Utrecht Gender Dysphoria Scale (UGDS), a self-report measure of GD-related discomfort. We used the Children's Global Assessment Scale (CGAS) to assess the psychosocial functioning of adolescents. At baseline, GD adolescents showed poor functioning with a CGAS mean score of 57.7 ± 12.3. GD adolescents' global functioning improved significantly after 6 months of psychological support (CGAS mean score: 60.7 ± 12.5; P < 0.001). Moreover, GD adolescents receiving also puberty suppression had significantly better psychosocial functioning after 12 months of GnRHa (67.4 ± 13.9) compared with when they had received only psychological support (60.9 ± 12.2, P = 0.001). Psychological support and puberty suppression were both associated with an improved global psychosocial functioning in GD adolescents. Both these interventions may be considered effective in the clinical management of psychosocial functioning difficulties in GD adolescents. © 2015 International Society for Sexual Medicine.

Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study

PubMed Central

Henningsson, S; Madsen, K H; Pinborg, A; Heede, M; Knudsen, G M; Siebner, H R; Frokjaer, V G

2015-01-01

Sex-hormone fluctuations may increase risk for developing depressive symptoms and alter emotional processing as supported by observations in menopausal and pre- to postpartum transition. In this double-blinded, placebo-controlled study, we used blood−oxygen level dependent functional magnetic resonance imaging (fMRI) to investigate if sex-steroid hormone manipulation with a gonadotropin-releasing hormone agonist (GnRHa) influences emotional processing. Fifty-six healthy women were investigated twice: at baseline (follicular phase of menstrual cycle) and 16±3 days post intervention. At both sessions, fMRI-scans during exposure to faces expressing fear, anger, happiness or no emotion, depressive symptom scores and estradiol levels were acquired. The fMRI analyses focused on regions of interest for emotional processing. As expected, GnRHa initially increased and subsequently reduced estradiol to menopausal levels, which was accompanied by an increase in subclinical depressive symptoms relative to placebo. Women who displayed larger GnRHa-induced increase in depressive symptoms had a larger increase in both negative and positive emotion-elicited activity in the anterior insula. When considering the post-GnRHa scan only, depressive responses were associated with emotion-elicited activity in the anterior insula and amygdala. The effect on regional activity in anterior insula was not associated with the estradiol net decline, only by the GnRHa-induced changes in mood. Our data implicate enhanced insula recruitment during emotional processing in the emergence of depressive symptoms following sex-hormone fluctuations. This may correspond to the emotional hypersensitivity frequently experienced by women postpartum. PMID:26624927

[Endometriosis medical treatment: Hormonal treatment for the management of pain and endometriotic lesions recurrence. CNGOF-HAS Endometriosis Guidelines].

PubMed

Geoffron, S; Cohen, J; Sauvan, M; Legendre, G; Wattier, J M; Daraï, E; Fernandez, H; Chabbert-Buffet, N

2018-03-01

The available literature, from 2006 to 2017, on hormonal treatment has been analysed as a contribution to the HAS-CNGOF task force for the treatment of endometriosis. Available data are heterogeneous and the general level of evidence is moderate. Hormonal treatment is usually offered as the primary option to women suffering from endometriosis. It cannot be used in women willing to conceive. In women who have not been operated, the first line of hormonal treatment includes combined oral contraceptives (COC) and the levonorgestrel-releasing intra uterine system (52mg LNG-IUS). As a second line, desogestrel progestin only pills, etonogestrel implants, GnRH analogs (GnRHa) with add back therapy and dienogest can be offered. Add back therapy should include estrogens to prevent bone loss and improve quality of life, it can be introduced before the third month of treatment to prevent side effects. The literature does not support preoperative hormonal treatment for the sole purpose of reducing complications or recurrence, or facilitating surgical procedures. After surgical treatment, hormonal treatment is recommended to prevent pain recurrence and improve quality of life. COCs or LNG IUS are recommended as a first line. To prevent recurrence of endometriomas COC is advised and maintained as long as tolerance is good in the absence of pregnancy plans. In case of dysmenorrhea, postoperative COC should be used in a continuous scheme. GnRHa are not recommended in the sole purpose of reducing endometrioma recurrence risk. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Privacy-Assured Aggregation Protocol for Smart Metering: A Proactive Fault-Tolerant Approach [Proactive Fault-Tolerant Aggregation Protocol for Privacy-Assured Smart Metering

DOE PAGES

Won, Jongho; Ma, Chris Y. T.; Yau, David K. Y.; ...

2016-06-01

Smart meters are integral to demand response in emerging smart grids, by reporting the electricity consumption of users to serve application needs. But reporting real-time usage information for individual households raises privacy concerns. Existing techniques to guarantee differential privacy (DP) of smart meter users either are not fault tolerant or achieve (possibly partial) fault tolerance at high communication overheads. In this paper, we propose a fault-tolerant protocol for smart metering that can handle general communication failures while ensuring DP with significantly improved efficiency and lower errors compared with the state of the art. Our protocol handles fail-stop faults proactively bymore » using a novel design of future ciphertexts, and distributes trust among the smart meters by sharing secret keys among them. We prove the DP properties of our protocol and analyze its advantages in fault tolerance, accuracy, and communication efficiency relative to competing techniques. We illustrate our analysis by simulations driven by real-world traces of electricity consumption.« less

Privacy-Assured Aggregation Protocol for Smart Metering: A Proactive Fault-Tolerant Approach [Proactive Fault-Tolerant Aggregation Protocol for Privacy-Assured Smart Metering

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

Won, Jongho; Ma, Chris Y. T.; Yau, David K. Y.

Smart meters are integral to demand response in emerging smart grids, by reporting the electricity consumption of users to serve application needs. But reporting real-time usage information for individual households raises privacy concerns. Existing techniques to guarantee differential privacy (DP) of smart meter users either are not fault tolerant or achieve (possibly partial) fault tolerance at high communication overheads. In this paper, we propose a fault-tolerant protocol for smart metering that can handle general communication failures while ensuring DP with significantly improved efficiency and lower errors compared with the state of the art. Our protocol handles fail-stop faults proactively bymore » using a novel design of future ciphertexts, and distributes trust among the smart meters by sharing secret keys among them. We prove the DP properties of our protocol and analyze its advantages in fault tolerance, accuracy, and communication efficiency relative to competing techniques. We illustrate our analysis by simulations driven by real-world traces of electricity consumption.« less

"CAN Stop" - Implementation and evaluation of a secondary group prevention for adolescent and young adult cannabis users in various contexts - study protocol

PubMed Central

2011-01-01

Background Current research shows that overall numbers for cannabis use among adolescents and young adults dropped in recent years. However, this trend is much less pronounced in continuous cannabis use. With regard to the heightened risk for detrimental health- and development-related outcomes, adolescents and young adults with continuous cannabis use need special attention. The health services structure for adolescents and young adults with substance related problems in Germany, is multifaceted, because different communal, medical and judicial agencies are involved. This results in a rather decentralized organizational structure of the help system. This and further system-inherent characteristics make the threshold for young cannabis users rather high. Because of this, there is a need to establish evidence-based low-threshold help options for young cannabis users, which can be easily disseminated. Therefore, a training programme for young cannabis users (age 14-21) was developed in the "CAN Stop" project. Within the project, we seek to implement and evaluate the training programme within different institutions of the help system. The evaluation is sensitive to the different help systems and their specific prerequisites. Moreover, within this study, we also test the practicability of a training provision through laypersons. Methods/Design The CAN Stop study is a four-armed randomized wait-list controlled trial. The four arms are needed for the different help system settings, in which the CAN Stop training programme is evaluated: (a) the drug addiction aid and youth welfare system, (b) the out-patient medical system, (c) the in-patient medical system and (d) prisons for juvenile offenders. Data are collected at three points, before and after the training or a treatment as usual, and six months after the end of either intervention. Discussion The CAN Stop study is expected to provide an evidence-based programme for young cannabis users seeking to reduce or quit their cannabis use. Moreover, we seek to gain knowledge about the programme's utility within different settings of the German help system for young cannabis users and information about the settings' specific clientele. The study protocol is discussed with regard to potential difficulties within the different settings. Trial registration ISRCTN: ISRCTN57036983 PMID:21501479

Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

PubMed

Bayram, N; van Wely, M; van der Veen, F

2004-01-01

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in women with polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in these women. Although ovulation and pregnancy have been achieved, the effectiveness of pulsatile GnRH in women with PCOS has not been clearly demonstrated. To assess the effectiveness of pulsatile GnRH administration in women with polycystic ovary syndrome (PCOS), in terms of ongoing pregnancy, ovulation, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, miscarriage, and multifollicular growth. We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched 13 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, August 2001), MEDLINE (January 1966 to August 2003), EMBASE (January 1985 to August 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. All relevant published randomised clinical trials were selected for inclusion if treatment consisted of pulsatile GnRH administration versus another treatment for ovulation induction in subfertile women with PCOS. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto method. Four randomised clinical trials involving 57 women were identified comparing four different treatments: GnRH versus HMG, GnRH and FSH versus FSH, GnRH following pretreatment with GnRH agonist (GnRHa) versus GnRH only, GnRH following pretreatment with GnRHa versus clomiphene citrate. This means that there was only one trial in any one comparison. In two studies, data of pre- and post-crossover were not described separately. All trials were small and of too short duration to show any significant differences in pregnancy results. The odds ratio for ongoing pregnancy, only described in one trial, was 7.5 (95% CI 0.44 to 127) in the comparison GnRH following pretreatment with GnRHa versus GnRH only in favour of the first group. Multiple pregnancies were not seen. Ovarian hyperstimulation syndrome was seen only in women allocated to ovulation induction with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design.

PubMed

Levin, Bruce; Thompson, John L P; Chakraborty, Bibhas; Levy, Gilberto; MacArthur, Robert; Haley, E Clarke

2011-08-01

TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Design complexity and evolving regulatory requirements lengthened the review process. (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.

Delamanid susceptibility testing of Mycobacterium tuberculosis using the resazurin microtitre assay and the BACTEC™ MGIT™ 960 system.

PubMed

Schena, Elisa; Nedialkova, Lubov; Borroni, Emanuele; Battaglia, Simone; Cabibbe, Andrea Maurizio; Niemann, Stefan; Utpatel, Christian; Merker, Matthias; Trovato, Alberto; Hofmann-Thiel, Sabine; Hoffmann, Harald; Cirillo, Daniela Maria

2016-06-01

The objective of this study was to develop standardized protocols for rapid delamanid drug susceptibility testing (DST) using the colorimetric resazurin microtitre assay (REMA) and semi-automated BACTEC™ MGIT™ 960 system (MGIT) by establishing breakpoints that accurately discriminate between susceptibility and resistance of Mycobacterium tuberculosis to delamanid. MICs of delamanid were determined by the MGIT, the REMA and the solid agar method for 19 pre-characterized strains. The MIC distribution of delamanid was then established for a panel of clinical strains never exposed to the drug and characterized by different geographical origins and susceptibility patterns. WGS was used to investigate genetic polymorphisms in five genes (ddn, fgd1, fbiA, fbiB and fbiC) involved in intracellular delamanid activation. We demonstrated that the REMA and MGIT can both be used for the rapid and accurate determination of delamanid MIC, showing excellent concordance with the solid agar reference method, as well as high reproducibility and repeatability. We propose the tentative breakpoint of 0.125 mg/L for the REMA and MGIT, allowing reliable discrimination between M. tuberculosis susceptible and resistant to delamanid. Stop codon mutations in ddn (Trp-88 → STOP) and fbiA (Lys-250 → STOP) have only been observed in strains resistant to delamanid. We established protocols for DST of delamanid in the MGIT and REMA, confirming their feasibility in routine TB diagnostics, utilizing the same discriminative concentration for both methods. Moreover, taking advantage of WGS analysis, we identified polymorphisms potentially associated with resistance in two genes involved in delamanid activation. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study: Protocol and baseline characteristics of a randomized controlled trial.

PubMed

Diamantidis, Clarissa J; Bosworth, Hayden B; Oakes, Megan M; Davenport, Clemontina A; Pendergast, Jane F; Patel, Sejal; Moaddeb, Jivan; Barnhart, Huiman X; Merrill, Peter D; Baloch, Khaula; Crowley, Matthew J; Patel, Uptal D

2018-06-01

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the United States. Multiple risk factors contribute to DKD development, yet few interventions target more than a single DKD risk factor at a time. This manuscript describes the study protocol, recruitment, and baseline participant characteristics for the Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study. The STOP-DKD study is a randomized controlled trial designed to evaluate the effectiveness of a multifactorial behavioral and medication management intervention to mitigate kidney function decline at 3 years compared to usual care. The intervention consists of up to 36 monthly educational modules delivered via telephone by a study pharmacist, home blood pressure monitoring, and medication management recommendations delivered electronically to primary care physicians. Patients seen at seven primary care clinics in North Carolina, with diabetes and [1] uncontrolled hypertension and [2] evidence of kidney dysfunction (albuminuria or reduced estimated glomerular filtration rate [eGFR]) were eligible to participate. Study recruitment completed in December 2014. Of the 281 participants randomized, mean age at baseline was 61.9; 52% were male, 56% were Black, and most were high school graduates (89%). Baseline co-morbidity was high- mean blood pressure was 134/76 mmHg, mean body mass index was 35.7 kg/m 2 , mean eGFR was 80.7 ml/min/1.73 m 2 , and mean glycated hemoglobin was 8.0%. Experiences of recruiting and implementing a comprehensive DKD program to individuals at high risk seen in the primary care setting are provided. NCT01829256. Copyright © 2018 Elsevier Inc. All rights reserved.

Stopping-power ratios for clinical electron beams from a scatter-foil linear accelerator.

PubMed

Kapur, A; Ma, C M

1999-09-01

Restricted mass collision stopping-power ratios for electron beams from a scatter-foil medical linear accelerator (Varian Clinac 2100C) were calculated for various combinations of beams, phantoms and detector materials using the Monte Carlo method. The beams were of nominal energy 6, 12 or 20 MeV, with square dimensions 1 x 1 cm2 to 10 x 10 cm2. They were incident at nominal SSDs of 100 or 120 cm and inclined at 90 degrees or 30 degrees to the surface of homogeneous water phantoms or water phantoms interspersed with layered lung or bone-like materials. The broad beam water-to-air stopping-power ratios were within 1.3% of the AAPM TG21 protocol values and consistent with the results of Ding et al to within 0.2%. On the central axis the stopping-power ratio variations for narrow beams compared with normally incident broad beams were 0.1% or less for water-to-LiF-100, graphite, ferrous sulfate dosimeter solution, polystyrene and PMMA, 0.5% for water-to-silicon and 1% for water-to-air and water-to-photographic-film materials. The transverse variations of the stopping-power ratios were up to 4% for water-to-silicon, 7% for water-to-photographic-film materials and 10% for water-to-air in the penumbral regions (where the dose was 10% of the global dose maximum) at shallow depths compared with the values at the same depths on the central axis. In the inhomogeneous phantoms studied, the stopping-power ratio correction factors varied more significantly for air, followed by photographic materials and silicon, at various depths on the central axis in the heterogeneous regions. For the simple layered phantoms studied, the estimation of the stopping-power ratio correction factors based on the relative electron-density derived effective depth approach yielded results that were within 0.5% of the Monte Carlo derived values for all the detector materials studied.

Models for Access to Maternal Smoking cessation Support (MAMSS): a study protocol of a quasi-experiment to increase the engagement of pregnant women who smoke in NHS Stop Smoking Services.

PubMed

Bennett, Lorna; Grant, Aimee; Jones, Siobhan; Bowley, Mererid; Heathcote-Elliott, Christian; Ford, Catrin; Jones, Angela; Lewis, Rachel; Munkley, Margaret; Owen, Carol; Petherick, Annie; Paranjothy, Shantini

2014-10-06

Maternal smoking is a key cause of poor outcomes for mothers, babies and children and Wales has higher rates of smoking in pregnancy than any other UK country. Despite various improvements within the NHS Stop Smoking Service to strengthen the intervention for pregnant women, referrals and successful quit attempts for this group have continued to remain extremely low. A key element of UK national guidance for smoking cessation during pregnancy is to provide a flexible and tailored service to help increase levels of engagement. This study aims to test the effectiveness of three different models of service delivery to address the gap in the evidence base about how to deliver a flexible, tailored smoking cessation service to pregnant women. This study will adopt a quasi-experimental design over a 12 month period. The setting is four of Wales' seven Health Boards using an integrated approach between maternity services, local public health teams and the NHS Stop Smoking Service. Core recommendations from UK public health guidance are being implemented across intervention and usual care sites. Stop smoking support for pregnant women in intervention sites is being delivered more flexibly than in usual care sites. Both qualitative and quantitative approaches will be adopted to capture important contextual information and consider multiple perspectives. A health economic analysis will be undertaken using a cost-consequences analysis approach. The primary outcome measure is engagement with stop smoking services (defined as having at least one face-to-face therapeutic contact with a clinician). Supporting pregnant women to stop smoking is a challenging area of public health. The proposed study will address several areas where there are key evidence gaps relating to smoking cessation interventions for pregnant women. Specifically, how best to encourage pregnant women to attend a specialist stop smoking support service, how to deliver the service and who should provide it.

Fertility status of Hodgkin lymphoma patients treated with chemotherapy and adjuvant gonadotropin-releasing hormone analogues.

PubMed

Huser, M; Smardova, L; Janku, P; Crha, I; Zakova, J; Stourac, P; Jarkovsky, J; Mayer, J; Ventruba, P

2015-08-01

Aim of this prospective observational study was to analyze fertility status of Hodgkin lymphoma (HL) patients treated with different types of chemotherapy while receiving GnRH analogues to preserve ovarian function. Fertility status was assessed among 108 females in reproductive age treated by curative chemotherapy for freshly diagnosed HL between 2005 and 2010 in university-based tertiary fertility and oncology center. All patients received GnRH analogues during chemotherapy to preserve their ovarian function. Their reproductive functions were assessed by follicle-stimulating hormone (FSH) measurement and pregnancy achievement. Ovarian function was determined separately in three groups with increasing gonadotoxicity of chemotherapy. One year following the treatment, normal ovarian function was found in 89 (82.4%) of patients. Two years after chemotherapy, 98 (90.7%) of patients retained their ovarian function, and 23 (21.3%) achieved clinical pregnancy during the follow-up period. Average FSH after chemotherapy was 11.6 ± 17.9 IU/l 1 year after the treatment resp. 9.0 ± 13.8 at the 2 years interval. There were significantly more patients with chemotherapy induced diminished ovarian reserve (chDOR) among the group receiving escalated BEACOPP chemotherapy in comparison with the other types of treatment (58.1% vs. 87.9% resp. 95.5%). The rate of chDOR is significantly higher after EB poly-chemotherapy and there is no tendency for improvement in time. The 2 + 2 chemotherapy with GnRH-a required for more advanced HL retained ovarian function significantly better after 2 years. Another important advantage of GnRH-a co-treatment is the excellent control of patient's menstrual cycle.

Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study.

PubMed

de Vries, Annelou L C; Steensma, Thomas D; Doreleijers, Theo A H; Cohen-Kettenis, Peggy T

2011-08-01

Puberty suppression by means of gonadotropin-releasing hormone analogues (GnRHa) is used for young transsexuals between 12 and 16 years of age. The purpose of this intervention is to relieve the suffering caused by the development of secondary sex characteristics and to provide time to make a balanced decision regarding actual gender reassignment. To compare psychological functioning and gender dysphoria before and after puberty suppression in gender dysphoric adolescents. Of the first 70 eligible candidates who received puberty suppression between 2000 and 2008, psychological functioning and gender dysphoria were assessed twice: at T0, when attending the gender identity clinic, before the start of GnRHa; and at T1, shortly before the start of cross-sex hormone treatment. Behavioral and emotional problems (Child Behavior Checklist and the Youth-Self Report), depressive symptoms (Beck Depression Inventory), anxiety and anger (the Spielberger Trait Anxiety and Anger Scales), general functioning (the clinician's rated Children's Global Assessment Scale), gender dysphoria (the Utrecht Gender Dysphoria Scale), and body satisfaction (the Body Image Scale) were assessed. Behavioral and emotional problems and depressive symptoms decreased, while general functioning improved significantly during puberty suppression. Feelings of anxiety and anger did not change between T0 and T1. While changes over time were equal for both sexes, compared with natal males, natal females were older when they started puberty suppression and showed more problem behavior at both T0 and T1. Gender dysphoria and body satisfaction did not change between T0 and T1. No adolescent withdrew from puberty suppression, and all started cross-sex hormone treatment, the first step of actual gender reassignment. Puberty suppression may be considered a valuable contribution in the clinical management of gender dysphoria in adolescents. © 2010 International Society for Sexual Medicine.

The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats.

PubMed

Camats, N; García, F; Parrilla, J J; Calaf, J; Martín-Mateo, M; Caldés, M Garcia

2009-10-02

There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F(0)) with reproductive parameters, and in the somatic cells of the resulting foetuses (F(1)) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

Manipulations of the reproductive system of fishes by means of exogenous chemicals

USGS Publications Warehouse

Patino, R.

1997-01-01

Environmental control of reproductive activity of captive fish is feasible (or potentially feasible) but, with few exceptions, is currently impractical for most species. Therefore, chemical methods of manipulating reproductive activity continue to be widely used in fish production operations worldwide. However, the control of fish reproduction in captivity cannot be exercised without regard to adequate environmental conditions, which can differ markedly for different species. This review provides a synopsis of relevant aspects of fish reproductive physiology and addresses current and promising future chemical methods of sex control, gonadal recrudescence, and spawning. Most research on the control of reproduction in fishes has focused on female physiology because ovarian development and maturation are easily disturbed by environmental stressors. Control of sex ratios by steroid treatment has become a well-established technique for several fish species, but the technique continues to be problematic in some cases. Final gonadal growth and spawning usually can be achieved by implant treatment with gonadotropin-releasing hormone analogs (GnRHa), which in some species have to be applied in combination with dopamine antagonists to enhance responsiveness to GnRHa. However, efforts to accelerate gonadal recrudescence and maturational competence by chemical means have yielded mixed results, reflecting a relative lack of understanding of the basic physiological and biochemic mechanisms controlling these processes. The potential benefits of using reproductive pheromone, to manipulate gonadal development and spawning has been demonstrated in a few species, but further research is needed to determine whether this technique is applicable to fish culture. Because a reliable supply of young fish is critical for the expansion and diversification of fish culture operations, the use of chemicals in combination with adequate environmental conditions to contain gametogenesis and spawning in fishes will continue to be an important tool for the fish culture.

[Protective effect of GnRH analogues on the reproductive capacity of women with neoplasia or autoimmune disease who require chemotherapy. Final results of a phase ii clinical trial].

PubMed

Gris-Martínez, José M; Trillo-Urrutia, Lourdes; Gómez-Cabeza, Juan José; Encabo-Duró, Gloria

2016-02-05

In order to avoid the toxic effect of chemotherapy, it has been proposed to use GnRH agonist analogues (GnRHa) to inhibit the depletion of ovarian follicles. Nevertheless, there is controversy about its effectiveness. This clinical trial has been conducted with the aim to assess the protective effect of GnRH analogues on the reproductive capacity of women with malignancies or autoimmune diseases, which require chemotherapy. Open phase ii single-center clinical trial. During chemotherapy, a total of 5 doses of GnRH antagonist analogue at a dose interval of 3 days and/or a monthly dose of GnRHa were administered. Hormonal determinations prior to the start of the CT treatment were conducted during treatment and at the end of it. The inclusion of patients was prematurely concluded when incorporating the determination of anti-Müllerian hormone (AMH) as a parameter for assessing the ovarian reserve. Out of 38 patients, 23 (60.5%, 95%CI 43.4-76.0) had AMH values below normal following completion of treatment. An intermediate analysis was carried out observing that while most patients were recovering the menstrual cycle (86.6% 95%CI 71.9-95.6), they had reduced levels of AMH. Although most patients recovered their menstrual cycles, the ovarian reserve, assessed by the concentration of AMH, decreased in many patients. Therefore, we can conclude that the concomitant treatment of chemotherapy and GnRH analogues does not preserve the loss of follicular ovarian reserve. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Developing and refining the methods for a 'one-stop shop' for research evidence about health systems.

PubMed

Lavis, John N; Wilson, Michael G; Moat, Kaelan A; Hammill, Amanda C; Boyko, Jennifer A; Grimshaw, Jeremy M; Flottorp, Signe

2015-02-25

Policymakers, stakeholders and researchers have not been able to find research evidence about health systems using an easily understood taxonomy of topics, know when they have conducted a comprehensive search of the many types of research evidence relevant to them, or rapidly identify decision-relevant information in their search results. To address these gaps, we developed an approach to building a 'one-stop shop' for research evidence about health systems. We developed a taxonomy of health system topics and iteratively refined it by drawing on existing categorization schemes and by using it to categorize progressively larger bundles of research evidence. We identified systematic reviews, systematic review protocols, and review-derived products through searches of Medline, hand searches of several databases indexing systematic reviews, hand searches of journals, and continuous scanning of listservs and websites. We developed an approach to providing 'added value' to existing content (e.g., coding systematic reviews according to the countries in which included studies were conducted) and to expanding the types of evidence eligible for inclusion (e.g., economic evaluations and health system descriptions). Lastly, we developed an approach to continuously updating the online one-stop shop in seven supported languages. The taxonomy is organized by governance, financial, and delivery arrangements and by implementation strategies. The 'one-stop shop', called Health Systems Evidence, contains a comprehensive inventory of evidence briefs, overviews of systematic reviews, systematic reviews, systematic review protocols, registered systematic review titles, economic evaluations and costing studies, health reform descriptions and health system descriptions, and many types of added-value coding. It is continuously updated and new content is regularly translated into Arabic, Chinese, English, French, Portuguese, Russian, and Spanish. Policymakers and stakeholders can now easily access and use a wide variety of types of research evidence about health systems to inform decision-making and advocacy. Researchers and research funding agencies can use Health Systems Evidence to identify gaps in the current stock of research evidence and domains that could benefit from primary research, systematic reviews, and review overviews.

An Extensible NetLogo Model for Visualizing Message Routing Protocols

DTIC Science & Technology

2017-08-01

the hard sciences to the social sciences to computer-generated art. NetLogo represents the world as a set of...describe the model is shown here; for the supporting methods , refer to the source code. Approved for public release; distribution is unlimited. 4 iv...if ticks - last-inject > time-to-inject [inject] if run# > #runs [stop] end Next, we present some basic statistics collected for the

A prospective gating method to acquire a diverse set of free-breathing CT images for model-based 4DCT

NASA Astrophysics Data System (ADS)

O'Connell, D.; Ruan, D.; Thomas, D. H.; Dou, T. H.; Lewis, J. H.; Santhanam, A.; Lee, P.; Low, D. A.

2018-02-01

Breathing motion modeling requires observation of tissues at sufficiently distinct respiratory states for proper 4D characterization. This work proposes a method to improve sampling of the breathing cycle with limited imaging dose. We designed and tested a prospective free-breathing acquisition protocol with a simulation using datasets from five patients imaged with a model-based 4DCT technique. Each dataset contained 25 free-breathing fast helical CT scans with simultaneous breathing surrogate measurements. Tissue displacements were measured using deformable image registration. A correspondence model related tissue displacement to the surrogate. Model residual was computed by comparing predicted displacements to image registration results. To determine a stopping criteria for the prospective protocol, i.e. when the breathing cycle had been sufficiently sampled, subsets of N scans where 5  ⩽  N  ⩽  9 were used to fit reduced models for each patient. A previously published metric was employed to describe the phase coverage, or ‘spread’, of the respiratory trajectories of each subset. Minimum phase coverage necessary to achieve mean model residual within 0.5 mm of the full 25-scan model was determined and used as the stopping criteria. Using the patient breathing traces, a prospective acquisition protocol was simulated. In all patients, phase coverage greater than the threshold necessary for model accuracy within 0.5 mm of the 25 scan model was achieved in six or fewer scans. The prospectively selected respiratory trajectories ranked in the (97.5  ±  4.2)th percentile among subsets of the originally sampled scans on average. Simulation results suggest that the proposed prospective method provides an effective means to sample the breathing cycle with limited free-breathing scans. One application of the method is to reduce the imaging dose of a previously published model-based 4DCT protocol to 25% of its original value while achieving mean model residual within 0.5 mm.

[Results of a health education intervention in the continuity of breastfeeding].

PubMed

Molinero Diaz, Patricia; Burgos Rodríguez, María José; Mejía Ramírez de Arellano, Mercedes

2015-01-01

evaluate the efficacy of a nursing intervention based on active observation and resolution of the problems of breastfeeding in the period 24-48h post-partum as regards stopping breastfeeding in mothers who gave birth in Hospital General Universitario, Ciudad Real. A clinical trial was conducted on 100 healthy women who had given birth to a healthy baby in the maternity unit of the Hospital General Universitario Ciudad Real. The results showed that 39.8% of women have problems, and 72% need help to initiate the breastfeeding. Approximately 79.9% continue with breastfeeding after hospital discharge as a result of our intervention. Breastfeeding was stopped by 31.1% of the control group, and by 10.9% in the experimental group (nursing intervention), with significant differences being observed in both groups, with RR 1.29 and 95% CI; 1.04-1.61. Hypogalactia (low milk production) was the most frequent reason for stopping, with no differences in both groups. At 3 months, 16.9% had stopped breastfeeding in the control group, and 9% in the experimental group. At 6 months, 19.3% of the control group did not continue with breastfeeding versus 15.9% in the experimental group. Action, and not only intervention, protocols in the period 48h pospartum when there were problems with breastfeeding were effective for initiation breastfeeding at hospital discharge. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Should ovulation be induced in women recovering from an eating disorder or who are compulsive exercisers?

PubMed

Abraham, S; Mira, M; Llewellyn-Jones, D

1990-03-01

The eating and exercise history of women with secondary amenorrhea and failure of ovulation using CC was studied in 14 consecutive women on a GnRH-a program. All had a history of an eating or exercise disorder. At the time of the interview, 7 women continued to have an eating or exercise disorder. There were 15 pregnancies (12 women) with 12 live births, of which 4 weighed less than 2,500 g. Infertility specialists should inquire routinely about a woman's body weight and eating and exercise behaviors, and consider treatment for these before prescribing drugs to induce ovulation.

Influence of apixaban on antifactor Xa levels in a patient with acute kidney injury.

PubMed

Wendte, Jodi; Voss, Glenn; VanOverschelde, Beau

2016-04-15

The case of a patient requiring conversion from apixaban to heparin in the setting of acute kidney injury is reported. A 70-year-old man was initiated on apixaban 5 mg twice daily for new-onset, nonvalvular atrial fibrillation with a CHA2DS2-VASc score of 4, indicating a high risk of stroke. Soon after starting apixaban, he experienced pulmonary edema with pneumonia requiring hospitalization. During the course of hospitalization, the patient developed acute kidney injury requiring hemodialysis, and apixaban was stopped due to concerns about altered pharmacokinetics and impaired drug elimination in this setting. A heparin infusion was started 36 hours after the last dose of apixaban was administered. Antifactor Xa levels were monitored consistent with the hospital's standard practice protocols. The initial and repeat antifactor Xa concentrations were elevated (1.8-4.4 IU/mL) for up 72 hours after stopping the heparin infusion. Given the suspected interference of apixaban with standard antifactor Xa level monitoring, the heparin protocol was modified to reflect drip-rate adjustments based on activated partial thromboplastin times (aPTTs). The hospital protocol for heparin infusions was reinstituted on hospital day 7, with dosage adjustments based on antifactor Xa levels. The patient remained on a continuous heparin infusion for atrial fibrillation for the remainder of his hospitalization without complications or bleeding events. A 70-year-old man with new-onset nonvalvular atrial fibrillation and receiving apixaban discontinued this therapy and was given heparin instead due to acute kidney injury. His heparin dosage was successfully adjusted based on antifactor Xa levels and aPPTs. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy

PubMed Central

Vickery, Brian P.; Scurlock, Amy M.; Kulis, Michael; Steele, Pamela H.; Kamilaris, Janet; Berglund, Jelena P.; Burk, Caitlin; Hiegel, Anne; Carlisle, Suzanna; Christie, Lynn; Perry, Tamara T.; Pesek, Robbie D.; Sheikh, Saira; Virkud, Yamini; Smith, P. Brian; Shamji, Mohamed H.; Durham, Stephen R.; Jones, Stacie M.; Burks, A. Wesley

2013-01-01

Background Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. Objective Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness following withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at two U.S. centers. Subjects aged 1–16 were recruited and treated for up to five years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg peanut protein/day. Blood was collected at multiple time points. Clinical endpoints were measured with 5000 mg double-blinded, placebo-controlled food challenges once specific criteria were met. Results Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. 12/24 (50%) successfully passed a challenge one month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin tests as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2, and lower ratios of peanut-specific:total IgE, compared to subjects not passing. There were no differences in peanut IgG4 levels or functional activity at end-of-study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated up to five years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin tests and lower allergen-specific IgE levels were predictive of successful outcome. PMID:24361082

Cycle regimens for frozen-thawed embryo transfer.

PubMed

Ghobara, T; Vandekerckhove, P

2008-01-23

Pregnancy rates following frozen-thawed embryo transfer (FET) treatment have always been found to be lower than following embryo transfer using fresh embryos. Nevertheless, FET increases the (cumulative) pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period compared to repeated 'fresh' cycles. FET is performed using different cycle regimens: spontaneous ovulatory cycles, cycles in which ovulation is induced by drugs and cycles in which the endometrium is artificially prepared by oestrogen (O) and progesterone (P) hormones, with or without a gonadotrophin releasing hormone agonist (GnRHa). To determine whether there is a difference in outcome between natural cycle FET, artificial cycle FET and ovulation induction cycle FET. Our search included CENTRAL,DARE, MEDLINE (1950 to 2007), EMBASE (1980 to 2007) and CINAHL (1982 to 2007). Randomised controlled trials (RCTs) comparing the various cycle regimens and different methods used to prepare the endometrium during FET in assisted reproductive technology (ART). The two authors independently extracted data. Dichotomous outcomes results (e.g. clinical pregnancy rate) were expressed as an odds ratio (OR) with 95% confidence intervals (CI) for each study. Continuous outcome results (endometrial thickness) were expressed as weighted mean difference (WMD). Where suitable, results were combined for meta-analysis with RevMan software using the Peto-modified Mantel-Haenszel method. Seven randomised controlled studies assessing six comparisons and including 1120 women in total were included in this review.1) O + P FET versus natural cycle FET: this comparison demonstrated no significant differences in outcomes but confidence intervals remain wide, and therefore moderate differences in either direction remain possible (OR 1.06, 95% CI 0.40 to 2.80, P 0.91).2) GnRHa + O + P FET versus O + P FET: this comparison showed that the live birth rate per woman was significantly higher in the former group (OR 0.38, 95% CI 0.17 to 0.84, P 0.02). The clinical pregnancy rate was also higher but not significantly so (OR 0.76, 95% CI 0.52 to 1.10, P 0.14).3) O + P FET versus follicle stimulating hormone (FSH) FET, 4) O + P FET versus clomiphene FET and 5) GnRHa + O + P FET versus clomiphene FET: there were no differences in the outcomes in the comparison of these cycle regimens.6) Clomiphene + human menopausal gonadotrophin (HMG) FET versus HMG FET: in a comparison of two ovulation induction regimes the pregnancy rate was found to be significantly higher in the HMG group (OR 0.46, 95% CI 0.23 to 0.92). There were also fewer cycle cancellations and a lower multiple pregnancy rate when HMG was used without clomiphene but these did not reach statistical significance. At the present time there is insufficient evidence to support the use of one intervention in preference to another.

Nail Biting; Etiology, Consequences and Management

PubMed Central

Ghanizadeh, Ahmad

2011-01-01

Nail biting (NB) is a common, but unresolved, problem in psychiatry, psychology, medicine and dentistry. While it seems that NB is a simple behavior that can be stopped easily, many of the children with NB have already tried to stop it, but they have not been successful. The frustrations due to failed attempt involve others such as parents and siblings. The present review aims at providing an overview of prevalence, co-morbidities, education and counseling, and management for NB. Overall, the reviewed literatures suggest that co-morbidities of psychiatric disorders and other stereotypic behaviors in clinical sample of children with NB is more than 80%, and more than half of the parents suffer from psychiatric disorders mainly depression. Treatment of NB, however, is not as easy as it seems. The management of NB is much more complicated than just focusing on stopping it. Nail biting cannot be managed without considering its co-morbidities, antecedents and consequences. It might be concluded form the reviewed literature that children with NB, parents, siblings, and teachers should be educated about what to do and what not to do about NB. Punishment is not effective. Moreover, clinical randomized controlled trials are required to make available evidence-based behavioral and pharmacologic treatment protocols. PMID:23358880

Slimming World in Stop Smoking Services (SWISSS): study protocol for a randomized controlled trial.

PubMed

Lycett, Deborah; Aveyard, Paul; Farmer, Andrew; Lewis, Amanda; Munafò, Marcus

2013-06-19

Quitting smokers gain weight. This deters some from trying to stop smoking and may explain the increased incidence of type 2 diabetes after cessation. Dieting when stopping smoking may be counterproductive. Hunger increases cravings for smoking and tackling two behaviours together may undermine quitting success. A meta-analysis of randomized controlled trials (RCTs) showed individualized dietary support may prevent weight gain, although there is insufficient evidence whether it undermines smoking cessation. Commercial weight management providers (CWMPs), such as Slimming World, provide individualized dietary support for National Health Service (NHS) patients; however, there is no evidence that they can prevent cessation-related weight gain.Our objective is to determine whether attending Slimming World from quit date, through referral from NHS Stop Smoking Services, is more effective than usual care at preventing cessation-related weight gain. This RCT will examine the effectiveness of usual cessation support plus referral to Slimming World compared to usual cessation support alone. Healthy weight, overweight and obese adult smokers attending Stop Smoking Services will be included. The primary outcome is weight change in quitters 12 weeks post-randomization. Multivariable linear regression analysis will compare weight change between trial arms and adjust for known predictors of cessation-related weight gain.We will recruit 320 participants, with 160 participants in each arm. An alpha error rate of 5% and 90% power will detect a 2 kg (SD = 2.5) difference in weight gain at 12 weeks, assuming 20% remain abstinent by then. This trial will establish whether referral to the 12-week Slimming World programme plus usual care is an effective intervention to prevent cessation-related weight gain. If so, we will seek to establish whether weight control comes at the expense of a successful quit attempt in a further non-inferiority trial.Positive results from both these trials would provide a potential solution to cessation-related weight gain, which could be rolled out across England within Stop Smoking Services to better meet the needs of 0.75 million smokers stopping with NHS support every year. Current Controlled Trials ISRCTN65705512.

The Power of Proofs-of-Possession: Securing Multiparty Signatures against Rogue-Key Attacks

NASA Astrophysics Data System (ADS)

Ristenpart, Thomas; Yilek, Scott

Multiparty signature protocols need protection against rogue-key attacks, made possible whenever an adversary can choose its public key(s) arbitrarily. For many schemes, provable security has only been established under the knowledge of secret key (KOSK) assumption where the adversary is required to reveal the secret keys it utilizes. In practice, certifying authorities rarely require the strong proofs of knowledge of secret keys required to substantiate the KOSK assumption. Instead, proofs of possession (POPs) are required and can be as simple as just a signature over the certificate request message. We propose a general registered key model, within which we can model both the KOSK assumption and in-use POP protocols. We show that simple POP protocols yield provable security of Boldyreva's multisignature scheme [11], the LOSSW multisignature scheme [28], and a 2-user ring signature scheme due to Bender, Katz, and Morselli [10]. Our results are the first to provide formal evidence that POPs can stop rogue-key attacks.

Subconscious Visual Cues during Movement Execution Allow Correct Online Choice Reactions

PubMed Central

Leukel, Christian; Lundbye-Jensen, Jesper; Christensen, Mark Schram; Gollhofer, Albert; Nielsen, Jens Bo; Taube, Wolfgang

2012-01-01

Part of the sensory information is processed by our central nervous system without conscious perception. Subconscious processing has been shown to be capable of triggering motor reactions. In the present study, we asked the question whether visual information, which is not consciously perceived, could influence decision-making in a choice reaction task. Ten healthy subjects (28±5 years) executed two different experimental protocols. In the Motor reaction protocol, a visual target cue was shown on a computer screen. Depending on the displayed cue, subjects had to either complete a reaching movement (go-condition) or had to abort the movement (stop-condition). The cue was presented with different display durations (20–160 ms). In the second Verbalization protocol, subjects verbalized what they experienced on the screen. Again, the cue was presented with different display durations. This second protocol tested for conscious perception of the visual cue. The results of this study show that subjects achieved significantly more correct responses in the Motor reaction protocol than in the Verbalization protocol. This difference was only observed at the very short display durations of the visual cue. Since correct responses in the Verbalization protocol required conscious perception of the visual information, our findings imply that the subjects performed correct motor responses to visual cues, which they were not conscious about. It is therefore concluded that humans may reach decisions based on subconscious visual information in a choice reaction task. PMID:23049749

["Do not do" also as regards tobacco].

PubMed

Olano-Espinosa, Eduardo; Minué-Lorenzo, César

2016-01-01

We do have very effective and efficient interventions to help our patients to stop smoking. The strategy that has more evidence and consensus in primary care is the 5 A's, that is, ask, advise, assess willingness to try to quit smoking, helping those who want to try and make follow-up visits. However, we intervene lot less than we should. The available protocols oversized interventions, and propose elements without scientific evidence or therapeutic effect. It is therefore necessary to develop more simple, useful and evidence-based interventions to assist us in carrying out our work interventions, and stop doing those that dońt contribute. In this article we will use as an example a critical review of Smoker Care Service Portfolio of Madrid Health Service, and we will propose a number of alternatives to allow a simple, effective and evidence-based intervention. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Efficient Data Gathering in 3D Linear Underwater Wireless Sensor Networks Using Sink Mobility

PubMed Central

Akbar, Mariam; Javaid, Nadeem; Khan, Ayesha Hussain; Imran, Muhammad; Shoaib, Muhammad; Vasilakos, Athanasios

2016-01-01

Due to the unpleasant and unpredictable underwater environment, designing an energy-efficient routing protocol for underwater wireless sensor networks (UWSNs) demands more accuracy and extra computations. In the proposed scheme, we introduce a mobile sink (MS), i.e., an autonomous underwater vehicle (AUV), and also courier nodes (CNs), to minimize the energy consumption of nodes. MS and CNs stop at specific stops for data gathering; later on, CNs forward the received data to the MS for further transmission. By the mobility of CNs and MS, the overall energy consumption of nodes is minimized. We perform simulations to investigate the performance of the proposed scheme and compare it to preexisting techniques. Simulation results are compared in terms of network lifetime, throughput, path loss, transmission loss and packet drop ratio. The results show that the proposed technique performs better in terms of network lifetime, throughput, path loss and scalability. PMID:27007373

Efficient Data Gathering in 3D Linear Underwater Wireless Sensor Networks Using Sink Mobility.

PubMed

Akbar, Mariam; Javaid, Nadeem; Khan, Ayesha Hussain; Imran, Muhammad; Shoaib, Muhammad; Vasilakos, Athanasios

2016-03-19

Due to the unpleasant and unpredictable underwater environment, designing an energy-efficient routing protocol for underwater wireless sensor networks (UWSNs) demands more accuracy and extra computations. In the proposed scheme, we introduce a mobile sink (MS), i.e., an autonomous underwater vehicle (AUV), and also courier nodes (CNs), to minimize the energy consumption of nodes. MS and CNs stop at specific stops for data gathering; later on, CNs forward the received data to the MS for further transmission. By the mobility of CNs and MS, the overall energy consumption of nodes is minimized. We perform simulations to investigate the performance of the proposed scheme and compare it to preexisting techniques. Simulation results are compared in terms of network lifetime, throughput, path loss, transmission loss and packet drop ratio. The results show that the proposed technique performs better in terms of network lifetime, throughput, path loss and scalability.

[Benzodiazepin addiction: a silent addiction among older people].

PubMed

Oude Voshaar, R C

2012-06-01

Benzodiazepines are frequently prescribed for a longer period of time for anxiety disorders and insomnia in spite of the many guidelines to prescribe these drugs only short-term. These guidelines are based on the risk-benefit balance between long-term effectiveness and side effects like addiction, anterograde amnesia, and increased risk on falling (resulting in hip fractures), traffic accidents and even mortality. Also low-dose benzodiazepine use can lead to benzodiazepine dependence. Although initially most attention has been paid to the physical withdrawal syndrome, psychological aspects of benzodiazepine dependence have received more and more attention in the past decades. Recently, a relationship between the brain-reward system, involved in addiction, and benzodiazepine use, was demonstrated. When long-term benzodiazepine use is recognised as problematic by both physician and patient, different treatment modalities are available to support patients in achieving abstinence. One of every four patients is able to stop by themselves with the aid of a minimal intervention providing psychoeducation and encouragement. Two out of three long-term uses are able to stop their usage with the aid of systematic tapering protocols guided by a physician or psychologist. In case of an underlying insomnia or anxiety disorder, cognitive-behavioural therapy should be added to the tapering protocol. In contrast to the general opinion, advanced old age has no negative impact on the treatment response.

Hybrid optimal scheduling for intermittent androgen suppression of prostate cancer

NASA Astrophysics Data System (ADS)

Hirata, Yoshito; di Bernardo, Mario; Bruchovsky, Nicholas; Aihara, Kazuyuki

2010-12-01

We propose a method for achieving an optimal protocol of intermittent androgen suppression for the treatment of prostate cancer. Since the model that reproduces the dynamical behavior of the surrogate tumor marker, prostate specific antigen, is piecewise linear, we can obtain an analytical solution for the model. Based on this, we derive conditions for either stopping or delaying recurrent disease. The solution also provides a design principle for the most favorable schedule of treatment that minimizes the rate of expansion of the malignant cell population.

Leuprolide acetate-stimulated androgen response during female puberty.

PubMed

Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

2015-08-01

A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with insulin sensitivity in early puberty and with LH only in late puberty. © 2014 John Wiley & Sons Ltd.

Operative Strategies during Awake Surgery Affect Deterioration of Paresis a Month after Surgery for Brain Lesions in the Primary Motor Area.

PubMed

Shinoura, Nobusada; Midorikawa, Akira; Yamada, Ryoji; Hiromitsu, Kentaro; Itoi, Chihiro; Saito, Shoko; Yagi, Kazuo

2017-07-01

Introduction  We analyzed factors associated with worsened paresis at 1-month follow-up in patients with brain tumors located in the primary motor area (M1) to establish protocols for safe awake craniotomy for M1 lesions. Methods  Patients with M1 brain tumors who underwent awake surgery in our hospital ( n  = 61) were evaluated before, during, and immediately and 1 month after surgery for severity of paresis, tumor location, extent of resection, complications, preoperative motor strength, histology, and operative strategies (surgery stopped or continued after deterioration of motor function). Results  Worsened paresis at 1-month follow-up was significantly associated with worsened paresis immediately after surgery and also with operative strategy. Specifically, when motor function deteriorated during awake surgery and did not recover within 5 to 10 minutes, no deterioration was observed at 1-month follow-up in cases where we stopped surgery, whereas 6 of 13 cases showed deteriorated motor function at 1-month follow-up in cases where we continued surgery. Conclusion  Stopping tumor resection on deterioration of motor function during awake surgery may help prevent worsened paresis at 1-month follow-up. Georg Thieme Verlag KG Stuttgart · New York.

Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

PubMed

Bayram, N; van Wely, M; Vandekerckhove, P; Lilford, R; van Der Veen, F

2000-01-01

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in patients with PCOS. But, although ovulation and pregnancy has been achieved, the use of pulsatile GnRH in PCOS patients is controversial. To assess the effectiveness of pulsatile GnRH administration in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of ovulation induction, pregnancy, miscarriage, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. All relevant published RCTs were selected. Non-randomised controlled trials were eligible for inclusion if treatment consisted of GnRH administration versus another treatment to induce ovulation in subfertile women with PCOS. A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. One RCT (Bringer 1985a) and one abstract (Coelingh 1983) were identified this way. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Three RCTs and one non-randomised comparative trial were identified comparing four different treatments: GnRH versus HMG, GnRH following GnRHa pre-treatment versus no pre-treatment, GnRH and FSH versus FSH, and GnRH following GnRHa pre-treatment versus GnRH following oral contraceptive pre-treatment. This means that there was only one trial in any one comparison. In the first two studies, data of pre- and post-cross-over were not described separately. Therefore, these results could not be included in the MetaView analysis. The odds ratio for ovulation rate was 16 (95 % CI: 1.1-239) in the study comparing GnRH and FSH with FSH. When GnRH after GnRHa pre-treatment was compared with GnRH after oral contraceptive pre-treatment, an odds ratio of 7.5 (95 % CI: 1.2-46) was obtained. All trials were small and of too short duration to show any significance in pregnancy results. Per study only one to four pregnancies occurred. Multiple pregnancies were not seen. OHSS was seen only in the patients stimulated with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Speech outcome in unilateral complete cleft lip and palate patients: a descriptive study.

PubMed

Rullo, R; Di Maggio, D; Addabbo, F; Rullo, F; Festa, V M; Perillo, L

2014-09-01

In this study, resonance and articulation disorders were examined in a group of patients surgically treated for cleft lip and palate, considering family social background, and children's ability of self monitoring their speech output while speaking. Fifty children (32 males and 18 females) mean age 6.5 ± 1.6 years, affected by non-syndromic complete unilateral cleft of the lip and palate underwent the same surgical protocol. The speech level was evaluated using the Accordi's speech assessment protocol that focuses on intelligibility, nasality, nasal air escape, pharyngeal friction, and glottal stop. Pearson product-moment correlation analysis was used to detect significant associations between analysed parameters. A total of 16% (8 children) of the sample had severe to moderate degree of nasality and nasal air escape, presence of pharyngeal friction and glottal stop, which obviously compromise speech intelligibility. Ten children (10%) showed a barely acceptable phonological outcome: nasality and nasal air escape were mild to moderate, but the intelligibility remained poor. Thirty-two children (64%) had normal speech. Statistical analysis revealed a significant correlation between the severity of nasal resonance and nasal air escape (p ≤ 0.05). No statistical significant correlation was found between the final intelligibility and the patient social background, neither between the final intelligibility nor the age of the patients. The differences in speech outcome could be explained with a specific, subjective, and inborn ability, different for each child, in self-monitoring their speech output.

Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2)

PubMed Central

Briel, Matthias; Lane, Melanie; Montori, Victor M; Bassler, Dirk; Glasziou, Paul; Malaga, German; Akl, Elie A; Ferreira-Gonzalez, Ignacio; Alonso-Coello, Pablo; Urrutia, Gerard; Kunz, Regina; Culebro, Carolina Ruiz; da Silva, Suzana Alves; Flynn, David N; Elamin, Mohamed B; Strahm, Brigitte; Murad, M Hassan; Djulbegovic, Benjamin; Adhikari, Neill KJ; Mills, Edward J; Gwadry-Sridhar, Femida; Kirpalani, Haresh; Soares, Heloisa P; Elnour, Nisrin O Abu; You, John J; Karanicolas, Paul J; Bucher, Heiner C; Lampropulos, Julianna F; Nordmann, Alain J; Burns, Karen EA; Mulla, Sohail M; Raatz, Heike; Sood, Amit; Kaur, Jagdeep; Bankhead, Clare R; Mullan, Rebecca J; Nerenberg, Kara A; Vandvik, Per Olav; Coto-Yglesias, Fernando; Schünemann, Holger; Tuche, Fabio; Chrispim, Pedro Paulo M; Cook, Deborah J; Lutz, Kristina; Ribic, Christine M; Vale, Noah; Erwin, Patricia J; Perera, Rafael; Zhou, Qi; Heels-Ansdell, Diane; Ramsay, Tim; Walter, Stephen D; Guyatt, Gordon H

2009-01-01

Background Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. Methods/Design We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation. Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed biases. Discussion A better understanding of the extent to which tRCTs exaggerate treatment effects and of the factors associated with the magnitude of this bias can optimize trial design and data monitoring charters, and may aid in the interpretation of the results from trials stopped early for benefit. PMID:19580665

When enough is enough: how the decision was made to stop the FEAST trial: data and safety monitoring in an African trial of Fluid Expansion As Supportive Therapy (FEAST) for critically ill children

PubMed Central

2013-01-01

In resource-rich countries, bolus fluid expansion is routinely used for the treatment of poor perfusion and shock, but is less commonly used in many African settings. Controversial results from the recently completed FEAST (Fluid Expansion As Supportive Therapy) trial in African children have raised questions about the use of intravenous bolus fluid for the treatment of shock. Prior to the start of the trial, the Independent data monitoring committee (IDMC) developed stopping rules for the proof of benefit that bolus fluid resuscitation would bring. Although careful safety monitoring was put in place, there was less expectation that bolus fluid expansion would be harmful and differential stopping rules for harm were not formulated. In July 2010, two protocol amendments were agreed to increase the sample size from 2,880 to 3,600 children, and to increase bolus fluid administration. There was a non-significant trend against bolus treatment, but although the implications were discussed, the IDMC did not comment on the results, or on the amendments, in order to avoid inadvertent partial unblinding of the study. In January 2011, the trial was stopped for futility, as the combined intervention arms had significantly higher mortality (relative risk 1.46, 95% CI 1.13 to 1.90, P = 0.004) than the control arm. The stopping rule for proof of benefit was not achieved, and the IDMC stopped the trial with a lower level of significance (P = 0.01) due to futility and an increased risk of mortality from bolus fluid expansion in children enrolled in the trial. The basis for this decision was that the local standard of care was not to use bolus fluid for the care of children with shock in these African countries, and this was a different standard of care to that used in the UK. These decisions emphasize two important principles: firstly, the IDMC should avoid inadvertent unblinding of the trial by commenting on amendments, and secondly, when considering stopping a trial, the IDMC should be guided by the local standard of care rather than standards of care in other parts of the world. PMID:23531379

When enough is enough: how the decision was made to stop the FEAST trial: data and safety monitoring in an African trial of Fluid Expansion As Supportive Therapy (FEAST) for critically ill children.

PubMed

Todd, Jim; Heyderman, Robert S; Musoke, Philippa; Peto, Tim

2013-03-26

In resource-rich countries, bolus fluid expansion is routinely used for the treatment of poor perfusion and shock, but is less commonly used in many African settings. Controversial results from the recently completed FEAST (Fluid Expansion As Supportive Therapy) trial in African children have raised questions about the use of intravenous bolus fluid for the treatment of shock. Prior to the start of the trial, the Independent data monitoring committee (IDMC) developed stopping rules for the proof of benefit that bolus fluid resuscitation would bring. Although careful safety monitoring was put in place, there was less expectation that bolus fluid expansion would be harmful and differential stopping rules for harm were not formulated.In July 2010, two protocol amendments were agreed to increase the sample size from 2,880 to 3,600 children, and to increase bolus fluid administration. There was a non-significant trend against bolus treatment, but although the implications were discussed, the IDMC did not comment on the results, or on the amendments, in order to avoid inadvertent partial unblinding of the study.In January 2011, the trial was stopped for futility, as the combined intervention arms had significantly higher mortality (relative risk 1.46, 95% CI 1.13 to 1.90, P = 0.004) than the control arm. The stopping rule for proof of benefit was not achieved, and the IDMC stopped the trial with a lower level of significance (P = 0.01) due to futility and an increased risk of mortality from bolus fluid expansion in children enrolled in the trial. The basis for this decision was that the local standard of care was not to use bolus fluid for the care of children with shock in these African countries, and this was a different standard of care to that used in the UK. These decisions emphasize two important principles: firstly, the IDMC should avoid inadvertent unblinding of the trial by commenting on amendments, and secondly, when considering stopping a trial, the IDMC should be guided by the local standard of care rather than standards of care in other parts of the world.

Measurements of output factors with different detector types and Monte Carlo calculations of stopping-power ratios for degraded electron beams.

PubMed

Björk, Peter; Knöös, Tommy; Nilsson, Per

2004-10-07

The aim of the present study was to investigate three different detector types (a parallel-plate ionization chamber, a p-type silicon diode and a diamond detector) with regard to output factor measurements in degraded electron beams, such as those encountered in small-electron-field radiotherapy and intraoperative radiation therapy (IORT). The Monte Carlo method was used to calculate mass collision stopping-power ratios between water and the different detector materials for these complex electron beams (nominal energies of 6, 12 and 20 MeV). The diamond detector was shown to exhibit excellent properties for output factor measurements in degraded beams and was therefore used as a reference. The diode detector was found to be well suited for practical measurements of output factors, although the water-to-silicon stopping-power ratio was shown to vary slightly with treatment set-up and irradiation depth (especially for lower electron energies). Application of ionization-chamber-based dosimetry, according to international dosimetry protocols, will introduce uncertainties smaller than 0.3% into the output factor determination for conventional IORT beams if the variation of the water-to-air stopping-power ratio is not taken into account. The IORT system at our department includes a 0.3 cm thin plastic scatterer inside the therapeutic beam, which furthermore increases the energy degradation of the electrons. By ignoring the change in the water-to-air stopping-power ratio due to this scatterer, the output factor could be underestimated by up to 1.3%. This was verified by the measurements. In small-electron-beam dosimetry, the water-to-air stopping-power ratio variation with field size could mostly be ignored. For fields with flat lateral dose profiles (>3 x 3 cm2), output factors determined with the ionization chamber were found to be in close agreement with the results of the diamond detector. For smaller field sizes the lateral extension of the ionization chamber hampers its use. We therefore recommend that the readily available silicon diode detector should be used for output factor measurements in complex electron fields.

Is there a difference between the STOP-BANG and the Berlin Obstructive Sleep Apnoea Syndrome questionnaires for determining respiratory complications during the perioperative period?

PubMed

Gokay, Pervin; Tastan, Sevinc; Orhan, Mehmet Emin

2016-05-01

This study aimed to compare the efficiency of the STOP-BANG and Berlin Obstructive Sleep Apnoea Syndrome questionnaires for evaluating potential respiratory complications during the perioperative period. Questionnaires that are used to determine obstructive sleep apnoea risk are not widely used for surgical patients. Among the questionnaires that are commonly used for obstructive sleep apnoea screening, it remains unclear whether the STOP-BANG or Berlin Obstructive Sleep Apnoea Syndrome questionnaire is more effective in terms of ease of use, usage period and diagnosis of surgical patients with obstructive sleep apnoea risk. This study was designed as a descriptive and prospective study. The study included 126 patients over 18 years of age who were American Society of Anesthesiologists classification class I-II and underwent laparoscopic cholecystectomy. To determine the potential obstructive sleep apnoea syndrome risk, the STOP-BANG and Berlin questionnaires were administered. Respiratory complications were then observed during the perioperative period. During intubation and extubation, we observed statistically significant differences in difficult intubation, difficult facemask ventilation and desaturation frequency between the high- and low-risk groups for obstructive sleep apnoea syndrome, as determined by the STOP-BANG questionnaire. During extubation, statistically significant differences in coughing, breath-holding and desaturation frequency were observed between the high-risk and low-risk groups, according to the Berlin questionnaire. In the post-anaesthesia care unit, both questionnaires found statistically significant differences between the low- and high-risk groups. Obstructive sleep apnoea syndrome screening questionnaires administered during the preoperative period are useful for predicting perioperative respiratory complications. It may be most useful to administer the STOP-BANG questionnaire as the initial evaluation. Questionnaires may be used to determine the risk of obstructive sleep apnoea syndrome, which could impact the anaesthetisation of surgical patients. Questionnaires for determining the risk of obstructive sleep apnoea syndrome should be used regularly for surgical patients, and these questionnaires should be used to improve clinical protocols for anaesthesia and postanaesthesia care. © 2016 John Wiley & Sons Ltd.

La-CTP: Loop-Aware Routing for Energy-Harvesting Wireless Sensor Networks.

PubMed

Sun, Guodong; Shang, Xinna; Zuo, Yan

2018-02-02

In emerging energy-harvesting wireless sensor networks (EH-WSN), the sensor nodes can harvest environmental energy to drive their operation, releasing the user's burden in terms of frequent battery replacement, and even enabling perpetual sensing systems. In EH-WSN applications, usually, the node in energy-harvesting or recharging state has to stop working until it completes the energy replenishment. However, such temporary departures of recharging nodes severely impact the packet routing, and one immediate result is the routing loop problem. Controlling loops in connectivity-intermittent EH-WSN in an efficient way is a big challenge in practice, and so far, users still lack of effective and practicable routing protocols with loop handling. Based on the Collection Tree Protocol (CTP) widely used in traditional wireless sensor networks, this paper proposes a loop-aware routing protocol for real-world EH-WSNs, called La-CTP, which involves a new parent updating metric and a proactive, adaptive beaconing scheme to effectively suppress the occurrence of loops and unlock unavoidable loops, respectively. We constructed a 100-node testbed to evaluate La-CTP, and the experimental results showed its efficacy and efficiency.

Withdrawal of anticancer therapy in advanced disease: a systematic literature review.

PubMed

Clarke, G; Johnston, S; Corrie, P; Kuhn, I; Barclay, S

2015-11-11

Current guidelines set out when to start anticancer treatments, but not when to stop as the end of life approaches. Conventional cytotoxic agents are administered intravenously and have major life-threatening toxicities. Newer drugs include molecular targeted agents (MTAs), in particular, small molecule kinase-inhibitors (KIs), which are administered orally. These have fewer life-threatening toxicities, and are increasingly used to palliate advanced cancer, generally offering additional months of survival benefit. MTAs are substantially more expensive, between £2-8 K per month, and perceived as easier to start than stop. A systematic review of decision-making concerning the withdrawal of anticancer drugs towards the end of life within clinical practice, with a particular focus on MTAs. Nine electronic databases searched. PRISMA guidelines followed. Forty-two studies included. How are decisions made? Decision-making was shared and ongoing, including stopping, starting and trying different treatments. Oncologists often experienced 'professional role dissonance' between their self-perception as 'treaters', and talking about end of life care. Why are decisions made? Clinical factors: disease progression, worsening functional status, treatment side-effects. Non-clinical factors: physicians' personal experience, values, emotions. Some patients continued treatment to maintain 'hope', often reflecting limited understanding of palliative goals. When are decisions made? Limited evidence reveals patients' decisions based upon quality of life benefits. Clinicians found timing withdrawal particularly challenging. Who makes the decisions? Decisions were based within physician-patient interaction. Oncologists report that decisions around stopping chemotherapy treatment are challenging, with limited evidence-based guidance outside of clinical trial protocols. The increasing availability of oral MTAs is transforming the management of incurable cancer; blurring boundaries between active treatment and palliative care. No studies specifically addressing decision-making around stopping MTAs in clinical practice were identified. There is a need to develop an evidence base to support physicians and patients with decision-making around the withdrawal of these high cost treatments.

Analytical platform for metabolome analysis of microbial cells using methyl chloroformate derivatization followed by gas chromatography-mass spectrometry.

PubMed

Smart, Kathleen F; Aggio, Raphael B M; Van Houtte, Jeremy R; Villas-Bôas, Silas G

2010-09-01

This protocol describes an analytical platform for the analysis of intra- and extracellular metabolites of microbial cells (yeast, filamentous fungi and bacteria) using gas chromatography-mass spectrometry (GC-MS). The protocol is subdivided into sampling, sample preparation, chemical derivatization of metabolites, GC-MS analysis and data processing and analysis. This protocol uses two robust quenching methods for microbial cultures, the first of which, cold glycerol-saline quenching, causes reduced leakage of intracellular metabolites, thus allowing a more reliable separation of intra- and extracellular metabolites with simultaneous stopping of cell metabolism. The second, fast filtration, is specifically designed for quenching filamentous micro-organisms. These sampling techniques are combined with an easy sample-preparation procedure and a fast chemical derivatization reaction using methyl chloroformate. This reaction takes place at room temperature, in aqueous medium, and is less prone to matrix effect compared with other derivatizations. This protocol takes an average of 10 d to complete and enables the simultaneous analysis of hundreds of metabolites from the central carbon metabolism (amino and nonamino organic acids, phosphorylated organic acids and fatty acid intermediates) using an in-house MS library and a data analysis pipeline consisting of two free software programs (Automated Mass Deconvolution and Identification System (AMDIS) and R).

Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy

PubMed Central

Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

2017-01-01

Introduction Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. Methods and analysis The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. Ethics and dissemination This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11–1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants, and the investigators will explain the study to the participants in detail. As an ethical clinical trial, the control group will also be given conventional cessation treatments, including NRT and counselling. Participants will be screened and provided with a registration number to protect their personal information. Informed consent will be obtained from the participants prior to enrolling them in the trial. Participants will be allowed to withdraw at anytime without penalty. Trial registration number ClinicalTrials.gov (NCT02768025); pre-results. PMID:28576892

Management of complicated shunt infections: a clinical report.

PubMed

James, Hector E; Bradley, John S

2008-03-01

The authors present their experience with a protocol for the treatment of patients with complicated shunt infections. Complicated shunt infections are defined for the purpose of this protocol as multiple compartment hydrocephalus, multiple organism shunt infection, severe peritonitis, or infections in other sites of the body. The initial treatment protocol for these patients was 3 weeks of intravenous antibiotic therapy and 2 weeks of twice daily intraventricular/intrashunt antibiotic therapy. Cerebrospinal fluid (CSF) cultures were monitored during therapy and obtained again 48 hours after completion. The shunt was completely replaced. Additionally, follow-up cultures were obtained in all patients 3-6 months after therapy was completed. A cure of the infection was achieved in all patients as defined by negative cultures obtained at completion of antibiotic therapy and in follow-up studies. The follow-up period was 2-11 years (mean 4.4 +/- 2.5 years). The treatment protocol was modified in the patients treated after 1991, and 18 patients were treated with this modified treatment regime. In these patients, intraventricular antibiotics were administered only once daily for 14 days, and the CSF was cultured 24 hours after antibiotic therapy had been stopped instead of after 48 hours. The results were similar to those obtained with the initial protocol. Based on their prospective nonrandomized series, the authors believe that patients with complicated shunt infections can be successfully treated with 2 weeks of intraventricular antibiotic therapy administered once daily, concurrent with 3 weeks of intravenous antibiotic therapy. This protocol reduces length of treatment and hospital stay, and avoids recurrence of infection.

Hack-proof Synchronization Protocol for Multi-player Online Games

NASA Astrophysics Data System (ADS)

Fung, Yeung Siu; Lui, John C. S.

Modern multi-player online games are popular and attractive because they provide a sense of virtual world experience to users: players can interact with each other on the Internet but perceive a local area network responsiveness. To make this possible, most modern multi-player online games use similar networking architecture that aims to hide the effects of network latency, packet loss, and high variance of delay from players. Because real-time interactivity is a crucial feature from a player's point of view, any delay perceived by a player can affect his/her performance [16]. Therefore, the game client must be able to run and accept new user commands continuously regardless of the condition of the underlying communication channel, and that it will not stop responding because of waiting for update packets from other players. To make this possible, multi-player online games typically use protocols based on "dead-reckoning" [5, 6, 9] which allows loose synchronization between players.

Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols

PubMed Central

Villas-Boas, Silas G.; Aggio, Raphael

2017-01-01

Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells. PMID:29065530

Particle bombardment - mediated gene transfer and GFP transient expression in Seteria viridis.

PubMed

Mookkan, Muruganantham

2018-04-03

Setaria viridis is one of the most important model grasses in studying monocot plant biology. Transient gene expression study is a very important tool in plant biotechnology, functional genomics, and CRISPR-Cas9 genome editing technology via particle bombardment. In this study, a particle bombardment-mediated protocol was developed to introduce DNA into Setaria viridis in vitro leaf explants. In addition, physical and biological parameters, such as helium pressure, distance from stopping screen to the target tissues, DNA concentration, and number of bombardments, were tested and optimized. Optimum concentration of transient GFP expression was achieved using 1.5 ug plasmid DNA with 0.6 mm gold particles and 6 cm bombardment distance, using 1,100 psi. Doubling the bombardment instances provides the maximum number of foci of transient GFP expression. This simple protocol will be helpful for genomics studies in the S. viridis monocot model.

Comparison between TG-51 and TG-21: Calibration of photon and electron beams in water using cylindrical chambers.

PubMed

Cho, S H; Lowenstein, J R; Balter, P A; Wells, N H; Hanson, W F

2000-01-01

A new calibration protocol, developed by the AAPM Task Group 51 (TG-51) to replace the TG-21 protocol, is based on an absorbed-dose to water standard and calibration factor (N(D,w)), while the TG-21 protocol is based on an exposure (or air-kerma) standard and calibration factor (N(x)). Because of differences between these standards and the two protocols, the results of clinical reference dosimetry based on TG-51 may be somewhat different from those based on TG-21. The Radiological Physics Center has conducted a systematic comparison between the two protocols, in which photon and electron beam outputs following both protocols were compared under identical conditions. Cylindrical chambers used in this study were selected from the list given in the TG-51 report, covering the majority of current manufacturers. Measured ratios between absorbed-dose and air-kerma calibration factors, derived from the standards traceable to the NIST, were compared with calculated values using the TG-21 protocol. The comparison suggests that there is roughly a 1% discrepancy between measured and calculated ratios. This discrepancy may provide a reasonable measure of possible changes between the absorbed-dose to water determined by TG-51 and that determined by TG-21 for photon beam calibrations. The typical change in a 6 MV photon beam calibration following the implementation of the TG-51 protocol was about 1%, regardless of the chamber used, and the change was somewhat smaller for an 18 MV photon beam. On the other hand, the results for 9 and 16 MeV electron beams show larger changes up to 2%, perhaps because of the updated electron stopping power data used for the TG-51 protocol, in addition to the inherent 1% discrepancy presented in the calibration factors. The results also indicate that the changes may be dependent on the electron energy.

Protocolized fluid therapy in brain-dead donors: The multi-center randomized MOnIToR trial

PubMed Central

Al-Khafaji, Ali; Elder, Michele; Lebovitz, Daniel J; Murugan, Raghavan; Souter, Michael; Stuart, Susan; Wahed, Abdus S.; Keebler, Ben; Dils, Dorrie; Mitchell, Stephanie; Shutterly, Kurt; Wilkerson, Dawn; Pearse, Rupert; Kellum, John A

2015-01-01

BACKGROUND Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multi-center randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases organs transplanted. METHODS We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A “protocol-guided fluid therapy” algorithm targeting cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor and our primary analysis was intention-to-treat. Secondary analyses included: 1) modified intention-to-treat where only subjects able to receive the intervention were included, and 2) twelve-month survival in transplant recipients. The study was stopped early. RESULTS We enrolled 556 donors; 279 protocolized care, 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76% of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor, (95%CI: 3.14-3.63) with protocolized care, compared to usual care 3.29 (95%CI: 3.04-3.54) (mean difference, 0.1, 95%CI: -0.25 to 0.45; p=0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95%CI: 3.23-3.8) but was not statistically significant (mean difference, 0.23, 95%CI: -0.15-0.61; p=0.23). Among the 1430 recipients of organs from study subjects, with data available, 56 deaths (7.8%) occurred in the protocolized care arm and 56 (7.9%) in the usual care arm in the first year (Hazard Ratio: 0.97, p=0.86). CONCLUSIONS In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor. PMID:25583616

Evaluating low-resolution tomography neurofeedback by single dissociation of mental grotation task from stop signal task performance.

PubMed

Getter, Nir; Kaplan, Zeev; Todder, Doron

2015-10-01

Electroencephalography source localization neurofeedback, i.e Standardized low-resolution tomography (sLORETA) neurofeedback are non-invasive method for altering region specific brain activity. This is an improvement over traditional neurofeedback which were based on recordings from a single scalp-electrode. We proposed three criteria clusters as a methodological framework to evaluate electroencephalography source localization neurofeedback and present relevant data. Our objective was to evaluate standardized low resolution EEG tomography neurofeedback by examining how training one neuroanatomical area effects the mental rotation task (which is related to the activity of bilateral Parietal regions) and the stop-signal test (which is related to frontal structures). Twelve healthy participants were enrolled in a single session sLORETA neurofeedback protocol. The participants completed both the mental rotation task and the stop-signal test before and after one sLORETA neurofeedback session. During sLORETA neurofeedback sessions participants watched one sitcom episode while the picture quality co-varied with activity in the superior parietal lobule. Participants were rewarded for increasing activity in this region only. Results showed a significant reaction time decrease and an increase in accuracy after sLORETA neurofeedback on the mental rotation task but not after stop signal task. Together with behavioral changes a significant activity increase was found at the left parietal brain after sLORETA neurofeedback compared with baseline. We concluded that activity increase in the parietal region had a specific effect on the mental rotation task. Tasks unrelated to parietal brain activity were unaffected. Therefore, sLORETA neurofeedback could be used as a research, or clinical tool for cognitive disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Fatigue and muscle-tendon stiffness after stretch-shortening cycle and isometric exercise.

PubMed

Toumi, Hechmi; Poumarat, Georges; Best, Thomas M; Martin, Alain; Fairclough, John; Benjamin, Mike

2006-10-01

The purpose of the present study was to compare vertical jump performance after 2 different fatigue protocols. In the first protocol, subjects performed consecutive sets of 10 repetitions of stretch-shortening cycle (SSC) contractions. In the second protocol, successive sets of 10 repetitions of isometric contractions were performed for 10 s with the knee at 90 degrees of flexion. The exercises were stopped when the subjects failed to reach 50% of their maximum voluntary isometric contractions. Maximal isometric force and maximal concentric power were assessed by performing supine leg presses, squat jumps, and drop jumps. Surface EMG was used to determine changes in muscle activation before and after fatigue. In both groups, the fatigue exercises reduced voluntary isometric force, maximal concentric power, and drop jump performance. Kinematic data showed a decrease in knee muscle-tendon stiffness accompanied by a lengthened ground contact time. EMG analysis showed that the squat and drop jumps were performed similarly before and after the fatigue exercise for both groups. Although it was expected that the stiffness would decrease more after SSC than after isometric fatigue (as a result of a greater alteration of the reflex sensitivity SSC), our results showed that both protocols had a similar effect on knee muscle stiffness during jumping exercises. Both fatigue protocols induced muscle fatigue, and the decrease in jump performance was linked to a decrease in the strength and stiffness of the knee extensor muscles.

Ground testing of Arabidopsis preservation protocol for the microarray analysis to be used in the ISS EMCS Multigen-2 experiment

NASA Astrophysics Data System (ADS)

Kittang, Ann-Iren; Kvaløy, Brita; Winge, Per; Iversen, Tor-Henning

2010-11-01

Gene expression analysis using microarrays has proved to be an important method in life science. The opportunity to grow higher plants on the International Space Station (ISS) opens up the possibility for gene expression profiling of plants grown in microgravity. The work presented focuses on how to meet the scientific requirements of plant growth and the sample preservation, given the technical and operational constraints associated with space research. The growth chamber (Multigen-2 Science Testing Unit) and a protocol suggested to be used in the European Modular Cultivation System (EMCS) Multigen-2 experiment on the ISS to grow and later preserve Arabidopsis seedlings, were tested on ground. The results showed that most of the plants developed normally. In order to avoid high population stress the number of seedlings per growth area should be reduced. The RNAlater preservation method to be used in the space experiment was compared with a quick freeze in Liquid Nitrogen (LN2). The RNA from samples preserved in RNAlater at room temperature for 24 h was slightly more degraded than the RNA from the LN2 preserved samples (RNA integrity number, RIN: 7.7 and 8.6, respectively). However, the RNA quality and quantity was satisfactory for microarray analysis. Of the genes analysed, 74 genes (0.28%) were significantly differentially expressed, most of them showing moderate to low regulation. Among the genes induced in the RNAlater preserved samples, three salt inducible transcription factors (ZAT10, SZF1 and SZF2) were identified, suggesting that the high salt concentration in RNAlater causes salt stress before the transcription stopped. In conclusion, the Multigen-2 preservation protocol tested here will allow for the genes regulated by microgravity in the space experiment to be revealed. The results do indicate that not all the biological processes are stopped instantly by the RNAlater. The limited diffusion indirectly caused by the microgravity may potentially result in a different degree of salt stress in the test compared to the 1 × g control during the space experiment. This has to be accounted for during the evaluation of the results. Since slightly degraded RNA was observed, further optimalisation of the preservation protocol will be performed.

A synergic simulation-optimization approach for analyzing biomolecular dynamics in living organisms.

PubMed

Sadegh Zadeh, Kouroush

2011-01-01

A synergic duo simulation-optimization approach was developed and implemented to study protein-substrate dynamics and binding kinetics in living organisms. The forward problem is a system of several coupled nonlinear partial differential equations which, with a given set of kinetics and diffusion parameters, can provide not only the commonly used bleached area-averaged time series in fluorescence microscopy experiments but more informative full biomolecular/drug space-time series and can be successfully used to study dynamics of both Dirac and Gaussian fluorescence-labeled biomacromolecules in vivo. The incomplete Cholesky preconditioner was coupled with the finite difference discretization scheme and an adaptive time-stepping strategy to solve the forward problem. The proposed approach was validated with analytical as well as reference solutions and used to simulate dynamics of GFP-tagged glucocorticoid receptor (GFP-GR) in mouse cancer cell during a fluorescence recovery after photobleaching experiment. Model analysis indicates that the commonly practiced bleach spot-averaged time series is not an efficient approach to extract physiological information from the fluorescence microscopy protocols. It was recommended that experimental biophysicists should use full space-time series, resulting from experimental protocols, to study dynamics of biomacromolecules and drugs in living organisms. It was also concluded that in parameterization of biological mass transfer processes, setting the norm of the gradient of the penalty function at the solution to zero is not an efficient stopping rule to end the inverse algorithm. Theoreticians should use multi-criteria stopping rules to quantify model parameters by optimization. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Effectiveness of Injury Prevention Programs to Modify Risk Factors for Non-Contact Anterior Cruciate Ligament and Hamstring Injuries in Uninjured Team Sports Athletes: A Systematic Review.

PubMed

Monajati, Alireza; Larumbe-Zabala, Eneko; Goss-Sampson, Mark; Naclerio, Fernando

2016-01-01

Hamstring strain and anterior cruciate ligament injuries are, respectively, the most prevalent and serious non-contact occurring injuries in team sports. Specific biomechanical and neuromuscular variables have been used to estimate the risk of incurring a non-contact injury in athletes. The aim of this study was to systematically review the evidences for the effectiveness of injury prevention protocols to modify biomechanical and neuromuscular anterior cruciate and/or hamstring injuries associated risk factors in uninjured team sport athletes. PubMed, Science Direct, Web of Science, Cochrane Libraries, U.S. National Institutes of Health clinicaltrials.gov, Sport Discuss and Google Scholar databases were searched for relevant journal articles published until March 2015. A manual review of relevant articles, authors, and journals, including bibliographies was performed from identified articles. Nineteen studies were included in this review. Four assessment categories: i) landing, ii) side cutting, iii) stop-jump, and iv) muscle strength outcomes, were used to analyze the effectiveness of the preventive protocols. Eight studies using multifaceted interventions supported by video and/or technical feedback showed improvement in landing and/or stop-jump biomechanics, while no effects were observed on side-cutting maneuver. Additionally, multifaceted programs including hamstring eccentric exercises increased hamstring strength, hamstring to quadriceps functional ratio and/or promoted a shift of optimal knee flexion peak torque toward a more open angle position. Multifaceted programs, supported by proper video and/or technical feedback, including eccentric hamstring exercises would positively modify the biomechanical and or neuromuscular anterior cruciate and/or hamstring injury risk factors.

Mission Operations Center (MOC) - Precipitation Processing System (PPS) Interface Software System (MPISS)

NASA Technical Reports Server (NTRS)

Ferrara, Jeffrey; Calk, William; Atwell, William; Tsui, Tina

2013-01-01

MPISS is an automatic file transfer system that implements a combination of standard and mission-unique transfer protocols required by the Global Precipitation Measurement Mission (GPM) Precipitation Processing System (PPS) to control the flow of data between the MOC and the PPS. The primary features of MPISS are file transfers (both with and without PPS specific protocols), logging of file transfer and system events to local files and a standard messaging bus, short term storage of data files to facilitate retransmissions, and generation of file transfer accounting reports. The system includes a graphical user interface (GUI) to control the system, allow manual operations, and to display events in real time. The PPS specific protocols are an enhanced version of those that were developed for the Tropical Rainfall Measuring Mission (TRMM). All file transfers between the MOC and the PPS use the SSH File Transfer Protocol (SFTP). For reports and data files generated within the MOC, no additional protocols are used when transferring files to the PPS. For observatory data files, an additional handshaking protocol of data notices and data receipts is used. MPISS generates and sends to the PPS data notices containing data start and stop times along with a checksum for the file for each observatory data file transmitted. MPISS retrieves the PPS generated data receipts that indicate the success or failure of the PPS to ingest the data file and/or notice. MPISS retransmits the appropriate files as indicated in the receipt when required. MPISS also automatically retrieves files from the PPS. The unique feature of this software is the use of both standard and PPS specific protocols in parallel. The advantage of this capability is that it supports users that require the PPS protocol as well as those that do not require it. The system is highly configurable to accommodate the needs of future users.

La-CTP: Loop-Aware Routing for Energy-Harvesting Wireless Sensor Networks

PubMed Central

Sun, Guodong; Shang, Xinna; Zuo, Yan

2018-01-01

In emerging energy-harvesting wireless sensor networks (EH-WSN), the sensor nodes can harvest environmental energy to drive their operation, releasing the user’s burden in terms of frequent battery replacement, and even enabling perpetual sensing systems. In EH-WSN applications, usually, the node in energy-harvesting or recharging state has to stop working until it completes the energy replenishment. However, such temporary departures of recharging nodes severely impact the packet routing, and one immediate result is the routing loop problem. Controlling loops in connectivity-intermittent EH-WSN in an efficient way is a big challenge in practice, and so far, users still lack of effective and practicable routing protocols with loop handling. Based on the Collection Tree Protocol (CTP) widely used in traditional wireless sensor networks, this paper proposes a loop-aware routing protocol for real-world EH-WSNs, called La-CTP, which involves a new parent updating metric and a proactive, adaptive beaconing scheme to effectively suppress the occurrence of loops and unlock unavoidable loops, respectively. We constructed a 100-node testbed to evaluate La-CTP, and the experimental results showed its efficacy and efficiency. PMID:29393876

How to Stop Disagreeing and Start Cooperatingin the Presence of Asymmetric Packet Loss.

PubMed

Morales-Ponce, Oscar; Schiller, Elad M; Falcone, Paolo

2018-04-22

We consider the design of a disagreement correction protocol in multi-vehicle systems. Vehicles broadcast in real-time vital information such as position, direction, speed, acceleration, intention, etc. This information is then used to identify the risks and adapt their trajectory to maintain the highest performance without compromising the safety. To minimize the risk due to the use of inconsistent information, all cooperating vehicles must agree whether to use the exchanged information to operate in a cooperative mode or use the only local information to operate in an autonomous mode. However, since wireless communications are prone to failures, it is impossible to deterministically reach an agreement. Therefore, any protocol will exhibit necessary disagreement periods. In this paper, we investigate whether vehicles can still cooperate despite communication failures even in the scenario where communication is suddenly not available. We present a deterministic protocol that allows all participants to either operate a cooperative mode when vehicles can exchange all the information in a timely manner or operate in autonomous mode when messages are lost. We show formally that the disagreement time is bounded by the time that the communication channel requires to deliver messages and validate our protocol using NS-3 simulations. We explain how the proposed solution can be used in vehicular platooning to attain high performance and still guarantee high safety standards despite communication failures.

How to Stop Disagreeing and Start Cooperatingin the Presence of Asymmetric Packet Loss

PubMed Central

2018-01-01

We consider the design of a disagreement correction protocol in multi-vehicle systems. Vehicles broadcast in real-time vital information such as position, direction, speed, acceleration, intention, etc. This information is then used to identify the risks and adapt their trajectory to maintain the highest performance without compromising the safety. To minimize the risk due to the use of inconsistent information, all cooperating vehicles must agree whether to use the exchanged information to operate in a cooperative mode or use the only local information to operate in an autonomous mode. However, since wireless communications are prone to failures, it is impossible to deterministically reach an agreement. Therefore, any protocol will exhibit necessary disagreement periods. In this paper, we investigate whether vehicles can still cooperate despite communication failures even in the scenario where communication is suddenly not available. We present a deterministic protocol that allows all participants to either operate a cooperative mode when vehicles can exchange all the information in a timely manner or operate in autonomous mode when messages are lost. We show formally that the disagreement time is bounded by the time that the communication channel requires to deliver messages and validate our protocol using NS-3 simulations. We explain how the proposed solution can be used in vehicular platooning to attain high performance and still guarantee high safety standards despite communication failures. PMID:29690572

Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands.

PubMed

van den Bogert, Cornelis A; Souverein, Patrick C; Brekelmans, Cecile T M; Janssen, Susan W J; Koëter, Gerard H; Leufkens, Hubert G M; Bouter, Lex M

2017-08-01

The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol. All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators. Reasons for trial discontinuation were the primary outcome of the study. Three reasons for discontinuation were analyzed separately: all cause, recruitment failure, and efficacy related (when an interim analysis had demonstrated futility or superiority). Among the efficacy-related discontinuations, we examined whether the data monitoring committee, the stopping rule, and the moment of the interim analysis in the trial progress were specified in the trial protocol. Of the 574 trials, 102 (17.8%) were discontinued. The most common reasons were recruitment failure (33 of 574; 5.7%) and solely efficacy related (30 of 574; 5.2%). Of the efficacy-related discontinuations, 10 of 30 (33.3%) of the trial protocols reported all three aspects in the trial protocol, and 20 of 30 (66.7%) reported at least one aspect in the trial protocol. One out of five clinical drug trials is discontinued before the planned trial end, with recruitment failure and futility as the most common reasons. The target sample size of trials should be feasible, and interim analyses should be adequately described in trial protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

A randomized study comparing the side effects and hormonal status of triptorelin and leuprorelin following conservative laparoscopic surgery for ovarian endometriosis in Chinese women.

PubMed

Li, Zheng; Zhang, Hong Yuan; Zhu, Ying Jun; Hu, Yuan Jing; Qu, Peng Peng

2014-12-01

Different gonadotropin-releasing-hormone agonist (GnRH-a) formulations with different potency and associated side effects, therefore, different compliance and persistence of therapy. This study was to evaluate the difference of hormonal profile and side effects due to hypoestrogenic status after treatment of leuprorelin and triptorelin in Chinese women with ovarian endometrioma after conservative surgical treatment. A total of 302 women underwent laparoscopic excision of ovarian endometriomas with rASRM III and IV were enrolled in the study.Subjects were randomized into two groups with use of a random table. Twenty two patients dropped out during the study. Thus 142 patients had three doses of i.m. leuprorelin (group A) and 138 patients had three doses of i.m. triptorelin(group B) at 4 weeks intervals after surgical treatment. Menopausal symptoms were evalutaed using a questionnaire and serum sex hormonal levels were also measured during the follow-up. At week 4 after the treatment, most of the patients in leuprorelin group have no obvious side effects. After 9 weeks, bone pain, hot flashes and sweating, and irregular bleeding were the main side effects and showed no difference between the groups. Anxiety, depression, vaginal dryness, headache, and acne rates were all significantly higher in triptorelin group than in leuprorelin group. A significant difference in FSH (p=0.003), LH (p=0.026) and E2 (p=0.002) levels between the groups were observed after 21 days of the GnRHa treatment. The FSH (p=0.021) and E2 (p=0.033) levels remained higher in the leuprorelin group than the triptorelin group after six weeks of treatment, but the difference of LH(p=0.917) level was no longer discernible. Leuprorelin in down-regulating the pituitary-ovarian function was more moderate, and the hormonal levels decrease progressively and gradually, therefore, with lower rate of menopausal symptoms. Leuprorelin acetate maybe better tolerated than triptorelin. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

STOP smoking and alcohol drinking before OPeration for bladder cancer (the STOP-OP study), perioperative smoking and alcohol cessation intervention in relation to radical cystectomy: study protocol for a randomised controlled trial.

PubMed

Lauridsen, Susanne Vahr; Thomsen, Thordis; Thind, Peter; Tønnesen, Hanne

2017-07-17

To evaluate the effect of a smoking-, alcohol- or combined-cessation intervention starting shortly before surgery and lasting 6 weeks on overall complications after radical cystectomy. Secondary objectives are to examine the effect on types and grades of complications, smoking cessation and alcohol cessation, length of hospital stay, health-related quality of life and return to work or habitual level of activity up to 12 months postoperatively. The study is a multi-institutional randomised clinical trial involving 110 patients with a risky alcohol intake and daily smoking who are scheduled for radical cystectomy. Patients will be randomised to the 6-week Gold Standard Programme (GSP) or treatment as usual (control). The GSP combines patient education and pharmacologic strategies. Smoking and alcohol intake is biochemically validated (blood, urine and breath tests) at the weekly meetings and at follow-up. Herein, we report the design of the STOP-OP study, objectives and accrual up-date. This study will provide new knowledge about how to prevent smoking and alcohol-related postoperative complications at the time of bladder cancer surgery. Till now 77 patients have been enrolled. Patient accrual is expected to be finalised before the end of 2017 and data will be published in 2018. ClinicalTrials.gov, ID: NCT02188446 . Registered on 28 May 2014.

Childhood acute promyelocytic leukemia: no benefit of all-trans-retinoic acid administered in a short-course schedule.

PubMed

Zubizarreta, P A; Rose, A B; Felice, M S; Alfaro, E; Delfino, S; Cygler, A M; Sackmann-Muriel, F

2000-03-01

From January 1990 to August 1997, 29 consecutive patients were treated with newly diagnosed primary acute promyelocytic leukemia (APL) at the authors' Institution. Of these, 27 (16 boys and 11 girls) were evaluable. Median age at diagnosis was 6.3 (range: 1.9-15.7) years. This population was treated with two consecutive protocols: 13 patients were included in the AML-HPG-90 protocol and 14 in the AML-HPG-95. The initial treatment was the same for both protocols: an induction 8-day phase with cytarabine, idarubicin, and etoposide was followed by a consolidation with cyclophosphamide, cytarabine, 6-mercaptopurine, vincristine, doxorubicin, and prednisone. Two courses of intensification with high-dose (HD) cytarabine and etoposide were given in the first study. Only one intensification course was administered in the second study, with HD cytarabine plus idarubicin or etoposide decided by randomization. Complete remission was achieved in 67% (18/27) of cases. Mortality on induction was quite high, 30% (8/27) mainly due to hemorrhages from disseminated intravascular coagulation (DIC). The event-free survival estimate for all patients was 0.47 (SE: 0.1). From April 1994, all-trans-retinoic acid (ATRA) was administered just during the first days of the induction phase (median: 9, range: 2-27) to stop or prevent DIC. Eighteen patients received ATRA and 9 did not. Three patients developed signs of ATRA syndrome during the first days of administration but no one died due to this toxicity. The impact of a short course of ATRA on early control of DIC was studied by analyzing the number of platelet, cryoprecipitate, and fresh frozen plasma transfusions during the induction phase in both groups. No statistical differences in complete remission rate, early mortality, need of transfusion of blood components for DIC, and survival estimates could be established between patients who received ATRA and those who did not. ATRA used in a short-course schedule during induction of APL did not stop early mortality due to DIC. Moreover, survival results did not improve with this method of ATRA usage. Longer periods of ATRA administration during APL therapy are strongly recommended.

Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.

PubMed

Al-Khafaji, Ali; Elder, Michele; Lebovitz, Daniel J; Murugan, Raghavan; Souter, Michael; Stuart, Susan; Wahed, Abdus S; Keebler, Ben; Dils, Dorrie; Mitchell, Stephanie; Shutterly, Kurt; Wilkerson, Dawn; Pearse, Rupert; Kellum, John A

2015-03-01

Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multicenter randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases the number of organs transplanted. We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A "protocol-guided fluid therapy" algorithm targeting the cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor, and our primary analysis was intention to treat. Secondary analyses included: (1) modified intention to treat where only subjects able to receive the intervention were included and (2) 12-month survival in transplant recipients. The study was stopped early. We enrolled 556 donors: 279 protocolized care and 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76 % of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor (95 % CI 3.14-3.63) with protocolized care compared to 3.29 usual care (95 % CI 3.04-3.54; mean difference, 0.1, 95 % CI -0.25 to 0.45; p = 0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95 % CI 3.23-3.8), but not statistically significantly (mean difference, 0.23, 95 % CI -0.15 to 0.61; p = 0.23). Among the 1,430 recipients of organs from study subjects with data available, 56 deaths (7.8 %) occurred in the protocolized care arm and 56 (7.9 %) in the usual care arm in the first year (hazard ratio: 0.97, p = 0.86). In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor.

The Effectiveness of Injury Prevention Programs to Modify Risk Factors for Non-Contact Anterior Cruciate Ligament and Hamstring Injuries in Uninjured Team Sports Athletes: A Systematic Review

PubMed Central

Monajati, Alireza; Larumbe-Zabala, Eneko; Goss-Sampson, Mark; Naclerio, Fernando

2016-01-01

Background Hamstring strain and anterior cruciate ligament injuries are, respectively, the most prevalent and serious non-contact occurring injuries in team sports. Specific biomechanical and neuromuscular variables have been used to estimate the risk of incurring a non-contact injury in athletes. Objective The aim of this study was to systematically review the evidences for the effectiveness of injury prevention protocols to modify biomechanical and neuromuscular anterior cruciate and/or hamstring injuries associated risk factors in uninjured team sport athletes. Data Sources PubMed, Science Direct, Web of Science, Cochrane Libraries, U.S. National Institutes of Health clinicaltrials.gov, Sport Discuss and Google Scholar databases were searched for relevant journal articles published until March 2015. A manual review of relevant articles, authors, and journals, including bibliographies was performed from identified articles. Main Results Nineteen studies were included in this review. Four assessment categories: i) landing, ii) side cutting, iii) stop-jump, and iv) muscle strength outcomes, were used to analyze the effectiveness of the preventive protocols. Eight studies using multifaceted interventions supported by video and/or technical feedback showed improvement in landing and/or stop-jump biomechanics, while no effects were observed on side-cutting maneuver. Additionally, multifaceted programs including hamstring eccentric exercises increased hamstring strength, hamstring to quadriceps functional ratio and/or promoted a shift of optimal knee flexion peak torque toward a more open angle position. Conclusions Multifaceted programs, supported by proper video and/or technical feedback, including eccentric hamstring exercises would positively modify the biomechanical and or neuromuscular anterior cruciate and/or hamstring injury risk factors. PMID:27171282

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Al-Shahi Salman, Rustam; Dennis, Martin S; Murray, Gordon D; Innes, Karen; Drever, Jonathan; Dinsmore, Lynn; Williams, Carol; White, Philip M; Whiteley, William N; Sandercock, Peter A G; Sudlow, Cathie L M; Newby, David E; Sprigg, Nikola; Werring, David J

2018-03-05

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 ( www.isrctn.com/ISRCTN71907627 ). Prospectively registered on 25 April 2013.

Combined application of prophylactic corneal cross-linking and laser in-situ keratomileusis - a review of literature.

PubMed

Chan, Tommy C Y; Ng, Alex L K; Chan, Karen K W; Cheng, George P M; Wong, Ian Y H; Jhanji, Vishal

2017-11-01

Laser in-situ keratomileusis (LASIK) is safe and effective laser refractive procedures in treating refractive errors. However, regression of treatment and iatrogenic keratectasia remain to be a major concern, especially in treating thin cornea with high ametropia. Collagen cross-linking (CXL) is an effective method in stopping keratoconus progression through increasing the biomechanical strength of the cornea. Adjuvant cross-linking to refractive procedures can theoretically help prevent regression and reduce the risk of keratectasia development by increasing the mechanical stability of cornea. During the procedure, riboflavin is directly applied to the corneal stroma, thereby reducing the need of de-epithelialization as in the conventional protocol for keratoconus. Currently, there is still no consensus regarding the indication of CXL during refractive procedure, nor any standardized treatment protocol. This article aims to summarize the current evidence regarding the use of adjuvant CXL in LASIK. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Five year follow-up of a smoking withdrawal clinic population.

PubMed Central

West, D W; Graham, S; Swanson, M; Wilkinson, G

1977-01-01

Eight hundred volunteers who attended smoking clinics at Roswell Park Memorial Institute from 1964-1965 were followed up five years later to ascertain their current smoking status. From three waves of a mailed questionnaire, plus a telephone campaign, we obtained 559 usable responses. The relationship between smoking status at the five-year follow-up and clinic protocols and selected social and psychological characteristics as determined during the clinics were examined. Of those individuals contacted five years after the clinic, 17.8 per cent were not smoking. Variations in clinic protocol in terms of drugs and education methods had no relation to long-term smoking withdrawal. Several social and psychological variables, however, were related to smoking behavior five years after the clinics. Non-smokers were more likely than smokers to be males, to be older, to have smoked less before the clinic, to have started smoking at a later age, to have a milieu that was supportive of their stopping, and to have fewer indices of neurosis and fewer psychosomatic symptoms. PMID:869086

The role of hypnosis in the detection of psychogenic seizures.

PubMed

Martínez-Taboas, Alfonso

2002-07-01

In this preliminary clinical investigation, hypnosis was used in the differential diagnosis of epileptic versus psychogenic seizures (PS). Eight patients with a clinical profile suggesting the presence of PS were given a hypnotic suggestion in which they had to go back in time to the exact moment of their last seizure. They were then asked to concentrate their attention on any unusual feeling or bodily sensation. All 8 patients presented a PS during the age regression protocol. In 6 cases, independent testimony from family members corroborated the morphological similarity of the induced attack and the ones presented in their natural environment. Also, the seizures ended abruptly after a command was given to stop them. A control group of 5 epileptic subjects did not present any signs of discomfort or seizure behavior during the hypnotic protocol. It is argued that a simple procedure as the one described in this investigation can be useful as a diagnostic tool in the differentiation of epileptic from PS attacks.

Responsibility for managing healthcare-associated infections: where does the buck stop?

PubMed

Duerden, B I

2009-12-01

The prevention and control of healthcare-associated infections (HCAIs) requires a tripartite partnership between clinicians and carers, managers and government/Department of Health (DoH) across the whole health and social care community. Mandatory surveillance of meticillin-resistant Staphylococcus aureus bacteraemia and Clostridium difficile infection has shown a significant fall from peak numbers in 2003/04 and 2006, respectively, and there is now a zero tolerance approach to preventable infections and poor practice. Success so far has been based on senior management commitment, enhanced real-time surveillance, implementation of clinical protocols (high impact interventions, prudent prescribing), improved hand hygiene and environmental cleaning, and training and audit, backed up by a heightened performance management focus through targets and legislation (Code of Practice). DoH improvement teams have supported National Health Service trusts in implementing change. Responsibility for managing HCAI is a combination of managerial responsibility based upon compliance assurance that procedures and protocols are being implemented and personal professional responsibility of all clinicians and other healthcare workers.

Study protocol for a randomised trial of nicotine-free cigarettes as an adjunct to usual NRT-based cessation practice, in people who wish to stop smoking

PubMed Central

2011-01-01

Background Current smoking cessation treatments focus on addressing the pharmacological dependence of smokers on nicotine. However, new strategies are needed that address both nicotine dependence and the psychological dependence on cigarettes as the source of nicotine. Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates. This paper describes the protocol for a large randomised-controlled trial to test the effect of using nicotine-free cigarettes together with NRT on long-term quit rates. Methods/design This single-blind, randomised trial aims to recruit 1,410 participants through the national telephone-based Quitline service in New Zealand. Participants in the treatment arm will be asked to stop smoking nicotine-containing cigarettes on their chosen Quit day and smoke ad libitum nicotine-free (Quest 3) cigarettes for six weeks. At the same time people in this group will be asked to start using NRT patches, gum and/or lozenges (as recommended by Quitline) for eight weeks. Participants in the control arm will be asked to stop smoking completely on their chosen Quit day and start using NRT patches, gum and/or lozenges (as recommended by Quitline) for eight weeks. Data collection will occur at baseline, three and six weeks, and three and six months after Quit day. The primary outcome is the proportion of participants who self-report seven-day point prevalence abstinence at six months since Quit date. Discussion Smoking prevalence in New Zealand has changed little in recent years (particularly in Māori, the indigenous people of New Zealand) and additional options for smokers who want to quit are needed. Although a variety of methods are available to help, many are expensive, have side effects, and despite their use most quit attempts still fail. This trial will test the balance of benefits and risks of a new strategy for people to overcome nicotine dependence. Since smoking is the leading cause of lost healthy life years in New Zealand, if proven effective this strategy is likely to have substantial public health benefits. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000410358 PMID:21232155

Protograph LDPC Codes Over Burst Erasure Channels

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Dolinar, Sam; Jones, Christopher

2006-01-01

In this paper we design high rate protograph based LDPC codes suitable for binary erasure channels. To simplify the encoder and decoder implementation for high data rate transmission, the structure of codes are based on protographs and circulants. These LDPC codes can improve data link and network layer protocols in support of communication networks. Two classes of codes were designed. One class is designed for large block sizes with an iterative decoding threshold that approaches capacity of binary erasure channels. The other class is designed for short block sizes based on maximizing minimum stopping set size. For high code rates and short blocks the second class outperforms the first class.

CT myocardial perfusion imaging: current status and future perspectives.

PubMed

Yang, Dong Hyun; Kim, Young-Hak

2017-07-01

Computed tomography myocardial perfusion (CTP) combined with coronary computed tomography angiography (CCTA) may constitute a "1-stop shop" for the noninvasive diagnosis of hemodynamically significant coronary stenosis during a single CT examination. CTP shows high diagnostic performance and provides incremental value over CCTA for the detection of hemodynamically significant coronary stenosis in patients with a high Agatston calcium score or coronary artery stents. Future studies should determine the optimal protocol and clinical value of CTP for guiding revascularization strategy and prognostication. In this article, we review the current status and future perspectives of CTP, focusing on technical considerations, clinical applications, and future research topics.

A novel protocol to evaluate ankle movements during reaching tasks using pediAnklebot.

PubMed

Martelli, Francesca; Palermo, Eduardo; Rossi, Stefano

2017-07-01

The aim of the study is to design a novel protocol to characterize the ankle movements during dorsal and plantar flexion reaching tasks using the pediAnklebot. Five healthy children were instructed to control a pointer and hit targets appearing on the monitor, by moving their ankle alternatively up and down. The protocol consisted of 60 targets, 30 up and 30 down, reachable via dorsiflexion and plantarflexion movements, respectively. Ankle angular displacements and torques were gathered by encoders and load cells embedded in the robot. Ankle motor performance was evaluated by means of kinematic, submovements and dynamic indices. Results suggest that (i) plantarflexion movements are faster and more accurate than the dorsiflexion ones, but children are able to perform with a higher level of smoothness the latter ones; (ii) children are able to stop the ankle movement more easily at the end of dorsiflexion rather than plantarflexion; (iii) the central nervous system plans plantarflexion and dorsiflexion movements with the same efficiency; (iv) children apply different torque levels during the two motor tasks and they cannot balance the inversion and eversion moments during dorsiflexion. These findings provide an important starting point for the assessment of a reference baseline of motor indices for the ankle joint.

The effects of Low Level LASER Therapy (LLLT) on blood glucose levels in patients with Diabetes Mellitus type I : a case report

NASA Astrophysics Data System (ADS)

Longo, Leonardo; Postiglione, Marco; Buccioni, Tommaso; Longo, Diego

2009-06-01

Diabetes Mellitus (DM) is a widespread disease and a serious public health problem. Low Level LASER Therapy (LLLT) has been found to reduce glycaemia on DM type 1 patients, an observation requiring further research especially as regards characteristics of treatment protocol. The purpose of this work is to continue the line of research and propose a specific protocol for LLLT use. In spring 2008 a 48 year old man, DM type 1 insulin dependent patient has been submitted to 810 nm wavelength LLLT treatment in specific body areas daily for 3 weeks and then once a week for 4 weeks until normalization of glycaemia. Medical supervision was present before, during and after application. Insulin was reduced progressively and then stopped. A gradual reduction of glycaemia was noted during the course of treatment. In successive follow-ups a reduction in HbA1c was noted. Results confirm previous observations and need for further research on large cohorts. The indication that LASER may become a valuable addition to DM type 1 treatment is confirmed and the proposed protocol appears to be effective. The case presented merits review since it reports a therapeutic challenge, contributes to advance in medical science and spawns research.

Comparison of futility monitoring guidelines using completed phase III oncology trials.

PubMed

Zhang, Qiang; Freidlin, Boris; Korn, Edward L; Halabi, Susan; Mandrekar, Sumithra; Dignam, James J

2017-02-01

Futility (inefficacy) interim monitoring is an important component in the conduct of phase III clinical trials, especially in life-threatening diseases. Desirable futility monitoring guidelines allow timely stopping if the new therapy is harmful or if it is unlikely to demonstrate to be sufficiently effective if the trial were to continue to its final analysis. There are a number of analytical approaches that are used to construct futility monitoring boundaries. The most common approaches are based on conditional power, sequential testing of the alternative hypothesis, or sequential confidence intervals. The resulting futility boundaries vary considerably with respect to the level of evidence required for recommending stopping the study. We evaluate the performance of commonly used methods using event histories from completed phase III clinical trials of the Radiation Therapy Oncology Group, Cancer and Leukemia Group B, and North Central Cancer Treatment Group. We considered published superiority phase III trials with survival endpoints initiated after 1990. There are 52 studies available for this analysis from different disease sites. Total sample size and maximum number of events (statistical information) for each study were calculated using protocol-specified effect size, type I and type II error rates. In addition to the common futility approaches, we considered a recently proposed linear inefficacy boundary approach with an early harm look followed by several lack-of-efficacy analyses. For each futility approach, interim test statistics were generated for three schedules with different analysis frequency, and early stopping was recommended if the interim result crossed a futility stopping boundary. For trials not demonstrating superiority, the impact of each rule is summarized as savings on sample size, study duration, and information time scales. For negative studies, our results show that the futility approaches based on testing the alternative hypothesis and repeated confidence interval rules yielded less savings (compared to the other two rules). These boundaries are too conservative, especially during the first half of the study (<50% of information). The conditional power rules are too aggressive during the second half of the study (>50% of information) and may stop a trial even when there is a clinically meaningful treatment effect. The linear inefficacy boundary with three or more interim analyses provided the best results. For positive studies, we demonstrated that none of the futility rules would have stopped the trials. The linear inefficacy boundary futility approach is attractive from statistical, clinical, and logistical standpoints in clinical trials evaluating new anti-cancer agents.

Smoking cessation treatment by Dutch respiratory nurses: reported practice, attitudes and perceived effectiveness.

PubMed

Kotz, D; van Litsenburg, W; van Duurling, R; van Schayck, C P; Wesseling, G J

2008-01-01

To describe Dutch respiratory nurses' current smoking cessation practices, attitudes and beliefs, and to compare these with a survey from the year 2000, before the national introduction of a protocol for the treatment of nicotine and tobacco addiction (the L-MIS protocol). Questionnaire survey among all 413 registered respiratory nurses in the Netherlands in 2006. The response rate was 62%. Seventy-seven percent of the respondents reported to have "fairly good" or "good" knowledge of all steps of the L-MIS protocol. Seven out of 10 behavioural techniques for smoking cessation from the protocol were used by more than 94% of the respondents. Seventy-four percent of the respiratory nurses recommended the use of either nicotine replacement therapy (70%) or bupropion (44%). Almost two-thirds (65% of 254) perceived lack of patient's motivation as the most important barrier for smoking cessation treatment; a four-fold increase compared to the year 2000. We conclude that respiratory nurses are compliant with the L-MIS protocol. They offer intensive support and use behavioural techniques for smoking cessation more frequently than evidence-based pharmacological aids for smoking cessation. Perceived lack of patient's motivation forms the most important threat to respiratory nurses' future smoking cessation activities. International guidelines acknowledge that respiratory patients have a more urgent need to stop smoking but have more difficulty doing so. They should be offered the most intensive smoking cessation counselling in combination with pharmacotherapy. This kind of counselling may be more feasible for respiratory nurses than for physicians who often lack time. Their efforts could be increased by reimbursing pharmacological aids for smoking cessation and by developing simple tools to systematically assess motivation to quit and psychiatric co-morbidity in smoking patients.

Effects of medication and subthalamic nucleus deep brain stimulation on tongue movements in speakers with Parkinson's disease using electropalatography: a pilot study.

PubMed

Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J; Limousin, Patricia

2011-03-01

Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using electropalatography (EPG). Two patients, PT1 and PT2, were studied under four conditions: on and off medication and ON and OFF stimulation. The EPG protocol consisted of a number of target words with alveolar and velar stops, repeated 10 times in random order. The motor part III of the Unified Parkinson Disease Rating Scale (UPDRS) indicated significantly improved motor scores in the ON stimulation condition in both patients. However, PT1's articulation patterns deteriorated with stimulation whereas PT2 showed improving articulatory accuracy in the same condition. The results revealed different effects of stimulation and medication on articulation particularly with regard to timing. The study quantified less articulatory undershoot for velar stops in comparison to alveolars. Furthermore, the findings provided preliminary evidence that stimulation with medication has a more detrimental effect on articulation than stimulation without medication.

Objective determination of the predefined duration of a constant-load diagnostic tests in arterial claudication.

PubMed

Mahe, Guillaume; Abraham, Pierre; Zeenny, Maya; Bruneau, Antoine; Vielle, Bruno; Leftheriotis, Georges

2010-04-01

The predefined duration to arbitrarily stop the tests during constant-load treadmill exercise is a subject of debate and widely variable in the literature. We hypothesized that the upper and lower limits for predefined durations of constant-load 3.2 km/hour 10% grade tests could be derived from the distribution of walking distances observed on a treadmill in a population of subjects referred for claudication or from the optimal cutoff point distance on a treadmill to confirm a limitation self-reported by history. We conducted a retrospective analysis using a referral center, institutional practice, and ambulatory patients. We studied 1290 patients (86% male), 62.1 +/- 11.2 years of age, 169 +/- 8 cm height, 75.7 +/- 14.2 kg weight. Patients performed a standard constant-load treadmill test: 3.2 km hour(-1), 10% slope, maximized to 1000 meters (approximately 20 minutes). We analyzed the maximal walking distance self-reported (MWD(SR)) by history and the maximal walking distance measured on the treadmill (MWD(TT)). Patients reporting MWD(SR) >or=1000 meters were considered unlimited by history. Only 197 patients (15.3%) completed the 20-minute treadmill test. Among the 504 patients who did not stop before 250 meters, 47.8% stopped within the next 250 meters (were unable to walk 500 meters). This proportion falls to 7.5% among the 213 patients who did not stop before 750 meters. When the final goal was to estimate whether the treadmill test can discriminate patients with or without limitation by history, area under the receiver operating characteristic (ROC) curve was 0.809 +/- 0.016 (95% confidence interval [CI], 0.778-0.841; P < .0001), the best diagnostic performance was attained for an MWD(TT) of 299 meters (approximately 6.15 minutes). In patients undergoing constant-load treadmill exercise with a protocol of 3.2 km hour(-1) and 10% slope: a predefined duration of 7 minutes could be proposed as a lower limit for the predefined duration of the tests specifically if one aims at confirming the limitation by history with treadmill testing. Owing to the low risk that patients that could walk 750 meters (approximately 15 minutes) will have to stop in the next 250 meters, 15 minutes seems a reasonable upper limit for the predefined test duration in clinical routine.

Labeling proteins on live mammalian cells using click chemistry.

PubMed

Nikić, Ivana; Kang, Jun Hee; Girona, Gemma Estrada; Aramburu, Iker Valle; Lemke, Edward A

2015-05-01

We describe a protocol for the rapid labeling of cell-surface proteins in living mammalian cells using click chemistry. The labeling method is based on strain-promoted alkyne-azide cycloaddition (SPAAC) and strain-promoted inverse-electron-demand Diels-Alder cycloaddition (SPIEDAC) reactions, in which noncanonical amino acids (ncAAs) bearing ring-strained alkynes or alkenes react, respectively, with dyes containing azide or tetrazine groups. To introduce ncAAs site specifically into a protein of interest (POI), we use genetic code expansion technology. The protocol can be described as comprising two steps. In the first step, an Amber stop codon is introduced--by site-directed mutagenesis--at the desired site on the gene encoding the POI. This plasmid is then transfected into mammalian cells, along with another plasmid that encodes an aminoacyl-tRNA synthetase/tRNA (RS/tRNA) pair that is orthogonal to the host's translational machinery. In the presence of the ncAA, the orthogonal RS/tRNA pair specifically suppresses the Amber codon by incorporating the ncAA into the polypeptide chain of the POI. In the second step, the expressed POI is labeled with a suitably reactive dye derivative that is directly supplied to the growth medium. We provide a detailed protocol for using commercially available ncAAs and dyes for labeling the insulin receptor, and we discuss the optimal surface-labeling conditions and the limitations of labeling living mammalian cells. The protocol involves an initial cloning step that can take 4-7 d, followed by the described transfections and labeling reaction steps, which can take 3-4 d.

Luteal estrogen supplementation in pregnancies associated with low serum estradiol concentrations.

PubMed

Kaider, A S; Coulam, C B

2000-07-01

The role of luteal phase estrogen in pregnancy outcome has been a matter of considerable debate. In order to evaluate the effectiveness of estrogen supplementation in gonadotropin releasing hormone agonist (GnRHa)/human menopausal gonadotropin (hMG)-stimulated cycles associated with low luteal estrogen concentration, a study was performed comparing the ongoing pregnancy rates in cycles with serum concentrations of estradiol (E2) <100 pg/ml 11 days post embryo transfer (p-ET), treated with luteal phase progesterone (P4) vs. E2 and P4 supplementation. Among 1106 serum samples studied, 951 were from women receiving GnRHa and follicle stimulating hormone (FSH) prior to oocyte retrieval and P4 (50 mg-100 mg IM daily) as luteal phase supplementation beginning day 11 after retrieval. The remaining 155 were from women receiving both E2 (2 mg-6 mg estrace orally each day) and P4 during the luteal phase. Significantly greater frequencies of preclinical losses were observed among women with human chorionic gonadotropin (hCG) concentrations>5 mIU/ml and concurrent E2 concentrations <100 pg/ml compared with E2 >100 pg/ml (p<0.00001). Among the 128 women who had hCG concentrations >5 mIU/ml and E2 concentrations <100 pg/ml, 102 received P4 only during the luteal phase and 26 were treated with estrace 2 mg-6 mg daily, as well as P4 during the luteal phase. The frequency of preclinical pregnancy losses among the 102 women with hCG >5 mIU/ml and E2 <100 pg/ml who did not receive luteal E2 supplementation was 72%, compared with 50% who received luteal E2 supplementation (p=0.04) The increase in preclinical pregnancy loss rates among women not receiving luteal E2 resulted in a decrease in ongoing pregnancy rate (8%), compared to those receiving luteal E2 supplementation (31%) (p=0.002). Our results indicated that a subset of women losing pregnancies preclinically after GnRHa and FSH stimulation due to low luteal phase serum E2 level may benefit from luteal estrogen supplementation. More sensitive and specific markers are needed to identify prospectively women in this risk group.

Successful outpatient graded administration of trimethoprim-sulfamethoxazole in patients without HIV and with a history of sulfonamide adverse drug reaction.

PubMed

Pyle, Regan C; Butterfield, Joseph H; Volcheck, Gerald W; Podjasek, Jenna C; Rank, Matthew A; Li, James T C; Harish, Amitha; Poe, Kimberly L; Park, Miguel A

2014-01-01

The outcomes of trimethoprim-sulfamethoxazole (TMP-SMX) desensitization have been widely reported in the HIV literature but less so in the non-HIV literature. To evaluate the safety and efficacy of graded administration of TMP-SMX in patients without HIV and with a history of TMP-SMX adverse drug reaction (ADR). A retrospective chart review, 2004-2012, of all the patients without HIV seen in the Division of Allergic Diseases and with a history of TMP-SMX ADR who underwent outpatient graded administration of TMP-SMX was conducted. The medical record was reviewed for age, sex, details of the initial ADR to TMP-SMX, an indication for TMP-SMX administration, and outcome. Patients also were contacted by telephone, and medical records were reviewed to determine long-term outcomes. Seventy-two patients (46 women [64%]; mean [SD] age, 57.7 ± 13.89 years]) were included. The most common patient-reported reactions to TMP-SMX were rash 39 (54%), and hives 9 (13%). TMP-SMX administration was needed for the following indications: prophylaxis (62 [86%]) and treatment of infection (10 [14%]). Forty-three of the patients (60%) underwent a 1-day TMP-SMX administration protocol. Thirty-five of the 43 (81%) underwent a 6-step (90 minutes to 6 hours) protocol and 7 of the 43 (16%) underwent a novel 14-step TMP-SMX protocol. Twenty-nine (40%) underwent a >1-day TMP-SMX administration protocol. Our overall success rate was 90% (mean duration of 11 months). Ninety-eight percent of the patients successfully completed a 1-day graded administration protocol, and 76% successfully completed a >1-day protocol. TMP-SMX was stopped in 8 patients because of the ADR. We report the largest case series of successful outpatient graded administration of TMP-SMX with both 1-day and >1-day protocols, which have shown to be safe and well tolerated in patients without HIV and with a history of sulfonamide ADR. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Testing ZigBee Motes for Monitoring Refrigerated Vegetable Transportation under Real Conditions

PubMed Central

Ruiz-Garcia, Luis; Barreiro, Pilar; Robla, Jose Ignacio; Lunadei, Loredana

2010-01-01

Quality control and monitoring of perishable goods during transportation and delivery services is an increasing concern for producers, suppliers, transport decision makers and consumers. The major challenge is to ensure a continuous ‘cold chain’ from producer to consumer in order to guaranty prime condition of goods. In this framework, the suitability of ZigBee protocol for monitoring refrigerated transportation has been proposed by several authors. However, up to date there was not any experimental work performed under real conditions. Thus, the main objective of our experiment was to test wireless sensor motes based in the ZigBee/IEEE 802.15.4 protocol during a real shipment. The experiment was conducted in a refrigerated truck traveling through two countries (Spain and France) which means a journey of 1,051 kilometers. The paper illustrates the great potential of this type of motes, providing information about several parameters such as temperature, relative humidity, door openings and truck stops. Psychrometric charts have also been developed for improving the knowledge about water loss and condensation on the product during shipments. PMID:22399917

Testing ZigBee motes for monitoring refrigerated vegetable transportation under real conditions.

PubMed

Ruiz-Garcia, Luis; Barreiro, Pilar; Robla, Jose Ignacio; Lunadei, Loredana

2010-01-01

Quality control and monitoring of perishable goods during transportation and delivery services is an increasing concern for producers, suppliers, transport decision makers and consumers. The major challenge is to ensure a continuous 'cold chain' from producer to consumer in order to guaranty prime condition of goods. In this framework, the suitability of ZigBee protocol for monitoring refrigerated transportation has been proposed by several authors. However, up to date there was not any experimental work performed under real conditions. Thus, the main objective of our experiment was to test wireless sensor motes based in the ZigBee/IEEE 802.15.4 protocol during a real shipment. The experiment was conducted in a refrigerated truck traveling through two countries (Spain and France) which means a journey of 1,051 kilometers. The paper illustrates the great potential of this type of motes, providing information about several parameters such as temperature, relative humidity, door openings and truck stops. Psychrometric charts have also been developed for improving the knowledge about water loss and condensation on the product during shipments.

Tobacco cessation intervention: how to communicate with tobacco using patients.

PubMed

Stafne, E E; Bakdash, B

2000-11-15

Tobacco use is a dental as well as a medical problem. When dental team members assist their patients in becoming tobacco free, they are eliminating a causative/contributing factor for a number of oral conditions including cancer and periodontal diseases. Studies have shown that brief tobacco use cessation interventions in the dental office can be effective in helping many patients to stop using tobacco. Interventions can be optimized through understanding the stage of change the tobacco user is in when an intervention is attempted. Only then can we use the appropriate intervention at the right time. This article discusses and demonstrates a protocol for tobacco cessation interventions that can be used in the dental office.

The calibration of a Scanditronix-Wellhöfer thimble chamber for photon dosimetry using the IAEA TRS 277 code of practice.

PubMed

Fourie, O L

2004-03-01

This note investigates the calibration of a Scanditronix-Wellhöfer type FC65-G ionisation chamber to be used in clinical photon dosimetry. The current Adaptation by the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) of the IAEA TRS 277 dosimetry protocol makes no provision for this type of chamber. The absorbed dose to air calibration coefficient ND was therefore calculated from the air kerma calibration coefficient NK using the formalism of the IAEA TRS 277 protocol and it is shown that the value of the correction factor kmkatt for the FC65-G chamber is identical to that of the NE 2571 chamber. ND was also determined experimentally from a cross calibration against an NE 2571 dosimetry. It was found that there is a good correspondence between the calculated and measured values. To establish to what extent the ACPSEM Adaptation can be used for the FC65-G chamber, values for the ratio of stopping powers in water and air (Sw,air)Q and the perturbation correction factor pQ were calculated using the TRS 277 protocol. From these results it is shown that over the range of beam qualities TPR20,10 = 0.59 to TPR20,10 = 0.78 the Adaptation can be used for the FC65-G chamber.

Idiopathic constipation: A challenging but manageable problem.

PubMed

Bischoff, Andrea; Brisighelli, Giulia; Dickie, Belinda; Frischer, Jason; Levitt, Marc A; Peña, Alberto

2017-10-10

A protocol to treat idiopathic constipation is presented. A contrast enema is performed in every patient and, when indicated, patients are initially submitted to a "clean out" protocol. All patients are started on a Senna-based laxative. The initial dosage is empirically determined and adjusted daily, during a one week period, based on history and abdominal radiographs, until the amount of Senna that empties the colon is reached. The management is considered successful when patients empty their colon daily and stop soiling. If the laxatives dose provokes abdominal cramping, distension, and vomiting, without producing bowel movements, patients are considered nonmanageable. From 2005 to 2012, 215 patients were treated. 121 (56%) were males. The average age was 8.2years (range: 1-20). 160 patients (74%) presented encopresis. 67 patients (32%) needed a clean out. After one week, 181 patients (84%) achieved successful management, with an average Senna dose of 67mg (range: 5-175mg). In 34 patients (16%) the treatment was unsuccessful: 19 were nonmanageable, 3 noncompliant, and 12 continued soiling. At a later follow-up (median: 329days) the success rate for 174 patients was 81%. We designed a successful protocol to manage idiopathic constipation. The key points are clean out before starting laxatives, individual adjustments of laxative, and radiological monitoring of colonic emptying. Level IV. Copyright © 2017 Elsevier Inc. All rights reserved.

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 11: Commissioning of a system for the measurement of electron stopping powers

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

McEwen, Malcolm; Roy, Timothy; Tessier, Frederic

Purpose: To develop the techniques required to experimentally determine electron stopping powers for application in primary standards and dosimetry protocols. Method and Materials: A large-volume HPGe detector system (>80% efficiency) was commissioned for the measurement of high energy (5–35 MeV) electron beams. As a proof of principle the system was used with a Y-90/Sr-90 radioactive source. Thin plates of absorbing material (< 0.1 gcm-2) were then placed between the source and detector and the emerging electron spectrum was acquired. The full experimental geometry was modelled using the EGSnrc package to validate the detector design, optimize the experimental setup and comparemore » measured and calculated spectra. Results: The biggest challenge using a beta source was to identify a robust spectral parameter to determine for each measurement. An end-point-fitting routine was used to determine the maximum energy, Emax, of the beta spectrum for each absorber thickness t. The parameter dEmax/dt is related to the electron stopping power and the same routine was applied to both measured and simulated spectra. Although the standard uncertainty in dEmax/dt was of the order of 5 %, by taking the ratio of measured and Monte Carlo values for dEmax/dt the uncertainty of the fitting routine was eliminated and the uncertainty was reduced to less than 2 %. The agreement between measurement and simulation was within this uncertainty estimate. Conclusion: The investigation confirmed the experimental approach and demonstrated that EGSnrc could accurately determine correction factors that will be required for the final measurement setup in a linac beam.« less

Investigating the Effects of Glottal Stop Productions on Voice in Children With Cleft Palate Using Multidimensional Voice Assessment Methods.

PubMed

Aydınlı, Fatma Esen; Özcebe, Esra; Kulak Kayıkçı, Maviş E; Yılmaz, Taner; Özgür, Fatma F

2016-11-01

The aim was to investigate the effects of glottal stop productions (GS) on voice in children with cleft palate using multidimensional voice assessment methods. This is a prospective case-control study. Children with repaired cleft palate (n = 34) who did not have any vocal fold lesions were separated into two groups based on the results of the articulation test. The glottal stop group (GSG) consisted of 17 children who had GS. The control group (CG) consisted of an equal number of age- and gender-matched children who did not have GS. The voice evaluation protocol included acoustic analysis, Pediatric Voice Handicap Index (pVHI), and perceptual analysis (Grade, Roughness, Breathiness, Asthenia, Strain method). The velopharyngeal statuses of the groups were compared using the nasopharyngoscopy and the nasometer. The total pVHI score and the subscales of the pVHI were found to be significantly higher in the GSG. The F0, jitter, and shimmer were found to be numerically higher in the GSG with the difference being statistically significant in jitter (P < 0.05). Audioperceptual analysis revealed a difference in overall voice quality and roughness between the groups. Greater incidence of significant velopharyngeal insufficiency and higher nasalance scores were found in the GSG (P < 0.05). These results may indicate that the vocal quality characteristics of children with GS differ from children who do not have this type of production. It is suggested that children with cleft palate who have GS should receive a comprehensive speech and language pathology intervention including voice therapy techniques. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Distribution of breeding Arizona Grasshopper Sparrow (Ammodramus savannarum ammolegus) in the southwestern United States: Past, present, and future

USGS Publications Warehouse

Ruth, Janet M.

2008-01-01

The Arizona Grasshopper Sparrow (Ammodramus savannarum ammolegus) breeds in desert grasslands of southeastern Arizona and southwestern New Mexico in the US, and in adjacent parts of northern Sonora and Chihuahua, Mexico. Roads that were surveyed in 1982 and 1987 in Arizona and New Mexico were relocated and roadside survey protocols were repeated in 2004 and 2005 to identify changes in distribution or abundance of the subspecies during the subsequent 17 yr. The Sonoita and San Rafael valleys in Arizona and the Animas Valley in New Mexico remain as primary population centers, supporting the highest mean numbers of singing males per stop, as well as the largest populations of Arizona Grasshopper Sparrows in the US. Mean number of singing males per stop was highest in the San Rafael Valley. Mean number of singing males per survey stop showed an increasing pattern from 1982–1987 and a subsequent decline to the present (2004–2005). Present bird densities are intermediate in value between 1982 and 1987 values. Small populations remain in the Altar, San Pedro, Sulphur Springs, and San Bernardino valleys in Arizona. The valleys evaluated in this and historical surveys represent the areas in which almost all Arizona Grasshopper Sparrows breed in the US; if any additional areas exist, they support peripheral, small, or remnant populations. Although historic, current, and future land use, and current and future threats differ among valleys, the primary factors posing threats to the future of Arizona Grasshopper Sparrow populations appear to be loss and/or degradation of habitat due to exurban development, overgrazing, and the effects of long-term drought.

Increasing the fidelity of noncanonical amino acid incorporation in cell-free protein synthesis.

PubMed

Gan, Qinglei; Fan, Chenguang

2017-11-01

Cell-free protein synthesis provides a robust platform for co-translational incorporation of noncanonical amino acid (ncAA) into proteins to facilitate biological studies and biotechnological applications. Recently, eliminating the activity of release factor 1 has been shown to increase ncAA incorporation in response to amber codons. However, this approach could promote mis-incorporation of canonical amino acids by near cognate suppression. We performed a facile protocol to remove near cognate tRNA isoacceptors of the amber codon from total tRNAs, and used the phosphoserine (Sep) incorporation system as validation. By manipulating codon usage of target genes and tRNA species introduced into the cell-free protein synthesis system, we increased the fidelity of Sep incorporation at a specific position. By removing three near cognate tRNA isoacceptors of the amber stop codon [tRNA Lys , tRNA Tyr , and tRNA Gln (CUG)] from the total tRNA, the near cognate suppression decreased by 5-fold without impairing normal protein synthesis in the cell-free protein synthesis system. Mass spectrometry analyses indicated that the fidelity of ncAA incorporation was improved. Removal of near cognate tRNA isoacceptors of the amber codon could increase ncAA incorporation fidelity towards the amber stop codon in release factor deficiency systems. We provide a general strategy to improve fidelity of ncAA incorporation towards stop, quadruplet and sense codons in cell-free protein synthesis systems. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2016 Elsevier B.V. All rights reserved.

Should the presence of a culture positive urinary tract infection exclude patients from rapid evaluation hematuria protocols?

PubMed

Vasdev, Nikhil; Thorpe, Andrew C

2013-08-01

Current rapid evaluation protocols for patients with hematuria tend to exclude those with urinary tract infection since this is assumed to be evidence of a benign treatable cause. The likelihood of a urinary tract cancer in such patients is, however, uncertain, and we have therefore analyzed a prospective hematuria clinic database to determine risk. A total of 1,740 patients were enrolled prospectively in this study at our unit's one stop fast track hematuria clinic between April 2003 and March 2006. Evaluation of patients consisted of basic demographics, history and examination, urinalysis, urine culture, urine cytology, and serum creatinine. All patients then underwent a renal ultrasound, intravenous urogram, and cystoscopy. A total of 1,067 males and 673 females with a mean (range) age of 60.8 (16-96) years were included in the study. One hundred sixty-one patients had a positive mid-stream urine (MSU) on a specimen collected at the hematuria clinic. Amongst this group 20% (32) patients had a urologic malignancy diagnosed, of whom 12% (4) had metastatic disease at presentation. Only 1% (3) of patients had a urologic malignancy with a previous history of a treated urinary tract infection (UTI) and negative MSU at the clinic. The risk of urologic malignancy was 24% (303) in the remaining 1,249 patients with no history of a UTI prior to presentation and a negative MSU on a specimen collected at the one stop fast track hematuria clinic. Despite selection bias inherent in this analysis, it appears that the presence of UTI does not decrease the likelihood of having a urologic malignancy diagnosed. Hence, there is no indication to delay prompt evaluation in patients with hematuria and a positive urine culture collected at the hematuria clinic. Copyright © 2013 Elsevier Inc. All rights reserved.

[Volumes of services supplied by Italian Stop-Smoking Services and their characteristics predictive of abstinence].

PubMed

Gorini, Giuseppe; Ameglio, Matteo; Martini, Andrea; Bosi, Sandra; Laezza, Maurizio

2013-01-01

to evaluate differences in terms of smokers' attendance to National Health System (NHS) Stop-Smoking Services with a prevalent individual approach (SSSi), and to those with a prevalent group approach (SSSg). To identify predictive characteristics of success, in terms of quit rates at the end of treatment (QR0) and after 6 months (QR1), according to SSS type (SSSi/SSSg), treatment (individual/ group counseling with/without pharmacologic treatments), 5 SSS scores: type of structure (S), number and hours per week of SSS health professionals (P), SSS involvement in local tobacco control networks (N), and type of smokers' assessment (A); and 3 principal components of SSS characteristics. survey to 19 SSSs, and survey to smokers attending these SSSs, with a six month follow-up. 1,276 smokers attending 19 SSSs (664 at 7 SSSi; 612 at 12 SSSg) in 9 months in the period 2008-2010. smokers' attendance to scheduled sessions; QR0; QR1. even though SSSi treated more smokers per month (12 vs. 8 in SSSg), SSSi scheduled fewer treatment sessions (7 vs. 9 sessions) in a wider treatment period (3 months vs. 2 in SSSg). SSSg recorded lower P and higher A scores. Four out of 5 smokers attending SSSg and 2/5 of smokers attending SSSi completed treatment protocols. Considering all smokers, QR1 in both types of SSS were around 36%. Smokers treated with pharmacotherapy, those more motivated and with high self-efficacy, and those non-living together with smokers were more likely to recorded higher QR1. the most relevant interventions in order to increase the number of smokers treated at SSS and to improve cessation rates among them were: for SSSi, increasing completion to treatment protocol; for SSSg, improving the P scores to increase the number of treated smokers; for all SSS, increasing the use of pharmacotherapy in combination with individual/group counseling to sustain abstinence.

Nephrologists' perceptions regarding dialysis withdrawal and palliative care in Europe: lessons from a European Renal Best Practice survey

PubMed Central

van Biesen, Wim; van de Luijtgaarden, Moniek W.M.; Brown, Edwina A.; Michel, Jean-Pierre; van Munster, Barbara C.; Jager, Kitty J.; van der Veer, Sabine N.

2015-01-01

Background There is a variation in dialysis withdrawal rates, but reasons for this variation across European countries are largely unknown. We therefore surveyed nephrologists' perceptions of factors concerning dialysis withdrawal and palliative care and explored relationships between these perceptions and reports of whether withdrawal actually occurred in practice. Methods We developed a 33-item electronic survey, disseminated via an email blast to all European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) members. In our data analyses, we distinguished those respondents who reported occurrence from those reporting no dialysis withdrawal in their unit. With multilevel logistic regression, we investigated the association between respondents' characteristics and perceptions and whether they reported occurrence of dialysis withdrawal or not. Results Five hundred and twenty-eight nephrologists from 45 countries completed the questionnaire; 42% reported occurrence of withdrawal in their unit in the past year, and 56% perceived that stopping life-prolonging treatment in terminally ill patients was allowed. Few respondents reported presence in their unit of protocols on withdrawal decision making (7%) or palliative care (10%) or the common involvement of a geriatrician in withdrawal decisions (10%). The majority stated that palliative care had not been part of their core curriculum (74%) and that they had not recently attended continuous medical education sessions on this topic (73%). Respondents from Eastern and Southern Europe had a 42 and 40% lower probability, respectively, of reporting withdrawal compared with those from North European countries. Working in a public centre [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.36–4.25] and respondents' perception that stopping life-prolonging treatment in terminally ill patients was allowed (OR, 1.96; 95% CI, 1.23–3.12), that withdrawal decisions were commonly shared between doctor and patient (OR, 1.97; 95% CI, 1.26–3.08) and that palliative care was reimbursed (OR, 1.81; 95% CI, 1.16–2.83) increased the odds of reporting occurrence of withdrawal. Conclusion Reports of dialysis withdrawal occurrence varied between European countries. Occurrence reports were more likely if respondents worked in a public centre, if stopping life-prolonging treatments was perceived as allowed, if withdrawal decisions were considered shared between doctors and patients and if reimbursement of palliative care was believed to be in place. There is room for improvement regarding protocols on withdrawal and palliative care processes and regarding nephrologists' training and education on end-of-life care. PMID:26268713

Novel Telestroke Program Improves Thrombolysis for Acute Stroke Across 21 Hospitals of an Integrated Healthcare System.

PubMed

Nguyen-Huynh, Mai N; Klingman, Jeffrey G; Avins, Andrew L; Rao, Vivek A; Eaton, Abigail; Bhopale, Sunil; Kim, Anne C; Morehouse, John W; Flint, Alexander C

2018-01-01

Faster treatment with intravenous alteplase in acute ischemic stroke is associated with better outcomes. Starting in 2015, Kaiser Permanente Northern California redesigned its acute stroke workflow across all 21 Kaiser Permanente Northern California stroke centers to (1) follow a single standardized version of a modified Helsinki model and (2) have all emergency stroke cases managed by a dedicated telestroke neurologist. We examined the effect of Kaiser Permanente Northern California's Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke program on door-to-needle (DTN) time, alteplase use, and symptomatic intracranial hemorrhage rates. The program was introduced in a staggered fashion from September 2015 to January 2016. We compared DTN times for a seasonally adjusted 9-month period at each center before implementation to the corresponding 9-month calendar period from the start of implementation. The primary outcome was the DTN time for alteplase administration. Secondary outcomes included rate of alteplase administrations per month, symptomatic intracranial hemorrhage, and disposition at time of discharge. This study included 310 patients treated with alteplase in the pre-EXpediting the PRrocess of Evaluating and Stopping Stroke period and 557 patients treated with alteplase in the EXpediting the PRrocess of Evaluating and Stopping Stroke period. After implementation, alteplase administrations increased to 62/mo from 34/mo at baseline ( P <0.001). Median DTN time decreased to 34 minutes after implementation from 53.5 minutes prior ( P <0.001), and DTN time of <60 minutes was achieved in 87.1% versus 61.0% ( P <0.001) of patients. DTN times <30 minutes were much more common in the Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke period (40.8% versus 4.2% before implementation). There was no significant difference in symptomatic intracranial hemorrhage rates in the 2 periods (3.8% versus 2.2% before implementation; P =0.29). Introduction of a standardized modified Helsinki protocol across 21 hospitals using telestroke management was associated with increased alteplase administrations, significantly shorter DTN times, and no increase in adverse outcomes. © 2017 The Authors.

Recruiting community health centers into pragmatic research: Findings from STOP CRC.

PubMed

Coronado, Gloria D; Retecki, Sally; Schneider, Jennifer; Taplin, Stephen H; Burdick, Tim; Green, Beverly B

2016-04-01

Challenges of recruiting participants into pragmatic trials, particularly at the level of the health system, remain largely unexplored. As part of Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC), we recruited eight separate community health centers (consisting of 26 individual safety net clinics) into a large comparative effectiveness pragmatic study to evaluate methods of raising the rates of colorectal cancer screening. In partnership with STOP CRC's advisory board, we defined criteria to identify eligible health centers and applied these criteria to a list of health centers in Washington, Oregon, and California affiliated with Oregon Community Health Information Network, a 16-state practice-based research network of federally sponsored health centers. Project staff contacted centers that met eligibility criteria and arranged in-person meetings of key study investigators with health center leadership teams. We used the Consolidated Framework for Implementation Research to thematically analyze the content of discussions during these meetings to identify major facilitators of and barriers to health center participation. From an initial list of 41 health centers, 11 met the initial inclusion criteria. Of these, leaders at three centers declined and at eight centers (26 clinic sites) agreed to participate (73%). Participating and nonparticipating health centers were similar with respect to clinic size, percent Hispanic patients, and percent uninsured patients. Participating health centers had higher proportions of Medicaid patients and higher baseline colorectal cancer screening rates. Common facilitators of participation were perception by center leadership that the project was an opportunity to increase colorectal cancer screening rates and to use electronic health record tools for population management. Barriers to participation were concerns of center leaders about ability to provide fecal testing to and assure follow-up of uninsured patients, limited clinic capacity to prepare mailings required by the study protocol, discomfort with randomization, and concerns about delaying program implementation at some clinics due to the research requirements. Our findings address an important research gap and may inform future efforts to recruit community health centers into pragmatic research. © The Author(s) 2015.

Recruiting community health centers into pragmatic research: Findings from STOP CRC

PubMed Central

Coronado, Gloria D; Retecki, Sally; Schneider, Jennifer; Taplin, Stephen H; Burdick, Tim; Green, Beverly B

2015-01-01

Background Challenges of recruiting participants into pragmatic trials, particularly at the level of the health system, remain largely unexplored. As part of Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC), we recruited eight separate community health centers (consisting of 26 individual safety net clinics) into a large comparative effectiveness pragmatic study to evaluate methods of raising the rates of colorectal cancer screening. Methods In partnership with STOP CRC’s advisory board, we defined criteria to identify eligible health centers and applied these criteria to a list of health centers in Washington, Oregon, and California affiliated with OCHIN (formerly Oregon Community Health Information Network), a 16-state practice-based research network of federally sponsored health centers. Project staff contacted centers that met eligibility criteria and arranged in-person meetings of key study investigators with health center leadership teams. We used the Consolidated Framework for Implementation Research to thematically analyze the content of discussions during these meetings to identify major facilitators of and barriers to health center participation. Results From an initial list of 41 health centers, 11 met the initial inclusion criteria. Of these, leaders at three centers declined and at eight centers (26 clinic sites) agreed to participate (73%). Participating and nonparticipating health centers were similar with respect to clinic size, percent Hispanic patients, and percent uninsured patients. Participating health centers had higher proportions of Medicaid patients and higher baseline colorectal cancer screening rates. Common facilitators of participation were perception by center leadership that the project was an opportunity to increase colorectal cancer screening rates and to use electronic health record tools for population management. Barriers to participation were concerns of center leaders about ability to provide fecal testing to and assure follow up of uninsured patients, limited clinic capacity to prepare mailings required by the study protocol, discomfort with randomization, and concerns about delaying program implementation at some clinics due to the research requirements. Conclusion Our findings address an important research gap and may inform future efforts to recruit community health centers into pragmatic research. PMID:26419905

Do Bayesian adaptive trials offer advantages for comparative effectiveness research? Protocol for the RE-ADAPT study

PubMed Central

Luce, Bryan R; Broglio, Kristine R; Ishak, K Jack; Mullins, C Daniel; Vanness, David J; Fleurence, Rachael; Saunders, Elijah; Davis, Barry R

2013-01-01

Background Randomized clinical trials, particularly for comparative effectiveness research (CER), are frequently criticized for being overly restrictive or untimely for health-care decision making. Purpose Our prospectively designed REsearch in ADAptive methods for Pragmatic Trials (RE-ADAPT) study is a ‘proof of concept’ to stimulate investment in Bayesian adaptive designs for future CER trials. Methods We will assess whether Bayesian adaptive designs offer potential efficiencies in CER by simulating a re-execution of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study using actual data from ALLHAT. Results We prospectively define seven alternate designs consisting of various combinations of arm dropping, adaptive randomization, and early stopping and describe how these designs will be compared to the original ALLHAT design. We identify the one particular design that would have been executed, which incorporates early stopping and information-based adaptive randomization. Limitations While the simulation realistically emulates patient enrollment, interim analyses, and adaptive changes to design, it cannot incorporate key features like the involvement of data monitoring committee in making decisions about adaptive changes. Conclusion This article describes our analytic approach for RE-ADAPT. The next stage of the project is to conduct the re-execution analyses using the seven prespecified designs and the original ALLHAT data. PMID:23983160

Metabolomics of Pichia pastoris: impact of buffering conditions on the kinetics and nature of metabolite loss during quenching.

PubMed

Mattanovich, Matthias; Russmayer, Hannes; Scharl-Hirsch, Theresa; Puxbaum, Verena; Burgard, Jonas; Mattanovich, Diethard; Hann, Stephan

2017-05-01

Mass spectrometry-based metabolomic profiling is a powerful strategy to quantify the concentrations of numerous primary metabolites in parallel. To avoid distortion of metabolite concentrations, quenching is applied to stop the cellular metabolism instantly. For yeasts, cold methanol quenching is accepted to be the most suitable method to stop metabolism, while keeping the cells intact for separation from the supernatant. During this treatment, metabolite loss may occur while the cells are suspended in the quenching solution. An experiment for measuring the time-dependent loss of selected primary metabolites in differently buffered quenching solutions was conducted to study pH and salt concentration-dependent effects. Molecular properties of the observed metabolites were correlated with the kinetics of loss to gain insight into the mechanisms of metabolite leakage. Size and charge-related properties play a major role in controlling metabolite loss. We found evidence that interaction with the cell wall is the main determinant to retain a molecule inside the cell. Besides suggesting an improved quenching protocol to keep loss at a minimum, we could establish a more general understanding of the process of metabolite loss during quenching, which will allow to predict optimal conditions for hitherto not analysed metabolites. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Inhibitory motor control based on complex stopping goals relies on the same brain network as simple stopping

PubMed Central

Wessel, Jan R.; Aron, Adam R.

2014-01-01

Much research has modeled action-stopping using the stop-signal task (SST), in which an impending response has to be stopped when an explicit stop-signal occurs. A limitation of the SST is that real-world action-stopping rarely involves explicit stop-signals. Instead, the stopping-system engages when environmental features match more complex stopping goals. For example, when stepping into the street, one monitors path, velocity, size, and types of objects; and only stops if there is a vehicle approaching. Here, we developed a task in which participants compared the visual features of a multidimensional go-stimulus to a complex stopping-template, and stopped their go-response if all features matched the template. We used independent component analysis of EEG data to show that the same motor inhibition brain network that explains action-stopping in the SST also implements motor inhibition in the complex-stopping task. Furthermore, we found that partial feature overlap between go-stimulus and stopping-template lead to motor slowing, which also corresponded with greater stopping-network activity. This shows that the same brain system for action-stopping to explicit stop-signals is recruited to slow or stop behavior when stimuli match a complex stopping goal. The results imply a generalizability of the brain’s network for simple action-stopping to more ecologically valid scenarios. PMID:25270603

[Climatic change and public health: scenarios after the coming into force of the Kyoto Protocol].

PubMed

Ballester, Ferran; Díaz, Julio; Moreno, José Manuel

2006-03-01

According to the reports of the intergovernmental panel for climatic change (IPCC) human beings of the present and near future are going to experiment, in fact we are already experimenting, important changes in the world climate. Conscious of the magnitude of the problem, international organizations have taken a series of initiatives headed to stop the climatic change and to reduce its impact. This willingness has been shaped into the agreements established in the Kyoto protocol, where countries commit to reduce greenhouse-effect gas emissions. Kyoto protocol has come into force on February 16th 2005 with the support of 141 signing countries. Among the major worries are the effects which climatic change may have upon health, such as: 1) changes in the morbidity- mortality related to temperature; 2) Effects on health related with extreme meteorological events (tornados, storms, hurricanes and extreme raining); 3) Air pollution and increase of associated health effects; d) Diseases transmitted by food and water and 4) Infectious diseases transmitted by vectors and by rodents. Even if all the countries in the world committed to the Kyoto Protocol, some consequences of the climatic change will be inevitable; among them some will have a negative impact on health. It would be necessary to adapt a key response strategy to minimize the impacts of climatic change and to reduce, at minimum cost, its adverse effects on health. From the Public Health position, a relevant role can and must be played concerning the understanding of the risks for health of such climatic changes, the design of surveillance systems to evaluate possible impacts, and the establishment of systems to prevent or reduce damages as well as the identification and development of investigation needs.

The implementation of biosecurity practices and visitor protocols on non-commercial horse properties in New Zealand.

PubMed

Rosanowski, S M; Rogers, C W; Cogger, N; Benschop, J; Stevenson, M A

2012-11-01

A survey was conducted to investigate biosecurity practices on non-commercial horse properties, to describe the number of visits by horse professionals and any protocols that visitors were required to follow before interacting with resident horses. Data were collected in November 2009 during a cross-sectional study of non-commercial horse properties, in New Zealand, selected using generalised random-tessellated stratified design and a self-administered postal questionnaire. Data were described and the associations between property-level factors and biosecurity practices were analysed using logistic regression analysis. In total there were 791 respondents from non-commercial horse properties, of which 660 (83%) answer at least one question relating to biosecurity practices. Of the respondents, 95% had at least one biosecurity practice for arriving horses. Only 31% of properties isolated horses for more than four days, and few respondents checked for pyrexia or other clinical signs of infectious disease in new horses. Moving horses from a property was associated with the implementation of biosecurity practices and practices specific to the clinical signs of respiratory disease. Overall, 79% of properties had horse professional's visit, but only 33% of respondents reported biosecurity protocols for these visitors. Most properties had some knowledge about newly arriving horses, but the effectiveness of these practices for biosecurity were questionable, as few practices would stop disease spread to resident horses. Horse professionals are likely candidates for disease spread due to contact with horses, limited visitor protocols and the frequency of visits. The development of a plan to improve biosecurity for endemic and exotic disease is recommended. Copyright © 2012 Elsevier B.V. All rights reserved.

South Asian women with polycystic ovary syndrome exhibit greater sensitivity to gonadotropin stimulation with reduced fertilization and ongoing pregnancy rates than their Caucasian counterparts.

PubMed

Palep-Singh, M; Picton, H M; Vrotsou, K; Maruthini, D; Balen, A H

2007-10-01

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome. In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is required for PCOS cases that are refractory to standard ovulation induction or have co-existing infertility factors in women with PCOS and Tubal factor subfertility. Assess ethnic variations in response to IVF/ICSI treatment. Observational Comparative study in a University hospital fertility clinic in women with PCOS and Tubal factor subfertility. Women with PCOS (Asians: AP=104; Caucasians: CP=220) and those with tubal factor infertility seeking fertility treatment were assessed (Asians: AC=84; Caucasians: CC=200). Six hundred and eight fresh IVF or ICSI cycles using long protocol of GnRHa suppression and resulting in a fresh embryo transfer were compared. The primary endpoint was to assess the dose of gonadotropins used in the cycles. The secondary outcomes were: total number of oocytes retrieved, fertilization and ongoing clinical pregnancy rates. We found that the South Asian women presented at a younger age for the management of sub-fertility. An extended stimulation phase and Caucasian ethnicity showed an inverse correlation with the number of oocytes retrieved in the PCOS subgroup. Caucasian ethnicity was associated with a higher fertilization rate however increase in body mass index (BMI) and the laboratory technique of IVF appeared to have a negative impact on fertilization rates in the PCOS subgroup. Commencing down regulation on day 1 of the cycles was negatively associated with fertilization rates in the tubal group. In terms of clinical pregnancy rates, the Caucasian PCOS had a 2.5 times (95% CI: 1.25-5) higher chance of an ongoing clinical pregnancy as compared with their Asian counterpart. Also, a unit increase in the basal FSH concentration reduced the odds of pregnancy by 18.6% (95% CI: 1.8-32.6%) in the PCOS group. The Asian PCOS have a greater sensitivity to gonadotropin stimulation with lower fertilization and ongoing clinical pregnancy rates as compared with their Caucasian counterparts.

The Effects of Prompting and Feedback on Drivers' Stopping at Stop Signs

PubMed Central

Austin, John; Hackett, Stacey; Gravina, Nicole; Lebbon, Angela

2006-01-01

Complete stops at a high-traffic intersection on the campus of a public university were increased with a prompting and consequence intervention. Data were collected at two opposing stop signs (Stop A and Stop B); however, the intervention was implemented only at Stop A. During the intervention, a volunteer stood next to Stop A holding a poster that read, “Please Stop—I Care,” with “Thank You For Stopping” on the reverse side. The poster was held by the volunteer so that drivers approaching Stop A could read the sign. Drivers approaching Stop B could see the volunteer but could not read the sign. When vehicles approaching Stop A made a complete stop, the volunteer flashed the “thank you” side of the poster to the driver. The strategy was evaluated using a multielement design. The intervention increased stops completed at Stop A from a baseline average of 13% to an intervention average of 52%. Stop B also showed improved stopping, from a baseline average of 6% to an intervention average of 28%. Data showed no relation between complete stops made and the drivers' use of turn signals and safety belts. PMID:16602391

Involvement of hormones in olfactory imprinting and homing in chum salmon.

PubMed

Ueda, Hiroshi; Nakamura, Shingo; Nakamura, Taro; Inada, Kaoru; Okubo, Takashi; Furukawa, Naohiro; Murakami, Reiichi; Tsuchida, Shigeo; Zohar, Yonathan; Konno, Kotaro; Watanabe, Masahiko

2016-02-16

The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker.

Measurement profiles of nano-scale ion beam for optimized radiation energy losses

NASA Astrophysics Data System (ADS)

Woo, T. H.; Cho, H. S.

2011-10-01

The behavior of charged particles is investigated for nano-scale ion beam therapy using a medical accelerator. Computational work is performed for the Bragg-peak simulation, which is focused on human organ material of pancreas and thyroid. The Results show that the trends of the dose have several different kinds of distributions. Before constructing a heavy ion collider, this study can give us the reliability of the therapeutic effect. Realistic treatment using human organs is calculated in a simple and cost effective manner using the computational code, the Stopping and Range of Ions in Matter 2008 (SRIM 2008). Considering the safety of the therapy, it is suggested to give a patient orient planning of the cancer therapy. The energy losses in ionization and phonon are analyzed, which are the behaviors in the molecular level nano-scopic investigation. The different fluctuations are shown at 150 MeV, where the lowest temperature is found in proton and pancreas case. Finally, the protocol for the radiation therapy is constructed by the simulation in which the procedure for a better therapy is selected. An experimental measurement incorporated with the simulations could be programmed by this protocol.

Earth Observing System Data Gateway

NASA Technical Reports Server (NTRS)

Pfister, Robin; McMahon, Joe; Amrhein, James; Sefert, Ed; Marsans, Lorena; Solomon, Mark; Nestler, Mark

2006-01-01

The Earth Observing System Data Gateway (EDG) software provides a "one-stop-shopping" standard interface for exploring and ordering Earth-science data stored at geographically distributed sites. EDG enables a user to do the following: 1) Search for data according to high-level criteria (e.g., geographic location, time, or satellite that acquired the data); 2) Browse the results of a search, viewing thumbnail sketches of data that satisfy the user s criteria; and 3) Order selected data for delivery to a specified address on a chosen medium (e.g., compact disk or magnetic tape). EDG consists of (1) a component that implements a high-level client/server protocol, and (2) a collection of C-language libraries that implement the passing of protocol messages between an EDG client and one or more EDG servers. EDG servers are located at sites usually called "Distributed Active Archive Centers" (DAACs). Each DAAC may allow access to many individual data items, called "granules" (e.g., single Landsat images). Related granules are grouped into collections called "data sets." EDG enables a user to send a search query to multiple DAACs simultaneously, inspect the resulting information, select browseable granules, and then order selected data from the different sites in a seamless fashion.

Advantage of four-electrode over two-electrode defibrillators

NASA Astrophysics Data System (ADS)

Bragard, J.; Šimić, A.; Laroze, D.; Elorza, J.

2015-12-01

Defibrillation is the standard clinical treatment used to stop ventricular fibrillation. An electrical device delivers a controlled amount of electrical energy via a pair of electrodes in order to reestablish a normal heart rate. We propose a technique that is a combination of biphasic shocks applied with a four-electrode system rather than the standard two-electrode system. We use a numerical model of a one-dimensional ring of cardiac tissue in order to test and evaluate the benefit of this technique. We compare three different shock protocols, namely a monophasic and two types of biphasic shocks. The results obtained by using a four-electrode system are compared quantitatively with those obtained with the standard two-electrode system. We find that a huge reduction in defibrillation threshold is achieved with the four-electrode system. For the most efficient protocol (asymmetric biphasic), we obtain a reduction in excess of 80% in the energy required for a defibrillation success rate of 90%. The mechanisms of successful defibrillation are also analyzed. This reveals that the advantage of asymmetric biphasic shocks with four electrodes lies in the duration of the cathodal and anodal phase of the shock.

The Effects of Prompting and Feedback on Drivers' Stopping at Stop Signs

ERIC Educational Resources Information Center

Austin, John; Hackett, Stacey; Gravina, Nicole; Lebbon, Angela

2006-01-01

Complete stops at a high-traffic intersection on the campus of a public university were increased with a prompting and consequence intervention. Data were collected at two opposing stop signs (Stop A and Stop B); however, the intervention was implemented only at Stop A. During the intervention, a volunteer stood next to Stop A holding a poster…

Acquisition of initial /s/-stop and stop-/s/ sequences in Greek

PubMed Central

Syrika, Asimina; Nicolaidis, Katerina; Edwards, Jan; Beckman, Mary E.

2010-01-01

Previous work on children’s acquisition of complex sequences points to a tendency for affricates to be acquired before clusters, but there is no clear evidence of a difference in order of acquisition between clusters with /s/ that violate the Sonority Sequencing Principle (SSP), such as /s/ followed by stop in onset position, and other clusters that obey the SSP. One problem with studies that have compared the acquisition of SSP-obeying and SSP-violating clusters is that the component sounds in the two types of sequences were different. This paper examines the acquisition of initial /s/-stop and stop-/s/ sequences by sixty Greek children aged 2 through 5 years. Results showed greater accuracy for the /s/-stop relative to the stop-/s/ sequences, but no difference in accuracy between /ts/, which is usually analyzed as an affricate in Greek, and the other stop-/s/ sequences. Moreover, errors for the /s/-stop sequences and /ts/ primarily involved stop substitutions, whereas errors for /ps/ and /ks/ were more variable and often involved fricative substitutions, a pattern which may have a perceptual explanation. Finally, /ts/ showed a distinct temporal pattern relative to the stop-/s/ clusters /ps/ and /ks/, similarly to what has been reported for productions of Greek adults. PMID:22070044

Inhibitory Effects on Response Force in the Stop-Signal Paradigm

ERIC Educational Resources Information Center

Ko, Yao-Ting; Alsford, Toni; Miller, Jeff

2012-01-01

The forcefulness of key press responses was measured in stop-all and selective stopping versions of the stop-signal paradigm. When stop signals were presented too late for participants to succeed in stopping their responses, response force was nonetheless reduced relative to trials in which no stop signal was presented. This effect shows that…

Lifespan Changes in Global and Selective Stopping and Performance Adjustments

PubMed Central

van de Laar, Maria C.; van den Wildenberg, Wery P. M.; van Boxtel, Geert J. M.; van der Molen, Maurits W.

2011-01-01

This study examined stopping and performance adjustments in four age groups (M ages: 8, 12, 21, and 76 years). All participants performed on three tasks, a standard two-choice task and the same task in which stop-signal trials were inserted requiring either the suppression of the response activated by the choice stimulus (global stop task) or the suppression of the response when one stop-signal was presented but not when the other stop-signal occurred (selective stop task). The results showed that global stopping was faster than selective stopping in all age groups. Global stopping matured more rapidly than selective stopping. The developmental gain in stopping was considerably more pronounced compared to the loss observed during senescence. All age groups slowed the response on trials without a stop-signal in the stop task compared to trials in the choice task, the elderly in particular. In addition, all age groups slowed on trials following stop-signal trials, except the elderly who did not slow following successful inhibits. By contrast, the slowing following failed inhibits was disproportionally larger in the elderly compared to young adults. Finally, sequential effects did not alter the pattern of performance adjustments. The results were interpreted in terms of developmental change in the balance between proactive and reactive control. PMID:22180746

Acquisition of initial /s/-stop and stop-/s/sequences in Greek.

PubMed

Syrika, Asimina; Nicolaidis, Katerina; Edwards, Jan; Beckman, Mary E

2011-09-01

Previous work on children's acquisition of complex sequences points to a tendency for affricates to be acquired before clusters, but there is no clear evidence of a difference in order of acquisition between clusters with /s/ that violate the Sonority Sequencing Principle (SSP), such as /s/ followed by stop in onset position, and other clusters that obey the SSP. One problem with studies that have compared the acquisition of SSP-obeying and SSP-violating clusters is that the component sounds in the two types of sequences were different.This paper examines the acquisition of initial /s/-stop and stop-/s/ sequences by sixty Greek children aged 2 through 5 years. Results showed greater accuracy for the /s/-stop relative to the stop-/s/ sequences, but no difference in accuracy between /ts/, which is usually analyzed as an affricate in Greek, and the other stop-/s/ sequences. Moreover, errors for the /s/-stop sequences and /ts/ primarily involved stop substitutions, whereas errors for /ps/ and /ks/ were more variable and often involved fricative substitutions, a pattern which may have a perceptual explanation. Finally, /ts/ showed a distinct temporal pattern relative to the stop-/s/ clusters /ps/ and /ks/, similar to what has been reported for productions of Greek adults.

Scientific Communication and the Unified Laboratory Sequence1

NASA Astrophysics Data System (ADS)

Silverstein, Todd P.; Hudak, Norman J.; Chapple, Frances H.; Goodney, David E.; Brink, Christina P.; Whitehead, Joyce P.

1997-02-01

The "Temperature Dependent Relaxation Kinetics" lab was first implemented in 1987; it uses stopped-flow pH jump techniques to determine rate constants and activation parameters (H, S, G) for a reaction mechanism. Two new experiments (Monoamine Oxidase, and Molecular Modeling) will be implemented in the fall of 1997. The "Monoamine Oxidase" project uses chromatography and spectrophotometry to purify and characterize the enzyme. Subsequent photometric assays explore the enzyme's substrate specificity, activation energy, and denaturation. Finally, in the "Molecular Modeling"project, students characterize enzyme - substrate and drug - receptor interactions. Energy minimization protocols are used to make predictions about protein structure and ligand binding, and to explore pharmacological and biomedical implications. With these additions, the twelve Unified Laboratory projects introduce our chemistry majors to nearly all of the instrumental methods commonly encountered in modern chemistry.

Measured values of coal mine stopping resistance

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

Oswald, N.; Prosser, B.; Ruckman, R.

2008-12-15

As coal mines become larger, the number of stoppings in the ventilation system increases. Each stopping represents a potential leakage path which must be adequately represented in the ventilation model. Stopping resistance can be calculated using two methods, the USBM method, used to determine a resistance for a single stopping, and the MVS technique, in which an average resistance is calculated for multiple stoppings. Through MVS data collected from ventilation surveys of different subsurface coal mines, average resistances for stoppings were determined for stopping in poor, average, good, and excellent conditions. The calculated average stoppings resistance were determined for concretemore » block and Kennedy stopping. Using the average stopping resistance, measured and calculated using the MVS method, provides a ventilation modeling tool which can be used to construct more accurate and useful ventilation models. 3 refs., 3 figs.« less

Effectiveness of a web-based self-help smoking cessation intervention: protocol of a randomised controlled trial.

PubMed

Kramer, Jeannet Jam; Willemsen, Marc C; Conijn, Barbara; van Emst, Andrée J; Brunsting, Suzanne; Riper, Heleen

2009-01-22

Cigarette smoking is a major risk factor for many chronic and fatal illnesses. Stopping smoking directly reduces those risks. The aim of this study is to investigate the effectiveness of a web-based interactive self-help programme for smoking cessation, known as the StopSite, by comparing it to an online self-help guide. Both interventions were based on cognitive-behavioural and self-control principles, but the former provided exercises, feedback and interactive features such as one-to-one chatrooms and a user forum, which facilitated mutual support and experience sharing. We conducted a randomised controlled trial to compare the interactive intervention with the self-help guide. The primary outcome measure was prolonged abstinence from smoking. Secondary outcomes were point-prevalence abstinence, number of cigarettes smoked, and incidence of quit attempts reported at follow-up assessments. Follow-up assessments took place three and six months after a one-month grace period for starting the intervention after baseline. Analyses were based on intention-to-treat principles using a conservative imputation method for missing data, whereby non-responders were classified as smokers. The trial should add to the body of knowledge on the effectiveness of web-based self-help smoking cessation interventions. Effective web-based programmes can potentially help large numbers of smokers to quit, thus having a major public health impact. ISRCTN74423766.

Failsafe automation of Phase II clinical trial interim monitoring for stopping rules.

PubMed

Day, Roger S

2010-02-01

In Phase II clinical trials in cancer, preventing the treatment of patients on a study when current data demonstrate that the treatment is insufficiently active or too toxic has obvious benefits, both in protecting patients and in reducing sponsor costs. Considerable efforts have gone into experimental designs for Phase II clinical trials with flexible sample size, usually implemented by early stopping rules. The intended benefits will not ensue, however, if the design is not followed. Despite the best intentions, failures can occur for many reasons. The main goal is to develop an automated system for interim monitoring, as a backup system supplementing the protocol team, to ensure that patients are protected. A secondary goal is to stimulate timely recording of patient assessments. We developed key concepts and performance needs, then designed, implemented, and deployed a software solution embedded in the clinical trials database system. The system has been in place since October 2007. One clinical trial tripped the automated monitor, resulting in e-mails that initiated statistician/investigator review in timely fashion. Several essential contributing activities still require human intervention, institutional policy decisions, and institutional commitment of resources. We believe that implementing the concepts presented here will provide greater assurance that interim monitoring plans are followed and that patients are protected from inadequate response or excessive toxicity. This approach may also facilitate wider acceptance and quicker implementation of new interim monitoring algorithms.

Dietary approaches to stop hypertension diet and obesity: A cross-sectional study of Iranian children and adolescents.

PubMed

Golpour-Hamedani, Sahar; Mohammadifard, Noushin; Khosravi, Alireza; Feizi, Awat; Safavi, Sayyed Morteza

2017-01-01

Few studies have investigated the effects of dietary approaches to stop hypertension (DASH) diet on obesity in children. The present study was conducted to examine adherence to the DASH diet in relation to obesity in children and adolescents, Isfahan, Iran. A cross-sectional study was carried out among 456 children aged 11-18 years who were selected by random cluster sampling method. Dietary intakes were assessed using a validated Food Frequency Questionnaire (FFQ). The DASH score was constructed based on food items emphasized or minimized in the DASH diet. Anthropometric measurements were conducted based on standard protocols. General and abdominal obesity were defined based on body mass index ≥ 95th percentiles and waist: height ratio of more than 0.5, respectively. Higher adherence to DASH diet was inversely associated with general obesity (odds ratioT1 vs. T3 3.34, 95% confidence interval 1.28-8.75); however, after controlling for confounding factors, this association disappeared. Furthermore, higher adherence to DASH diet was negatively associated with central obesity in children, but the relation was not statistically significant. We concluded that there was an inverse nonsignificant association between adherence to DASH diet and general obesity indices after adjustment for potential confounders. Further, well-designed randomized clinical trial studies are suggested to find out the effect of DASH diet on obesity obviously.

20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

Code of Federal Regulations, 2011 CFR

2011-04-01

... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

Code of Federal Regulations, 2013 CFR

2013-04-01

... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop...

20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

Code of Federal Regulations, 2014 CFR

2014-04-01

... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop...

20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

Code of Federal Regulations, 2010 CFR

2010-04-01

... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

Code of Federal Regulations, 2012 CFR

2012-04-01

... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop...

Selection and stopping in voluntary action: A meta-analysis and combined fMRI study☆

PubMed Central

Rae, Charlotte L.; Hughes, Laura E.; Weaver, Chelan; Anderson, Michael C.; Rowe, James B.

2014-01-01

Voluntary action control requires selection of appropriate responses and stopping of inappropriate responses. Selection and stopping are often investigated separately, but they appear to recruit similar brain regions, including the pre-supplementary motor area (preSMA) and inferior frontal gyrus. We therefore examined the evidence for overlap of selection and stopping using two approaches: a meta-analysis of existing studies of selection and stopping, and a novel within-subject fMRI study in which action selection and a stop signal task were combined factorially. The novel fMRI study also permitted us to investigate hypotheses regarding a common mechanism for selection and stopping. The preSMA was identified by both methods as common to selection and stopping. However, stopping a selected action did not recruit preSMA more than stopping a specified action, nor did stop signal reaction times differ significantly across the two conditions. These findings suggest that the preSMA supports both action selection and stopping, but the two processes may not require access to a common inhibition mechanism. Instead, the preSMA might represent information about potential actions that is used in both action selection and stopping in order to resolve conflict between competing available responses. PMID:24128740

Initial Stop Voicing in Bilingual Children With Cochlear Implants and Their Typically Developing Peers With Normal Hearing.

PubMed

Bunta, Ferenc; Goodin-Mayeda, C Elizabeth; Procter, Amanda; Hernandez, Arturo

2016-08-01

This study focuses on stop voicing differentiation in bilingual children with normal hearing (NH) and their bilingual peers with hearing loss who use cochlear implants (CIs). Twenty-two bilingual children participated in our study (11 with NH, M age = 5;1 [years;months], and 11 with CIs, M hearing age = 5;1). The groups were matched on hearing age and a range of demographic variables. Single-word picture elicitation was used with word-initial singleton stop consonants. Repeated measures analyses of variance with three within-subject factors (language, stop voicing, and stop place of articulation) and one between-subjects factor (NH vs. CI user) were conducted with voice onset time and percentage of prevoiced stops as dependent variables. Main effects were statistically significant for language, stop voicing, and stop place of articulation on both voice onset time and prevoicing. There were no significant main effects for NH versus CI groups. Both children with NH and with CIs differentiated stop voicing in their languages and by stop place of articulation. Stop voicing differentiation was commensurate across the groups of children with NH versus CIs. Stop voicing differentiation is accomplished in a similar fashion by bilingual children with NH and CIs, and both groups differentiate stop voicing in a language-specific fashion.

Reducing the number of CTs performed to monitor personalized dosimetry during peptide receptor radionuclide therapy (PRRT).

PubMed

Chicheportiche, Alexandre; Artoul, Faozi; Schwartz, Arnon; Grozinsky-Glasberg, Simona; Meirovitz, Amichay; Gross, David J; Godefroy, Jeremy

2018-06-19

Peptide receptor radionuclide therapy (PRRT) with [ 177 Lu]-DOTA-TATE is an effective treatment of neuroendocrine tumors (NETs). After each cycle of treatment, patient dosimetry evaluates the radiation dose to the risk organs, kidneys, and bone marrow, the most radiosensitive tissues. Absorbed doses are calculated from the radioactivity in the blood and from single photon emission computed tomography (SPECT) images corrected by computed tomography (CT) acquired after each course of treatment. The aim of this work is to assess whether the dosimetry along all treatment cycles can be calculated using a single CT. We hypothesize that the absorbed doses to the risk organs calculated with a single CT will be accurate enough to correctly manage the patients, i.e., whether or not to continue PRRT. Twenty-four patients diagnosed with metastatic NETs undergoing PRRT with [ 177 Lu]-DOTA-TATE were retrospectively included in this study. We compared radiation doses to the kidneys and bone marrow using two protocols. In the "classical" one, dosimetry is calculated based on a SPECT and a CT after each treatment cycle. In the new protocol, dosimetry is calculated based on a SPECT study after each cycle but with the first acquired CT for all cycles. The decision whether or not to stop PRRT because of unsafe absorbed dose to the risk organs would have been the same had the classical or the new protocol been used. The agreement between the cumulative doses to the kidneys and bone marrow obtained from the two protocols was excellent with Pearson's correlation coefficients r = 0.95 and r = 0.99 (P < 0.0001) and mean relative differences of 5.30 ± 6.20% and 0.48 ± 4.88%, respectively. Dosimetry calculations for a given patient can be done using a single CT registered to serial SPECTs. This new protocol reduces the need for a hybrid camera in the follow-up of patients receiving [ 177 Lu]-DOTA-TATE.

A protocol for searching the most probable phase-retrieved maps in coherent X-ray diffraction imaging by exploiting the relationship between convergence of the retrieved phase and success of calculation.

PubMed

Sekiguchi, Yuki; Hashimoto, Saki; Kobayashi, Amane; Oroguchi, Tomotaka; Nakasako, Masayoshi

2017-09-01

Coherent X-ray diffraction imaging (CXDI) is a technique for visualizing the structures of non-crystalline particles with size in the submicrometer to micrometer range in material sciences and biology. In the structural analysis of CXDI, the electron density map of a specimen particle projected along the direction of the incident X-rays can be reconstructed only from the diffraction pattern by using phase-retrieval (PR) algorithms. However, in practice, the reconstruction, relying entirely on the computational procedure, sometimes fails because diffraction patterns miss the data in small-angle regions owing to the beam stop and saturation of the detector pixels, and are modified by Poisson noise in X-ray detection. To date, X-ray free-electron lasers have allowed us to collect a large number of diffraction patterns within a short period of time. Therefore, the reconstruction of correct electron density maps is the bottleneck for efficiently conducting structure analyses of non-crystalline particles. To automatically address the correctness of retrieved electron density maps, a data analysis protocol to extract the most probable electron density maps from a set of maps retrieved from 1000 different random seeds for a single diffraction pattern is proposed. Through monitoring the variations of the phase values during PR calculations, the tendency for the PR calculations to succeed when the retrieved phase sets converged on a certain value was found. On the other hand, if the phase set was in persistent variation, the PR calculation tended to fail to yield the correct electron density map. To quantify this tendency, here a figure of merit for the variation of the phase values during PR calculation is introduced. In addition, a PR protocol to evaluate the similarity between a map of the highest figure of merit and other independently reconstructed maps is proposed. The protocol is implemented and practically examined in the structure analyses for diffraction patterns from aggregates of gold colloidal particles. Furthermore, the feasibility of the protocol in the structure analysis of organelles from biological cells is examined.

A customized protocol to assess bone quality in the metacarpal head, metacarpal shaft and distal radius: a high resolution peripheral quantitative computed tomography precision study.

PubMed

Feehan, Lynne; Buie, Helen; Li, Linda; McKay, Heather

2013-12-24

High Resolution-Peripheral Quantitative Computed Tomography (HR-pQCT) is an emerging technology for evaluation of bone quality in Rheumatoid Arthritis (RA). However, there are limitations with standard HR-pQCT imaging protocols for examination of regions of bone commonly affected in RA. We developed a customized protocol for evaluation of volumetric bone mineral density (vBMD) and microstructure at the metacarpal head (MH), metacarpal shaft (MS) and ultra-ultra-distal (UUD) radius; three sites commonly affected in RA. The purpose was to evaluate short-term measurement precision for bone density and microstructure at these sites. 12 non-RA participants, individuals likely to have no pre-existing bone damage, consented to participate [8 females, aged 23 to 71 y [median (IQR): 44 (28) y]. The custom protocol includes more comfortable/stable positioning and adapted cortical segmentation and direct transformation analysis methods. Dominant arm MH, MS and UUD radius scans were completed on day one; repeated twice (with repositioning) three to seven days later. Short-term precision for repeated measures was explored using intraclass correlational coefficient (ICC), mean coefficient of variation (CV%), root mean square coefficient of variation (RMSCV%) and least significant change (LSC%95). Bone density and microstructure precision was excellent: ICCs varied from 0.88 (MH2 trabecular number) to .99 (MS3 polar moment of inertia); CV% varied from < 1 (MS2 vBMD) to 6 (MS3 marrow space diameter); RMSCV% varied from < 1 (MH2 full bone vBMD) to 7 (MS3 marrow space diameter); and LSC%95 varied from 2 (MS2 full bone vBMD to 21 (MS3 marrow space diameter). Cortical porosity measures were the exception; RMSCV% varying from 19 (MS3) to 42 (UUD). No scans were stopped for discomfort. 5% (5/104) were repeated due to motion during imaging. 8% (8/104) of final images had motion artifact graded > 3 on 5 point scale. In our facility, this custom protocol extends the potential for in vivo HR-pQCT imaging to assess, with high precision, regional differences in bone quality at three sites commonly affected in RA. Our methods are easy to adopt and we recommend other users of HR-pQCT consider this protocol for further evaluations of its precision and feasibility in their imaging facilities.

Should I Stop or Should I Go? The Role of Associations and Expectancies

PubMed Central

2015-01-01

Following exposure to consistent stimulus–stop mappings, response inhibition can become automatized with practice. What is learned is less clear, even though this has important theoretical and practical implications. A recent analysis indicates that stimuli can become associated with a stop signal or with a stop goal. Furthermore, expectancy may play an important role. Previous studies that have used stop or no-go signals to manipulate stimulus–stop learning cannot distinguish between stimulus-signal and stimulus-goal associations, and expectancy has not been measured properly. In the present study, participants performed a task that combined features of the go/no-go task and the stop-signal task in which the stop-signal rule changed at the beginning of each block. The go and stop signals were superimposed over 40 task-irrelevant images. Our results show that participants can learn direct associations between images and the stop goal without mediation via the stop signal. Exposure to the image-stop associations influenced task performance during training, and expectancies measured following task completion or measured within the task. But, despite this, we found an effect of stimulus–stop learning on test performance only when the task increased the task-relevance of the images. This could indicate that the influence of stimulus–stop learning on go performance is strongly influenced by attention to both task-relevant and task-irrelevant stimulus features. More generally, our findings suggest a strong interplay between automatic and controlled processes. PMID:26322688

Alignment-based and alignment-free methods converge with experimental data on amino acids coded by stop codons at split between nuclear and mitochondrial genetic codes.

PubMed

Seligmann, Hervé

2018-05-01

Genetic codes mainly evolve by reassigning punctuation codons, starts and stops. Previous analyses assuming that undefined amino acids translate stops showed greater divergence between nuclear and mitochondrial genetic codes. Here, three independent methods converge on which amino acids translated stops at split between nuclear and mitochondrial genetic codes: (a) alignment-free genetic code comparisons inserting different amino acids at stops; (b) alignment-based blast analyses of hypothetical peptides translated from non-coding mitochondrial sequences, inserting different amino acids at stops; (c) biases in amino acid insertions at stops in proteomic data. Hence short-term protein evolution models reconstruct long-term genetic code evolution. Mitochondria reassign stops to amino acids otherwise inserted at stops by codon-anticodon mismatches (near-cognate tRNAs). Hence dual function (translation termination and translation by codon-anticodon mismatch) precedes mitochondrial reassignments of stops to amino acids. Stop ambiguity increases coded information, compensates endocellular mitogenome reduction. Mitochondrial codon reassignments might prevent viral infections. Copyright © 2018 Elsevier B.V. All rights reserved.

Improving stopping construction to minimize leakage

PubMed Central

Grau, Roy H.; Mazzella, Andrew L.; Martikainen, Anu L.

2015-01-01

The proper sealing of stoppings is an important step in reducing leakage from the intake to the return airways. Leakage and the subsequent loss of ventilation resulting from improperly sealed stoppings can lead to unhealthy and unsafe working conditions. The research presented in this paper investigates the total leakage of a stopping, including air leakage through the stopping, at the stopping perimeter, and through the coalbed. The study also examines sealing considerations for stoppings that are constructed under roof control screen, the effects that wooden wedges had on inhibiting efficient application of polyurethane foam sealant, and airflow leakage through the surrounding coal. The work involved building a stopping in a dead end room of the NIOSH Safety Research Coal Mine and then pressurising the room using compressed air. Stopping leakage was evaluated by measuring air pressure loss in the enclosed room due to the air leakage. Part of the research utilises a diluted soap solution that was applied to the stopping and the surrounding coal to detect air leakage signified by bubble formations. The results show that stopping leakage can be minimised with proper sealing PMID:26379366

Interventions for the prevention of OHSS in ART cycles: an overview of Cochrane reviews.

PubMed

Mourad, Selma; Brown, Julie; Farquhar, Cindy

2017-01-23

Ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology (ART) cycles is a treatment-induced disease that has an estimated prevalence of 20% to 33% in its mild form and 3% to 8% in its moderate or severe form. These numbers might even be higher for high-risk women such as those with polycystic ovaries or a high oocyte yield from ovum pickup. The objective of this overview is to identify and summarise all evidence from Cochrane systematic reviews on interventions for prevention or treatment of moderate, severe and overall OHSS in couples with subfertility who are undergoing ART cycles. Published Cochrane systematic reviews reporting on moderate, severe or overall OHSS as an outcome in ART cycles were eligible for inclusion in this overview. We also identified Cochrane submitted protocols and title registrations for future inclusion in the overview. The evidence is current to 12 December 2016. We identified reviews, protocols and titles by searching the Cochrane Gynaecology and Fertility Group Database of Systematic Reviews and Archie (the Cochrane information management system) in July 2016 on the effectiveness of interventions for outcomes of moderate, severe and overall OHSS. We undertook in duplicate selection of systematic reviews, data extraction and quality assessment. We used the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the quality of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables. We included a total of 27 reviews in this overview. The reviews were generally of high quality according to AMSTAR ratings, and included studies provided evidence that ranged from very low to high in quality. Ten reviews had not been updated in the past three years. Seven reviews described interventions that provided a beneficial effect in reducing OHSS rates, and we categorised one additional review as 'promising'. Of the effective interventions, all except one had no detrimental effect on pregnancy outcomes. Evidence of at least moderate quality indicates that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Metformin treatment before and during an ART cycle for women with PCOS (moderate-quality evidence).• Gonadotrophin-releasing hormone (GnRH) antagonist protocol in ART cycles (moderate-quality evidence).• GnRH agonist (GnRHa) trigger in donor oocyte or 'freeze-all' programmes (moderate-quality evidence). Evidence of low or very low quality suggests that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Clomiphene citrate for controlled ovarian stimulation in ART cycles (low-quality evidence).• Cabergoline around the time of human chorionic gonadotrophin (hCG) administration or oocyte pickup in ART cycles (low-quality evidence).• Intravenous fluids (plasma expanders) around the time of hCG administration or oocyte pickup in ART cycles (very low-quality evidence).• Progesterone for luteal phase support in ART cycles (low-quality evidence).• Coasting (withholding gonadotrophins) - a promising intervention that needs to be researched further for reduction of OHSS.On the basis of this overview, we must conclude that evidence is currently insufficient to support the widespread practice of embryo cryopreservation. Currently, 27 reviews in the Cochrane Library were conducted to report on or to try to report on OHSS in ART cycles. We identified four review protocols but no new registered titles that can potentially be included in this overview in the future. This overview provides the most up-to-date evidence on prevention of OHSS in ART cycles from all currently published Cochrane reviews on ART. Clinicians can use the evidence summarised in this overview to choose the best treatment regimen for individual patients - a regimen that not only reduces the chance of developing OHSS but does not compromise other outcomes such as pregnancy or live birth rate. Review results, however, are limited by the lack of recent primary studies or updated reviews. Furthermore, this overview can be used by policymakers in developing local and regional protocols or guidelines and can reveal knowledge gaps for future research.

Evaluating the Effects of Traffic on Driver Stopping and Turn Signal Use at a Stop Sign: A Systematic Replication

ERIC Educational Resources Information Center

Lebbon, Angela R.; Austin, John; Van Houten, Ron; Malenfant, Louis E.

2007-01-01

The current analyses of observational data found that oncoming traffic substantially affected driver stopping patterns and turn signal use at the target stop sign. The percentage of legal stops and turn signal use by drivers in the presence and absence of traffic was analyzed using a multi-element design. The results showed that legal stops were…

Study protocol for a pragmatic randomised controlled trial evaluating efficacy of a smoking cessation e-‘Tabac Info Service’: ee-TIS trial

PubMed Central

Cambon, L; Bergman, P; Le Faou, Al; Vincent, I; Le Maitre, B; Pasquereau, A; Arwidson, P; Thomas, D; Alla, F

2017-01-01

Introduction A French national smoking cessation service, Tabac Info Service, has been developed to provide an adapted quitline and a web and mobile application involving personalised contacts (eg, questionnaires, advice, activities, messages) to support smoking cessation. This paper presents the study protocol of the evaluation of the application (e-intervention Tabac Info Service (e-TIS)). The primary objective is to assess the efficacy of e-TIS. The secondary objectives are to (1) describe efficacy variations with regard to users' characteristics, (2) analyse mechanisms and contextual conditions of e-TIS efficacy. Methods and analyses The study design is a two-arm pragmatic randomised controlled trial including a process evaluation with at least 3000 participants randomised to the intervention or to the control arm (current practices). Inclusion criteria are: aged 18 years or over, current smoker, having completed the online consent forms, possessing a mobile phone with android or apple systems and using mobile applications, wanting to stop smoking sooner or later. The primary outcome is the point prevalence abstinence of 7 days at 6 months later. Data will be analysed in intention to treat (primary) and per protocol analyses. A logistic regression will be carried out to estimate an OR (95% CI) for efficacy. A multivariate multilevel analysis will explore the influence on results of patients' characteristics (sex, age, education and socioprofessional levels, dependency, motivation, quit experiences) and contextual factors, conditions of use, behaviour change techniques. Ethics and dissemination The study protocol was reviewed by the ethical and deontological institutional review board of the French Institute for Public Health Surveillance on 18 April 2016. The findings of this study will allow us to characterise the efficacy of e-TIS and conditions of its efficacy. These findings will be disseminated through peer-reviewed articles. Trial registration number NCT02841683; Pre-results. PMID:28237958

Effects of stop-signal probability in the stop-signal paradigm: the N2/P3 complex further validated.

PubMed

Ramautar, J R; Kok, A; Ridderinkhof, K R

2004-11-01

The aim of this study was to examine the effects of frequency of occurrence of stop signals in the stop-signal paradigm. Presenting stop signals less frequently resulted in faster reaction times to the go stimulus and a lower probability of inhibition. Also, go stimuli elicited larger and somewhat earlier P3 responses when stop signals occurred less frequently. Since the amplitude effect was more pronounced on trials when go signals were followed by fast than slow reactions, it probably reflected a stronger set to produce fast responses. N2 and P3 components to stop signals were observed to be larger and of longer latency when stop signals occurred less frequently. The amplitude enhancement of these N2 and P3 components were more pronounced for unsuccessful than for successful stop-signal trials. Moreover, the successfully inhibited stop trials elicited a frontocentral P3 whereas unsuccessfully inhibited stop trials elicited a more posterior P3 that resembled the classical P3b. P3 amplitude in the unsuccessfully inhibited condition also differed between waveforms synchronized with the stop signal and waveforms synchronized with response onset whereas N2 amplitude did not. Taken together these findings suggest that N2 reflected a greater significance of failed inhibitions after low probability stop signals while P3 reflected continued processing of the erroneous response after response execution.

Implementing Istanbul Protocol standards for forensic evidence of torture in Kyrgyzstan.

PubMed

Moreno, Alejandro; Crosby, Sondra; Xenakis, Stephen; Iacopino, Vincent

2015-02-01

The Kyrgyz government declared a policy of "zero tolerance" for torture and began reforms to stop such practice, a regular occurrence in the country's daily life. This study presents the results of 10 forensic evaluations of individuals alleging torture; they represent 35% of all criminal investigations into torture for the January 2011-July 2012 period. All individuals evaluated were male with an average age of 34 years. Police officers were implicated as perpetrators in all cases. All individuals reported being subjected to threats and blunt force trauma from punches, kicks, and blows with objects such as police batons. The most common conditions documented during the evaluations were traumatic brain injury and chronic seizures. Psychological sequelae included post-traumatic stress disorder and major depressive disorder, which was diagnosed in seven individuals. In all cases, the physical and psychological evidence was highly consistent with individual allegations of abuse. These forensic evaluations, which represent the first ever to be conducted in Kyrgyzstan in accordance with Istanbul Protocol standards, provide critical insight into torture practices in the country. The evaluations indicate a pattern of brutal torture practices and inadequate governmental and nongovernmental forensic evaluations. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Progress in understanding heavy-ion stopping

NASA Astrophysics Data System (ADS)

Sigmund, P.; Schinner, A.

2016-09-01

We report some highlights of our work with heavy-ion stopping in the energy range where Bethe stopping theory breaks down. Main tools are our binary stopping theory (PASS code), the reciprocity principle, and Paul's data base. Comparisons are made between PASS and three alternative theoretical schemes (CasP, HISTOP and SLPA). In addition to equilibrium stopping we discuss frozen-charge stopping, deviations from linear velocity dependence below the Bragg peak, application of the reciprocity principle in low-velocity stopping, modeling of equilibrium charges, and the significance of the so-called effective charge.

Intracranial EEG reveals a time- and frequency-specific role for the right inferior frontal gyrus and primary motor cortex in stopping initiated responses.

PubMed

Swann, Nicole; Tandon, Nitin; Canolty, Ryan; Ellmore, Timothy M; McEvoy, Linda K; Dreyer, Stephen; DiSano, Michael; Aron, Adam R

2009-10-07

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band ( approximately 16 Hz) for successful versus unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping. In addition, the right IFG response occurred 100-250 ms after the stop signal, a time range consistent with a putative inhibitory control process rather than with stop-signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased GABA inhibition in M1. Together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta frequency band in a right IFG/basal ganglia network, with downstream effects on M1.

Intracranial EEG reveals a time– and frequency–specific role for the right inferior frontal gyrus and primary motor cortex in stopping initiated responses

PubMed Central

Swann, Nicole; Tandon, Nitin; Canolty, Ryan; Ellmore, Timothy M; McEvoy, Linda K; Dreyer, Stephen; DiSano, Michael; Aron, Adam R

2009-01-01

Inappropriate response tendencies may be stopped via a specific fronto/basal-ganglia/primary-motor-cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from sub-dural electrodes in four patients while they performed a stop signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band (∼16 Hz) for successful vs. unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping. In addition, the right IFG response occurred 100 - 250 ms after the stop signal – a time range consistent with a putative inhibitory control process, rather than stop signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta-band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased gamma-aminobutyric acid inhibition in M1. Taken together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta-frequency band in a right IFG/basal-ganglia network, with downstream effects on M1. PMID:19812342

STOP-IT: Windows executable software for the stop-signal paradigm.

PubMed

Verbruggen, Frederick; Logan, Gordon D; Stevens, Michaël A

2008-05-01

The stop-signal paradigm is a useful tool for the investigation of response inhibition. In this paradigm, subjects are instructed to respond as fast as possible to a stimulus unless a stop signal is presented after a variable delay. However, programming the stop-signal task is typically considered to be difficult. To overcome this issue, we present software called STOP-IT, for running the stop-signal task, as well as an additional analyzing program called ANALYZE-IT. The main advantage of both programs is that they are a precompiled executable, and for basic use there is no need for additional programming. STOP-IT and ANALYZE-IT are completely based on free software, are distributed under the GNU General Public License, and are available at the personal Web sites of the first two authors or at expsy.ugent.be/tscope/stop.html.

Can I Stop Myself From Having a Wet Dream? (For Teens)

MedlinePlus

... Can I Stop Myself From Having a Wet Dream? KidsHealth / For Teens / Can I Stop Myself From Having a Wet Dream? Print Can I stop myself from having a wet dream? – Tom* You really can't stop wet dreams, ...

Early Action on HFCs Mitigates Future Atmospheric Change

NASA Technical Reports Server (NTRS)

Hurwitz, Margaret M.; Fleming, Eric L.; Newman, Paul A.; Li, Feng; Liang, Qing

2017-01-01

As countries take action to mitigate global warming, both by ratifying the UNFCCC Paris Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases (GHGs), the distinct structure of their atmospheric impacts, and how the timing of potential GHG regulations would affect future changes in atmospheric temperature and ozone. Chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid-21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19K at 80hPa. Three HFC mitigation scenarios demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90 of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

Early Action on HFCs Mitigates Future Atmospheric Change

NASA Astrophysics Data System (ADS)

Hurwitz, Margaret; Fleming, Eric; Newman, Paul; Li, Feng; Liang, Qing

2017-04-01

As countries take action to mitigate global warming, both by ratifying the UNFCCC Paris Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases (GHGs), the distinct structure of their atmospheric impacts, and how the timing of potential GHG regulations would affect future changes in atmospheric temperature and ozone. Chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid-21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19K at 80hPa. Three HFC mitigation scenarios demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90% of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

Water-equivalence of gel dosimeters for radiology medical imaging.

PubMed

Valente, M; Vedelago, J; Chacón, D; Mattea, F; Velásquez, J; Pérez, P

2018-03-08

International dosimetry protocols are based on determinations of absorbed dose to water. Ideally, the phantom material should be water equivalent; that is, it should have the same absorption and scatter properties as water. This study presents theoretical, experimental and Monte Carlo modeling of water-equivalence of Fricke and polymer (NIPAM, PAGAT and itaconic acid ITABIS) gel dosimeters. Mass and electronic densities along with effective atomic number were calculated by means of theoretical approaches. Samples were scanned by standard computed tomography. Photon mass attenuation coefficients and electron stopping powers were examined. Theoretical, Monte Carlo and experimental results confirmed good water-equivalence for all gel dosimeters. Overall variations with respect to water in the low energy radiology range (up to 130 kVp) were found to be less than 3% in average. Copyright © 2018 Elsevier Ltd. All rights reserved.

History and Use of del Nido Cardioplegia Solution at Boston Children’s Hospital

PubMed Central

Matte, Gregory S.; del Nido, Pedro J.

2012-01-01

Abstract: Cardioplegia is an integral and essential method of myocardial protection for patients of all ages requiring cardiac surgery in which the heart must be stopped. Numerous cardioplegia solutions and delivery methods have been developed. The del Nido cardioplegia solution has been in use for 18 years at Boston Children’s Hospital. This is a unique four parts crystalloid to one part whole blood formulation that is generally used in a single-dose fashion. Although the formulation was originally developed for use in pediatric and infant patients, its use for adult cardiac surgery has been expanding. National and international inquiries to our institution regarding this cardioplegia have been increasing over the last 2 years. We present the developmental history, supporting theory, and current protocol for use of what is now referred to as del Nido cardioplegia. PMID:23198389

History and use of del Nido cardioplegia solution at Boston Children's Hospital.

PubMed

Matte, Gregory S; del Nido, Pedro J

2012-09-01

Cardioplegia is an integral and essential method of myocardial protection for patients of all ages requiring cardiac surgery in which the heart must be stopped. Numerous cardioplegia solutions and delivery methods have been developed. The del Nido cardioplegia solution has been in use for 18 years at Boston Children's Hospital. This is a unique four parts crystalloid to one part whole blood formulation that is generally used in a single-dose fashion. Although the formulation was originally developed for use in pediatric and infant patients, its use for adult cardiac surgery has been expanding. National and international inquiries to our institution regarding this cardioplegia have been increasing over the last 2 years. We present the developmental history, supporting theory, and current protocol for use of what is now referred to as del Nido cardioplegia.

Inseparability of Go and Stop in Inhibitory Control: Go Stimulus Discriminability Affects Stopping Behavior.

PubMed

Ma, Ning; Yu, Angela J

2016-01-01

Inhibitory control, the ability to stop or modify preplanned actions under changing task conditions, is an important component of cognitive functions. Two lines of models of inhibitory control have previously been proposed for human response in the classical stop-signal task, in which subjects must inhibit a default go response upon presentation of an infrequent stop signal: (1) the race model, which posits two independent go and stop processes that race to determine the behavioral outcome, go or stop; and (2) an optimal decision-making model, which posits that observers decides whether and when to go based on continually (Bayesian) updated information about both the go and stop stimuli. In this work, we probe the relationship between go and stop processing by explicitly manipulating the discrimination difficulty of the go stimulus. While the race model assumes the go and stop processes are independent, and therefore go stimulus discriminability should not affect the stop stimulus processing, we simulate the optimal model to show that it predicts harder go discrimination should result in longer go reaction time (RT), lower stop error rate, as well as faster stop-signal RT. We then present novel behavioral data that validate these model predictions. The results thus favor a fundamentally inseparable account of go and stop processing, in a manner consistent with the optimal model, and contradicting the independence assumption of the race model. More broadly, our findings contribute to the growing evidence that the computations underlying inhibitory control are systematically modulated by cognitive influences in a Bayes-optimal manner, thus opening new avenues for interpreting neural responses underlying inhibitory control.

Neural Architecture of Selective Stopping Strategies: Distinct Brain Activity Patterns Are Associated with Attentional Capture But Not with Outright Stopping.

PubMed

Sebastian, Alexandra; Rössler, Kora; Wibral, Michael; Mobascher, Arian; Lieb, Klaus; Jung, Patrick; Tüscher, Oliver

2017-10-04

In stimulus-selective stop-signal tasks, the salient stop signal needs attentional processing before genuine response inhibition is completed. Differential prefrontal involvement in attentional capture and response inhibition has been linked to the right inferior frontal junction (IFJ) and ventrolateral prefrontal cortex (VLPFC), respectively. Recently, it has been suggested that stimulus-selective stopping may be accomplished by the following different strategies: individuals may selectively inhibit their response only upon detecting a stop signal (independent discriminate then stop strategy) or unselectively whenever detecting a stop or attentional capture signal (stop then discriminate strategy). Alternatively, the discrimination process of the critical signal (stop vs attentional capture signal) may interact with the go process (dependent discriminate then stop strategy). Those different strategies might differentially involve attention- and stopping-related processes that might be implemented by divergent neural networks. This should lead to divergent activation patterns and, if disregarded, interfere with analyses in neuroimaging studies. To clarify this crucial issue, we studied 87 human participants of both sexes during a stimulus-selective stop-signal task and performed strategy-dependent functional magnetic resonance imaging analyses. We found that, regardless of the strategy applied, outright stopping displayed indistinguishable brain activation patterns. However, during attentional capture different strategies resulted in divergent neural activation patterns with variable activation of right IFJ and bilateral VLPFC. In conclusion, the neural network involved in outright stopping is ubiquitous and independent of strategy, while different strategies impact on attention-related processes and underlying neural network usage. Strategic differences should therefore be taken into account particularly when studying attention-related processes in stimulus-selective stopping. SIGNIFICANCE STATEMENT Dissociating inhibition from attention has been a major challenge for the cognitive neuroscience of executive functions. Selective stopping tasks have been instrumental in addressing this question. However, recent theoretical, cognitive and behavioral research suggests that different strategies are applied in successful execution of the task. The underlying strategy-dependent neural networks might differ substantially. Here, we show evidence that, regardless of the strategy used, the neural network involved in outright stopping is ubiquitous. However, significant differences can only be found in the attention-related processes underlying those different strategies. Thus, when studying attentional processing of salient stop signals, strategic differences should be considered. In contrast, the neural networks implementing outright stopping seem less or not at all affected by strategic differences. Copyright © 2017 the authors 0270-6474/17/379786-10$15.00/0.

Synthesis and Characterization of Mixed-Conducting Corrosion Resistant Oxide Supports

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

Ramani, Vijay K.

An extensive search and evaluation of electrochemically stable catalyst supports (including metal oxides like RuO2-SiO2, RuO2-TiO2, and ITO was perfomed during the 4 years of the project. The suports were also catalyzed by deposition of Pt and tested for its performance and electrochemical stability in RDE and fuel cell experiments. For testing the electrochemical stability and fuel cell performance of the catalysts and supports, we have employed the protocols in use at the Department of Energy and Nissan Technological Center North America (NTCNA). The use of such procedures allows a precise and reproducible estimation of the performance and stability ofmore » the materials and permits comparisons among laboratories and DOE funded projects. RuO2-SiO2 catalyst supports showed no loss in surface area during start-stop stability tests that were performed by cycling the electrode potential between 0 V to 1.8 V for 1000 cycles. Catalyzed support (40% Pt/RuO2-SiO2; 1:1 mole ratio) were tested in a PEFC, resulting in a current density of 750 mA/cm2 at 0.6 Volts, and a maximum power density of 570 mW/cm2. Measurements were conducted at 80 ºC with 75% relative humidity of the inlet gases (H2/O2); Pt loadings were 0.4 mg/cm2 at the cathode and 0.2 mg/cm2 at the anode. Start-stop stability tests for support and catalyzed support performed in RDE and PEFC set-ups have confirmed RuO2-TiO2 support stability. The beginning of life performance was exactly equal to end of life performance (in an MEA that has been subjected to severe start-stop cycling for 10,000 start/stop cycles between 1 V to 1.5 V). This result was in sharp contrast to baseline Pt/C catalyst that showed significant performance deterioration after accelerated stability tests. The Pt/TRO showed minimal loss in performance upon exposure to start-stop cycles. The loss in cell voltage at 1 A/cm2 at 100% RH was almost 700 mV for Pt/C whereas it was only ca. 15 mV for Pt/TRO. 40% RH data (of inlet gases) revealed a similar trend in terms of stability – exceptional stability for Pt/TRO as opposed to very poor stability for Pt/HSAC. These observations were attributed to the much higher stability of the TRO support compared to Carbon. The carbon dioxide concentration in the cathode exit stream during the accelerated degradation test with Pt/TRO (start-stop protocol) was extremely low (between 3 to 10 ppm of CO2). In contrast, the CO2 emission levels from a conventional Pt/C catalyst were found to be approx. 200 ppm. This observation was a clear indicator that the main source of carbon being oxidized to carbon dioxide in an MEA was the carbon catalyst support, and not the gas diffusion layer or the graphite flow fields. Indium tin oxide (ITO) was also evaluated as a catalyst support for PEFCs. Pt/ITO was very stable under start-up/shutdown accelerated degradation protocol (RDE tests in perchloric acid). The ECSA change was less than 4% over 10,000 cycles. The load cycling accelerated protocol (from 0.6 to 0.95 V vs. RHE) resulted in a loss of approximately 34% of the initial ECSA after 10,000 cycles. However, fuel cell testing resulted in a very low performing catalyst. XPS spectroscopy was employed to investigate the changes in the catalysts occuring during fuel cell operation. It was observed a shift of In 3d5/2 and In 3d3/2 peaks towards higher binding energies. This can be explained by the formation of hydroxides or oxy-hydroxides in the surface of the catalyst. O1s spectrum for Pt/ITO catalyst after being operated in the fuel cell, also confirmed the formation of significant amounts of surface hydroxides (12 to 16%). The presence of surface hydroxides in the catalyst increased the electrode resistivity affecting fuel cell performance. NTCNA performed a detailed analysis of transport phenomena (reactants and products to/from the Pt active sites) in both commercial catalyst and Pt/RTO (in order to have a better understanding at the basic level). The proton resistance (Rionomer) in Pt/C and Pt/RTO cathode catalyst layers were 150 and 12 mΩ-cm2, respectively. Pt/RTO catalyst layer has about an order or magnitude lower proton transfer resistance than Pt/C catalyst layer. Since the ionomer/support ratio that was used in formulating the ink for both catalysts was the same (0.9), it is expected that the volumetric coverage of ionomer of both catalysts will be significantly different due to the disparity in the surface areas (Pt/C had ~ 800 m2/g, while Pt/RTO had ~ 50 m2/g). The differences in the ionomer volumetric coverage and the ionomer film thickness may explain the significantly higher proton conductivity in the Pt/RTO catalyst layer when compared to Pt/HSAC. It is therefore very important to optimize the ionomer loadings when synthesizing new catalyst supports (and never rely on values for carbon-based commercial catalysts). Finally, NTCNA has elaborated a cost model for non-carbon support materials considering their durability benefits. Material costs for production of Pt/ RuO2-TiO2 electrodes were compared to Pt/C. RuO2-TiO2 support was more expensive than carbon but the total material cost was still dominated by platinum cost. Though ruthenium is considered a precious metal, its cost is far less than platinum. It should also be noted that ruthenium only makes up 38% of the mass of the support, while the rest is inexpensive TiO2. After considering the durability advantages of Pt/RTO, cost model showed that even with almost double the Pt loading (0.35 vs 0.18 mgPt/cm2), Pt/RTO ($22.7/kWnet) is only slightly more expensive than Pt/C ($21.9/kWnet).« less

48 CFR 42.1303 - Stop-work orders.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Stop-work orders. 42.1303... CONTRACT ADMINISTRATION AND AUDIT SERVICES Suspension of Work, Stop-Work Orders, and Government Delay of Work 42.1303 Stop-work orders. (a) Stop-work orders may be used, when appropriate, in any negotiated...

48 CFR 42.1303 - Stop-work orders.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Stop-work orders. 42.1303... CONTRACT ADMINISTRATION AND AUDIT SERVICES Suspension of Work, Stop-Work Orders, and Government Delay of Work 42.1303 Stop-work orders. (a) Stop-work orders may be used, when appropriate, in any negotiated...

Proactive and Reactive Stopping When Distracted: An Attentional Account

PubMed Central

2014-01-01

Performance in response inhibition paradigms is typically attributed to inhibitory control. Here we examined the idea that stopping may largely depend on the outcome of a sensory detection process. Subjects performed a speeded go task, but they were instructed to withhold their response when a visual stop signal was presented. The stop signal could occur in the center of the screen or in the periphery. On half of the trials, perceptual distractors were presented throughout the trial. We found that these perceptual distractors impaired stopping, especially when stop signals could occur in the periphery. Furthermore, the effect of the distractors on going was smallest in the central stop-signal condition, medium in a condition in which no signals could occur, and largest in the condition in which stop signals could occur in the periphery. The results show that an important component of stopping is finding a balance between ignoring irrelevant information in the environment and monitoring for the occurrence of occasional stop signals. These findings highlight the importance of sensory detection processes when stopping and could shed new light on a range of phenomena and findings in the response inhibition literature. PMID:24842070

The characteristics of vasa gene from Japanese sea bass ( Lateolabrax japonicas) and its response to the external hormones

NASA Astrophysics Data System (ADS)

Chi, Meili; Wen, Haishen; Ni, Meng; Qian, Kun; Zhang, Pei; Chai, Senhao

2015-08-01

The RNA helicase Vasa is an important regulator of primordial germ cell development. Its function in mature fish, especially the hormone-related differences in maturing male fish has seldom been documented. In this study, a full length cDNA sequence of the vasa gene was cloned from Japanese sea bass, Lateolabrax japonicas, and it was named jsb-vasa. Homology analysis showed that jsb-vasa was closely related to its teleost homologs. The spatial distribution of jsb-vasa indicated that it was only highly expressed in testis, showing its germ cell-specific expression pattern. During the testicular development cycle, jsb-vasa was highly expressed during early period of spermatogenesis, and reduced when spermatogenesis advanced. In addition, the jsb-vasa gene expression was significantly inhibited at 6 h, 12 h and 24 h after injecting hCG (human chorionic gonadotropin) and GnRHa (Gonadotropin-releasing hormone analogue), indicating that jsb-vasa gene may play an important role in spermatogenesis of Japanese sea bass, and be under the regulation of external sex hormones.

The Lower Extremity Biomechanics of Single- and Double-Leg Stop-Jump Tasks

PubMed Central

2011-01-01

The anterior cruciate ligament (ACL) injury is a common occurrence in sports requiring stop-jump tasks. Single- and double-leg stop-jump techniques are frequently executed in sports. The higher risk of ACL injury in single-leg drop landing task compared to a double-leg drop landing task has been identified. However the injury bias between single- and double-leg landing techniques has not been investigated for stop-jump tasks. The purpose of this study was to determine the differences between single- and double-leg stop-jump tasks in knee kinetics that were influenced by the lower extremity kinematics during the landing phase. Ground reaction force, lower extremity kinematics, and knee kinetics data during the landing phase were obtained from 10 subjects performing single- and double-leg stop-jump tasks, using motion-capture system and force palates. Greater peak posterior and vertical ground reaction forces, and peak proximal tibia anterior and lateral shear forces (p < 0.05) during landing phase were observed of single-leg stop-jump. Single-leg stop-jump exhibited smaller hip and knee flexion angle, and knee flexion angular velocity at initial foot contact with the ground (p < 0.05). We found smaller peak hip and knee flexion angles (p < 0.05) during the landing phase of single-leg stop-jump. These results indicate that single-leg landing may have higher ACL injury risk than double-leg landing in stop-jump tasks that may be influenced by the lower extremity kinematics during the landing phase. Key points Non-contact ACL injuries are more likely to occur during the single-leg stop-jump task than during the double-leg stop-jump task. Single-leg stop-jump exhibited greater peak proximal tibia anterior and lateral shear forces, and peak posterior and vertical ground reaction forces during the landing phase than the double-leg stop-jump task. Single-leg stop-jump exhibited smaller hip flexion angle, knee flexion angle, and knee flexion angular velocity at initial foot contact with the ground. Single-leg stop-jump exhibited greater peak knee extension and valgus moment during the landing phase than the double-leg stop-jump task. Single-leg stop-jump extended the hip joint at initial foot contact with the ground. PMID:24149308

Focusing the lens of language experience: Perception of Ma'di stops by Greek and English bilinguals and monolinguals

PubMed Central

Antoniou, Mark; Best, Catherine T.; Tyler, Michael D.

2013-01-01

Monolingual listeners are constrained by native language experience when categorizing and discriminating unfamiliar non-native contrasts. Are early bilinguals constrained in the same way by their two languages, or do they possess an advantage? Greek–English bilinguals in either Greek or English language mode were compared to monolinguals on categorization and discrimination of Ma'di stop-voicing distinctions that are non-native to both languages. As predicted, English monolinguals categorized Ma'di prevoiced plosive and implosive stops and the coronal voiceless stop as English voiced stops. The Greek monolinguals categorized the Ma'di short-lag voiceless stops as Greek voiceless stops, and the prevoiced implosive stops and the coronal prevoiced stop as Greek voiced stops. Ma'di prenasalized stops were uncategorized. Greek monolinguals discriminated the non-native voiced-voiceless contrasts very well, whereas the English monolinguals did poorly. Bilinguals were given all oral and written instructions either in English or in Greek (language mode manipulation). Each language mode subgroup categorized Ma'di stop-voicing comparably to the corresponding monolingual group. However, the bilinguals’ discrimination was unaffected by language mode: both subgroups performed intermediate to the monolinguals for the prevoiced-voiceless contrast. Thus, bilinguals do not possess an advantage for unfamiliar non-native contrasts, but are nonetheless uniquely configured language users, differing from either monolingual group. PMID:23556605

Focusing the lens of language experience: perception of Ma'di stops by Greek and English bilinguals and monolinguals.

PubMed

Antoniou, Mark; Best, Catherine T; Tyler, Michael D

2013-04-01

Monolingual listeners are constrained by native language experience when categorizing and discriminating unfamiliar non-native contrasts. Are early bilinguals constrained in the same way by their two languages, or do they possess an advantage? Greek-English bilinguals in either Greek or English language mode were compared to monolinguals on categorization and discrimination of Ma'di stop-voicing distinctions that are non-native to both languages. As predicted, English monolinguals categorized Ma'di prevoiced plosive and implosive stops and the coronal voiceless stop as English voiced stops. The Greek monolinguals categorized the Ma'di short-lag voiceless stops as Greek voiceless stops, and the prevoiced implosive stops and the coronal prevoiced stop as Greek voiced stops. Ma'di prenasalized stops were uncategorized. Greek monolinguals discriminated the non-native voiced-voiceless contrasts very well, whereas the English monolinguals did poorly. Bilinguals were given all oral and written instructions either in English or in Greek (language mode manipulation). Each language mode subgroup categorized Ma'di stop-voicing comparably to the corresponding monolingual group. However, the bilinguals' discrimination was unaffected by language mode: both subgroups performed intermediate to the monolinguals for the prevoiced-voiceless contrast. Thus, bilinguals do not possess an advantage for unfamiliar non-native contrasts, but are nonetheless uniquely configured language users, differing from either monolingual group.

The Next Stop of One-Stop

ERIC Educational Resources Information Center

Bouman, Penny; Gomber, Gerri; Higgs, Ronnie; Westman, Craig

2006-01-01

This article focuses on the migration of the best practices of a one-stop setup to a communication center allowing for a one-stop shop experience via phone. Specifically, the article describes how enrollment managers at Ferris State University chose elements of their one-stop student service center to migrate into the Enrollment Services…

CRISPR-Mediated Base Editing Enables Efficient Disruption of Eukaryotic Genes through Induction of STOP Codons.

PubMed

Billon, Pierre; Bryant, Eric E; Joseph, Sarah A; Nambiar, Tarun S; Hayward, Samuel B; Rothstein, Rodney; Ciccia, Alberto

2017-09-21

Standard CRISPR-mediated gene disruption strategies rely on Cas9-induced DNA double-strand breaks (DSBs). Here, we show that CRISPR-dependent base editing efficiently inactivates genes by precisely converting four codons (CAA, CAG, CGA, and TGG) into STOP codons without DSB formation. To facilitate gene inactivation by induction of STOP codons (iSTOP), we provide access to a database of over 3.4 million single guide RNAs (sgRNAs) for iSTOP (sgSTOPs) targeting 97%-99% of genes in eight eukaryotic species, and we describe a restriction fragment length polymorphism (RFLP) assay that allows the rapid detection of iSTOP-mediated editing in cell populations and clones. To simplify the selection of sgSTOPs, our resource includes annotations for off-target propensity, percentage of isoforms targeted, prediction of nonsense-mediated decay, and restriction enzymes for RFLP analysis. Additionally, our database includes sgSTOPs that could be employed to precisely model over 32,000 cancer-associated nonsense mutations. Altogether, this work provides a comprehensive resource for DSB-free gene disruption by iSTOP. Copyright © 2017 Elsevier Inc. All rights reserved.

Multi-arm group sequential designs with a simultaneous stopping rule.

PubMed

Urach, S; Posch, M

2016-12-30

Multi-arm group sequential clinical trials are efficient designs to compare multiple treatments to a control. They allow one to test for treatment effects already in interim analyses and can have a lower average sample number than fixed sample designs. Their operating characteristics depend on the stopping rule: We consider simultaneous stopping, where the whole trial is stopped as soon as for any of the arms the null hypothesis of no treatment effect can be rejected, and separate stopping, where only recruitment to arms for which a significant treatment effect could be demonstrated is stopped, but the other arms are continued. For both stopping rules, the family-wise error rate can be controlled by the closed testing procedure applied to group sequential tests of intersection and elementary hypotheses. The group sequential boundaries for the separate stopping rule also control the family-wise error rate if the simultaneous stopping rule is applied. However, we show that for the simultaneous stopping rule, one can apply improved, less conservative stopping boundaries for local tests of elementary hypotheses. We derive corresponding improved Pocock and O'Brien type boundaries as well as optimized boundaries to maximize the power or average sample number and investigate the operating characteristics and small sample properties of the resulting designs. To control the power to reject at least one null hypothesis, the simultaneous stopping rule requires a lower average sample number than the separate stopping rule. This comes at the cost of a lower power to reject all null hypotheses. Some of this loss in power can be regained by applying the improved stopping boundaries for the simultaneous stopping rule. The procedures are illustrated with clinical trials in systemic sclerosis and narcolepsy. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

A randomised-controlled trial in England of a postnatal midwifery intervention on breast-feeding duration.

PubMed

Wallace, Louise M; Dunn, Orla M; Alder, Elizabeth M; Inch, Sally; Hills, Robert K; Law, Susan M

2006-09-01

To determine whether postnatal 'hands off' care by midwives on positioning and attachment of the newborn baby improves breast-feeding duration. Mothers were randomised at the first postnatal feed to receive either care by a midwife trained in the experimental protocol or by a control midwife undertaking routine care. Eight wards in four English Midlands hospitals. 370 primiparous mothers with term babies who intended to breast feed, and could sit out of bed to do so. Experimental protocol of verbal-only advice on positioning and attachment, delivered at the first postnatal ward feed compared with routine care by a qualified midwife. Duration of breast feeding up to 17 weeks as assessed by diaries and interviews with mothers and protocol adherence from self-completed checklist by the midwife. The mothers' self-reported experience of care and support before, during and after delivery were assessed at 6 weeks, and feeding outcomes and employment status at 17 weeks. Experimental group mothers more often held the baby across their lap and received 'hands off advice', but fewer babies in the experimental than control groups attached and fed: 59% (106/180) vs. 67% (118/175), p=0.1. No significant differences were found in the numbers of mothers breast feeding at 6 or 17 weeks in the experimental and control groups (stopped exclusive breast feeding: 76% (130/172) vs. 77% (126/163) at 6 weeks; 96% (167/174) vs. 96% (161/168) at 17 weeks; odds ratio 1.02, 95% CI 0.77 to 1.22; p=0.8; stopped any breast feeding: 35% (61/172) vs. 32% (53/167) at 6 weeks; 63% (109/173) vs. 60% (101/167) at 17 weeks; odds ratio 1.10, 0.84 to 1.45; p=0.5). There were no significant differences in the incidence of problems with breast feeding and care experienced by mothers before or during hospitalisation (other than at the first postnatal ward feed), nor after discharge home. No significant beneficial effect was found on breast-feeding duration of the verbal- only advice on positioning and attachment, perhaps because aspects of the intervention are already within routine UK practice. Other care practices at subsequent feeds may negate benefits of care at earlier feeds. 'Hands off' care at the first feed may be less important to subsequent feeding than achieving a first feed under supervision in the postnatal ward. Midwives can be trained in a 4-hr workshop to achieve improved knowledge of 'hands off' positioning and attachment care, and these can be translated into clinical practice. Future studies should differentiate the elements of the care that are effective in achieving postnatal feeds, and apply this advice consistently at successive feeds.

Benefits of E-Cigarettes Among Heavy Smokers Undergoing a Lung Cancer Screening Program: Randomized Controlled Trial Protocol.

PubMed

Lucchiari, Claudio; Masiero, Marianna; Veronesi, Giulia; Maisonneuve, Patrick; Spina, Stefania; Jemos, Costantino; Omodeo Salè, Emanuela; Pravettoni, Gabriella

2016-02-03

Smoking is a global public health problem. For this reason, experts have called smoking dependence a global epidemic. Over the past 5 years, sales of electronic cigarettes, or e-cigarettes, have been growing strongly in many countries. Yet there is only partial evidence that e-cigarettes are beneficial for smoking cessation. In particular, although it has been proven that nicotine replacement devices may help individuals stop smoking and tolerate withdrawal symptoms, e-cigarettes' power to increase the quitting success rate is still limited, ranging from 5% to 20% dependent on smokers' baseline conditions as shown by a recent Cochrane review. Consequently, it is urgent to know if e-cigarettes may have a higher success rate than other nicotine replacement methods and under what conditions. Furthermore, the effects of the therapeutic setting and the relationship between individual characteristics and the success rate have not been tested. This protocol is particularly innovative, because it aims to test the effectiveness of electronic devices in a screening program (the COSMOS II lung cancer prevention program at the European Institute of Oncology), where tobacco reduction is needed to lower individuals' lung cancer risks. This protocol was designed with the primary aim of investigating the role of tobacco-free cigarettes in helping smokers improve lung health and either quit smoking or reduce their tobacco consumption. In particular, we aim to investigate the impact of a 3-month e-cigarettes program to reduce smoking-related respiratory symptoms (eg, dry cough, shortness of breath, mouth irritation, and phlegm) through reduced consumption of tobacco cigarettes. Furthermore, we evaluate the behavioral and psychological (eg, well-being, mood, and quality of life) effects of the treatment. This is a prospective, randomized, placebo-controlled, double-blind, three-parallel group study. The study is organized as a nested randomized controlled study with 3 branches: a nicotine e-cigarettes group, a nicotine-free e-cigarettes group, and a control group. The study is nested in a screening program for early lung cancer detection in heavy smokers. The study is open and is still recruiting. Stopping or reducing tobacco consumption should be a main goal of any health organization. However, traditional antismoking programs are expensive and not always effective. Therefore, favoring a partial or complete shift to e-cigarettes in heavy smokers (eg, persons at high risk for a number of diseases) could be considered a moral imperative. However, before following this path, sound and reliable data on large samples and in a variety of contexts are required. Clinicaltrials.gov NCT02422914; https://clinicaltrials.gov/ct2/show/NCT02422914 (Archived by WebCite at http://www.webcitation.org/6etwz1bPL).

Stopping power: Effect of the projectile deceleration

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

Kompaneets, Roman, E-mail: kompaneets@mpe.mpg.de; Ivlev, Alexei V.; Morfill, Gregor E.

2014-11-15

The stopping force is the force exerted on the projectile by its wake. Since the wake does not instantly adjust to the projectile velocity, the stopping force should be affected by the projectile deceleration caused by the stopping force itself. We address this effect by deriving the corresponding correction to the stopping force in the cold plasma approximation. By using the derived expression, we estimate that if the projectile is an ion passing through an electron-proton plasma, the correction is small when the stopping force is due to the plasma electrons, but can be significant when the stopping force ismore » due to the protons.« less

The Canadian STOP-PAIN project: the burden of chronic pain-does sex really matter?

PubMed

Racine, Mélanie; Dion, Dominique; Dupuis, Gilles; Guerriere, Denise N; Zagorski, Brandon; Choinière, Manon; Banner, Robert; Barton, Pamela M; Boulanger, Aline; Clark, Alexander J; Gordon, Allan; Guertin, Marie-Claude; Intrater, Howard M; Lefort, Sandra M; Lynch, Mary E; Moulin, Dwight E; Ong-Lam, May; Peng, Philip; Rashiq, Saifee; Shir, Yoram; Taenzer, Paul; Ware, Mark

2014-05-01

The Canadian STOP-PAIN Project assessed the human and economic burden of chronic pain (CP) in individuals on waitlists of Canadian multidisciplinary pain treatment facilities. This article focuses on sex differences. Objectives were to (1) determine the pain characteristics and related biopsychosocial factors that best differentiated women and men with CP; and (2) examine whether public and private costs associated with CP differed according to sex. Sample consisted of 441 women and 287 men who were evaluated using self-administered questionnaires and a structured interview protocol. A subsample (233 women and 137 men) recorded all pain-related expenditures in a comprehensive diary over 3 months. Results revealed that the burden of illness associated with CP was comparable in both sexes for average and worst pain intensity, pain impact on daily living, quality of life, and psychological well-being. The same was true for pain-related costs. The results of a hierarchical logistic regression analysis, in which sex was treated as the dependent variable, showed that factors that differentiated men and women were: work status, certain circumstances surrounding pain onset, present pain intensity, intake of particular types of pain medication, use of certain pain management strategies, pain beliefs, and utilization of particular health care resources. This study suggests that women and men who are referred to multidisciplinary pain treatment facilities do not differ significantly in terms of their pain-related experience. However, the aspects that differ may warrant further clinical attention when assessing and managing pain.

Automated stopped-in-dual-loop flow analysis system for catalytic determination of vanadium in drinking water.

PubMed

Teshima, Norio; Kuno, Masami; Ueda, Minoru; Ueda, Hisashi; Ohno, Shinsuke; Sakai, Tadao

2009-07-15

An automated stopped-in-dual-loop flow analysis (SIDL-FA) system is proposed for the determination of vanadium in drinking water. The chemistry is based on the vanadium-catalyzed oxidation reaction of p-anisidine by bromate in the presence of Tiron as an activator to produce a dye (lambda(max)=510 nm). A SIDL-FA system basically consists of a selection valve, three pumps (one is for delivering of standard/sample, and others are for reagents), two six-way injection valves, a spectrophotometric detector and a data acquisition device. A 100-microL coiled loop around a heated device is fitted onto each six-way injection valve. A well-mixed solution containing reagents and standard/sample is loaded into the first loop on a six-way valve, and then the same solution is loaded into the second loop on another six-way valve. The solutions are isolated by switching these two six-way valves, so that the catalytic reaction can be promoted. The net waste can be zero in this stage, because all pumps are turned off. Then each resulting solution is dispensed to the detector with suitable time lag. A touchscreen controller is developed to automatically carry out the original SIDL-FA protocol. The proposed SIDL-FA method allows vanadium to be quantified in the range of 0.1-2 microg L(-1) and is applied to the determination of vanadium in drinking water samples.

Stopping a response has global or nonglobal effects on the motor system depending on preparation

PubMed Central

Greenhouse, Ian; Oldenkamp, Caitlin L.

2012-01-01

Much research has focused on how people stop initiated response tendencies when instructed by a signal. Stopping of this kind appears to have global effects on the motor system. For example, by delivering transcranial magnetic stimulation (TMS) over the leg area of the primary motor cortex, it is possible to detect suppression in the leg when the hand is being stopped (Badry R et al. Suppression of human cortico-motoneuronal excitability during the stop-signal task. Clin Neurophysiol 120: 1717–1723, 2009). Here, we asked if such “global suppression” can be observed proactively, i.e., when people anticipate they might have to stop. We used a conditional stop signal task, which allows the measurement of both an “anticipation phase” (i.e., where proactive control is applied) and a “stopping” phase. TMS was delivered during the anticipation phase (experiment 1) and also during the stopping phase (experiments 1 and 2) to measure leg excitability. During the anticipation phase, we did not observe leg suppression, but we did during the stopping phase, consistent with Badry et al. (2009). Moreover, when we split the subject groups into those who slowed down behaviorally (i.e., exercised proactive control) and those who did not, we found that subjects who slowed did not show leg suppression when they stopped, whereas those who did not slow did show leg suppression when they stopped. These results suggest that if subjects prepare to stop, then they do so without global effects on the motor system. Thus, preparation allows them to stop more selectively. PMID:22013239

Depression - stopping your medicines

MedlinePlus

... gov/ency/patientinstructions/000570.htm Depression - stopping your medicines To use the sharing features on this page, ... no longer taking them. Before You Stop Your Medicine Stopping your medicine may be the right choice ...

Automaticity of Cognitive Control: Goal Priming in Response-Inhibition Paradigms

ERIC Educational Resources Information Center

Verbruggen, Frederick; Logan, Gordon D.

2009-01-01

Response inhibition is a hallmark of cognitive control. An executive system inhibits responses by activating a stop goal when a stop signal is presented. The authors asked whether the stop goal could be primed by task-irrelevant information in stop-signal and go/no-go paradigms. In Experiment 1, the task-irrelevant primes "GO," ###, or "STOP" were…

Creating Workforce Development Systems That Work: A Guide for Practitioners.

ERIC Educational Resources Information Center

Kogan, Deborah; Dickinson, Katherine P.; Fedrau, Ruth; Midling, Michael J.; Wolff, Kristin E.

This guide describes common One-Stop Career Center system-building goals and summarizes strategies used by states and local One-Stop sites to further each goal. Part I, Organizing and Governing One-Stop Systems, has these two chapters: Guiding One-Stop Systems: The State Role; and Building Local Partnerships and Governing One-Stop Systems. Part…

Long-lived stops in MSSM scenarios with a neutralino LSP

NASA Astrophysics Data System (ADS)

Johansen, M.; Edsjö, J.; Hellman, S.; Milstead, D.

2010-08-01

This work investigates the possibility of a long-lived stop squark in supersymmetric models with the neutralino as the lightest supersymmetric particle (LSP). We study the implications of meta-stable stops on the sparticle mass spectra and the dark matter density. We find that in order to obtain a sufficiently long stop lifetime so as to be observable as a stable R-hadron at an LHC experiment, we need to fine tune the mass degeneracy between the stop and the LSP considerably. This increases the stop-neutralino co-anihilation cross section, leaving the neutralino relic density lower than what is expected from the WMAP results for stop masses ≲1.5 TeV/ c 2. However, if such scenarios are realised in nature we demonstrate that the long-lived stops will be produced at the LHC and that stop-based R-hadrons with masses up to 1 TeV/c2 can be detected after one year of running at design luminosity.

Event-related fields evoked by vocal response inhibition: a comparison of younger and older adults.

PubMed

Castro-Meneses, Leidy J; Johnson, Blake W; Sowman, Paul F

2016-06-01

The current study examined event-related fields (ERFs) evoked by vocal response inhibition in a stimulus-selective stop-signal task. We compared inhibition-related ERFs across a younger and an older group of adults. Behavioural results revealed that stop-signal reaction times (RTs), go-RTs, ignore-stop RTs and failed stop RTs were longer in the older, relative to the younger group by 38, 123, 149 and 116 ms, respectively. The amplitude of the ERF M2 peak (approximately 200 ms after the stop signal) evoked on successful stop trials was larger compared to that evoked on both failed stop and ignore-stop trials. The M4 peak (approximately 450 ms after stop signal) was of larger amplitude in both successful and failed stops compared to ignore-stop trials. In the older group, the M2, M3 and M4 peaks were smaller in amplitude and peaked later in time (by 24, 50 and 76 ms, respectively). We demonstrate that vocal response inhibition-related ERFs exhibit a similar temporal evolution to those previously described for manual response inhibition: an early peak at 200 ms (i.e. M2) that differentiates successful from failed stopping, and a later peak (i.e. M4) that is consistent with a neural marker of response checking and error processing. Across groups, our data support a more general decline of stimulus processing speed with age.

Accurate, simple, and inexpensive assays to diagnose F8 gene inversion mutations in hemophilia A patients and carriers.

PubMed

Dutta, Debargh; Gunasekera, Devi; Ragni, Margaret V; Pratt, Kathleen P

2016-12-27

The most frequent mutations resulting in hemophilia A are an intron 22 or intron 1 gene inversion, which together cause ∼50% of severe hemophilia A cases. We report a simple and accurate RNA-based assay to detect these mutations in patients and heterozygous carriers. The assays do not require specialized equipment or expensive reagents; therefore, they may provide useful and economic protocols that could be standardized for central laboratory testing. RNA is purified from a blood sample, and reverse transcription nested polymerase chain reaction (RT-NPCR) reactions amplify DNA fragments with the F8 sequence spanning the exon 22 to 23 splice site (intron 22 inversion test) or the exon 1 to 2 splice site (intron 1 inversion test). These sequences will be amplified only from F8 RNA without an intron 22 or intron 1 inversion mutation, respectively. Additional RT-NPCR reactions are then carried out to amplify the inverted sequences extending from F8 exon 19 to the first in-frame stop codon within intron 22 or a chimeric transcript containing F8 exon 1 and the VBP1 gene. These latter 2 products are produced only by individuals with an intron 22 or intron 1 inversion mutation, respectively. The intron 22 inversion mutations may be further classified (eg, as type 1 or type 2, reflecting the specific homologous recombination sites) by the standard DNA-based "inverse-shifting" PCR assay if desired. Efficient Bcl I and T4 DNA ligase enzymes that cleave and ligate DNA in minutes were used, which is a substantial improvement over previous protocols that required overnight incubations. These protocols can accurately detect F8 inversion mutations via same-day testing of patient samples.

Results of the Intravascular Cooling in the Treatment of Acute Stroke 2 Trial (ICTuS-2)

PubMed Central

Lyden, Patrick; Hemmen, Thomas; Grotta, James; Rapp, Karen; Ernstrom, Karin; Rzesiewicz, Teresa; Parker, Stephanie; Concha, Mauricio; Syed, Hussain; Agarwal, Sachin; Meyer, Brett; Jurf, Julie; Altafullah, Irfan; Raman, Rema

2016-01-01

Background and Purpose Therapeutic hypothermia (TH) is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. TH for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster TH in stroke patients. Methods Safety procedures and 4°C saline infusions for faster cooling were added to the Intravascular Cooling Treatment in Acute Stroke (ICTuS) trial protocol. A femoral venous intravascular cooling catheter following intravenous rt-PA in eligible patients provided 24 hours cooling followed by a 12 hour re-warm. Serial safety assessments and imaging were performed. The primary endpoint was 3-month modified Rankin score 0,1. Results Of the intended 1600 subjects, 120 were enrolled before the study was stopped. Randomly, 63 were to receive hypothermia (HY) plus anti-shivering treatment and 57 normothermia (NT). Compared to prior studies, cooling rates were improved with a cold saline bolus, without fluid overload. The intention-to-treat primary outcome of 90-day mRS 0,1 occurred in 33% HY and 38% NT subjects, OR (95% CL) of 0.81 (0.36, 1.85). Serious adverse events occurred equally. Mortality was 15.9% HY and 8.8% NT subjects, OR (95% CL) of 1.95 (0.56, 7.79). Pneumonia occurred in 19% HY vs. 10.5% in NT subjects, OR (95% CL) of 1.99 (0.63, 6.98). Conclusion Intravascular TH was confirmed to be safe and feasible in rt-PA treated acute ischemic stroke patients. Protocol changes designed to reduce pneumonia risk appeared to fail, although the sample is small. Clinical trial registration clinicaltrials.gov NCT 01123161. PMID:27834742

All in One Stop? The Accessibility of Work Support Programs at One-Stop Centers.

ERIC Educational Resources Information Center

Richer, Elise; Kubo, Hitomi; Frank, Abbey

The accessibility of work support programs at one-stop centers was examined in a study during which 33 telephone directors or managers of one-stop centers in 22 states were interviewed by telephone. The interviews established the existence of extensive differences between one-stop centers from the standpoint of all aspects of their operation,…

Automatic and Controlled Response Inhibition: Associative Learning in the Go/No-Go and Stop-Signal Paradigms

PubMed Central

Verbruggen, Frederick; Logan, Gordon D.

2008-01-01

In five experiments, the authors examined the development of automatic response inhibition in the go/no-go paradigm and a modified version of the stop-signal paradigm. They hypothesized that automatic response inhibition may develop over practice when stimuli are consistently associated with stopping. All five experiments consisted of a training phase and a test phase in which the stimulus mapping was reversed for a subset of the stimuli. Consistent with the automatic-inhibition hypothesis, the authors found that responding in the test phase was slowed when the stimulus had been consistently associated with stopping in the training phase. In addition, they found that response inhibition benefited from consistent stimulus-stop associations. These findings suggest that response inhibition may rely on the retrieval of stimulus-stop associations after practice with consistent stimulus-stop mappings. Stimulus-stop mapping is typically consistent in the go/no-go paradigm, so automatic inhibition is likely to occur. However, stimulus-stop mapping is typically inconsistent in the stop-signal paradigm, so automatic inhibition is unlikely to occur. Thus, the results suggest that the two paradigms are not equivalent because they allow different kinds of response inhibition. PMID:18999358

Effects of hormonal stimulation on the concentration and quality of excreted spermatozoa in the critically endangered Panamanian golden frog (Atelopus zeteki).

PubMed

Della Togna, Gina; Trudeau, Vance L; Gratwicke, Brian; Evans, Matthew; Augustine, Lauren; Chia, Han; Bronikowski, Edward J; Murphy, James B; Comizzoli, Pierre

2017-03-15

Knowledge of basic gamete biology is critical to better protect and propagate endangered amphibian species and also to develop reproductive technologies combined with germplasm cryopreservation. The objectives of the study were to test different hormonal stimulations and then characterize the quantity and quality of Panamanian golden frog (Atelopus zeteki) spermatozoa. Following intraperitoneal injection of the gonadotropin-releasing hormone agonist (des-Gly 10 , D-Ala 6 , Pro-NHEt 9- -GnRH 1, 2 or 4 μg/g of body weight), human chorionic gonadotropin (hCG; 5 or 10 IU/gbw), or Amphiplex™ (0.4 μg/gbw GnRH-A + 10 μg/gbw metoclopramide hydrochloride), spermic urine samples from 29 males were collected at different time points (from 0.5 to 24 h post-injection) to analyze the concentration, motility, and morphology of the spermatozoa. Peak of sperm concentration was observed at 3.5 h post injection for all hormonal treatments. Amphiplex™ led to the highest sperm concentrations (4.45 ± 0.07 × 10 6  cells/mL) followed by 4 μg/gbw GnRH-A (2.65 ± 0.21 × 10 6  cells/mL). Other stimulation protocols and doses induced sperm production, but at lower levels (ranging from 1.34 to 1.70 × 10 6  cells/mL). More than 60% of spermatozoa were motile following all treatments but the highest motility (>90%) was obtained from the 10 IU/gbw hCG treatment. Spermic urine samples obtained with all hormone treatments had higher pH (ranging from 7.1 to 7.8) than the urine alone (6.7-6.8). Spermatozoa were filiform and elongated with an apical acrosome, a mitochondrial sheath, a small midpiece and a long tail with an undulating membrane. More than 80% of cells were morphologically normal and 50-70% had intact DNA. These sperm characteristics were not influenced by hormonal treatments. This first comprehensive characterization of sperm samples following optimized hormonal stimulations in A. zeteki lays the foundation for more fundamental studies, reproductive technologies, and future preservation strategies. Copyright © 2016. Published by Elsevier Inc.

Incorporating body-type (apple vs. pear) in STOP-BANG questionnaire improves its validity to detect OSA.

PubMed

Sangkum, Lisa; Klair, Ikrita; Limsuwat, Chok; Bent, Sabrina; Myers, Leann; Thammasitboon, Supat

2017-09-01

The aim of this study is to evaluate whether adding the item of "apple body type" to the STOP-BANG questionnaire enhances diagnostic performance of the questionnaire for detecting obstructive sleep apnea (OSA). Cross-sectional study. Sleep center setting. Two hundred and eight subjects who were referred for an evaluation of possible OSA at Tulane Comprehensive Sleep Center. The exclusion criteria were age<18years old, incomplete or absent questionnaire, incomplete body type identification, polysomnography (PSG) refusal, and pregnant women. STOP-BANG items and body type data were collected on the initial clinic visit. An overnight PSG was performed on every participant. Descriptive analyses of the demographic data and PSG variables were performed. The predictive parameters of STOP and STOP-BANG without and with body type score (STOP-Apple and STOPBANG-Apple) were compared. The STOP questionnaire's sensitivity/specificity/positive likelihood ratio (+LR) (cut-off=2) was 96%/11%/1.1, respectively whereas the STOP-Apple questionnaire (cut-off=3) was 88%/39%/1.5. The STOP-BANG's sensitivity/specificity/+LR (cut-off=3) was 96%/19%/1.2, respectively whereas the STOP-BANG-Apple questionnaire (cut-off=4) was 90%/39%/1.5. The area under the Receiver Operating Characteristic (ROC) curve of STOP-Apple was comparable to the STOP-BANG (P=0.25). The addition of the apple body type item to the STOP-BANG questionnaire in participants with a score≥3 led to increased specificity (67.4%), increased the odds ratio of having OSA of 2.5 (95% CI, 1.2-5.3) and odds ratio of having moderate-severe OSA of 4.7 (95% CI, 2.5-8.7). In the sleep center setting, adding the body type item to the STOP-BANG questionnaire improves not only clinical prediction for PSG confirmed OSA but also predicts moderate to severe of OSA. Published by Elsevier Inc.

Basal forebrain neuronal inhibition enables rapid behavioral stopping

PubMed Central

Mayse, Jeffrey D.; Nelson, Geoffrey M.; Avila, Irene; Gallagher, Michela; Lin, Shih-Chieh

2015-01-01

Cognitive inhibitory control, the ability to rapidly suppress responses inappropriate for the context, is essential for flexible and adaptive behavior. While most studies on inhibitory control have focused on the fronto-basal-ganglia circuit, here we explore a novel hypothesis and show that rapid behavioral stopping is enabled by neuronal inhibition in the basal forebrain (BF). In rats performing the stop signal task, putative noncholinergic BF neurons with phasic bursting responses to the go signal were inhibited nearly completely by the stop signal. The onset of BF neuronal inhibition was tightly coupled with and temporally preceded the latency to stop, the stop signal reaction time. Artificial inhibition of BF activity in the absence of the stop signal was sufficient to reproduce rapid behavioral stopping. These results reveal a novel subcortical mechanism of rapid inhibitory control by the BF, which provides bidirectional control over the speed of response generation and inhibition. PMID:26368943

20 CFR 662.260 - What services, in addition to the applicable core services, are to be provided by One-Stop...

Code of Federal Regulations, 2011 CFR

2011-04-01

... core services, are to be provided by One-Stop partners through the One-Stop delivery system? 662.260... Responsibilities of Partners § 662.260 What services, in addition to the applicable core services, are to be provided by One-Stop partners through the One-Stop delivery system? In addition to the provision of core...

20 CFR 662.260 - What services, in addition to the applicable core services, are to be provided by One-Stop...

Code of Federal Regulations, 2010 CFR

2010-04-01

... core services, are to be provided by One-Stop partners through the One-Stop delivery system? 662.260... Responsibilities of Partners § 662.260 What services, in addition to the applicable core services, are to be provided by One-Stop partners through the One-Stop delivery system? In addition to the provision of core...

The Stop Transmission of Polio Data Management (STOP DM) assignment and its role in polio eradication and immunization data improvement in Africa

PubMed Central

Benke, Amalia; Williams, Alford Joseph; MacNeil, Adam

2017-01-01

The availability and use of high quality immunization and surveillance data are crucial for monitoring all components of the Global Polio Eradication Program (GPEI). The Stop Transmission of Polio (STOP) program was initiated in 1999 to train and mobilize human resources to provide technical support to polio endemic and at-risk countries and in 2002 the STOP data management (STOP DM) deployment was created to provide capacity development in the area of data management for immunization and surveillance data for these countries. Since 2002, Africa has received the majority of support from the STOP DM program, with almost 80% of assignments being placed in African countries. The STOP DM program has played a valuable role in improving the quality and use of data for the GPEI and has increasingly supported other immunization program data needs. In this report we provide an overview of the history, current status, and future of the STOP DM program, with a specific focus on the African continent. PMID:29296155

The Stop Transmission of Polio Data Management (STOP DM) assignment and its role in polio eradication and immunization data improvement in Africa.

PubMed

Benke, Amalia; Williams, Alford Joseph; MacNeil, Adam

2017-01-01

The availability and use of high quality immunization and surveillance data are crucial for monitoring all components of the Global Polio Eradication Program (GPEI). The Stop Transmission of Polio (STOP) program was initiated in 1999 to train and mobilize human resources to provide technical support to polio endemic and at-risk countries and in 2002 the STOP data management (STOP DM) deployment was created to provide capacity development in the area of data management for immunization and surveillance data for these countries. Since 2002, Africa has received the majority of support from the STOP DM program, with almost 80% of assignments being placed in African countries. The STOP DM program has played a valuable role in improving the quality and use of data for the GPEI and has increasingly supported other immunization program data needs. In this report we provide an overview of the history, current status, and future of the STOP DM program, with a specific focus on the African continent.

Novel measures of response performance and inhibition in children with ADHD.

PubMed

Morein-Zamir, Sharon; Hommersen, Paul; Johnston, Charlotte; Kingstone, Alan

2008-11-01

Fifteen children with ADHD aged 8 to 12 years and age and gender matched controls performed two different stopping tasks to examine response performance and inhibition and their respective moment-to-moment variability. One task was the well-established stop-signal task, while the other was a novel tracking task where the children tracked a spaceship on the screen until an alarm indicated they should stop. Although performance was discrete in the stop signal task and continuous in the tracking task, in both tasks latencies to the stop signal were significantly slowed in children with ADHD. Go performance and variability did not significantly differ between ADHD and control children in either task. Importantly, stopping latency in the novel spaceship tracking task also was more variable in children with ADHD. As stopping variability cannot be measured using the standard stop signal task, the new task offers compelling support for the heretofore untested prediction that stopping is both slowed and more variable in children with ADHD. The results support a response inhibition impairment in ADHD, whilst limiting the extent of an intra-trial variability deficit.

Laboratory activities involving transmissible spongiform encephalopathy causing agents

PubMed Central

Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

2013-01-01

Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

Integrated cognitive-behavioral and psychodynamic psychotherapy for intimate partner violent men.

PubMed

Lawson, David M; Kellam, Melanie; Quinn, Jamie; Malnar, Stevie G

2012-06-01

Intimate partner violence (IPV) continue to have widespread negative effects on victims, children who witness IPV, and perpetrators. Current treatments have proven to be only marginally effective in stopping or reducing IPV by men. The two most prominent treatment approaches are feminist sociocultural and cognitive-behavioral therapy (CBT). The feminist sociocultural approach has been criticized for failing to adequately consider the therapeutic alliance, personality factors, and sole focus on patriarchy as the cause for IPV, whereas CBT has been criticized for failing to attend to motivation issues in treatment protocols. This article reviews the effectiveness of current treatments for partner-violent men, examines relationship and personality variables related to IPV and its treatment, and presents an emerging IPV treatment model that combines CBT and psychodynamic therapy. The article addresses how psychodynamic therapy is integrated into the more content-based elements of CBT. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Early action on HFCs mitigates future atmospheric change

NASA Astrophysics Data System (ADS)

Hurwitz, Margaret M.; Fleming, Eric L.; Newman, Paul A.; Li, Feng; Liang, Qing

2016-11-01

As countries take action to mitigate global warming, both by ratifying the UNFCCC Paris Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases and the distinct structure of their atmospheric impacts, and how the timing of potential greenhouse gas regulations would affect future changes in atmospheric temperature and ozone. HFCs should be explicitly considered in upcoming climate and ozone assessments, since chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid-21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19 K at 80 hPa. The HFC mitigation scenarios described in this study demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90% of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

Early Action on Hfcs Mitigates Future Atmospheric Change

NASA Technical Reports Server (NTRS)

Hurwitz, Margaret M.; Fleming, Eric L.; Newman, Paul A.; Li, Feng; Liang, Qing

2016-01-01

As countries take action to mitigate global warming, both by ratifying theUNFCCCParis Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases and the distinct structure of their atmospheric impacts, and how the timing of potential greenhouse gas regulations would affect future changes in atmospheric temperature and ozone. HFCs should be explicitly considered in upcoming climate and ozone assessments, since chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid- 21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19 Kat 80 hPa. The HFCmitigation scenarios described in this study demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90% of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

Bacteriological evaluation of a new air turbine handpiece for preventing cross-contamination in dental procedures.

PubMed

Masuda, K; Ohta, M; Ohsuka, S; Matsuyama, M; Ashoori, M; Usami, T; Ito, M; Ueda, M; Kaneda, T

1994-03-01

An autoclavable air turbine handpiece, Air Flushing Clean System (AFCS) (Osada Electric Co., Ltd., Tokyo, Japan) was developed for use in dentistry with the objective of reducing cross-contamination. Its potential for bacterial contamination was investigated in vitro using two bacterial strains (Streptococcus mutants ATCC 25175 and Staphylococcus aureus FDA 209 P). In theory, this device should prevent cross-contamination of the internal water and air lines of the handpiece, by maintaining an internal positive pressure even after the turbine is stopped. In the present study, this AFCS device was found to reduce the bacterial contamination within the air turbine handpiece more effectively than the conventional handpiece used according to accepted protocol. The reduction of such contamination by the AFCS is in keeping with the recent objective of the American Dental Association to reduce cross-contamination during dental procedures.

Transmission and reflection of charge-density wave packets in a quantum Hall edge controlled by a metal gate

NASA Astrophysics Data System (ADS)

Matsuura, Masahiro; Mano, Takaaki; Noda, Takeshi; Shibata, Naokazu; Hotta, Masahiro; Yusa, Go

2018-02-01

Quantum energy teleportation (QET) is a proposed protocol related to quantum vacuum. The edge channels in a quantum Hall system are well suited for the experimental verification of QET. For this purpose, we examine a charge-density wave packet excited and detected by capacitively coupled front gate electrodes. We observe the waveform of the charge packet, which is proportional to the time derivative of the applied square voltage wave. Further, we study the transmission and reflection behaviors of the charge-density wave packet by applying a voltage to another front gate electrode to control the path of the edge state. We show that the threshold voltages where the dominant direction is switched in either transmission or reflection for dense and sparse wave packets are different from the threshold voltage where the current stops flowing in an equilibrium state.

Closed-Loop Optogenetic Intervention in Mice

PubMed Central

Oijala, Mikko; Soltesz, Ivan

2014-01-01

Optogenetic interventions offer novel ways of probing, in a temporally specific manner, the roles of specific cell types in neuronal network functions of awake, behaving animals. Despite the unique potential for temporally specific optogenetic interventions in disease states, a major hurdle in its broad application to unpredictable brain states in a laboratory setting is constructing a real-time responsive system. We recently created a closed-loop system for stopping spontaneous seizures in chronically epileptic mice using optogenetic intervention. This system performs with very high sensitivity and specificity, and the strategy is relevant not only to epilepsy, but can also be used to react in real time, with optogenetic or other interventions, to diverse brain states. The protocol presented here is highly modular and requires variable time to perform. We describe the basic construction of a complete system, and include our downloadable custom closed-loop detection software which can be employed for this purpose. PMID:23845961

How to Stop and Change a Response: The Role of Goal Activation in Multitasking

ERIC Educational Resources Information Center

Verbruggen, Frederick; Schneider, Darryl W.; Logan, Gordon D.

2008-01-01

Multitasking was studied in the stop-change paradigm, in which the response for a primary GO1 task had to be stopped and replaced by a response for a secondary GO2 task on some trials. In 2 experiments, the delay between the stop signal and the change signal was manipulated to determine which task goals (GO1, GO2, or STOP) were involved in…

Removing Gaps in the Exclusion of Top Squark Parameter Space

NASA Astrophysics Data System (ADS)

Czakon, Michal; Mitov, Alexander; Papucci, Michele; Ruderman, Joshua T.; Weiler, Andreas

2014-11-01

Light stops are a hallmark of the most natural realizations of weak-scale supersymmetry. While stops have been extensively searched for, there remain open gaps around and below the top mass, due to similarities of stop and top signals with current statistics. We propose a new fast-track avenue to improve light stop searches for R -parity-conserving supersymmetry by comparing top cross section measurements to the theoretical prediction. Stop masses below ˜180 GeV can now be ruled out for a light neutralino. The possibility of a stop signal contaminating the top mass measurement is also briefly addressed.

Effect of variability of sequence length of go trials preceding a stop trial on ability of response inhibition in stop-signal task.

PubMed

Hiraoka, Koichi; Kinoshita, Atsushi; Kunimura, Hiroshi; Matsuoka, Masakazu

2018-05-31

This study investigated whether the variability of the sequence length of the go trials preceding a stop trial enhanced or interfered with inhibitory control. The hypotheses tested were either inhibitory control improves when the sequence length of the go trials varies as a consequence of increased preparatory effort or it degrades as a consequence of the switching cost from the go trial to the stop trial. The right-handed participants abducted the left or right index finger in response to a go cue during the go trials. A stop cue was given at 50, 90, or 130 ms after the go cue, with 0.25 probability in the stop trial. In the less variable session, a stop trial was presented after two, three, or four consecutive go trials. In the variable session, a stop trial was presented after one, two, three, four, or five consecutive go trials. The reaction time and stop-signal reaction time were not significantly different between the sessions and between the response sides. Nevertheless, the probability of successful inhibition of the right-hand response in the variable session was higher than that in the less variable session when the stop cue was given 50 ms after a go cue. This finding supports the view that preparatory effort due to less predictability of the chance of a forthcoming response inhibition enhances the ability of the right-hand response inhibition when the stop process begins earlier.

Effect of bus-stop spacing on mobile emissions in urban areas.

DOT National Transportation Integrated Search

2003-01-01

The operational effect of bus-stop spacing has been a critical issue. Closely spaced bus stops : disrupt the traffic flow on the bus route, particularly during peak hours because buses make frequent stops : to provide services to customers. The disru...

Using all-way stop control for residential traffic management.

DOT National Transportation Integrated Search

1995-01-01

All-way, or multiway, stop signs are perhaps the most controversial form of residential traffic control. Residents are likely to request all-way stop signs more frequently than any other form of control. Stop signs are thought of as panaceas for many...

75 FR 21505 - Retroactive Stop Loss Special Pay Compensation; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... 0790-AI59] Retroactive Stop Loss Special Pay Compensation; Correction AGENCY: Office of the Under... Retroactive Stop Loss Special Pay Compensation that was authorized and appropriated in the Supplemental... the Act. The change of eligibility for Retroactive Stop Loss [[Page 21506

High post-movement parietal low-beta power during rhythmic tapping facilitates performance in a stop task.

PubMed

Fischer, Petra; Tan, Huiling; Pogosyan, Alek; Brown, Peter

2016-09-01

Voluntary movements are followed by a post-movement electroencephalography (EEG) beta rebound, which increases with practice and confidence in a task. We hypothesized that greater beta modulation reflects less load on cognitive resources and may thus be associated with faster reactions to new stimuli. EEG was recorded in 17 healthy subjects during rhythmically paced index finger tapping. In a STOP condition, participants had to interrupt the upcoming tap in response to an auditory cue, which was timed such that stopping was successful only in ~ 50% of all trials. In a second condition, participants carried on tapping twice after the stop signal (CONTINUE condition). Thus the conditions were distinct in whether abrupt stopping was required as a second task. Modulation of 12-20 Hz power over motor and parietal areas developed with time on each trial and more so in the CONTINUE condition. Reduced modulation in the STOP condition went along with reduced negative mean asynchronies suggesting less confident anticipation of the timing of the next tap. Yet participants were more likely to stop when beta modulation prior to the stop cue was more pronounced. In the STOP condition, expectancy of the stop signal may have increased cognitive load during movement execution given that the task might have to be stopped abruptly. However, within this condition, stopping ability was increased if the preceding tap was followed by a relatively larger beta increase. Significant, albeit weak, correlations confirmed that increased post-movement beta power was associated with faster reactions to new stimuli, consistent with reduced cognitive load. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Reasons Why Children and Adolescents With Attention-Deficit/Hyperactivity Disorder Stop and Restart Taking Medicine.

PubMed

Brinkman, William B; Simon, John O; Epstein, Jeffery N

2018-04-01

To describe the prevalence of reasons why children and adolescents stop and restart attention-deficit/hyperactivity disorder (ADHD) medicine and whether functional impairment is present after stopping medicine. We used the prospective longitudinal cohort from the Multimodal Treatment of Study of Children With ADHD. At the 12-year follow-up, when participants were a mean of 21.1 years old, 372 participants (76% male, 64% white) reported ever taking ADHD medicine. Participants reported the age when they last stopped and/or restarted ADHD medicine and also endorsed reasons for stopping and restarting. Seventy-seven percent (286 of 372) reported stopping medicine for a month or longer at some time during childhood or adolescence. Participants were a mean of 13.3 years old when they last stopped medicine. The most commonly endorsed reasons for stopping medication related to 1) medicine not needed/helping, 2) adverse effects, 3) logistical barriers of getting or taking medication, and 4) social concerns or stigma. Seventeen percent (64 of 372) reported restarting medicine after stopping for a month or longer. Commonly endorsed reasons for restarting related to medicine being needed or medicine helping; and resolution of logistical barriers to getting or taking medicine. For both stopping and restarting, the proportion endorsing some reasons differed by age range, with the overall pattern suggesting that parental involvement in decisions decreased with age. Nearly all participants had impairment at the assessment after stopping, regardless of whether medication was resumed. Different reasons for stopping and/or restarting medicine are relevant at different times for different teens. Tailored strategies may help engage adolescents as full partners in their treatment plan. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Characterization of CcSTOP1; a C2H2-type transcription factor regulates Al tolerance gene in pigeonpea.

PubMed

Daspute, Abhijit Arun; Kobayashi, Yuriko; Panda, Sanjib Kumar; Fakrudin, Bashasab; Kobayashi, Yasufumi; Tokizawa, Mutsutomo; Iuchi, Satoshi; Choudhary, Arbind Kumar; Yamamoto, Yoshiharu Y; Koyama, Hiroyuki

2018-01-01

Al-responsive citrate-transporting CcMATE1 function and its regulation by CcSTOP1 were analyzed using NtSTOP1 -KD tobacco- and pigeonpea hairy roots, respectively, CcSTOP1 binding sequence of CcMATE1 showed similarity with AtALMT1 promoter. The molecular mechanisms of Aluminum (Al) tolerance in pigeonpea (Cajanus cajan) were characterized to provide information for molecular breeding. Al-inducible citrate excretion was associated with the expression of MULTIDRUGS AND TOXIC COMPOUNDS EXCLUSION (CcMATE1), which encodes a citrate transporter. Ectopic expression of CcMATE1-conferred Al tolerance to hairy roots of transgenic tobacco with the STOP1 regulation system knocked down. This gain-of-function approach clearly showed CcMATE1 was involved in Al detoxification. The expression of CcMATE1 and another Al-tolerance gene, ALUMINUM SENSITIVE 3 (CcALS3), was regulated by SENSITIVE TO PROTON RHIZOTOXICITY1 (CcSTOP1) according to loss-of-function analysis of pigeonpea hairy roots in which CcSTOP1 was suppressed. An in vitro binding assay showed that the Al-responsive CcMATE1 promoter contained the GGNVS consensus bound by CcSTOP1. Mutation of GGNVS inactivated the Al-inducible expression of CcMATE1 in pigeonpea hairy roots. This indicated that CcSTOP1 binding to the promoter is critical for CcMATE1 expression. The STOP1 binding sites of both the CcMATE1 and AtALMT1 promoters contained GGNVS and a flanking 3' sequence. The GGNVS region was identical in both CcMATE1 and AtALMT1. By contrast, the 3' flanking sequence with binding affinity to STOP1 did not show similarity. Putative STOP1 binding sites with similar structures were also found in Al-inducible MATE and ALMT1 promoters in other plant species. The characterized Al-responsive CcSTOP1 and CcMATE1 genes will help in pigeonpea breeding in acid soil tolerance.

Biomechanical measurements of stopping and stripping torques during screw insertion in five types of human and artificial humeri.

PubMed

Aziz, Mina Sr; Tsuji, Matthew Rs; Nicayenzi, Bruce; Crookshank, Meghan C; Bougherara, Habiba; Schemitsch, Emil H; Zdero, Radovan

2014-05-01

During orthopedic surgery, screws are inserted by "subjective feel" in humeri for fracture fixation, that is, stopping torque, while trying to prevent accidental over-tightening that causes screw-bone interface failure, that is, stripping torque. However, no studies exist on stopping torque, stripping torque, or stopping/stripping torque ratio in human or artificial humeri. This study evaluated five types of humeri, namely, human fresh-frozen (n = 19), human embalmed (n = 18), human dried (n = 15), artificial "normal" (n = 13), and artificial "osteoporotic" (n = 13). An orthopedic surgeon used a torque screwdriver to insert 3.5-mm-diameter cortical screws into humeral shafts and 6.5-mm-diameter cancellous screws into humeral heads by "subjective feel" to obtain stopping and stripping torques. The five outcome measures were raw and normalized stopping torque, raw and normalized stripping torque, and stopping/stripping torque ratio. Normalization was done as raw torque/screw-bone interface area. For "gold standard" fresh-frozen humeri, cortical screw tests yielded averages of 1312 N mm (raw stopping torque), 30.4 N/mm (normalized stopping torque), 1721 N mm (raw stripping torque), 39.0 N/mm (normalized stripping torque), and 82% (stopping/stripping torque ratio). Similarly, fresh-frozen humeri gave cancellous screw average results of 307 N mm (raw stopping torque), 0.9 N/mm (normalized stopping torque), 392 N mm (raw stripping torque), 1.2 N/mm (normalized stripping torque), and 79% (stopping/stripping torque ratio). Of the five cortical screw parameters for fresh-frozen humeri versus other groups, statistical equivalence (p ≥ 0.05) occurred in four cases (embalmed), three cases (dried), four cases (artificial "normal"), and four cases (artificial "osteoporotic"). Of the five cancellous screw parameters for fresh-frozen humeri versus other groups, statistical equivalence (p ≥ 0.05) occurred in five cases (embalmed), one case (dried), one case (artificial "normal"), and zero cases (artificial "osteoporotic"). Stopping/stripping torque ratios were relatively constant for all groups at 77%-88% (cortical screws) and 79%-92% (cancellous screws). © IMechE 2014.

Attribution of Recovery in Lower-Stratospheric Ozone

NASA Technical Reports Server (NTRS)

Yang, Eun-Su; Cunnold, Derek M.; Salawitch, Ross J.; McCormick, M. Patrick; Russell, James, III; Zawodny, Joseph M.; Oltmans, Samuel; Newchurch, Michael J.

2005-01-01

Multiple satellite and ground-based observations provide consistent evidence that the thickness of Earth's protective ozone layer has stopped declining since 1997, close to the time of peak stratospheric halogen loading. Regression analyses with Effective Equivalent Stratospheric Chlorine (EESC) in conjunction with further analyses using more sophisticated photochemical model calculations constrained by satellite data demonstrate that the cessation of ozone depletion between 18-25 km altitude is consistent with a leveling off of stratospheric abundances of chlorine and bromine, due to the Montreal Protocol and its amendments. However, ozone increases in the lowest part of the stratosphere, from the tropopause to 18 km, account for about half of the improvement in total column ozone during the past 9 years at northern hemisphere mid-latitudes. The increase in ozone for altitudes below 18 km is most likely driven by changes in transport, rather than driven by declining chlorine and bromine. Even with this evidence that the Montreal Protocol and its amendments are having the desired, positive effect on ozone above 18 km, total column ozone is recovering faster than expected due to the apparent transport driven changes at lower altitudes. Accurate prediction of future levels of stratospheric ozone will require comprehensive understanding of the factors that drive temporal changes at various altitudes, and partitioning of the recent transport-driven increases between natural variability and changes in atmospheric structure perhaps related to anthropogenic climate change.

Attribution of Recovery in Lower-stratospheric Ozone

NASA Technical Reports Server (NTRS)

Yang, Eun-Su; Cunnold, Derek M.; Salawitch, Ross J.; McCormick, M. Patrick; Russell, James, III; Zawodny, Joseph M.; Oltmans, Samuel; Newchurch, Michael J.

2006-01-01

Multiple satellite and ground-based observations provide consistent evidence that the thickness of Earth's protective ozone layer has stopped declining since 1997, close to the time of peak stratospheric halogen loading. Regression analyses with Effective Equivalent Stratospheric Chlorine (EESC) in conjunction with further analyses using more sophisticated photochemical model calculations constrained by satellite data demonstrate that the cessation of ozone depletion between 18-25 km altitude is consistent with a leveling off of stratospheric abundances of chlorine and bromine, due to the Montreal Protocol and its amendments. However, ozone increases in the lowest part of the stratosphere, from the tropopause to 18 km, account for about half of the improvement in total column ozone during the past 9 years at northern hemisphere mid-latitudes. The increase in ozone for altitudes below 18 km is most likely driven by changes in transport, rather than driven by declining chlorine and bromine. Even with this evidence that the Montreal Protocol and its amendments are having the desired, positive effect on ozone above 18 km, total column ozone is recovering faster than expected due to the apparent transport driven changes at lower altitudes. Accurate prediction of future levels of stratospheric ozone will require comprehensive understanding of the factors that drive temporal changes at various altitudes, and partitioning of the recent transport-driven increases between natural variability and changes in atmospheric structure perhaps related to anthropogenic climate change.

Bio-derived Fuel Blend Dilution of Marine Engine Oil and Imapct on Friction and Wear Behavior

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

Ajayi, Oyelayo O.; Lorenzo-Martin, Cinta; Fenske, George R.

To reduce the amount of petroleum-derived fuel used in vehicles and vessels powered by internal combustion engines, the addition of bio-derived fuel extenders is a common practice. Ethanol is perhaps the most common bio-derived fuel used for blending, and butanol is being evaluated as a promising alternative. The present study determined the fuel dilution rate of three lubricating oils (E0, E10, and i-B16) in a marine engine operating in on-water conditions with a start-and-stop cycle protocol. The level of fuel dilution increased with the number of cycles for all three fuels. The most dilution was observed with i-B16 fuel, andmore » the least with E10 fuel. In all cases, fuel dilution substantially reduced the oil viscosity. The impacts of fuel dilution and the consequent viscosity reduction on the lubricating capability of the engine oil in terms of friction, wear, and scuffing prevention were evaluated by four different tests protocols. Although the fuel dilution of the engine oil had minimal effect on friction, because the test conditions were under the boundary lubrication regime, significant effects were observed on wear in many cases. Fuel dilution also was observed to reduce the load-carrying capacity of the engine oils in terms of scuffing load reduction.« less

Removing gaps in the exclusion of top squark parameter space.

PubMed

Czakon, Michal; Mitov, Alexander; Papucci, Michele; Ruderman, Joshua T; Weiler, Andreas

2014-11-14

Light stops are a hallmark of the most natural realizations of weak-scale supersymmetry. While stops have been extensively searched for, there remain open gaps around and below the top mass, due to similarities of stop and top signals with current statistics. We propose a new fast-track avenue to improve light stop searches for R-parity-conserving supersymmetry by comparing top cross section measurements to the theoretical prediction. Stop masses below ∼180  GeV can now be ruled out for a light neutralino. The possibility of a stop signal contaminating the top mass measurement is also briefly addressed.

Note on measuring electronic stopping of slow ions

NASA Astrophysics Data System (ADS)

Sigmund, P.; Schinner, A.

2017-11-01

Extracting stopping cross sections from energy-loss measurements requires careful consideration of the experimental geometry. Standard procedures for separating nuclear from electronic stopping treat electronic energy loss as a friction force, ignoring its dependence on impact parameter. In the present study we find that incorporating this dependence has a major effect on measured stopping cross sections, in particular for light ions at low beam energies. Calculations have been made for transmission geometry, nuclear interactions being quantified by Bohr-Williams theory of multiple scattering on the basis of a Thomas-Fermi-Molière potential, whereas electronic interactions are characterized by Firsov theory or PASS code. Differences between the full and the restricted stopping cross section depend on target thickness and opening angle of the detector and need to be taken into account in comparisons with theory as well as in applications of stopping data. It follows that the reciprocity principle can be violated when checked on restricted instead of full electronic stopping cross sections. Finally, we assert that a seeming gas-solid difference in stopping of low-energy ions is actually a metal-insulator difference. In comparisons with experimental results we mostly consider proton data, where nuclear stopping is only a minor perturbation.

Nonlinear effects contributing to hand-stopping tones in a horn.

PubMed

Ebihara, Takayasu; Yoshikawa, Shigeru

2013-05-01

Hand stopping is a technique for playing the French horn while closing the bell relatively tightly using the right hand. The resulting timbre is called "penetrating" and "metallic." The effect of hand stopping on the horn input impedance has been studied, but the tone quality has hardly ever been considered. In the present paper, the dominant physical cause of the stopped-tone quality is discussed in detail. Numerical calculations of the transmission function of the stopped-horn model and the measurements of both sound pressure and wall vibration in hand stopping are carried out. They strongly suggest that the metallicness of the stopped tone is characterized by the generation of higher harmonics extending over 10 kHz due to the rapidly corrugating waveform and that the associated wall vibration on the bell may be responsible for this higher harmonic generation. However, excitation experiments and immobilization experiments performed to elucidate the relationship between sound radiation and wall vibration deny their correlation. Instead, the measurement result of the mouthpiece pressure in hand stopping suggests that minute wave corrugations peculiar to the metallic stopped tones are probably formed by nonlinear sound propagation along the bore.

Stop-like modification of the dental fricative ∕ð∕: An acoustic analysis

PubMed Central

Zhao, Sherry Y.

2010-01-01

This study concentrates on one of the commonly occurring phonetic variations in English: the stop-like modification of the dental fricative ∕ð∕. The variant exhibits a drastic change from the canonical ∕ð∕; the manner of articulation is changed from one that is fricative to one that is stop-like. Furthermore, the place of articulation of stop-like ∕ð∕ has been a point of uncertainty, leading to confusion between stop-like ∕ð∕ and ∕d/. In this study, acoustic and spectral moment measures were taken from 100 stop-like ∕ð∕ and 102 ∕d/ tokens produced by 59 male and 23 female speakers in the TIMIT corpus. Data analysis indicated that stop-like ∕ð∕ is significantly different from ∕d/ in burst amplitude, burst spectrum shape, burst peak frequency, second formant at following-vowel onset, and spectral moments. Moreover, the acoustic differences from ∕d/ are consistent with those expected for a dental stop-like ∕ð∕. Automatic classification experiments involving these acoustic measures suggested that they are salient in distinguishing stop-like ∕ð∕ from ∕d/. PMID:20968372

Effects of age and sex on voice onset time: Evidence from Mandarin voiceless stops.

PubMed

Ma, Junzhou; Chen, Xiaoxiang; Wu, Yezhou; Zhang, Linjie

2018-07-01

Considerable studies have addressed effects of age and sex on voice onset time (VOT) in English. However, few studies have examined these effects on Mandarin stops. This study attempts to examine effects of age and sex on VOT in Mandarin. A total of 85 Mandarin-speaking children, aged 4-18 years old, and 13 adults as reference participated in a production experiment. Productions were elicited by reading target words in carrier phrases. Results showed that children aged 6-7 years old had longer VOTs than older ones for highly aspirated stops, and the same tendency was not observed for unaspirated stops. However, no linear developmental trend was observed for both highly aspirated and unaspirated stops. In addition, females displayed longer VOTs for highly aspirated stops and shorter for unaspirated stops, whereas significant sex differences in VOTs existed from 14 years old to adulthood for highly aspirated stops, and no significant sex differences in VOTs were found for unaspirated stops in each group, indicating that sex differences in VOTs varied with age and aspiration. The findings suggest that physiological changes in and differences between males and females provide account for some, but not all differences in VOTs across age and sex.

Evaluation of bus emissions generated near bus stops

NASA Astrophysics Data System (ADS)

Yu, Qian; Li, Tiezhu

2014-03-01

The purpose of this research is to demonstrate a methodology for quantification of bus emissions generated near bus stops based on the real-world on-road emissions data collected by the Portable Emission Measurement System (PEMS). Data collection was carried out on an urban diesel bus throughout a bus line under normal operation condition on four work days. Stop influence zone is defined as the area in which the normal bus driving is interrupted by bus stops. The second-by-second data were screened out within the stop influence zone. And the bus running state near a stop was classified into three driving modes, deceleration, idling, and acceleration. Then emission characteristics were analyzed for each mode. Under the idling condition, the emission rates (g s-1) were not constant all the time. The NOX emission rate decreased in the first 4-6 s while the corresponding emission rates of CO2, CO, NOX, and HC increased in the last 4 s of idling. Besides, the influence of bus stop characteristics on emissions was investigated using statistical methods. Platform type, length and location of bus stops showed significant effects on the length of the stop influence zone. However, there were no significant effects on distance-based emission factors.

The Influence of End-Stop Buffer Characteristics on the Severity of Suspension Seat End-Stop Impacts

NASA Astrophysics Data System (ADS)

Wu, X.; Griffin, M. J.

1998-08-01

Suspension seat end-stop impacts may be a source of increased risk of injury for the drivers of some machines and work vehicles, such as off-road vehicles. Most suspension seats use rubber buffers to reduce the severity of end-stop impacts, but they still result in a high magnitude of acceleration being transmitted to drivers when an end-stop impact occurs. An experimental study has been conducted to investigate the effect of buffer stiffness and buffer damping on the severity of end-stop impacts. The results show that the end-stop impact performance of suspension seats with only bottom buffers can be improved by the use of both top and bottom buffers. The force-deflection characteristics of rubber buffers had a significant influence on the severity of end-stop impacts. The optimum buffer should have medium stiffness which is nearly linear and occurs over a long deflection, without being compressed to its high stiffness stage. It is shown, theoretically, that buffer damping is capable of significantly reducing the severity of end-stop impacts. However, since current rubber material provides only low damping, alternative materials to those in current use, or either passive or active damping devices, are required.

On the Natural History of Preaspirated Stops

ERIC Educational Resources Information Center

Clayton, Ian D.

2010-01-01

This dissertation makes two contributions, one empirical, the other theoretical. Empirically, the dissertation deepens our understanding of the lifecycle and behavior of the preaspirated stop, an extremely rare phonological feature. I show that in most confirmed cases, preaspirated stops develop from earlier voiceless geminate stops, less commonly…

Does chronic warfarin cause increased blood loss and transfusion during lumbar spinal surgery?

PubMed

Young, Ernest Y; Ahmadinia, Kasra; Bajwa, Navkirat; Ahn, Nicholas U

2013-10-01

The use of oral anticoagulation therapy such as warfarin is projected to increase significantly as the population ages and the prevalence of cardiovascular disease increases. Current recommendations state that warfarin be discontinued before surgery and the international normalized ratio (INR) normalized. To determine if stopping warfarin 7 days before surgery and correcting INR had any effect on intraoperative blood loss or the requirements for blood product transfusion. This was a retrospective cohort study in a high-volume tertiary care center. Sample comprised 263 consecutive patients who underwent elective lumbar spinal surgery. The outcome measures were intraoperative blood loss, intraoperative blood transfusion, postoperative blood transfusion, and the number of blood products transfused. The records of patients undergoing elective spinal surgery were analyzed for patient demographic data, comorbidities, coagulation panel laboratory findings, operative characteristics, blood loss, and blood transfusion requirements. These included patients undergoing full laminectomies with or without posterolateral fusion and instrumentation. Patients on warfarin were analyzed for the mean dosage of warfarin and underlying pathology that required anticoagulation. All patients on warfarin had their anticoagulation therapy stopped 7 days before surgery and their INR checked preoperatively to confirm normalization. Both univariate and multiple linear regression analyses were performed. The patients on warfarin had a mean intraoperative blood loss of 839 mL compared with 441 mL for patients not on warfarin (p<.01). Multiple regression analysis determined that warfarin and number of spinal levels decompressed/fused/instrumented were predictors for increased blood loss (R(2)=0.37). Patients on warfarin also had increased postoperative blood transfusions (23.1% compared with 7.4%, p=.04). There was no significant difference between groups in terms of intraoperative blood transfusion or number of units transfused. Patients on chronic anticoagulation therapy with warfarin who have their therapy stopped 7 days before surgery and have their INR normalized still demonstrated increased intraoperative blood loss and requirement for postoperative transfusion. Surgeons should be aware of the increased propensity of these patients to bleed despite adherence to protocols and should attempt to mitigate this risk. Copyright © 2013 Elsevier Inc. All rights reserved.

SU-C-201-07: Towards Clinical Cherenkov Emission Dosimetry: Stopping Power-To-Cherenkov Power Ratios and Beam Quality Specification of Clinical Electron Beams

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

Zlateva, Y; Seuntjens, J; El Naqa, I

Purpose: We propose a Cherenkov emission (CE)-based reference dosimetry method, which in contrast to ionization chamber-based dosimetry, employs spectrum-averaged electron restricted mass collision stopping power-to-Cherenkov power ratios (SCRs), and we examine Monte Carlo-calculated SCRs and beam quality specification of clinical electron beams. Methods: The EGSnrc user code SPRRZnrc was modified to compute SCRs instead of stopping-power ratios (single medium: water; cut-off: CE threshold (observing Spencer-Attix conditions); CE power: Frank-Tamm). SCRs are calculated with BEAMnrc for realistic electron beams with nominal energies of 6–22 MeV from three Varian accelerators (TrueBeam Clinac 21EX, Clinac 2100C/D) and for mono-energetic beams of energies equalmore » to the mean electron energy at the water surface. Sources of deviation between clinical and mono-energetic SCRs are analyzed quantitatively. A universal fit for the beam-quality index R{sub 50} in terms of the depth of 50% CE C{sub 50} is carried out. Results: SCRs at reference depth are overestimated by mono-energetic values by up to 0.2% for a 6-MeV beam and underestimated by up to 2.3% for a 22-MeV beam. The variation is mainly due to the clinical beam spectrum and photon contamination. Beam angular spread has a small effect across all depths and energies. The influence of the electron spectrum becomes increasingly significant at large depths, while at shallow depths and high beam energies photon contamination is predominant (up to 2.0%). The universal data fit reveals a strong linear correlation between R{sub 50} and C{sub 50} (ρ > 0.99999). Conclusion: CE is inherent to radiotherapy beams and can be detected outside the beam with available optical technologies, which makes it an ideal candidate for out-of-beam high-resolution 3D dosimetry. Successful clinical implementation of CE dosimetry hinges on the development of robust protocols for converting measured CE to radiation dose. Our findings constitute a key step towards clinical CE dosimetry.« less

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial.

PubMed

Molenaar, Nina M; Brouwer, Marlies E; Bockting, Claudi L H; Bonsel, Gouke J; van der Veere, Christine N; Torij, Hanneke W; Hoogendijk, Witte J G; Duvekot, Johannes J; Burger, Huibert; Lambregtse-van den Berg, Mijke P

2016-03-18

Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk. This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy. Netherlands Trial Register (NTR): NTR4694 ; registration date: 16-jul-2014.

Motivational interviewing interactions and the primary health care challenges presented by smokers with low motivation to stop smoking: a conversation analysis.

PubMed

Codern-Bové, Núria; Pujol-Ribera, Enriqueta; Pla, Margarida; González-Bonilla, Javier; Granollers, Silvia; Ballvé, José L; Fanlo, Gemma; Cabezas, Carmen

2014-11-26

Research indicates that one third of smokers have low motivation to stop smoking. The purpose of the study was to use Conversational Analysis to enhance understanding of the process in Motivational Interviewing sessions carried out by primary care doctors and nurses to motivate their patients to quit smoking. The present study is a substudy of the Systematic Intervention on Smoking Habits in Primary Health Care Project (Spanish acronym: ISTAPS). Motivational interviewing sessions with a subset of nine participants (two interview sessions were conducted with two of the nine) in the ISTAPS study who were current smokers and scored fewer than 5 points on the Richmond test that measures motivation to quit smoking were videotaped and transcribed. A total of 11 interviews conducted by five primary health care professionals in Barcelona, Spain, were analysed. Qualitative Content Analysis was used to develop an analytical guide for coding transcriptions. Conversation Analysis allowed detailed study of the exchange of words during the interaction. Motivational Interviewing sessions had three phases: assessment, reflection on readiness to change, and summary. The interaction was constructed during an office visit, where interactional dilemmas arise and can be resolved in various ways. Some actions by professionals (use of reiterations, declarations, open-ended questions) helped to construct a framework of shared relationship; others inhibited this relationship (focusing on risks of smoking, clinging to the protocol, and prematurely emphasizing change). Some professionals tended to resolve interactional dilemmas (e.g., resistance) through a confrontational or directive style. Interactions that did not follow Motivational Interviewing principles predominated in seven of the interviews analysed. Conversational analysis showed that the complexity of the intervention increases when a health professional encounters individuals with low motivation for change, and interactional dilemmas may occur that make it difficult to follow Motivational Interview principles. Incorporating different forms of expression during the Motivational Interviewing could help to build patient-centred health care relationships and, for patients with low motivation to stop smoking, offer an opportunity to reflect on tobacco use during the office visit. The study findings could be included in professional training to improve the quality of motivational interviewing.

SU-E-T-407: Evaluation of the Stopping Power and Imaging Visibility for Iodine Based Contrast in Proton Therapy

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

Singh, H; Zhao, L; Rana, S

2015-06-15

Purpose: The purpose of this study was to investigate the difference between calculated and measured relative linear stopping power (RLSP) for contrast medium in proton therapy. Furthermore, the visibility for different concentrations in prostate phantom on orthogonal X-ray system was evaluated Methods and Materials: In prostate cancer patient, rectal balloon along with the contrast media was used to visualize the balloon position, thus facilitating the patient setup during each fraction of the uniform scanning proton treatment. There were no fiducial markers implanted in the prostate for this patient. A blue wax phantom with outer dimensions 10cm(H) x 14.5cm(L) x 10cm(W)more » was made in house. To hold iodine based contrast solution, a rectangular shaped hole with dimensions 7cm(H) x 8cm(L) x 4cm(W) was made inside the phantom. Organically bound 8.5% iodine based Cystografin Dilute contrast agent with molecular formula C11H9I3N2O4.C7H17NO5 was used in this study. Six solutions were prepared; each mixture of water and iodine based contrast agent at different concentrations as 0%, 5%, 10%, 20%, 30% and 50%. During computed tomographic(CT) simulation, solutions were placed together at the isocenter of CT and scanned at 120kVp using the same protocol as for prostate cancer patients. The treatment planning was done in CMS-XiO system. Multi-layer-ion-chamber (MLIC) was used to measure residual proton range. Results: The 50% concentration contrast solution was used during treatment for better visualization on orthogonal X-ray image. The measured RLSP for 5%, 10%, 20%, 30% & 50% solutions were 1.005, 1.010, 1.018, 1.023 & 1.033; and similarly calculated RLSP from XiO were 1.090, 1.135, 1.222, 1.299 & 1.448 respectively. Conclusion: The treatment planning system could overestimates the relative stopping power of contrast solution with high concentrations. It is recommended to override the contrast with measured RLSP for high atomic number based contrast solution in treatment planning for proton therapy.« less

49 CFR 236.335 - Dogs, stops and trunnions of mechanical locking.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Dogs, stops and trunnions of mechanical locking..., AND APPLIANCES Interlocking Rules and Instructions § 236.335 Dogs, stops and trunnions of mechanical locking. Driving pieces, dogs, stops and trunnions shall be rigidly secured to locking bars. Swing dogs...

49 CFR 236.335 - Dogs, stops and trunnions of mechanical locking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Dogs, stops and trunnions of mechanical locking..., AND APPLIANCES Interlocking Rules and Instructions § 236.335 Dogs, stops and trunnions of mechanical locking. Driving pieces, dogs, stops and trunnions shall be rigidly secured to locking bars. Swing dogs...

49 CFR 236.335 - Dogs, stops and trunnions of mechanical locking.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Dogs, stops and trunnions of mechanical locking..., AND APPLIANCES Interlocking Rules and Instructions § 236.335 Dogs, stops and trunnions of mechanical locking. Driving pieces, dogs, stops and trunnions shall be rigidly secured to locking bars. Swing dogs...

Estimating the crash reduction and vehicle dynamics effects of flashing LED stop signs : final report.

DOT National Transportation Integrated Search

2014-01-01

A flashing LED stop sign is essentially a normal octagonal stop sign with light emitted diodes (LED) on the : stop signs corners. A hierarchical Bayes observational before/after study found an estimated reduction of : about 41.5% in right-angle cr...

49 CFR 236.335 - Dogs, stops and trunnions of mechanical locking.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Dogs, stops and trunnions of mechanical locking..., AND APPLIANCES Interlocking Rules and Instructions § 236.335 Dogs, stops and trunnions of mechanical locking. Driving pieces, dogs, stops and trunnions shall be rigidly secured to locking bars. Swing dogs...

14 CFR 27.675 - Stops.

Code of Federal Regulations, 2013 CFR

2013-01-01

... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Control Systems § 27.675 Stops. (a) Each control system must have stops that positively limit the range of motion of the pilot's controls. (b) Each stop must be located in the system so that the range of travel of its control is not appreciably...

14 CFR 29.675 - Stops.

Code of Federal Regulations, 2013 CFR

2013-01-01

... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Control Systems § 29.675 Stops. (a) Each control system must have stops that positively limit the range of motionof the pilot's controls. (b) Each stop must be located in the system so that the range of travel of its control is not appreciably...

Quality of "Glottal" Stops in Tracheoesophageal Speakers

ERIC Educational Resources Information Center

van Rossum, M. A.; van As-Brooks, C. J.; Hilgers, F. J. M.; Roozen, M.

2009-01-01

Glottal stops are conveyed by an abrupt constriction at the level of the glottis. Tracheoesophageal (TE) speakers are known to have poor control over the new voice source (neoglottis), and this might influence the production of "glottal" stops. This study investigated how TE speakers realized "glottal" stops in abutting words…

Deciding where to Stop Speaking

ERIC Educational Resources Information Center

Tydgat, Ilse; Stevens, Michael; Hartsuiker, Robert J.; Pickering, Martin J.

2011-01-01

This study investigated whether speakers strategically decide where to interrupt their speech once they need to stop. We conducted four naming experiments in which pictures of colored shapes occasionally changed in color or shape. Participants then merely had to stop (Experiment 1); or they had to stop and resume speech (Experiments 2-4). They…

14 CFR 398.8 - Number of intermediate stops.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Number of intermediate stops. 398.8 Section 398.8 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION... Number of intermediate stops. (a) Except in Alaska, no more than one intermediate stop is permitted in...

14 CFR 398.8 - Number of intermediate stops.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Number of intermediate stops. 398.8 Section 398.8 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION... Number of intermediate stops. (a) Except in Alaska, no more than one intermediate stop is permitted in...

49 CFR 236.335 - Dogs, stops and trunnions of mechanical locking.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Dogs, stops and trunnions of mechanical locking..., AND APPLIANCES Interlocking Rules and Instructions § 236.335 Dogs, stops and trunnions of mechanical locking. Driving pieces, dogs, stops and trunnions shall be rigidly secured to locking bars. Swing dogs...

75 FR 19878 - Retroactive Stop Loss Special Pay Compensation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... 0790-AI59] Retroactive Stop Loss Special Pay Compensation AGENCY: Office of the Under Secretary of... Stop Loss Special Pay as authorized and appropriated in The Supplemental Appropriations Act, 2009. This... claims to the Secretaries of the Military Departments for Retroactive Stop Loss Special Pay is October 21...

3 Steps for Setting Healthy Eating Goals

Cancer.gov

3 Steps for Setting Healthy Eating Goals; weight Loss; quit smoking and weight loss; quitting smoking and weight loss; quit smoking weight loss; quitting smoking weight loss; weight loss and quitting smoking; weight loss smoking; weight loss and smoking; stop smoking; stop smoking and weight loss; stop smoking weight loss; stop smoking weight gain women; stopped smoking weight gain; i stopped smoking and i gained weight; stopped smoking gained weight; stop smoking weight gain; stop smoking and weight gain; stop smoking weight gain; stop smoking gain weight; stop smoking without weight gain; effects of smoking; side effects of quitting smoking weight gain; effects of smoking on weight loss; side effects of quitting smoking weight gain; smoking weight loss effects; effects giving up smoking; effect quit smoking; side effects when giving up smoking; effect quit smoking; when giving up smoking what side effects; leaving smoking effects; effects after stop smoking; quitting smoking effects; cigarette smoking; if i stop smoking will I gain weight; stopping cigarette smoking; quitting smoking cigarettes; when you stop smoking cigarettes; quit cigarette smoking; how to quit smoking cigarettes without gaining weight; ways to help stop smoking cigarettes; quitting cigarette smoking; smoking cessation; smoking cessation and weight gain; smoking cessation weight gain; weight gain and smoking cessation; weight gain smoking cessation; you quit; weight gain when you quit smoking; can you gain weight from quitting smoking; do you gain weight from quitting smoking; can quitting smoking make you gain weight; will quitting smoking make you gain weight; after you quit smoking cigarettes; does quitting smoking cause you to gain weight; when you quit smoking; you quit smoking; help you quit smoking; weight gain giving up smoking; after giving up smoking; put on weight; quit smoking put on weight; how to stop smoking and not put on weight; how to not put on weight when quitting smoking; put on weight after quitting smoking; does quitting smoking make you put on weight; weight after; weight gain after quit smoking; gained weight after quitting smoking; why people gain weight after quitting smoking; i gained weight after quitting smoking; how to gain weight after quitting smoking; do people gain weight after quitting smoking; gaining weight after quit smoking; gain weight after quit smoking; gaining weight after stopping smoking; gaining weight after smoking; not smoking; tips to quit smoking and not gain weight; how to not gain weight when you quit smoking; how not to gain weight while quitting smoking; quit smoking not gain weight; quitting smoking and not gaining weight; stop smoking and not gain weight; how to quit smoking and not gain weight; how to not gain weight when quitting smoking; tips for quitting smoking and not gaining weight; how to not gain weight when you quit smoking; how to avoid weight gain when quitting smoking; smoking weight; weight gain when quit smoking; weight gain with quitting smoking; gaining weight quitting smoking; gaining weight from quitting smoking; weight gain while quitting smoking; gaining weight while quitting smoking; gain weight quit smoking; weight gain and quitting smoking; weight gain from quitting smoking; weight gain quit smoking; weight gain; cigarette weight gain; about weight gain; quit smoking weight; smoking weight gain; quit smoking without weight gain

Study of the effective point of measurement for ion chambers in electron beams by Monte Carlo simulation

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

Wang, L. L. W.; Rogers, D. W. O.

In current dosimetry protocols for electron beams, for plane-parallel chambers, the effective point of measurement is at the front face of the cavity, and, for cylindrical chambers, it is at a point shifted 0.5r upstream from the cavity center. In this study, Monte Carlo simulations are employed to study the issue of effective point of measurement for both plane-parallel chambers and cylindrical thimble chambers in electron beams. It is found that there are two ways of determining the position of the effective point of measurement: One is to match the calculated depth-ionization curve obtained from a modeled chamber to amore » calculated depth-dose curve; the other is to match the electron fluence spectrum in the chamber cavity to that in the phantom. For plane-parallel chambers, the effective point of measurement determined by the first method is generally not at the front face of the chamber cavity, which is obtained by the second method, but shifted downstream toward the cavity center by an amount that could be larger than one-half a millimeter. This should not be ignored when measuring depth-dose curves in electron beams. For cylindrical chambers, these two methods also give different positions of the effective point of measurement: The first gives a shift of 0.5r, which is in agreement with measurements for high-energy beams and is the same as the value currently used in major dosimetry protocols; the latter gives a shift of 0.8r, which is closer to the value predicted by a theoretical calculation assuming no-scatter conditions. The results also show that the shift of 0.8r is more appropriate if the cylindrical chamber is to be considered as a Spencer-Attix cavity. In electron beams, since the water/air stopping-power ratio changes with depth in a water phantom, the difference of the two shifts (0.3r) will lead to an incorrect evaluation of the water/air stopping-power ratio at the point of measurement, thus resulting in a systematic error in determining the absorbed dose by cylindrical chambers. It is suggested that a shift of 0.8r be used for electron beam calibrations with cylindrical chambers and a shift of 0.4r-0.5r be used for depth-dose measurements.« less

Study of the effective point of measurement for ion chambers in electron beams by Monte Carlo simulation.

PubMed

Wang, L L W; Rogers, D W O

2009-06-01

In current dosimetry protocols for electron beams, for plane-parallel chambers, the effective point of measurement is at the front face of the cavity, and, for cylindrical chambers, it is at a point shifted 0.5r upstream from the cavity center. In this study, Monte Carlo simulations are employed to study the issue of effective point of measurement for both plane-parallel chambers and cylindrical thimble chambers in electron beams. It is found that there are two ways of determining the position of the effective point of measurement: One is to match the calculated depth-ionization curve obtained from a modeled chamber to a calculated depth-dose curve; the other is to match the electron fluence spectrum in the chamber cavity to that in the phantom. For plane-parallel chambers, the effective point of measurement determined by the first method is generally not at the front face of the chamber cavity, which is obtained by the second method, but shifted downstream toward the cavity center by an amount that could be larger than one-half a millimeter. This should not be ignored when measuring depth-dose curves in electron beams. For cylindrical chambers, these two methods also give different positions of the effective point of measurement: The first gives a shift of 0.5r, which is in agreement with measurements for high-energy beams and is the same as the value currently used in major dosimetry protocols; the latter gives a shift of 0.8r, which is closer to the value predicted by a theoretical calculation assuming no-scatter conditions. The results also show that the shift of 0.8r is more appropriate if the cylindrical chamber is to be considered as a Spencer-Attix cavity. In electron beams, since the water/air stopping-power ratio changes with depth in a water phantom, the difference of the two shifts (0.3r) will lead to an incorrect evaluation of the water/air stopping-power ratio at the point of measurement, thus resulting in a systematic error in determining the absorbed dose by cylindrical chambers. It is suggested that a shift of 0.8r be used for electron beam calibrations with cylindrical chambers and a shift of 0.4r-0.5r be used for depth-dose measurements.

Methodology on quantification of sonication duration for safe application of MR guided focused ultrasound for liver tumour ablation.

PubMed

Mihcin, Senay; Karakitsios, Ioannis; Le, Nhan; Strehlow, Jan; Demedts, Daniel; Schwenke, Michael; Haase, Sabrina; Preusser, Tobias; Melzer, Andreas

2017-12-01

Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for liver tumour ablation is a challenging task due to motion caused by breathing and occlusion due the ribcage between the transducer and the tumour. To overcome these challenges, a novel system for liver tumour ablation during free breathing has been designed. The novel TRANS-FUSIMO Treatment System (TTS, EUFP7) interacts with a Magnetic Resonance (MR) scanner and a focused ultrasound transducer to sonicate to a moving target in liver. To meet the requirements of ISO 13485; a quality management system for medical device design, the system needs to be tested for certain process parameters. The duration of sonication and, the delay after the sonication button is activated, are among the parameters that need to be quantified for efficient and safe ablation of tumour tissue. A novel methodology is developed to quantify these process parameters. A computerised scope is programmed in LabVIEW to collect data via hydrophone; where the coordinates of fiber-optic sensor assembly was fed into the TRANS-FUSIMO treatment software via Magnetic Resonance Imaging (MRI) to sonicate to the tip of the sensor, which is synchronised with the clock of the scope, embedded in a degassed water tank via sensor assembly holder. The sonications were executed for 50 W, 100 W, 150 W for 10 s to quantify the actual sonication duration and the delay after the emergency stop by two independent operators for thirty times. The deviation of the system from the predefined specs was calculated. Student's-T test was used to investigate the user dependency. The duration of sonication and the delay after the sonication were quantified successfully with the developed method. TTS can sonicate with a maximum deviation of 0.16 s (Std 0.32) from the planned duration and with a delay of 14 ms (Std 0.14) for the emergency stop. Student's T tests indicate that the results do not depend on operators (p > .05). The evidence obtained via this protocol is crucial for translation- of-research into the clinics for safe application of MRgFUS. The developed protocol could be used for system maintenance in compliance with quality systems in clinics for daily quality assurance routines. Copyright © 2017 Elsevier B.V. All rights reserved.

Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2): study protocol for a randomised controlled trial.

PubMed

Brown, Sarah; Smith, Isabelle L; Brown, Julia M; Hulme, Claire; McGinnis, Elizabeth; Stubbs, Nikki; Nelson, E Andrea; Muir, Delia; Rutherford, Claudia; Walker, Kay; Henderson, Valerie; Wilson, Lyn; Gilberts, Rachael; Collier, Howard; Fernandez, Catherine; Hartley, Suzanne; Bhogal, Moninder; Coleman, Susanne; Nixon, Jane E

2016-12-20

Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design. ISRCTN01151335 . Registered on 14 May 2013. Protocol version: 5.0, dated 25 September 2015 Trial sponsor: Clare Skinner, Faculty Head of Research Support, University of Leeds, Leeds, LS2 9JT; 0113 343 4897; C.E.Skinner@leeds.ac.uk.

Application of the Low-dose One-stop-shop Cardiac CT Protocol with Third-generation Dual-source CT.

PubMed

Lin, Lu; Wang, Yining; Yi, Yan; Cao, Jian; Kong, Lingyan; Qian, Hao; Zhang, Hongzhi; Wu, Wei; Wang, Yun; Jin, Zhengyu

2017-02-20

Objective To evaluate the feasibility of a low-dose one-stop-shop cardiac CT imaging protocol with third-generation dual-source CT (DSCT). Methods Totally 23 coronary artery disease (CAD) patients were prospectively enrolled between March to September in 2016. All patients underwent an ATP stress dynamic myocardial perfusion imaging (MPI) (data acquired prospectively ECG-triggered during end systole by table shuttle mode in 32 seconds) at 70 kV combined with prospectively ECG-triggered high-pitch coronary artery angiography (CCTA) on a third-generation DSCT system. Myocardial blood flow (MBF) was quantified and compared between perfusion normal and abnormal myocardial segments based on AHA-17-segment model. CCTA images were evaluated qualitatively based on SCCT-18-segment model and the effective dose(ED) was calculated. In patients with subsequent catheter coronary angiography (CCA) as reference,the diagnosis performance of MPI (for per-vessel ≥50% and ≥70% stenosis) and CCTA (for≥50% stenosis) were assessed. Results Of 23 patients who had completed the examination of ATP stress MPI plus CCTA,12 patients received follow-up CCA. At ATP stress MPI,77 segments (19.7%) in 13 patients (56.5%) had perfusion abnormalities. The MBF values of hypo-perfused myocardial segments decreased significantly compared with normal segments [(93±22)ml/(100 ml·min) vs. (147±27)ml/(100 ml·min);t=15.978,P=0.000]. At CCTA,93.9% (308/328) of the coronary segments had diagnostic image quality. With CCA as the reference standard,the per-vessel and per-segment sensitivity,specificity,and accuracy of CCTA for stenosis≥50% were 94.1%,93.5%,and 93.7% and 90.9%,97.8%,and 96.8%,and the per-vessel sensitivity,specificity and accuracy of ATP stress MPI for stenosis≥50% and ≥70% were 68.7%,100%,and 89.5% and 91.7%,100%,and 97.9%. The total ED of MPI and CCTA was (3.9±1.3) mSv [MPI:(3.5±1.2) mSv,CCTA:(0.3±0.1) mSv]. Conclusion The third-generation DSCT stress dynamic MPI at 70 kV combined with prospectively ECG-triggered high-pitch CCTA is a feasible and reliable tool for clinical diagnosis,with remarkably reduced radiation dose.

Prototype Stop Bar System Evaluation at John F. Kennedy International Airport

DTIC Science & Technology

1992-09-01

2 Red Stop Bar Visual Presentation 4 3 Green Stop Bar Visual Presentation 5 4 Photographs of Red and Green Inset Stop Bar Lights 6 5 Photographs of...to green. This provides pilots with a visual confirmation of the controller’s verbal clearance and is intended to prevent runway incursions. The Port...34 colocated with the red lights. The visual presentation of an individual stop bar appears as either five red lights (see figure 2), or five green

Nuclear reactor neutron shielding

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

Speaker, Daniel P; Neeley, Gary W; Inman, James B

A nuclear reactor includes a reactor pressure vessel and a nuclear reactor core comprising fissile material disposed in a lower portion of the reactor pressure vessel. The lower portion of the reactor pressure vessel is disposed in a reactor cavity. An annular neutron stop is located at an elevation above the uppermost elevation of the nuclear reactor core. The annular neutron stop comprises neutron absorbing material filling an annular gap between the reactor pressure vessel and the wall of the reactor cavity. The annular neutron stop may comprise an outer neutron stop ring attached to the wall of the reactormore » cavity, and an inner neutron stop ring attached to the reactor pressure vessel. An excore instrument guide tube penetrates through the annular neutron stop, and a neutron plug comprising neutron absorbing material is disposed in the tube at the penetration through the neutron stop.« less

MS Non-Pharmacological Countermeasure to Decrease Landing Sickness and Improve Functional Performance While Disorientad

NASA Technical Reports Server (NTRS)

Rosenberg, M. J. F.; Kreutzberg, G. A.; Galvan-Garza, R. C.; Mulavara, A. P.; Reschke, M. F.

2017-01-01

Upon return from spaceflight, a majority of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. No operational countermeasure currently exists to mitigate the risks associated with these sensorimotor disturbances. Stochastic resonance (SR) can be thought of simply as "noise benefit" or an increase in information transfer by a system when in the presence of a non-zero level of noise. We have shown that low levels of stochastic vestibular stimulation (SVS) improve balance and locomotor performance due to SR (Goel et al. 2015, Mulavara et al. 2011, 2015). Additionally, a study in a 6-hydroxydopamine (6-OHDA) hemi-lesioned rat model of Parkinson's disease demonstrated improvements in locomotor activity after low-level SVS delivery possibly due to an increase in nigral gamma-aminobutyric acid (GABA) release in a dopamine independent way (Samoudi et al. 2012). SVS specifically increased GABA release on the lesioned, but not the intact side. These results suggest that SVS can cause targeted alterations of GABA release to affect performance of functional tasks. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008). Magnusson et al. (2000) supported this finding by showing that the administration of a GABAB agonist caused a reversal of the symptoms that is normally seen after unilateral labyrinthectomy. Thus, GABA could play a significant role in reducing MS and promoting adaptability. We have taken advantage of the SR mechanism as a modulator of neurotransmitters to develop a unique SVS countermeasure system to mitigate MS symptoms and improve functional performance after landing. Healthy subjects (n=20) participated in two test sessions, one in which they received +/-400 microA of SVS and one where they received no stimulation (0 microA); the study design was counterbalanced. Subjects began by performing a series of four functional tasks 3-5 times as baseline measurements of task performance. Then, to induce MS, subjects walked an obstacle course with up-down reversing prisms. If they completed the course before achieving our pre-determined level of MS, they were asked to read a poster while making large up-down head movements to a metronome while still wearing the reversing prism goggles. Subjects were stopped every two minutes and asked to report their MS symptoms. Using the Pensacola Scale for motion sickness, test operators evaluated the level of MS of each subject. Once a subject reached an 8 on this scale, which is equivalent to mild malaise, or 30 minutes had passed since the start of the MS induction, this protocol was stopped. Finally, immediately after MS induction, subjects were asked to complete the four functional tasks again. Although, 100% of our subjects experienced at least one MS symptom, only 55% of our subjects experienced stomach awareness to any degree. Without SVS, only 40% of subjects lasted the full 30-minute MS induction protocol, while 65% of subjects lasted the full 30 minutes with SVS, which is nearly a significant increase (p=0.056). In addition, subjects showed significant improvement from baseline when performing a tandem walk and a prone-to-stand test immediately after the MS induction protocol was stopped but the stimulation level was continued. The results are promising and future work includes comparing MS progression between PMZ and SVS directly in subjects that are provoked to a minimum of nausea. Low levels of SVS stimulation may serve as a non-pharmacological countermeasure to replace or reduce the PMZ dosage requirements and concurrently improve functional performance during transitions to new gravitational environments after spaceflight.

Stopping while Going! Response Inhibition Does Not Suffer Dual-Task Interference

ERIC Educational Resources Information Center

Yamaguchi, Motonori; Logan, Gordon D.; Bissett, Patrick G.

2012-01-01

Although dual-task interference is ubiquitous in a variety of task domains, stop-signal studies suggest that response inhibition is not subject to such interference. Nevertheless, no study has directly examined stop-signal performance in a dual-task setting. In two experiments, stop-signal performance was examined in a psychological refractory…

Balancing Cognitive Demands: Control Adjustments in the Stop-Signal Paradigm

ERIC Educational Resources Information Center

Bissett, Patrick G.; Logan, Gordon D.

2011-01-01

Cognitive control enables flexible interaction with a dynamic environment. In 2 experiments, the authors investigated control adjustments in the stop-signal paradigm, a procedure that requires balancing speed (going) and caution (stopping) in a dual-task environment. Focusing on the slowing of go reaction times after stop signals, the authors…

The design of a minimal sensor configuration for a Cooperative Intersection Collision Avoidance System - Stop Sign Assist : (CICAS-SSA report #2).

DOT National Transportation Integrated Search

2010-08-01

The deployment of a Cooperative Intersection Collision Avoidance System Stop Sign Assist (CICAS-SSA) can save lives by addressing the causal factor of crashes at rural thru-Stop intersection: drivers who stop on the minor leg of the intersection,...

Post-Stop-Signal Adjustments: Inhibition Improves Subsequent Inhibition

ERIC Educational Resources Information Center

Bissett, Patrick G.; Logan, Gordon D.

2012-01-01

Performance in the stop-signal paradigm involves a balance between going and stopping, and one way that this balance is struck is through shifting priority away from the go task, slowing responses after a stop signal, and improving the probability of inhibition. In 6 experiments, the authors tested whether there is a corresponding shift in…

14 CFR 29.675 - Stops.

Code of Federal Regulations, 2010 CFR

2010-01-01

... stop must be located in the system so that the range of travel of its control is not appreciably...) Stops that are appropriate to the blade design must be provided to limit travel of the blade about its hinge points; and (2) There must be means to keep the blade from hitting the droop stops during any...

14 CFR 27.675 - Stops.

Code of Federal Regulations, 2010 CFR

2010-01-01

... stop must be located in the system so that the range of travel of its control is not appreciably...) Stops that are appropriate to the blade design must be provided to limit travel of the blade about its hinge points; and (2) There must be means to keep the blade from hitting the droop stops during any...

49 CFR 236.502 - Automatic brake application, initiation by restrictive block conditions stopping distance in...

Code of Federal Regulations, 2011 CFR

2011-10-01

... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Standards § 236.502 Automatic brake application, initiation by restrictive block conditions stopping distance in advance. An automatic train-stop or train-control system shall operate to...

46 CFR 64.41 - Stop valve closure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Stop valve closure. 64.41 Section 64.41 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.41 Stop valve closure. A stop valve that operates by a screwed...

33 CFR 183.528 - Fuel stop valves.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Fuel stop valves. 183.528 Section...) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Equipment Standards § 183.528 Fuel stop valves. (a) Each electrically operated fuel stop valve in a fuel line between the fuel tank and the engine...

Stopping Speech Suppresses the Task-Irrelevant Hand

ERIC Educational Resources Information Center

Cai, Weidong; Oldenkamp, Caitlin L.; Aron, Adam R.

2012-01-01

Some situations require one to quickly stop an initiated response. Recent evidence suggests that rapid stopping engages a mechanism that has diffuse effects on the motor system. For example, stopping the hand dampens the excitability of the task-irrelevant leg. However, it is unclear whether this "global suppression" could apply across wider motor…

Post-Stop-Signal Slowing: Strategies Dominate Reflexes and Implicit Learning

ERIC Educational Resources Information Center

Bissett, Patrick G.; Logan, Gordon D.

2012-01-01

Control adjustments are necessary to balance competing cognitive demands. One task that is well-suited to explore control adjustments is the stop-signal paradigm, in which subjects must balance initiation and inhibition. One common adjustment in the stop-signal paradigm is post-stop-signal slowing. Existing models of sequential adjustments in the…

Stop/Start: Overview

Science.gov Websites

1 Stop/Start vehicles use a combination of regenerative and conventional friction braking to slow , The gasoline engine in a start-stop hybrid is much like those in conventional vehicles. Unlike other hybrids that use an electric motor to help power the vehicle, the engine in a start-stop hybrid is usually

A Pause-then-Cancel model of stopping: evidence from basal ganglia neurophysiology.

PubMed

Schmidt, Robert; Berke, Joshua D

2017-04-19

Many studies have implicated the basal ganglia in the suppression of action impulses ('stopping'). Here, we discuss recent neurophysiological evidence that distinct hypothesized processes involved in action preparation and cancellation can be mapped onto distinct basal ganglia cell types and pathways. We examine how movement-related activity in the striatum is related to a 'Go' process and how going may be modulated by brief epochs of beta oscillations. We then describe how, rather than a unitary 'Stop' process, there appear to be separate, complementary 'Pause' and 'Cancel' mechanisms. We discuss the implications of these stopping subprocesses for the interpretation of the stop-signal reaction time-in particular, some activity that seems too slow to causally contribute to stopping when assuming a single Stop processes may actually be fast enough under a Pause-then-Cancel model. Finally, we suggest that combining complementary neural mechanisms that emphasize speed or accuracy respectively may serve more generally to optimize speed-accuracy trade-offs.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'. © 2017 The Author(s).

When Is Rapid On-Site Evaluation Cost-Effective for Fine-Needle Aspiration Biopsy?

PubMed Central

Schmidt, Robert L.; Walker, Brandon S.; Cohen, Michael B.

2015-01-01

Background Rapid on-site evaluation (ROSE) can improve adequacy rates of fine-needle aspiration biopsy (FNAB) but increases operational costs. The performance of ROSE relative to fixed sampling depends on many factors. It is not clear when ROSE is less costly than sampling with a fixed number of needle passes. The objective of this study was to determine the conditions under which ROSE is less costly than fixed sampling. Methods Cost comparison of sampling with and without ROSE using mathematical modeling. Models were based on a societal perspective and used a mechanistic, micro-costing approach. Sampling policies (ROSE, fixed) were compared using the difference in total expected costs per case. Scenarios were based on procedure complexity (palpation-guided or image-guided), adequacy rates (low, high) and sampling protocols (stopping criteria for ROSE and fixed sampling). One-way, probabilistic, and scenario-based sensitivity analysis was performed to determine which variables had the greatest influence on the cost difference. Results ROSE is favored relative to fixed sampling under the following conditions: (1) the cytologist is accurate, (2) the total variable cost ($/hr) is low, (3) fixed costs ($/procedure) are high, (4) the setup time is long, (5) the time between needle passes for ROSE is low, (6) when the per-pass adequacy rate is low, and (7) ROSE stops after observing one adequate sample. The model is most sensitive to variation in the fixed cost, the per-pass adequacy rate, and the time per needle pass with ROSE. Conclusions Mathematical modeling can be used to predict the difference in cost between sampling with and without ROSE. PMID:26317785

Challenging the foundations of the clinical model of foot function: further evidence that the root model assessments fail to appropriately classify foot function.

PubMed

Jarvis, Hannah L; Nester, Christopher J; Bowden, Peter D; Jones, Richard K

2017-01-01

The Root model of normal and abnormal foot function remains the basis for clinical foot orthotic practice globally. Our aim was to investigate the relationship between foot deformities and kinematic compensations that are the foundations of the model. A convenience sample of 140 were screened and 100 symptom free participants aged 18-45 years were invited to participate. The static biomechanical assessment described by the Root model was used to identify five foot deformities. A 6 segment foot model was used to measure foot kinematics during gait. Statistical tests compared foot kinematics between feet with and without foot deformities and correlated the degree of deformity with any compensatory motions. None of the deformities proposed by the Root model were associated with distinct differences in foot kinematics during gait when compared to those without deformities or each other. Static and dynamic parameters were not correlated. Taken as part of a wider body of evidence, the results of this study have profound implications for clinical foot health practice. We believe that the assessment protocol advocated by the Root model is no longer a suitable basis for professional practice. We recommend that clinicians stop using sub-talar neutral position during clinical assessments and stop assessing the non-weight bearing range of ankle dorsiflexion, first ray position and forefoot alignments and movement as a means of defining the associated foot deformities. The results question the relevance of the Root assessments in the prescription of foot orthoses.

The rapid access palliative radiotherapy program: blueprint for initiation of a one-stop multidisciplinary bone metastases clinic.

PubMed

Fairchild, A; Pituskin, E; Rose, B; Ghosh, S; Dutka, J; Driga, A; Tachynski, P; Borschneck, J; Gagnon, L; Macdonnell, S; Middleton, J; Thavone, K; Carstairs, S; Brent, D; Severin, D

2009-02-01

Radiotherapy (RT) for palliation of pain due to bone metastases (BM) is effective but underutilized likely due to the traditional practice of separate clinic visits for consultation, treatment planning, and RT delivery. However, recent evidence proves one RT treatment is as effective as multiple for analgesia, enabling investigation of an alternative model of RT delivery, the rapid access palliative radiotherapy program (RAPRP). Prior to the start of the program, needs assessment was performed to determine the composition of the optimal team. Screening tools were implemented to streamline holistic, multidisciplinary assessment. An advertising strategy, treatment and research protocols, and mechanisms for patient feedback were established. After RAPRP implementation, patient outcomes such as symptom relief were tracked. Eighty-six patients with painful BM were referred over the 25-week pilot. Median age was 69.9 years; 64% had prostate cancer, and median performance status was 70. Patient-rated pain was on average 6.1/10 at baseline, improving to 2.6/10 by week 4 post-RT. On average, 6.2 symptoms were reported (baseline) compared to 5.2 (week 4). Team members assessed 10-100% of patients and were successful in stabilizing or improving all symptoms in >75% contacted at week 4. One hundred percent of patients surveyed were satisfied with their experience. Early needs assessment was advantageous in determining the optimal team and methods of assessment for our 'one-stop' BM clinic. This approach was successful in improving pain and other symptoms, and the convenience of seeing multiple providers on 1 day was appreciated by the patients.

Self-motion improves head direction cell tuning

PubMed Central

Shinder, Michael E.

2014-01-01

Head direction (HD) cells respond when an animal faces a particular direction in the environment and form the basis for the animal's perceived directional heading. When an animal moves through its environment, accurate updating of the HD signal is required to reflect the current heading, but the cells still maintain a representation of HD even when the animal is motionless. This finding suggests that the HD system holds its current state in the absence of input, a view that we tested by rotating a head-restrained rat in the presence of a prominent visual landmark and then stopping it suddenly when facing the cell's preferred firing direction (PFD). Firing rates were unchanged for the first 100 ms, but then progressively decreased over the next 4 s and stabilized at ∼42% of their initial values. When the rat was stopped facing away from the PFD, there was no initial effect of braking, but the firing rate then increased steadily over 4 s and plateaued at ∼14% of its peak firing rate, substantially above initial background firing rates. In experiment 2, the rat was serially placed facing one of eight equidistant directions over 360° and held there for 30 s. Compared with the cell's peak firing rate during a passive rotation session, firing rates were reduced (51%) for in-PFD directions and increased (∼300%) from background levels for off-PFD directions, values comparable to those observed in the braking protocol. These differential HD cell responses demonstrate the importance of self-motion to the HD signal integrity. PMID:24671528

Control of trunk motion following sudden stop perturbations during cart pushing.

PubMed

Lee, Yun-Ju; Hoozemans, Marco J M; van Dieën, Jaap H

2011-01-04

External perturbations during pushing tasks have been suggested to be a risk factor for low-back symptoms. An experiment was designed to investigate whether self-induced and externally induced sudden stops while pushing a high inertia cart influence trunk motions, and how flexor and extensor muscles counteract these perturbations. Twelve healthy male participants pushed a 200 kg cart at shoulder height and hip height. Pushing while walking was compared to situations in which participants had to stop the cart suddenly (self-induced stop) or in which the wheels of the cart were unexpectedly blocked (externally induced stop). For the perturbed conditions, the peak values and the maximum changes from the reference condition (pushing while walking) of the external moment at L5/S1, trunk inclination and electromyographic amplitudes of trunk muscles were determined. In the self-induced stop, a voluntary trunk extension occurred. Initial responses in both stops consisted of flexor and extensor muscle cocontraction. In self-induced stops this was followed by sustained extensor activity. In the externally induced stops, an external extension moment caused a decrease in trunk inclination. The opposite directions of the internal moment and trunk motion in the externally induced stop while pushing at shoulder height may indicate insufficient active control of trunk posture. Consequently, sudden blocking of the wheels in pushing at shoulder height may put the low back at risk of mechanical injury. Copyright © 2010 Elsevier Ltd. All rights reserved.

Bus Stops and Pedestrian-Motor Vehicle Collisions in Lima, Peru: A Matched Case-Control Study

PubMed Central

Quistberg, D. Alex; Koepsell, Thomas D.; Johnston, Brian D.; Boyle, Linda Ng; Miranda, J. Jaime; Ebel, Beth E.

2015-01-01

Objective To evaluate the relationship between bus stop characteristics and pedestrian-motor vehicle collisions. Design Matched case-control study where the units of study were pedestrian crossing. Setting Random sample of 11 police commissaries in Lima, Peru. Data collection occurred from February, 2011 to September, 2011. Participants 97 intersection cases representing 1,134 collisions and 40 mid-block cases representing 469 collisions that occurred between October, 2010 and January, 2011 and their matched controls. Main Exposures Presence of a bus stop and specific bus stop characteristics. Main Outcome Occurrence of a pedestrian-motor vehicle collision. Results Intersections with bus stops were three times more likely to have a pedestrian-vehicle collision (OR 3.28, 95% CI 1.53-7.03), relative to intersections without bus stops. Both formal and informal bus stops were associated with a higher odds of a collision at intersections (OR 6.23, 95% CI 1.76-22.0 and OR 2.98, 1.37-6.49). At mid-block sites, bus stops on a bus-dedicated transit lane were also associated with collision risk (OR 2.36, 95% CI 1.02-5.42). All bus stops were located prior to the intersection, contrary to practices in most high income countries. Conclusions In urban Lima, the presence of a bus stop was associated with a three-fold increase in risk of a pedestrian collision. The highly competitive environment among bus companies may provide an economic incentive for risky practices such as dropping off passengers in the middle of traffic and jockeying for position with other buses. Bus stop placement should be considered to improve pedestrian safety. PMID:24357516

Abbreviated right-sided heart echocardiogram and the STOP-Bang questionnaire-a useful relationship for preoperative patient evaluation?

PubMed

Evans, Rebecca E; Zimmerman, Joshua; Shishido, Sonia; Heath, Elise; Bledsoe, Amber; Johnson, Ken

2016-05-01

The aims of this study were to (1) explore the incidence of right-sided heart dysfunction (RHD) and STOP-Bang questionnaire responses consistent with obstructive sleep apnea (OSA) and (2) assess the relationship between patients with STOP-Bang questionnaire responses consistent with OSA and echocardiographic findings suggestive of RHD. Observational study. Tertiary academic center preoperative clinic. Two hundred patients presenting for elective surgery to the University of Utah preoperative clinic. Abbreviated transthoracic right-sided echocardiogram and STOP-Bang questionnaire. Tricuspid annular plane systolic excursion, tissue Doppler-derived tricuspid lateral annular systolic velocity (S'), and the tricuspid inflow E wave to tricuspid annular tissue Doppler e' wave ratio (E/e') for the presence of RHD, as well as responses to STOP-Bang questionnaire. A total of 140 echocardiograms were analyzed after exclusion of participants with incomplete STOP-Bang questionnaires and inadequate images. Thirty-five patients (25%) reported 5 or more positive responses to the STOP-Bang questionnaire. Forty-six patients (35%) had abnormal right-sided heart measurements. Of the 35 patients with STOP-Bang scores 5 or greater, 11 (31%) had evidence of RHD. No correlation was observed between STOP-Bang scores and the echocardiography metrics of RHD. This preliminary study suggests that there are numerous sources of RHD, among one of which is sleep apnea, and/or the STOP-Bang questionnaire is not a sensitive tool for predicting RHD. We conclude that although the STOP-Bang questionnaire is easy to implement in a preoperative clinical setting, it is not useful in identifying patients at risk for RHD. Copyright © 2015 Elsevier Inc. All rights reserved.

Selective forces and mutational biases drive stop codon usage in the human genome: a comparison with sense codon usage.

PubMed

Trotta, Edoardo

2016-05-17

The three stop codons UAA, UAG, and UGA signal the termination of mRNA translation. As a result of a mechanism that is not adequately understood, they are normally used with unequal frequencies. In this work, we showed that selective forces and mutational biases drive stop codon usage in the human genome. We found that, in respect to sense codons, stop codon usage was affected by stronger selective forces but was less influenced by neutral mutational biases. UGA is the most frequent termination codon in human genome. However, UAA was the preferred stop codon in genes with high breadth of expression, high level of expression, AT-rich coding sequences, housekeeping functions, and in gene ontology categories with the largest deviation from expected stop codon usage. Selective forces associated with the breadth and the level of expression favoured AT-rich sequences in the mRNA region including the stop site and its proximal 3'-UTR, but acted with scarce effects on sense codons, generating two regions, upstream and downstream of the stop codon, with strongly different base composition. By favouring low levels of GC-content, selection promoted labile local secondary structures at the stop site and its proximal 3'-UTR. The compositional and structural context favoured by selection was surprisingly emphasized in the class of ribosomal proteins and was consistent with sequence elements that increase the efficiency of translational termination. Stop codons were also heterogeneously distributed among chromosomes by a mechanism that was strongly correlated with the GC-content of coding sequences. In human genome, the nucleotide composition and the thermodynamic stability of stop codon site and its proximal 3'-UTR are correlated with the GC-content of coding sequences and with the breadth and the level of gene expression. In highly expressed genes stop codon usage is compositionally and structurally consistent with highly efficient translation termination signals.

Identification of Patients with Sleep Disordered Breathing: Comparing the Four-Variable Screening Tool, STOP, STOP-Bang, and Epworth Sleepiness Scales

PubMed Central

Silva, Graciela E.; Vana, Kimberly D.; Goodwin, James L.; Sherrill, Duane L.; Quan, Stuart F.

2011-01-01

Study Objective: The Epworth Sleepiness Scale (ESS) has been used to detect patients with potential sleep disordered breathing (SDB). Recently, a 4-Variable screening tool was proposed to identify patients with SDB, in addition to the STOP and STOP-Bang questionnaires. This study evaluated the abilities of the 4-Variable screening tool, STOP, STOP-Bang, and ESS questionnaires in identifying subjects at risk for SDB. Methods: A total of 4,770 participants who completed polysomnograms in the baseline evaluation of the Sleep Heart Health Study (SHHS) were included. Subjects with RDIs ≥ 15 and ≥ 30 were considered to have moderate-to-severe or severe SDB, respectively. Variables were constructed to approximate those in the questionnaires. The risk of SDB was calculated by the 4-Variable screening tool according to Takegami et al. The STOP and STOP-Bang questionnaires were evaluated including variables for snoring, tiredness/sleepiness, observed apnea, blood pressure, body mass index, age, neck circumference, and gender. Sleepiness was evaluated using the ESS questionnaire and scores were dichotomized into < 11 and ≥ 11. Results: The STOP-Bang questionnaire had higher sensitivity to predict moderate-to-severe (87.0%) and severe (70.4%) SDB, while the 4-Variable screening tool had higher specificity to predict moderate-to-severe and severe SDB (93.2% for both). Conclusions: In community populations such as the SHHS, high specificities may be more useful in excluding low-risk patients, while avoiding false positives. However, sleep clinicians may prefer to use screening tools with high sensitivities, like the STOP-Bang, in order to avoid missing cases that may lead to adverse health consequences and increased healthcare costs. Citation: Silva GE; Vana KD; Goodwin JL; Sherrill DL; Quan SF. Identification of patients with sleep disordered breathing: comparing the Four-Variable screening tool, STOP, STOP-Bang, and Epworth Sleepiness Scales. J Clin Sleep Med 2011;7(5):467-472. PMID:22003341

Study protocol for a pragmatic randomised controlled trial evaluating efficacy of a smoking cessation e-'Tabac Info Service': ee-TIS trial.

PubMed

Cambon, L; Bergman, P; Le Faou, Al; Vincent, I; Le Maitre, B; Pasquereau, A; Arwidson, P; Thomas, D; Alla, F

2017-02-24

A French national smoking cessation service, Tabac Info Service, has been developed to provide an adapted quitline and a web and mobile application involving personalised contacts (eg, questionnaires, advice, activities, messages) to support smoking cessation. This paper presents the study protocol of the evaluation of the application (e-intervention Tabac Info Service (e-TIS)). The primary objective is to assess the efficacy of e-TIS. The secondary objectives are to (1) describe efficacy variations with regard to users' characteristics, (2) analyse mechanisms and contextual conditions of e-TIS efficacy. The study design is a two-arm pragmatic randomised controlled trial including a process evaluation with at least 3000 participants randomised to the intervention or to the control arm (current practices). Inclusion criteria are: aged 18 years or over, current smoker, having completed the online consent forms, possessing a mobile phone with android or apple systems and using mobile applications, wanting to stop smoking sooner or later. The primary outcome is the point prevalence abstinence of 7 days at 6 months later. Data will be analysed in intention to treat (primary) and per protocol analyses. A logistic regression will be carried out to estimate an OR (95% CI) for efficacy. A multivariate multilevel analysis will explore the influence on results of patients' characteristics (sex, age, education and socioprofessional levels, dependency, motivation, quit experiences) and contextual factors, conditions of use, behaviour change techniques. The study protocol was reviewed by the ethical and deontological institutional review board of the French Institute for Public Health Surveillance on 18 April 2016. The findings of this study will allow us to characterise the efficacy of e-TIS and conditions of its efficacy. These findings will be disseminated through peer-reviewed articles. NCT02841683; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effectiveness of a glutaraldehyde formulation in decontamination of dental unit water systems.

PubMed

Gigola, P; Angelillo, V; Garusi, G

2006-01-01

Dental-medical devices may transmit infections caused by bacteria that are usually found in water distribution systems, and which are difficult to treat and control. High bacterial contamination in the water systems of dental units is due to the presence of biofilm inside the pipes. Our study evaluated the efficacy of glutaraldehyde formulated with quarternary ammonium salts (Sanicide T4) examined in a previous study, employing a series of assays to confirm or otherwise the results obtained previously. A purification protocol for the dental unit water system, together with a protocol for daily maintenance treatment, were tested on two dental units (in the Departments of Conservative and Prosthetic Dentistry) taking specimens from the turbine, micro-engine and air-water gun. The chemical substance, at a concentration of 20 cc per litre of water, was allowed to act when the department closed, for a total of 15 days. The Sanicide T4 was handled with protective gloves and the dental units were fitted with two safety devices to avoid accidental ingestion. Laboratory results enabled us to compare values for bacterial load at 36 degrees C and at 22 degrees C and for Pseudomonas aeruginosa, before and after applying the test protocol. Data obtained are satisfactory except for Pseudo-monas in the fountain in the Department of Conservative Dentistry; the value was in any case below the safety level set by the American Dental Association, confirming the results obtained in our previous study. The two protocols may now be considered an excellent solution to control the development of biofilm. Should the product be found to be effective for a longer period of use, each dental unit should be provided with: an anti-reflux valve to stop accidental ingestion of disinfectant; a hydraulic mechanism to pump the product to the handpieces and other water supply devices; possibility of discriminating the use of the public water system from the use of that in the disinfectant circuit; an automatic mechanism whereby the disinfectant can be flushed out with drinking water every morning.

33 CFR 155.780 - Emergency shutdown.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the vessel to stop the flow of oil or hazardous material. (b) The means to stop the flow may be a pump control, a quick-acting, power actuated valve, or an operating procedure. If an emergency pump control is... through the stopped pump. (c) The means to stop the flow must be operable from the cargo deck, cargo...

33 CFR 155.780 - Emergency shutdown.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the vessel to stop the flow of oil or hazardous material. (b) The means to stop the flow may be a pump control, a quick-acting, power actuated valve, or an operating procedure. If an emergency pump control is... through the stopped pump. (c) The means to stop the flow must be operable from the cargo deck, cargo...

33 CFR 155.780 - Emergency shutdown.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the vessel to stop the flow of oil or hazardous material. (b) The means to stop the flow may be a pump control, a quick-acting, power actuated valve, or an operating procedure. If an emergency pump control is... through the stopped pump. (c) The means to stop the flow must be operable from the cargo deck, cargo...

33 CFR 155.780 - Emergency shutdown.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the vessel to stop the flow of oil or hazardous material. (b) The means to stop the flow may be a pump control, a quick-acting, power actuated valve, or an operating procedure. If an emergency pump control is... through the stopped pump. (c) The means to stop the flow must be operable from the cargo deck, cargo...

33 CFR 155.780 - Emergency shutdown.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the vessel to stop the flow of oil or hazardous material. (b) The means to stop the flow may be a pump control, a quick-acting, power actuated valve, or an operating procedure. If an emergency pump control is... through the stopped pump. (c) The means to stop the flow must be operable from the cargo deck, cargo...

Proactive Adjustments of Response Strategies in the Stop-Signal Paradigm

ERIC Educational Resources Information Center

Verbruggen, Frederick; Logan, Gordon D.

2009-01-01

In the stop-signal paradigm, fast responses are harder to inhibit than slow responses, so subjects must balance speed is the go task with successful stopping in the stop task. In theory, subjects achieve this balance by adjusting response thresholds for the go task, making proactive adjustments in response to instructions that indicate that…

Acquisition of Initial /s/-Stop and Stop-/s/ Sequences in Greek

ERIC Educational Resources Information Center

Syrika, Asimina; Nicolaidis, Katerina; Edwards, Jan; Beckman, Mary E.

2011-01-01

Previous work on children's acquisition of complex sequences points to a tendency for affricates to be acquired before clusters, but there is no clear evidence of a difference in order of acquisition between clusters with /s/ that violate the Sonority Sequencing Principle (SSP), such as /s/ followed by stop in onset position, and other clusters…

48 CFR 52.242-15 - Stop-Work Order.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Stop-Work Order. 52.242-15... Stop-Work Order. As prescribed in 42.1305(b), insert the following clause. The 90-day period stated in the clause may be reduced to less than 90 days. Stop-Work Order (AUG 1989) (a) The Contracting Officer...

48 CFR 52.242-15 - Stop-Work Order.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Stop-Work Order. 52.242-15... Stop-Work Order. As prescribed in 42.1305(b), insert the following clause. The 90-day period stated in the clause may be reduced to less than 90 days. Stop-Work Order (AUG 1989) (a) The Contracting Officer...

49 CFR 392.22 - Emergency signals; stopped commercial motor vehicles.

Code of Federal Regulations, 2011 CFR

2011-10-01

... is stopped upon the traveled portion of a highway or the shoulder of a highway for any cause other... commercial motor vehicle is stopped upon the traveled portion or the shoulder of a highway for any cause... 100 feet) from the stopped commercial motor vehicle in the center of the traffic lane or shoulder...

49 CFR 392.22 - Emergency signals; stopped commercial motor vehicles.

Code of Federal Regulations, 2014 CFR

2014-10-01

... is stopped upon the traveled portion of a highway or the shoulder of a highway for any cause other... commercial motor vehicle is stopped upon the traveled portion or the shoulder of a highway for any cause... 100 feet) from the stopped commercial motor vehicle in the center of the traffic lane or shoulder...

49 CFR 392.22 - Emergency signals; stopped commercial motor vehicles.

Code of Federal Regulations, 2013 CFR

2013-10-01

... is stopped upon the traveled portion of a highway or the shoulder of a highway for any cause other... commercial motor vehicle is stopped upon the traveled portion or the shoulder of a highway for any cause... 100 feet) from the stopped commercial motor vehicle in the center of the traffic lane or shoulder...

49 CFR 392.22 - Emergency signals; stopped commercial motor vehicles.

Code of Federal Regulations, 2012 CFR

2012-10-01

... is stopped upon the traveled portion of a highway or the shoulder of a highway for any cause other... commercial motor vehicle is stopped upon the traveled portion or the shoulder of a highway for any cause... 100 feet) from the stopped commercial motor vehicle in the center of the traffic lane or shoulder...

49 CFR 392.22 - Emergency signals; stopped commercial motor vehicles.

Code of Federal Regulations, 2010 CFR

2010-10-01

... is stopped upon the traveled portion of a highway or the shoulder of a highway for any cause other... commercial motor vehicle is stopped upon the traveled portion or the shoulder of a highway for any cause... 100 feet) from the stopped commercial motor vehicle in the center of the traffic lane or shoulder...

Strategies for the Production of Spanish Stop Consonants by Native Speakers of English.

ERIC Educational Resources Information Center

Zampini, Mary L.

A study examined patterns in production of Spanish voiced and voiceless stop consonants by native English speakers, focusing on the interaction between two acoustic cues of stops: voice closure interval and voice onset time (VOT). The study investigated whether learners acquire the appropriate phonetic categories with regard to these stops and if…

Investigation of nuclear stopping observable in heavy ion collisions

NASA Astrophysics Data System (ADS)

Deepshikha; Kumar, Suneel

2018-07-01

Detailed analysis has been made on nuclear stopping using various observable. Transport model, isospin dependent quantum molecular dynamics model (IQMD) has been used to study stopping over the whole mass range at incident energies between 10 MeV/nucleon and 1000 MeV/nucleon. Our study proves that ratio of width of transverse to longitudinal rapidity distribution i.e., < varxz > is the most suitable parameter to study nuclear stopping. Also, it has been observed that light mass fragments (LMF's) emitted from participant region can be used as barometer to study nuclear stopping.

The effect of facial makeup on the frequency of drivers stopping for hitchhikers.

PubMed

Guéguen, Nicolas; Lamy, Lubomir

2013-08-01

Judgments of photographs have shown that makeup enhances ratings of women's facial attractiveness. The present study assessed whether makeup affects the stopping behavior of drivers in response to a hitchhiker's signal. Four 20- to 22-year-old female confederates wore facial makeup, or not, while pretending to be hitchhiking. Frequency of stopping was compared in 1,600 male and female drivers. Facial makeup was associated with an increase in the number of male drivers who stopped to offer a ride. Makeup did not affect frequency of stopping by female drivers.

CRISPR-STOP: gene silencing through base-editing-induced nonsense mutations.

PubMed

Kuscu, Cem; Parlak, Mahmut; Tufan, Turan; Yang, Jiekun; Szlachta, Karol; Wei, Xiaolong; Mammadov, Rashad; Adli, Mazhar

2017-07-01

CRISPR-Cas9-induced DNA damage may have deleterious effects at high-copy-number genomic regions. Here, we use CRISPR base editors to knock out genes by changing single nucleotides to create stop codons. We show that the CRISPR-STOP method is an efficient and less deleterious alternative to wild-type Cas9 for gene-knockout studies. Early stop codons can be introduced in ∼17,000 human genes. CRISPR-STOP-mediated targeted screening demonstrates comparable efficiency to WT Cas9, which indicates the suitability of our approach for genome-wide functional screenings.

Sensitivity analyses of stopping distance for connected vehicles at active highway-rail grade crossings.

PubMed

Hsu, Chung-Jen; Jones, Elizabeth G

2017-02-01

This paper performs sensitivity analyses of stopping distance for connected vehicles (CVs) at active highway-rail grade crossings (HRGCs). Stopping distance is the major safety factor at active HRGCs. A sensitivity analysis is performed for each variable in the function of stopping distance. The formulation of stopping distance treats each variable as a probability density function for implementing Monte Carlo simulations. The result of the sensitivity analysis shows that the initial speed is the most sensitive factor to stopping distances of CVs and non-CVs. The safety of CVs can be further improved by the early provision of onboard train information and warnings to reduce the initial speeds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Addressing sexual health needs: a comparison of a one-stop shop with separate genitourinary medicine and family planning services.

PubMed

French, Rebecca S; Mercer, Catherine H; Robinson, Angela J; Gerressu, Makeda; Rogstad, Karen E

2010-10-01

Little evidence is available on the extent to which one-stop shops address users' sexual health needs and the extent to which they identify additional needs users may not have identified. As part of the One-Stop Shop Evaluation, a questionnaire was designed to compare the reasons for users' visits and the reported outcomes of visits at a one-stop shop with the experiences of users in separate genitourinary medicine (GUM) and contraceptive clinics. The difference in the proportions of those attending the one-stop shop and those attending the control sites services for a sexually transmitted infection (STI)-related reason who were diagnosed with an STI was minimal, but those attending for an STI-related reason in the one-stop shop were more likely to receive an additional contraceptive outcome. Women attending for a contraceptive-related reason at the one-stop shop were more likely to have an STI screen than those attending the control sites for the same reason, but there was little difference in the proportions amongst this group receiving an STI diagnosis or receiving treatment. When focusing on women attending for a pregnancy-related reason, one-stop shop users were more likely to have received contraceptive advice or supplies. It was not possible in our evaluation to determine the relative effectiveness of the one-stop shop in comparison to the traditional GUM and contraceptive clinics in improving sexual health status, however the one-stop shop was more likely to address additional sexual health needs that service users may not have previously identified.

Additional band broadening of peptides in the first size-exclusion chromatographic dimension of an automated stop-flow two-dimensional high performance liquid chromatography.

PubMed

Xu, Jucai; Sun-Waterhouse, Dongxiao; Qiu, Chaoying; Zhao, Mouming; Sun, Baoguo; Lin, Lianzhu; Su, Guowan

2017-10-27

The need to improve the peak capacity of liquid chromatography motivates the development of two-dimensional analysis systems. This paper presented a fully automated stop-flow two-dimensional liquid chromatography system with size exclusion chromatography followed by reversed phase liquid chromatography (SEC×RPLC) to efficiently separate peptides. The effects of different stop-flow operational parameters (stop-flow time, peak parking position, number of stop-flow periods and column temperature) on band broadening in the first dimension (1 st D) SEC column were quantitatively evaluated by using commercial small proteins and peptides. Results showed that the effects of peak parking position and the number of stop-flow periods on band broadening were relatively small. Unlike stop-flow analysis of large molecules with a long running time, additional band broadening was evidently observed for small molecule analytes due to the relatively high effective diffusion coefficient (D eff ). Therefore, shorter analysis time and lower 1 st D column temperature were suggested for analyzing small molecules. The stop-flow two-dimensional liquid chromatography (2D-LC) system was further tested on peanut peptides and an evidently improved resolution was observed for both stop-flow heart-cutting and comprehensive 2D-LC analysis (in spite of additional band broadening in SEC). The stop-flow SEC×RPLC, especially heart-cutting analysis with shorter analysis time and higher 1 st D resolution for selected fractions, offers a promising approach for efficient analysis of complex samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Perceptual assessment of fricative--stop coarticulation.

PubMed

Repp, B H; Mann, V A

1981-04-01

The perceptual dependence of stop consonants on preceding fricatives [Mann and Repp, J. Acoust. Soc. Am. 69, 548--558 (1981)] was further investigated in two experiments employing both natural and synthetic speech. These experiments consistently replicated our original finding that listeners, report velar stops following [s]. In addition, our data confirmed earlier reports that natural fricative noises (excerpted from utterances of [st alpha], [sk alpha], [(formula: see text)k alpha]) contain cues to the following stop consonants; this was revealed in subjects' identifications of stops from isolated fricative noises and from stimuli consisting of these noises followed by synthetic CV portions drawn from a [t alpha]--[k alpha] continuum. However, these cues in the noise portion could not account for the contextual effect of fricative identity ([formula: see text] versus [sp) on stop perception (more "k" responses following [s]). Rather, this effect seems to be related to a coarticulatory influence of a preceding fricative on stop production; Subjects' responses to excised natural CV portions (with bursts and aspiration removed) were biased towards a relatively more forward place of stop articulation when the CVs had originally been preceded by [s]; and the identification of a preceding ambiguous fricative was biased in the direction of the original fricative context in which a given CV portion had been produced. These findings support an articulatory explanation for the effect of preceding fricatives on stop consonant perception.

Developing Effective Linkages between Job Corps and One-Stop Systems: A Technical Assistance Guide.

ERIC Educational Resources Information Center

Dickinson, Katherine; Soukamneuth, Sengsouvanh

This document is intended to help Job Corps centers and Office of Acquisition Policy contractors establish linkages with one-stop systems. Chapter 1 summarizes the requirements for linkages between Job Corps and one-stop systems that are specified in the Workforce Investment Act (WIA) of 1998 and compares one-stop delivery systems before and under…

49 CFR Appendix A to Part 180 - Internal Self-closing Stop Valve Emergency Closure Test for Liquefied Compressed Gases

Code of Federal Regulations, 2011 CFR

2011-10-01

... Part 180—Internal Self-closing Stop Valve Emergency Closure Test for Liquefied Compressed Gases 1. In performing this test, all internal self-closing stop valves must be opened. Each emergency discharge control... 49 Transportation 3 2011-10-01 2011-10-01 false Internal Self-closing Stop Valve Emergency Closure...

49 CFR Appendix B to Part 180 - Acceptable Internal Self-closing Stop Valve Leakage Tests for Cargo Tanks Transporting Liquefied...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Acceptable Internal Self-closing Stop Valve... Pt. 180, App. B Appendix B to Part 180—Acceptable Internal Self-closing Stop Valve Leakage Tests for Cargo Tanks Transporting Liquefied Compressed Gases For internal self-closing stop valve leakage testing...

Low-bias flat band-stop filter based on velocity modulated gaussian graphene superlattice

NASA Astrophysics Data System (ADS)

Sattari-Esfahlan, S. M.; Shojaei, S.

2018-05-01

Transport properties of biased planar Gaussian graphene superlattice (PGGSL) with Fermi velocity barrier is investigated by transfer matrix method (TMM). It is observed that enlargement of bias voltage over miniband width breaks the miniband to WSLs leads to suppressing resonant tunneling. Transmission spectrum shows flat wide stop-band property controllable by external bias voltage with stop-band width of near 200 meV. The simulations demonstrate that strong velocity barriers prevent tunneling of Dirac electrons leading to controllable enhancement of stop-band width. By increasing ratio of Fermi velocity in barriers to wells υc stop-band width increase. As wide transmission stop-band width (BWT) of filter is tunable from 40 meV to 340 meV is obtained by enhancing ratio of υc from 0.2 to 1.5, respectively. Proposed structure suggests easy tunable wide band-stop electronic filter with a modulated flat stop-band characteristic by height of electrostatic barrier and structural parameters. Robust sensitivity of band width to velocity barrier intensity in certain bias voltages and flat band feature of proposed filter may be opens novel venue in GSL based flat band low noise filters and velocity modulation devices.

Evidence for interaction between the stop signal and the Stroop task conflict.

PubMed

Kalanthroff, Eyal; Goldfarb, Liat; Henik, Avishai

2013-04-01

Performance of the Stroop task reflects two conflicts--informational (between the incongruent word and ink color) and task (between relevant color naming and irrelevant word reading). The task conflict is usually not visible, and is only seen when task control is damaged. Using the stop-signal paradigm, a few studies demonstrated longer stop-signal reaction times for incongruent trials than for congruent trials. This indicates interaction between stopping and the informational conflict. Here we suggest that "zooming in" on task-control failure trials will reveal another interaction--between stopping and task conflict. To examine this suggestion, we combined stop-signal and Stroop tasks in the same experiment. When participants' control failed and erroneous responses to a stop signal occurred, a reverse facilitation emerged in the Stroop task (Experiment 1) and this was eliminated using methods that manipulated the emergence of the reverse facilitation (Experiment 2). Results from both experiments were replicated when all stimuli were used in the same task (Experiment 3). In erroneous response trials, only the task conflict increased, not the informational conflict. These results indicate that task conflict and stop-signal inhibition share a common control mechanism that is dissociable from the control mechanism activated by the informational conflict.

Dissociable brain mechanisms underlying the conscious and unconscious control of behavior.

PubMed

van Gaal, Simon; Lamme, Victor A F; Fahrenfort, Johannes J; Ridderinkhof, K Richard

2011-01-01

Cognitive control allows humans to overrule and inhibit habitual responses to optimize performance in challenging situations. Contradicting traditional views, recent studies suggest that cognitive control processes can be initiated unconsciously. To further capture the relation between consciousness and cognitive control, we studied the dynamics of inhibitory control processes when triggered consciously versus unconsciously in a modified version of the stop task. Attempts to inhibit an imminent response were often successful after unmasked (visible) stop signals. Masked (invisible) stop signals rarely succeeded in instigating overt inhibition but did trigger slowing down of response times. Masked stop signals elicited a sequence of distinct ERP components that were also observed on unmasked stop signals. The N2 component correlated with the efficiency of inhibitory control when elicited by unmasked stop signals and with the magnitude of slowdown when elicited by masked stop signals. Thus, the N2 likely reflects the initiation of inhibitory control, irrespective of conscious awareness. The P3 component was much reduced in amplitude and duration on masked versus unmasked stop trials. These patterns of differences and similarities between conscious and unconscious cognitive control processes are discussed in a framework that differentiates between feedforward and feedback connections in yielding conscious experience.

Nicotine Dependence

MedlinePlus

... smoke. You may stop going to smoke-free restaurants or stop socializing with certain family members or ... smoke-free. Encourage smoke-free public places, including restaurants. Become active in community and school-based stop- ...

Stopping distance for high energy jets in weakly coupled quark-gluon plasmas

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

Arnold, Peter; Cantrell, Sean; Xiao Wei

2010-02-15

We derive a simple formula for the stopping distance for a high-energy quark traveling through a weakly coupled quark-gluon plasma. The result is given to next-to-leading order in an expansion in inverse logarithms ln(E/T), where T is the temperature of the plasma. We also define a stopping distance for gluons and give a leading-log result. Discussion of stopping distance has a theoretical advantage over discussion of energy loss rates in that stopping distances can be generalized to the case of strong coupling, where one may not speak of individual partons.

Stopping power measurements with the Time-of-Flight (ToF) technique

DOE PAGES

Fontana, Cristiano L.; Chen, Chien-Hung; Crespillo, Miguel L.; ...

2015-11-10

In our review of measurements of the stopping power of ions in matter is presented along with new measurements of the stopping powers of O, Si, Ti, and Au ions in self-supporting thin foils of SiO 2, Nb 2O 5, and Ta 2O 5. Moreover, a Time-of-Flight system at the Ion Beam Materials Laboratory at the University of Tennessee, Knoxville, was used in transmission geometry in order to reduce experimental uncertainties. Finally, the resulting stopping powers show good precision and accuracy and corroborate previously quoted values in the literature. New stopping data are determined.

Stopping power measurements with the Time-of-Flight (ToF) technique

NASA Astrophysics Data System (ADS)

Fontana, Cristiano L.; Chen, Chien-Hung; Crespillo, Miguel L.; Graham, Joseph T.; Xue, Haizhou; Zhang, Yanwen; Weber, William J.

2016-01-01

A review of measurements of the stopping power of ions in matter is presented along with new measurements of the stopping powers of O, Si, Ti, and Au ions in self-supporting thin foils of SiO2, Nb2O5, and Ta2O5. A Time-of-Flight system at the Ion Beam Materials Laboratory at the University of Tennessee, Knoxville, was used in transmission geometry in order to reduce experimental uncertainties. The resulting stopping powers show good precision and accuracy and corroborate previously quoted values in the literature. New stopping data are determined.

Simultaneously firing two cylinders of an even firing camless engine

DOEpatents

Brennan, Daniel G

2014-03-11

A valve control system includes an engine speed control module that determines an engine speed and a desired engine stop position. A piston position module determines a desired stopping position of a first piston based on the desired engine stop position. A valve control module receives the desired stopping position, commands a set of valves to close at the desired stopping position if the engine speed is less than a predetermined shutdown threshold, and commands the set of valves to reduce the engine speed if the engine speed is greater than the predetermined shutdown threshold.

Dynamics of response-conflict monitoring and individual differences in response control and behavioral control: an electrophysiological investigation using a stop-signal task.

PubMed

Stahl, Jutta; Gibbons, Henning

2007-03-01

The aim of the present study was to investigate the functional significance of error (related) negativity Ne/ERN and individual differences in human action monitoring. A response-conflict model of Ne/ERN should be tested applying a stop-signal paradigm. After a few modifications of Ne/ERN response-conflict theory (Yeung N, Botvinick MM, Cohen JD. The neural basis of error detection: conflict monitoring and the error-related negativity. Psychological Review 2004:111(4);931-959), strength and time course of response conflict could be modeled as a function of stop-signal delay. In Experiment 1, 35 participants performed a visual two-choice response-time task but tried to withhold the response if an auditory stop signal was presented. Probability of stopping errors was held at 50% using variable delays between visual and auditory stimuli. Experiment 2 (n=10) employed both auditory go and stop signals and confirmed that Ne/ERN effects are due to conflict induced by the auditory stop signal, and not the mere presence or absence of an additional stimulus. As predicted, amplitudes of both the stimulus-locked and response-locked Ne/ERN were largest for non-stopped responses, followed by successfully stopped and go responses. However, independently of response type Ne/ERN also increased with increasing stop-signal delay. Since longer delay invokes stronger response conflict, results specifically support the notion of Ne/ERN reflecting response-conflict monitoring. Furthermore, individual differences related to measures of response control and behavioral control were observed. Both low response control estimated from stop-task performance and high psychometric impulsivity were accompanied by smaller Ne/ERN amplitude on stop trials, suggesting reduced response-conflict monitoring. The present study supported the response-conflict view of Ne/ERN. Furthermore, the observed relationship between impulsivity and Ne/ERN amplitude suggested that individuals with low behavioral control were characterized by lower activity in anterior cingulate cortex, the neural generator of Ne/ERN, in situations of strong response conflict. The present study, for the first time, employed a stop-signal paradigm to verify predictions regarding the temporal dynamics of response-conflict processing as derived from response-conflict theory of ERN.

30 CFR 57.22218 - Seals and stoppings (III, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (III, V-A, and V-B mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22218 Seals and stoppings (III, V-A, and V-B mines). (a) All seals, and those stoppings that separate main intake from main...

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

30 CFR 57.22218 - Seals and stoppings (III, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (III, V-A, and V-B mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22218 Seals and stoppings (III, V-A, and V-B mines). (a) All seals, and those stoppings that separate main intake from main...

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

Tobacco control programmes for universities: a feasibility study.

PubMed

Willcox, M L

1997-03-01

University may be a good time for smoking cessation, because younger, lighter smokers are more successful at stopping. An initial survey of 4141 students at Cambridge and Anglia Polytechnic universities identified the prevalence of smoking; questionnaires were given to smokers asking about desire to stop. Some respondents were invited to a discussion, but very few came. Those wanting to quit were sent a second questionnaire about what help they wanted. On National No Smoking Day, 101 students were interviewed about "stop smoking' advertisements, and those wanting to stop smoking were offered different forms of help. Lastly, student union welfare officers at 54 universities in the United Kingdom were interviewed over the telephone, about what motivation and support they provide for students to stop smoking, and what more they would consider providing. Prevalence of smoking varied according to university, subject studied and sex. Desire to quit varied with subject studied, duration of habit and amount smoked. Some "stop smoking' TV adverts were widely remembered, but their motivational impact remains unclear. Most of those wanting to stop found it difficult, but few requested help unless approached directly. Only books were widely used, and innovative ones seemed most popular. Few student unions provided effective encouragement or help for students to stop smoking. Most said they would consider doing more. There is a need for smoking cessation programmes at universities. More research is needed on ways of motivating those who do not want to stop. "Direct marketing' of books seems the best way of reaching those who want to stop. The effectiveness of different books needs to be evaluated. There is great potential for improving the quality, quantity and availability of cessation aids through student unions.

A new assessment method of outdoor tobacco smoke (OTS) exposure

NASA Astrophysics Data System (ADS)

Cho, Hyeri; Lee, Kiyoung

2014-04-01

Outdoor tobacco smoke (OTS) is concerned due to potential health effects. An assessment method of OTS exposure is needed to determine effects of OTS and validate outdoor smoking policies. The objective of this study was to develop a new method to assess OTS exposure. This study was conducted at 100 bus stops including 50 centerline bus stops and 50 roadside bus stops in Seoul, Korea. Using real-time aerosol monitor, PM2.5 was measured for 30 min at each bus stop in two seasons. ‘Peak analysis' method was developed to assess short term PM2.5 exposure by OTS. The 30-min average PM2.5 exposure at each bus stop was associated with season and bus stop location but not smoking activity. The PM2.5 peak occurrence rate by the peak analysis method was significantly associated with season, bus stop location, observed smoking occurrence, and the number of buses servicing a route. The PM2.5 peak concentration was significantly associated with season, smoking occurrence, and the number of buses servicing a route. When a smoker was standing still at the bus stop, magnitude of peak concentrations were significantly higher than when the smoker walking-through the bus stop. People were exposed to high short-term PM2.5 peak levels at bus stops, and the magnitude of peak concentrations were highest when a smoker was located close to the monitor. The magnitude of peak concentration was a good indicator helped distinguish nearby OTS exposure. Further research using ‘peak analysis' is needed to measure smoking-related exposure to PM2.5 in other outdoor locations.

Tourette Syndrome: Help Stop Bullying

MedlinePlus

... Submit Button Past Emails Tourette Syndrome: Help Stop Bullying Language: English (US) Español (Spanish) Recommend on Facebook ... you can increase acceptance by helping to stop bullying of children with TS. Bullying doesn’t just ...

Automobile Stopping Distances.

ERIC Educational Resources Information Center

Logue, L. J.

1979-01-01

Discusses the effect of vehicle mass on stopping distances. Analyzes an example of a sample vehicle and tire, and calculates the braking acceleration showing the effect of different factors on the stopping performance of the tires. (GA)

Pseudouridines have context-dependent mutation and stop rates in high-throughput sequencing.

PubMed

Zhou, Katherine I; Clark, Wesley C; Pan, David W; Eckwahl, Matthew J; Dai, Qing; Pan, Tao

2018-05-11

The abundant RNA modification pseudouridine (Ψ) has been mapped transcriptome-wide by chemically modifying pseudouridines with carbodiimide and detecting the resulting reverse transcription stops in high-throughput sequencing. However, these methods have limited sensitivity and specificity, in part due to the use of reverse transcription stops. We sought to use mutations rather than just stops in sequencing data to identify pseudouridine sites. Here, we identify reverse transcription conditions that allow read-through of carbodiimide-modified pseudouridine (CMC-Ψ), and we show that pseudouridines in carbodiimide-treated human ribosomal RNA have context-dependent mutation and stop rates in high-throughput sequencing libraries prepared under these conditions. Furthermore, accounting for the context-dependence of mutation and stop rates can enhance the detection of pseudouridine sites. Similar approaches could contribute to the sequencing-based detection of many RNA modifications.

Design and Analysis of a Triple Stop-band Filter Using Ratioed Periodical Defected Microstrip Structure

NASA Astrophysics Data System (ADS)

Jiang, Tao; Wang, Yanyan; Li, Yingsong

2017-07-01

In this paper, a triple stop-band filter with a ratioed periodical defected microstrip structure is proposed for wireless communication applications. The proposed ratioed periodical defected microstrip structures are spiral slots, which are embedded into a 50 Ω microstrip line to obtain multiple stop-bands. The performance of the proposed triple stop-band filter is investigated numerically and experimentally. Moreover, the equivalent circuit model of the proposed filter is also established and discussed. The results are given to verify that the proposed triple stop-band filter has three stop bands at 3.3 GHz, 5.2 GHz, 6.8 GHz to reject the unwanted signals, which is promising for integrating into UWB communication systems to efficiently prevent the potential interferences from unexpected narrowband signals such as WiMAX, WLAN and RFID communication systems.

Stop coannihilation in the CMSSM and SubGUT models

NASA Astrophysics Data System (ADS)

Ellis, John; Evans, Jason L.; Luo, Feng; Olive, Keith A.; Zheng, Jiaming

2018-05-01

Stop coannihilation may bring the relic density of heavy supersymmetric dark matter particles into the range allowed by cosmology. The efficiency of this process is enhanced by stop-antistop annihilations into the longitudinal (Goldstone) modes of the W and Z bosons, as well as by Sommerfeld enhancement of stop annihilations and the effects of bound states. Since the couplings of the stops to the Goldstone modes are proportional to the trilinear soft supersymmetry-breaking A-terms, these annihilations are enhanced when the A-terms are large. However, the Higgs mass may be reduced below the measured value if the A-terms are too large. Unfortunately, the interpretation of this constraint on the stop coannihilation strip is clouded by differences between the available Higgs mass calculators. For our study, we use as our default calculator FeynHiggs 2.13.0, the most recent publicly available version of this code. Exploring the CMSSM parameter space, we find that along the stop coannihilation strip the masses of the stops are severely split by the large A-terms. This suppresses the Higgs mass drastically for μ and A_0 > 0, whilst the extent of the stop coannihilation strip is limited for A_0 < 0 and either sign of μ . However, in sub-GUT models, reduced renormalization-group running mitigates the effect of the large A-terms, allowing larger LSP masses to be consistent with the Higgs mass calculation. We give examples where the dark matter particle mass may reach ≳ 8 TeV.

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

Jin, Ke; Zhang, Yanwen; Zhu, Zihua

Accurate information of electronic stopping power is fundamental for broad advances in electronic industry, space exploration, national security, and sustainable energy technologies. The Stopping and Range of Ions in Matter (SRIM) code has been widely applied to predict stopping powers and ion distributions for decades. Recent experimental results have, however, shown considerable errors in the SRIM predictions for stopping of heavy ions in compounds containing light elements, indicating an urgent need to improve current stopping power models. The electronic stopping powers of 35Cl, 80Br, 127I, and 197Au ions are experimentally determined in two important functional materials, SiC and SiO2, frommore » tens to hundreds keV/u based on a single ion technique. By combining with the reciprocity theory, new electronic stopping powers are suggested in a region from 0 to 15 MeV, where large deviations from SRIM predictions are observed. For independent experimental validation of the electronic stopping powers we determined, Rutherford backscattering spectrometry (RBS) and secondary ion mass spectrometry (SIMS) are utilized to measure the depth profiles of implanted Au ions in SiC with energies from 700 keV to 15 MeV. The measured ion distributions from both RBS and SIMS are considerably deeper (up to ~30%) than the predictions from the commercial SRIM code. In comparison, the new electronic stopping power values are utilized in a modified TRIM-85 (the original version of the SRIM) code, M-TRIM, to predict ion distributions, and the results are in good agreement with the experimentally measured ion distributions.« less

Rapid gait termination: effects of age, walking surfaces and footwear characteristics.

PubMed

Menant, Jasmine C; Steele, Julie R; Menz, Hylton B; Munro, Bridget J; Lord, Stephen R

2009-07-01

The aim of this study was to systematically investigate the influence of various walking surfaces and footwear characteristics on the ability to terminate gait rapidly in 10 young and 26 older people. Subjects walked at a self-selected speed in eight randomized shoe conditions (standard versus elevated heel, soft sole, hard sole, high-collar, flared sole, bevelled heel and tread sole) on three surfaces: control, irregular and wet. In response to an audible cue, subjects were required to stop as quickly as possible in three out of eight walking trials in each condition. Time to last foot contact, total stopping time, stopping distance, number of steps to stop, step length and step width post-cue and base of support length at total stop were calculated from kinematic data collected using two CODA scanner units. The older subjects took more time and a longer distance to last foot contact and were more frequently classified as using a three or more-steps stopping strategy compared to the young subjects. The wet surface impeded gait termination, as indicated by greater total stopping time and stopping distance. Subjects required more time to terminate gait in the soft sole shoes compared to the standard shoes. In contrast, the high-collar shoes reduced total stopping time on the wet surface. These findings suggest that older adults have more difficulty terminating gait rapidly than their younger counterparts and that footwear is likely to influence whole-body stability during challenging postural tasks on wet surfaces.

Higgs-stoponium mixing near the stop-antistop threshold

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

Bodwin, Geoffrey T.; Chung, Hee Sok; Wagner, Carlos E. M.

Supersymmetric extensions of the standard model contain additional heavy neutral Higgs bosons that are coupled to heavy scalar top quarks (stops). This system exhibits interesting field theoretic phenomena when the Higgs mass is close to the stop-antistop production threshold. Existing work in the literature has examined the digluon-to-diphoton cross section near threshold and has focused on enhancements in the cross section that might arise either from the perturbative contributions to the Higgs-to-digluon and Higgs-to-diphoton form factors or from mixing of the Higgs boson with stoponium states. Near threshold, enhancements in the relevant amplitudes that go as inverse powers of themore » stop-antistop relative velocity require resummations of perturbation theory and/or nonperturbative treatments. We present a complete formulation of threshold effects at leading order in the stop-antistop relative velocity in terms of nonrelativistic effective field theory. We give detailed numerical calculations for the case in which the stop-antistop Green’s function is modeled with a Coulomb-Schr¨odinger Green’s function. We find several general effects that do not appear in a purely perturbative treatment. Higgs-stop-antistop mixing effects displace physical masses from the threshold region, thereby rendering the perturbative threshold enhancements inoperative. In the case of large Higgs-stop-antistop couplings, the displacement of a physical state above threshold substantially increases its width, owing to its decay width to a stop-antistop pair, and greatly reduces its contribution to the cross section.« less

Light stop mass limits from Higgs rate measurements in the MSSM: Is MSSM electroweak baryogenesis still alive after all?

DOE PAGES

Liebler, Stefan; Profumo, Stefano; Stefaniak, Tim

2016-04-22

We investigate the implications of the Higgs rate measurements from Run 1 of the LHC for the mass of the light scalar top partner (stop) in the Minimal Supersymmetric Standard Model (MSSM). We focus on light stop masses, and we decouple the second, heavy stop and the gluino to the multi-TeV range in order to obtain a Higgs mass of ~125 GeV. We derive lower mass limits for the light stop within various scenarios, taking into account the effects of a possibly light scalar tau partner (stau) or chargino on the Higgs rates, of additional Higgs decays to undetectable “newmore » physics”, as well as of non-decoupling of the heavy Higgs sector. Under conservative assumptions, the stop can be as light as 123 GeV. Relaxing certain theoretical and experimental constraints, such as vacuum stability and model-dependent bounds on sparticle masses from LEP, we find that the light stop mass can be as light as 116 GeV. Lastly, our indirect limits are complementary to direct limits on the light stop mass from collider searches and have important implications for electroweak baryogenesis in the MSSM as a possible explanation for the observed matter-antimatter asymmetry of the Universe.« less

Sensorimotor-Independent Prefrontal Activity During Response Inhibition

PubMed Central

Cai, Weidong; Cannistraci, Christopher J.; Gore, John C.; Leung, Hoi-Chung

2015-01-01

A network of brain regions involving the ventral inferior frontal gyrus/anterior insula (vIFG/AI), presupplementary motor area (pre-SMA) and basal ganglia has been implicated in stopping impulsive, unwanted responses. However, whether this network plays an equal role in response inhibition under different sensorimotor contexts has not been tested systematically. Here, we conducted an fMRI experiment using the stop signal task, a sensorimotor task requiring occasional withholding of the planned response upon the presentation of a stop signal. We manipulated both the sensory modality of the stop signal (visual versus auditory) and the motor response modality (hand versus eye). Results showed that the vIFG/AI and the preSMA along with the right middle frontal gyrus were commonly activated in response inhibition across the various sensorimotor conditions. Our findings provide direct evidence for a common role of these frontal areas, but not striatal areas in response inhibition independent of the sensorimotor contexts. Nevertheless, these three frontal regions exhibited different activation patterns during successful and unsuccessful stopping. Together with the existing evidence, we suggest that the vIFG/AI is involved in the early stages of stopping such as triggering the stop process while the preSMA may play a role in regulating other cortical and subcortical regions involved in stopping. PMID:23798325

How does response inhibition influence decision making when gambling?

PubMed

Stevens, Tobias; Brevers, Damien; Chambers, Christopher D; Lavric, Aureliu; McLaren, Ian P L; Mertens, Myriam; Noël, Xavier; Verbruggen, Frederick

2015-03-01

Recent research suggests that response inhibition training can alter impulsive and compulsive behavior. When stop signals are introduced in a gambling task, people not only become more cautious when executing their choice responses, they also prefer lower bets when gambling. Here, we examined how stopping motor responses influences gambling. Experiment 1 showed that the reduced betting in stop-signal blocks was not caused by changes in information sampling styles or changes in arousal. In Experiments 2a and 2b, people preferred lower bets when they occasionally had to stop their response in a secondary decision-making task but not when they were instructed to respond as accurately as possible. Experiment 3 showed that merely introducing trials on which subjects could not gamble did not influence gambling preferences. Experiment 4 demonstrated that the effect of stopping on gambling generalized to different populations. Further, 2 combined analyses suggested that the effect of stopping on gambling preferences was reliable but small. Finally, Experiment 5 showed that the effect of stopping on gambling generalized to a different task. On the basis of our findings and earlier research, we propose that the presence of stop signals influences gambling by reducing approach behavior and altering the motivational value of the gambling outcome. PsycINFO Database Record (c) 2015 APA, all rights reserved.

How Does Response Inhibition Influence Decision Making When Gambling?

PubMed Central

2015-01-01

Recent research suggests that response inhibition training can alter impulsive and compulsive behavior. When stop signals are introduced in a gambling task, people not only become more cautious when executing their choice responses, they also prefer lower bets when gambling. Here, we examined how stopping motor responses influences gambling. Experiment 1 showed that the reduced betting in stop-signal blocks was not caused by changes in information sampling styles or changes in arousal. In Experiments 2a and 2b, people preferred lower bets when they occasionally had to stop their response in a secondary decision-making task but not when they were instructed to respond as accurately as possible. Experiment 3 showed that merely introducing trials on which subjects could not gamble did not influence gambling preferences. Experiment 4 demonstrated that the effect of stopping on gambling generalized to different populations. Further, 2 combined analyses suggested that the effect of stopping on gambling preferences was reliable but small. Finally, Experiment 5 showed that the effect of stopping on gambling generalized to a different task. On the basis of our findings and earlier research, we propose that the presence of stop signals influences gambling by reducing approach behavior and altering the motivational value of the gambling outcome. PMID:25559481

Design Considerations for a Stopped-Rotor Cyclocopter for Venus Exploration

NASA Technical Reports Server (NTRS)

Husseyin, S.; Warmbrodt, William G.

2016-01-01

This paper considers the use of a cycloidal blade system as a means of providing lift and propulsive thrust as well as combined with a stopped rotor system, to create a stopped-rotor cyclocopter vehicle, during a mission to Venus. This stopped-rotor cyclocopter will be capable of flying at all atmospheric levels of Venus as well as landing on the surface for scientific investigation. Three reference conceptual designs with different stopped-rotor cyclocopter yaw angles are tested in RotCFD as well as a model of a hovering cyclorotor for comparison with past work in the literature and innovative study for future projects.

Towards a model-based cognitive neuroscience of stopping - a neuroimaging perspective.

PubMed

Sebastian, Alexandra; Forstmann, Birte U; Matzke, Dora

2018-07-01

Our understanding of the neural correlates of response inhibition has greatly advanced over the last decade. Nevertheless the specific function of regions within this stopping network remains controversial. The traditional neuroimaging approach cannot capture many processes affecting stopping performance. Despite the shortcomings of the traditional neuroimaging approach and a great progress in mathematical and computational models of stopping, model-based cognitive neuroscience approaches in human neuroimaging studies are largely lacking. To foster model-based approaches to ultimately gain a deeper understanding of the neural signature of stopping, we outline the most prominent models of response inhibition and recent advances in the field. We highlight how a model-based approach in clinical samples has improved our understanding of altered cognitive functions in these disorders. Moreover, we show how linking evidence-accumulation models and neuroimaging data improves the identification of neural pathways involved in the stopping process and helps to delineate these from neural networks of related but distinct functions. In conclusion, adopting a model-based approach is indispensable to identifying the actual neural processes underlying stopping. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.

PubMed

Ellis, Giovanina M; Huang, Sharon; Hitti, Jane; Frenkel, Lisa M

2011-11-01

Compare the risk of HIV drug resistance in women stopping suppressive nelfinavir (NFV)-based or Nevirapine (NVP)-based antiretroviral therapy (ART) after pregnancy. Specimens collected after stopping ART were tested for drug resistance by an oligonucleotide ligation assay and consensus sequencing. When postpartum drug resistance was detected, specimens obtained at study entry and during ART were evaluated. Sixteen of 38 women with ART-induced suppression of viral replication suspended ART postpartum. Resistance mutations were detected in 75% who stopped NFV-ART and in 50% who stopped NVP-ART. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. HIV drug resistance was frequently observed among women who stopped suppressive NVP-ART or NFV-ART postpartum. This suggests that NFV-ART may have suboptimal potency, that staggering discontinuation of NVP-ART may be warranted, and/or ART adherence may be lax in women who choose to stop ART postpartum.

Caffeine and sports performance.

PubMed

Burke, Louise M

2008-12-01

Athletes are among the groups of people who are interested in the effects of caffeine on endurance and exercise capacity. Although many studies have investigated the effect of caffeine ingestion on exercise, not all are suited to draw conclusions regarding caffeine and sports performance. Characteristics of studies that can better explore the issues of athletes include the use of well-trained subjects, conditions that reflect actual practices in sport, and exercise protocols that simulate real-life events. There is a scarcity of field-based studies and investigations involving elite performers. Researchers are encouraged to use statistical analyses that consider the magnitude of changes, and to establish whether these are meaningful to the outcome of sport. The available literature that follows such guidelines suggests that performance benefits can be seen with moderate amounts (~3 mg.kg-1 body mass) of caffeine. Furthermore, these benefits are likely to occur across a range of sports, including endurance events, stop-and-go events (e.g., team and racquet sports), and sports involving sustained high-intensity activity lasting from 1-60 min (e.g., swimming, rowing, and middle and distance running races). The direct effects on single events involving strength and power, such as lifts, throws, and sprints, are unclear. Further studies are needed to better elucidate the range of protocols (timing and amount of doses) that produce benefits and the range of sports to which these may apply. Individual responses, the politics of sport, and the effects of caffeine on other goals, such as sleep, hydration, and refuelling, also need to be considered.

Collaboration using open standards and open source software (examples of DIAS/CEOS Water Portal)

NASA Astrophysics Data System (ADS)

Miura, S.; Sekioka, S.; Kuroiwa, K.; Kudo, Y.

2015-12-01

The DIAS/CEOS Water Portal is a part of the DIAS (Data Integration and Analysis System, http://www.editoria.u-tokyo.ac.jp/projects/dias/?locale=en_US) systems for data distribution for users including, but not limited to, scientists, decision makers and officers like river administrators. One of the functions of this portal is to enable one-stop search and access variable water related data archived multiple data centers located all over the world. This portal itself does not store data. Instead, according to requests made by users on the web page, it retrieves data from distributed data centers on-the-fly and lets them download and see rendered images/plots. Our system mainly relies on the open source software GI-cat (http://essi-lab.eu/do/view/GIcat) and open standards such as OGC-CSW, Opensearch and OPeNDAP protocol to enable the above functions. Details on how it works will be introduced during the presentation. Although some data centers have unique meta data format and/or data search protocols, our portal's brokering function enables users to search across various data centers at one time. And this portal is also connected to other data brokering systems, including GEOSS DAB (Discovery and Access Broker). As a result, users can search over thousands of datasets, millions of files at one time. Users can access the DIAS/CEOS Water Portal system at http://waterportal.ceos.org/.

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments.

PubMed

Connick, Peter; Kolappan, Madhan; Patani, Rickie; Scott, Michael A; Crawley, Charles; He, Xiao-Ling; Richardson, Karen; Barber, Kelly; Webber, Daniel J; Wheeler-Kingshott, Claudia A M; Tozer, Daniel J; Samson, Rebecca S; Thomas, David L; Du, Ming-Qing; Luan, Shi L; Michell, Andrew W; Altmann, Daniel R; Thompson, Alan J; Miller, David H; Compston, Alastair; Chandran, Siddharthan

2011-03-02

No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach". MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway. Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm. In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS--the sentinel lesion approach--serving as proof of principle for its future wider applicability. ClinicalTrials.gov (NCT00395200).

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments

PubMed Central

2011-01-01

Background No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes - the "sentinel lesion approach". Methods/design MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway. Results Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm. Conclusions In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS - the sentinel lesion approach - serving as proof of principle for its future wider applicability. Trial registration ClinicalTrials.gov (NCT00395200). PMID:21366911

The Phenomenon of Unduly Hardening [C] (Palatal Stop) to [K] (Velar Stop) in Turkish Speech and Its Remedy through Minimal Pairs

ERIC Educational Resources Information Center

Yurtbasi, Metin

2016-01-01

The voiceless allophones of (alveolo) palatal stop consonant [c] and velar stop consonant [k] of the phoneme /k/ represented by the letter "K" exists in almost all languages of the world. Which of these will be sounded in speech is determined by the type of the vowel that are adjacent to them. In Turkish, the dark variant [k] occurs…

Computational prediction of muon stopping sites using ab initio random structure searching (AIRSS)

NASA Astrophysics Data System (ADS)

Liborio, Leandro; Sturniolo, Simone; Jochym, Dominik

2018-04-01

The stopping site of the muon in a muon-spin relaxation experiment is in general unknown. There are some techniques that can be used to guess the muon stopping site, but they often rely on approximations and are not generally applicable to all cases. In this work, we propose a purely theoretical method to predict muon stopping sites in crystalline materials from first principles. The method is based on a combination of ab initio calculations, random structure searching, and machine learning, and it has successfully predicted the MuT and MuBC stopping sites of muonium in Si, diamond, and Ge, as well as the muonium stopping site in LiF, without any recourse to experimental results. The method makes use of Soprano, a Python library developed to aid ab initio computational crystallography, that was publicly released and contains all the software tools necessary to reproduce our analysis.

Evaluation of undergraduate geologists' problem solving and cognition during field exams using a mixed methods approach

NASA Astrophysics Data System (ADS)

Balliet, Russell N.

Understanding how geologists conduct fieldwork through analysis of problem solving has significant potential impact on field instruction methods. Recent progress has been made in this area but the problem solving behaviors displayed by geologists during fieldwork and the associated underlying cognition remains poorly understood. We present research showing how geology students initiate and develop geologic models as part of the problem solving process. We qualitatively analyzed field notes and interview data from 36 undergraduate geoscientists engaged in field exams while enrolled in a six-week advanced field camp. Eight cognitive frameworks grouped in two broad categories emerged from the data that show how students develop geologic models. Students employ both single and multiple model approaches with varying degrees of success and frequency. The success of any given approach is dependent on the level of students' geologic situational awareness. The development of multiple geologic models leads to a higher rate of success in general, because of the inherent flexibility to accommodate newly collected data. Instructors should continue to teach a multiple model approach until students have the proper geologic skills to ensure a high level of situational awareness and exhibit expert characteristics in the field. In addition, we collected GPS navigation data from students during these field exams in order to understand the relationship between navigation, cognition, and performance. From the analysis of this data we found that over half of all stops are 1-4 minutes long, while very few of students' stops are longer than 9 minutes as the frequency of stops decreases as the duration increases. Regardless of performance or framework, there is an increase in shorter stops and decrease in longer stops from exam one to three, indicating that students changed the way they investigated as the field course progressed. Temporal signatures categorized by performance only show slight differences, but do indicate that there is an increase in very short and longer stops with declining performance. In contrast, higher performance is linked to an increase in short and medium length stops, suggesting that stops 4-14 minutes long are a "sweet spot" for investigation. We speculate that a high percentage of very short stops involve basic field tasks such as locating or data collection and that the decreasing frequency of long stops indicates that there is a relationship between the length of the stop and the complexity of the activities performed during that stop. Students increased experience leads to more efficient stops as they become more competent with field tasks and more versed in the regional geology. The GPS data we collected from these students while they took these notes allowing us to connect the duration of a stop to the types of notes produced during that stop. Note taking species occurred in various frequencies with the most common type being those that focused on lithologic, or lithologic & structural data collection. Stops that produced geologic models, specifically structural models, were much less frequent. The more frequent data collection stops are very short in length (typically 1-4 minutes), while the more complex stops tend to be longer in duration as the note taking gets more complex. Poor performing students had a high proportion of stops where they only collect lithologic data or stops where they don't generate any hypotheses. In contrast, successful students have more structural data and hypothesis generation in their notes. From this analysis we conclude that too much effort spent on stops with only basic data collection leaves less time for the cognitive effort required for model development, eventually leading to poor exam performance. Specifically, a higher frequency of lithologic data stops and lack of structural data leads to the development of incomplete geologic models or lack of comprehensive models altogether. Field instructors often educate their students on good note taking practices and critique the content of their students' field notebooks, and these findings can inform the content of that critique. Students' utilize many different problem solving approaches in the field, but we suggest that instructors continue to advocate a multiple model approach until students are capable of using a single model approach. In this approach students should decrease the number of geologic models they are using as the day progresses to avoid overwhelming themselves with data and hypothesis. Furthermore, field instructors need to work with students on developing their geologic investigation skills further and improving their efficiency. Specifically students need to collect a higher proportion of structural data and develop complete geologic models earlier in the day. (Abstract shortened by UMI.)

Modeling level-of-safety for bus stops in China.

PubMed

Ye, Zhirui; Wang, Chao; Yu, Yongbo; Shi, Xiaomeng; Wang, Wei

2016-08-17

Safety performance at bus stops is generally evaluated by using historical traffic crash data or traffic conflict data. However, in China, it is quite difficult to obtain such data mainly due to the lack of traffic data management and organizational issues. In light of this, the primary objective of this study is to develop a quantitative approach to evaluate bus stop safety performance. The concept of level-of-safety for bus stops is introduced and corresponding models are proposed to quantify safety levels, which consider conflict points, traffic factors, geometric characteristics, traffic signs and markings, pavement conditions, and lighting conditions. Principal component analysis and k-means clustering methods were used to model and quantify safety levels for bus stops. A case study was conducted to show the applicability of the proposed model with data collected from 46 samples for the 7 most common types of bus stops in China, using 32 of the samples for modeling and 14 samples for illustration. Based on the case study, 6 levels of safety for bus stops were defined. Finally, a linear regression analysis between safety levels and the number of traffic conflicts showed that they had a strong relationship (R(2) value of 0.908). The results indicated that the method was well validated and could be practically used for the analysis and evaluation of bus stop safety in China. The proposed model was relatively easy to implement without the requirement of traffic crash data and/or traffic conflict data. In addition, with the proposed method, it was feasible to evaluate countermeasures to improve bus stop safety (e.g., exclusive bus lanes).

Stress, social support, and stopping smoking after myocardial infarction in England.

PubMed Central

Greenwood, D C; Muir, K R; Packham, C J; Madeley, R J

1995-01-01

STUDY OBJECTIVE--To examine the effect on mortality of stopping smoking after myocardial infarction and the psychosocial factors that influence the decision to stop. DESIGN--Analysis of smokers in a large prospective study. Self completed questionnaires provided information on psychosocial factors. SETTING--Coronary care units at six English hospitals participating in a multicentre clinical trial. SUBJECTS--These comprised consenting myocardial infarction survivors who had been identified as smokers and who completed questionnaires within seven days of infarct at six hospitals participating in the Anglo-Scandinavian study of early thrombolysis. The 532 patients identified have been followed for over five and a half years. The main outcome measure was five year all cause mortality. MAIN RESULTS--Smokers who stopped within one month showed significantly reduced mortality compared with those who persisted, adjusting for other prognostic indicators (odds ratio 0.56, 95% confidence interval 0.33, 0.98). Overall, 74% stopped smoking. Being married, low life stress levels before infarct, and higher social class were associated with stopping smoking but the differentials were small. Of the clinical variables, a final diagnosis of definite myocardial infarction was associated with stopping smoking. All associations remained after multiple logistic regression. CONCLUSION--Smoking cessation can halve the smokers' odds of dying after myocardial infarction and psychosocial factors play a small but important role in the important decision to stop smoking. Health professionals should continue to stress the importance of stopping smoking to all patients as there is little evidence to support specific directing of advice to relatively "stress or "socially isolated" groups. PMID:8596092

Soil pH Mapping with an On-The-Go Sensor

PubMed Central

Schirrmann, Michael; Gebbers, Robin; Kramer, Eckart; Seidel, Jan

2011-01-01

Soil pH is a key parameter for crop productivity, therefore, its spatial variation should be adequately addressed to improve precision management decisions. Recently, the Veris pH Manager™, a sensor for high-resolution mapping of soil pH at the field scale, has been made commercially available in the US. While driving over the field, soil pH is measured on-the-go directly within the soil by ion selective antimony electrodes. The aim of this study was to evaluate the Veris pH Manager™ under farming conditions in Germany. Sensor readings were compared with data obtained by standard protocols of soil pH assessment. Experiments took place under different scenarios: (a) controlled tests in the lab, (b) semicontrolled test on transects in a stop-and-go mode, and (c) tests under practical conditions in the field with the sensor working in its typical on-the-go mode. Accuracy issues, problems, options, and potential benefits of the Veris pH Manager™ were addressed. The tests demonstrated a high degree of linearity between standard laboratory values and sensor readings. Under practical conditions in the field (scenario c), the measure of fit (r2) for the regression between the on-the-go measurements and the reference data was 0.71, 0.63, and 0.84, respectively. Field-specific calibration was necessary to reduce systematic errors. Accuracy of the on-the-go maps was considerably higher compared with the pH maps obtained by following the standard protocols, and the error in calculating lime requirements was reduced by about one half. However, the system showed some weaknesses due to blockage by residual straw and weed roots. If these problems were solved, the on-the-go sensor investigated here could be an efficient alternative to standard sampling protocols as a basis for liming in Germany. PMID:22346591

Cold wall effect eliminating method to determine the contrast recovery coefficient for small animal PET scanners using the NEMA NU-4 image quality phantom

NASA Astrophysics Data System (ADS)

Lajtos, Imre; Czernin, Johannes; Dahlbom, Magnus; Daver, Freddie; Emri, Miklos; Farshchi-Heydari, Salman; Forgacs, Attila; Hoh, Carl K.; Joszai, Istvan; Krizsan, Aron K.; Lantos, Judit; Major, Peter; Molnar, Jozsef; Opposits, Gabor; Tron, Lajos; Vera, David R.; Balkay, Laszlo

2014-06-01

The contrast recovery coefficients (CRC) were evaluated for five different small animal PET scanners: GE Explore Vista, Genisys4, MiniPET-2, nanoScan PC and Siemens Inveon. The NEMA NU-4 2008 performance test with the suggested image quality phantom (NU4IQ) does not allow the determination of the CRC values for the hot regions in the phantom. This drawback of NU4IQ phantom motivated us to develop a new method for this purpose. The method includes special acquisition and reconstruction protocols using the original phantom, and results in an artificially merged image enabling the evaluation of CRC values. An advantageous feature of this method is that it stops the cold wall effect from distorting the CRC calculation. Our suggested protocol results in a set of CRC values contributing to the characterization of small animal PET scanners. GATE simulations were also performed to validate the new method and verify the evaluated CRC values. We also demonstrated that the numerical values of this parameter depend on the actual object contrast of the hot region(s) and this mainly comes from the spillover effect. This effect was also studied while analysing the background activity level around the hot rods. We revealed that the calculated background mean values depended on the target contrast in a scanner specific manner. Performing the artificially merged imaging procedure and additional simulations using the micro hollow sphere (MHS) phantom geometry, we also proved that the inactive wall around the hot spheres can have a remarkable impact on the calculated CRC. In conclusion, we have shown that the proposed artificial merging procedure and the commonly used NU4IQ phantom prescribed by the NEMA NU-4 can easily deliver reliable CRC data otherwise unavailable for the NU4IQ phantom in the conventional protocol or the MHS phantom.

Cold wall effect eliminating method to determine the contrast recovery coefficient for small animal PET scanners using the NEMA NU-4 image quality phantom.

PubMed

Lajtos, Imre; Czernin, Johannes; Dahlbom, Magnus; Daver, Freddie; Emri, Miklos; Farshchi-Heydari, Salman; Forgacs, Attila; Hoh, Carl K; Joszai, Istvan; Krizsan, Aron K; Lantos, Judit; Major, Peter; Molnar, Jozsef; Opposits, Gabor; Tron, Lajos; Vera, David R; Balkay, Laszlo

2014-06-07

The contrast recovery coefficients (CRC) were evaluated for five different small animal PET scanners: GE Explore Vista, Genisys4, MiniPET-2, nanoScan PC and Siemens Inveon. The NEMA NU-4 2008 performance test with the suggested image quality phantom (NU4IQ) does not allow the determination of the CRC values for the hot regions in the phantom. This drawback of NU4IQ phantom motivated us to develop a new method for this purpose. The method includes special acquisition and reconstruction protocols using the original phantom, and results in an artificially merged image enabling the evaluation of CRC values. An advantageous feature of this method is that it stops the cold wall effect from distorting the CRC calculation. Our suggested protocol results in a set of CRC values contributing to the characterization of small animal PET scanners. GATE simulations were also performed to validate the new method and verify the evaluated CRC values. We also demonstrated that the numerical values of this parameter depend on the actual object contrast of the hot region(s) and this mainly comes from the spillover effect. This effect was also studied while analysing the background activity level around the hot rods. We revealed that the calculated background mean values depended on the target contrast in a scanner specific manner. Performing the artificially merged imaging procedure and additional simulations using the micro hollow sphere (MHS) phantom geometry, we also proved that the inactive wall around the hot spheres can have a remarkable impact on the calculated CRC. In conclusion, we have shown that the proposed artificial merging procedure and the commonly used NU4IQ phantom prescribed by the NEMA NU-4 can easily deliver reliable CRC data otherwise unavailable for the NU4IQ phantom in the conventional protocol or the MHS phantom.

The role of the Data and Safety Monitoring Board in a clinical trial: The CRISIS Study

PubMed Central

Holubkov, Richard; Casper, T. Charles; Dean, J. Michael; Anand, K. J. S.; Zimmerman, Jerry; Meert, Kathleen L.; Newth, Christopher J. L.; Berger, John; Harrison, Rick; Willson, Douglas F.; Nicholson, Carol

2012-01-01

Objective Randomized clinical trials are commonly overseen by a data and safety monitoring board (DSMB) comprised of experts in medicine, ethics, and biostatistics. DSMB responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. DSMB decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate DSMB oversight into the design, monitoring, and reporting of randomized trials. Design Case study, narrative review. Methods The DSMB’s role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described. Findings The NIH-appointed CRISIS DSMB was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested DSMB interim review before opening CRISIS to children below one year of age. The first interim analysis found higher 28-day mortality in one treatment arm. The DSMB maintained trial closure to younger children, and requested a second interim data review six months later. At this second meeting, mortality was no longer of concern, while a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the DSMB elected to examine conditional power, and unmask treatment arm identities. Upon finding somewhat greater efficacy in the placebo arm, the DSMB recommended stopping CRISIS due to futility. Conclusions The design and operating procedures of a multicenter randomized trial must consider a pivotal DSMB role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The DSMB must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups. PMID:23392377

Soil pH mapping with an on-the-go sensor.

PubMed

Schirrmann, Michael; Gebbers, Robin; Kramer, Eckart; Seidel, Jan

2011-01-01

Soil pH is a key parameter for crop productivity, therefore, its spatial variation should be adequately addressed to improve precision management decisions. Recently, the Veris pH Manager™, a sensor for high-resolution mapping of soil pH at the field scale, has been made commercially available in the US. While driving over the field, soil pH is measured on-the-go directly within the soil by ion selective antimony electrodes. The aim of this study was to evaluate the Veris pH Manager™ under farming conditions in Germany. Sensor readings were compared with data obtained by standard protocols of soil pH assessment. Experiments took place under different scenarios: (a) controlled tests in the lab, (b) semicontrolled test on transects in a stop-and-go mode, and (c) tests under practical conditions in the field with the sensor working in its typical on-the-go mode. Accuracy issues, problems, options, and potential benefits of the Veris pH Manager™ were addressed. The tests demonstrated a high degree of linearity between standard laboratory values and sensor readings. Under practical conditions in the field (scenario c), the measure of fit (r(2)) for the regression between the on-the-go measurements and the reference data was 0.71, 0.63, and 0.84, respectively. Field-specific calibration was necessary to reduce systematic errors. Accuracy of the on-the-go maps was considerably higher compared with the pH maps obtained by following the standard protocols, and the error in calculating lime requirements was reduced by about one half. However, the system showed some weaknesses due to blockage by residual straw and weed roots. If these problems were solved, the on-the-go sensor investigated here could be an efficient alternative to standard sampling protocols as a basis for liming in Germany.

Quit Smoking >

Cancer.gov

Quit smoking; Stop smoking; Quit smoking women; Stop smoking women easy way for women to stop smoking; Smoking effects on women; effects of smoking on women; effects of smoking in women; smoking side effects for women; quit smoking cigarettes; smoking cessation; smoking cessation women

The effect of speakers' sex on voice onset time in Mandarin stops

PubMed Central

Li, Fangfang

2013-01-01

The goal of the present study is to examine the effect of speakers' gender on voice onset time in Mandarin speakers' stop productions. Word-initial lingual stops were elicited from 10 male and 10 female Mandarin speakers using a word-repetition task. The results revealed differentiated voice onset time (VOT) patterns between the two genders for all four lingual stops on raw VOT values. After factoring out speech rate variation, gender-related differences remained for voiced stops only with females' VOTs being shorter than males. The results, together with previous findings from other languages, suggest a sociolinguistic/stylistic account on the relation between gender and VOT that vary in a language-specific manner. PMID:23363195

Stop-catalyzed baryogenesis beyond the MSSM

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

Katz, Andrey; Perelstein, Maxim; Ramsey-Musolf, Michael J.

2015-11-19

Nonminimal supersymmetric models that predict a tree-level Higgs mass above the minimal supersymmetric standard model (MSSM) bound are well motivated by naturalness considerations. Indirect constraints on the stop sector parameters of such models are significantly relaxed compared to the MSSM; in particular, both stops can have weak-scale masses. We revisit the stop-catalyzed electroweak baryogenesis (EWB) scenario in this context. We find that the LHC measurements of the Higgs boson production and decay rates already rule out the possibility of stop-catalyzed EWB. Here, we also introduce a gauge-invariant analysis framework that may generalize to other scenarios in which interactions outside themore » gauge sector drive the electroweak phase transition.« less

Curing the noise epidemic

NASA Astrophysics Data System (ADS)

Mazer, Susan

2005-09-01

The argument is made that design does not stop when the fixed architectural and acoustical components are in place. Spaces live and breathe with the people who reside in them. Research and examples are presented that show that noise, auditory clutter, thrives on itself in hospitals. Application of the Lombard reflex studies fit into the hospital setting, but do not offer solutions as to how one might reduce the impact. In addition, the basis for looking at the noise component as a physical as well cultural dynamic will be addressed. Whether the result of the wrong conversation in the wrong place or the right conversation in an unfortunate place, talk mixed with sounds of technology is shown to cause its own symptoms. From heightened anxiety and stress to medical errors, staff burnout, or HIPAA violations, the case is made that noise is pandemic in hospitals and demands financial and operational investment. An explanation of how to reduce noise by design of the dynamic environment - equipment, technology, staff protocols is also provided.

Design and implementation of a medium speed communications interface and protocol for a low cost, refreshed display computer

NASA Technical Reports Server (NTRS)

Phyne, J. R.; Nelson, M. D.

1975-01-01

The design and implementation of hardware and software systems involved in using a 40,000 bit/second communication line as the connecting link between an IMLAC PDS 1-D display computer and a Univac 1108 computer system were described. The IMLAC consists of two independent processors sharing a common memory. The display processor generates the deflection and beam control currents as it interprets a program contained in the memory; the minicomputer has a general instruction set and is responsible for starting and stopping the display processor and for communicating with the outside world through the keyboard, teletype, light pen, and communication line. The processing time associated with each data byte was minimized by designing the input and output processes as finite state machines which automatically sequence from each state to the next. Several tests of the communication link and the IMLAC software were made using a special low capacity computer grade cable between the IMLAC and the Univac.

A safety mechanism for observational learning.

PubMed

Badets, Arnaud; Boutin, Arnaud; Michelet, Thomas

2018-04-01

This empirical article presents the first evidence of a "safety mechanism" based on an observational-learning paradigm. It is accepted that during observational learning, a person can use different strategies to learn a motor skill, but it is unknown whether the learner is able to circumvent the encoding of an uncompleted observed skill. In this study, participants were tested in a dyadic protocol in which an observer watched a participant practicing two different motor sequences during a learning phase. During this phase, one of the two motor sequences was interrupted by a stop signal that precluded motor learning. The results of the subsequent retention test revealed that both groups learned the two motor sequences, but only the physical practice group showed worse performance for the interrupted sequence. The observers were consequently able to use a safety strategy to learn both sequences equally. Our findings are discussed in light of the implications of the action observation network for sequence learning and the cognitive mechanisms of error-based observation.

A choice-based screening method for compulsive drug users in rats.

PubMed

Lenoir, Magalie; Augier, Eric; Vouillac, Caroline; Ahmed, Serge H

2013-07-01

We describe a protocol for screening compulsive drug users among cocaine self-administering rats, the most frequently used animal model in addiction research. Rats are first trained on several alternating days to self-administer either cocaine (i.v.) or saccharin-sweetened water (by mouth)--a potent, albeit nonessential, nondrug reward. Then rats are allowed to choose between the two rewards over several days until the preference stabilizes. Most rats choose to stop using cocaine and pursue the alternative reward. Only a minority of Wistar strain rats (generally 15%) persist in taking the drug, regardless of the severity of past cocaine use and even when made hungry and offered the possibility to relieve their physiological need. Persistence of cocaine use in the face of a high-stakes choice is a core defining feature of compulsion. This choice-based screening method for compulsive drug users is easy to implement, has several important applications, and compares well with other methods in the field. 2013 by John Wiley & Sons, Inc.

Zinc Supplementation in Treatment of Children With Urinary Tract Infection.

PubMed

Yousefichaijan, Parsa; Naziri, Mahdyieh; Taherahmadi, Hassan; Kahbazi, Manijeh; Tabaei, Aram

2016-07-01

Urinary tract infection (UTI) is very common in children. Precocious diagnosis and appropriate treatment are important because of the permanent disease complications. Zinc increases the response to treatment in many infections. In this study, we explored the effect of zinc in treating UTI. Two hundred children with UTI were divided into 2 groups of 100 who were comparable in terms of age, sex, urine laboratory profiles, and clinical signs and symptoms. The control group received a standard treatment protocol for UTI and the intervention group received oral zinc sulfate syrup plus routine treatment of UTI. A faster recovery was observed in the patients receiving zinc, but abdominal pain was exacerbated by zinc and lasted longer. Three months after the treatment, there was no significant difference between the two groups in the time of fever stop and negative urine culture. In children with UTI, zinc supplementation has a positive effect in ameliorating severe dysuria and urinary frequency while the use of this medication is not recommended in the presence of abdominal pain.

Network information security in a phase III Integrated Academic Information Management System (IAIMS).

PubMed

Shea, S; Sengupta, S; Crosswell, A; Clayton, P D

1992-01-01

The developing Integrated Academic Information System (IAIMS) at Columbia-Presbyterian Medical Center provides data sharing links between two separate corporate entities, namely Columbia University Medical School and The Presbyterian Hospital, using a network-based architecture. Multiple database servers with heterogeneous user authentication protocols are linked to this network. "One-stop information shopping" implies one log-on procedure per session, not separate log-on and log-off procedures for each server or application used during a session. These circumstances provide challenges at the policy and technical levels to data security at the network level and insuring smooth information access for end users of these network-based services. Five activities being conducted as part of our security project are described: (1) policy development; (2) an authentication server for the network; (3) Kerberos as a tool for providing mutual authentication, encryption, and time stamping of authentication messages; (4) a prototype interface using Kerberos services to authenticate users accessing a network database server; and (5) a Kerberized electronic signature.

Robust ultrasensitive tunneling-FET biosensor for point-of-care diagnostics

PubMed Central

Gao, Anran; Lu, Na; Wang, Yuelin; Li, Tie

2016-01-01

For point-of-care (POC) applications, robust, ultrasensitive, small, rapid, low-power, and low-cost sensors are highly desirable. Here, we present a novel biosensor based on a complementary metal oxide semiconductor (CMOS)-compatible silicon nanowire tunneling field-effect transistor (SiNW-TFET). They were fabricated “top-down” with a low-cost anisotropic self-stop etching technique. Notably, the SiNW-TFET device provided strong anti-interference capacity by applying the inherent ambipolarity via both pH and CYFRA21-1 sensing. This offered a more robust and portable general protocol. The specific label-free detection of CYFRA21-1 down to 0.5 fgml−1 or ~12.5 aM was achieved using a highly responsive SiNW-TFET device with a minimum sub-threshold slope (SS) of 37 mVdec−1. Furthermore, real-time measurements highlighted the ability to use clinically relevant samples such as serum. The developed high performance diagnostic system is expected to provide a generic platform for numerous POC applications. PMID:26932158

A thermoresponsive nanorattle containing two different catalysts for controllable one-pot tandem catalysis

NASA Astrophysics Data System (ADS)

Niu, Chengrong; Hu, Jie; Li, Yinfeng; Leng, Jinghang; Li, Songjun

2018-03-01

In the present work, a thermoresponsive nanorattle with a Ag nanoparticle (NP) core (one catalyst in the nanorattle), and a poly(N-isopropylacrylamide) shell was developed. An imidazole group was grafted on the polymer shell by copolymerization as the other catalyst. Owing to the catalytic activities of the imidazole group and Ag NP with regards to hydrolysis and reduction, respectively, this nanorattle exhibited tandem-reaction catalytic abilities. In addition, because of the shrinkage of the poly(N-isopropylacrylamide) shell at high temperatures, the tandem reaction could be controlled to stop at the first reaction step. That is to say, only the hydrolysis reaction was catalyzed by the imidazole group being grafted on the surface of the shell. The reduction step in the tandem reaction catalyzed by the Ag particle, however, was switched off by the shrinkage of the poly(N-isopropylacrylamide) shell. This protocol opens up an opportunity to develop controllable catalysts for complicated chemical processes.

GCN/TAN: A Status Report

NASA Astrophysics Data System (ADS)

Barthelmy, Scott

2015-04-01

The Gamma-ray Coordinates Network / Transient Astronomy Network (GCN/TAN) is your one-stop shopping place for all transient astronomy. It collects nearly all the astrophysical transients from the missions (space-based and ground-based), puts them into a standard format, and distributes them to whomever wishes to receive them. This is all done autonomously (completely autonomous within GCN/TAN, and almost always autonomously within the producer end of operations). This automation means minimal time delays (<0.1 sec within GCN for socket-based distribution methods, and up to 30 sec for email-based which is dependant on the internet email protocol and the number of hops (both of which are out of the control of GCN/TAN). A status report on the current set of sources of transient information, plus recently-added and soon-to-be-added source will be given. Also, a standing request for GCN/TAN to incorporate your transient data stream; plus instruction for customers to receive GCN/TAAN Notice and Circular information.

The electronic stopping powers and angular energy-loss dependence of helium and lithium ions in the silicon crystal

NASA Astrophysics Data System (ADS)

Mikšová, R.; Macková, A.; Malinský, P.

2017-09-01

We have measured the electronic stopping powers of helium and lithium ions in the channelling direction of the Si〈1 0 0〉 crystal. The energy range used (2.0-8.0 MeV) was changed by 200 and 400-keV steps. The ratio α between the channelling and random stopping powers was determined as a function of the angle for 2, 3 and 4 MeV 4He+ ions and for 3 and 6 MeV 7Li+,2+ ions. The measurements were carried out using the Rutherford backscattering spectrometry in the channelling mode (RBS-C) in a silicon-on-insulator material. The experimental channelling stopping-power values measured in the channelling direction were then discussed in the frame of the random energy stopping predictions calculated using SRIM-2013 code and the theoretical unitary convolution approximation (UCA) model. The experimental channelling stopping-power values decrease with increasing ion energy. The stopping-power difference between channelled and randomly moving ions increases with the enhanced initial ion energy. The ratio between the channelling and random ion stopping powers α as a function of the ion beam incoming angle for 2, 3 and 4 MeV He+ ions and for 3 and 6 MeV Li+,2+ ions was observed in the range 0.5-1.

Uncover compressed supersymmetry via boosted bosons from the heavier stop/sbottom

NASA Astrophysics Data System (ADS)

Kang, Zhaofeng; Li, Jinmian; Zhang, Mengchao

2017-06-01

A light stop around the weak scale is a hopeful messenger of natural supersymmetry (SUSY), but it has not shown up at the current stage of LHC. Such a situation raises the question of the fate of natural SUSY. Actually, a relatively light stop can easily be hidden in a compressed spectra such as mild mass degeneracy between stop and neutralino plus top quark. Searching for such a stop at the LHC is a challenge. On the other hand, in terms of the argument of natural SUSY, other members in the stop sector, including a heavier stop \\tilde{t}_2 and lighter sbottom \\tilde{b}_1 (both assumed to be left-handed-like), are also supposed to be relatively light and therefore searching for them would provide an alternative method to probe natural SUSY with a compressed spectra. In this paper we consider quasi-natural SUSY which tolerates relatively heavy colored partners near the TeV scale, with a moderately large mass gap between the heavier members and the lightest stop. Then W / Z / h as companions of \\tilde{t}_2 and \\tilde{b}_1 decaying into \\tilde{t}_1 generically are well boosted, and they, along with other visible particles from \\tilde{t}_1 decay, are a good probe to study compressed SUSY. We find that the resulting search strategy with boosted bosons can have better sensitivity than those utilizing multi-leptons.

Stopping epilepsy treatment in seizure remission: Good or bad or both?

PubMed

Schmidt, Dieter; Sillanpää, Matti

2017-01-01

To review the outcome of epilepsy after stopping antiepileptic drugs in remission. Stopping antiepileptic drugs (AEDs) in remission is routinely done in many patients. Although the consequences of an unexpected relapse seizure in the 2 years after stopping AEDs may cause anguish and social issues, the impact on the long term seizure outlook of the epilepsy is minimal, if any. Discontinuation of drug treatment does not seem to affect the long-term prognosis but exposes patients who were seizure-free for years to a transient two-fold risk of seizures for the first 2 years after stopping AEDs. In addition, 20% of patients who were seizure-free for years, do not become seizure-free immediately after restarting AED treatment after relapse. The list of potential pitfalls is long. Patients with juvenile myoclonic epilepsy, those with prior withdrawal attempts and late remission have a higher risk of relapse. Stopping AEDs in remission does not affect the long-term patterns of epilepsy and some patients report a better general health in a life without AEDs. High-risk patients should not be generally encouraged to stop their AEDs in remission. We need new drugs that combine anti-seizure and antiepileptogenic effects to prevent seizure relapse and flare up of epilepsy after stopping AEDs in remission. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Effect of innovative building design on physical activity.

PubMed

Nicoll, Gayle; Zimring, Craig

2009-01-01

Stair climbing can be a low-cost and relatively accessible way to add everyday physical activity, but many building stairwells are inaccessible or unpleasant and elevators are far more convenient. This study explores the use of and attitude toward stairs in an innovative office building where the main elevators for able-bodied users stop only at every third floor ("skip-stop" elevators). These users are expected to walk up or down nearby stairs that have been made open and appealing ("skip-stop" stairs). The study takes advantage of a natural experiment. Some workers' offices were clustered around the skip-stop elevator and the stairs, whereas others had access to a traditional elevator core, that is, an elevator that stopped at each floor with nearby fire exit stairs. Stair use on the open skip-stop stairs and enclosed fire stairs was measured using infrared monitors and card-reader activity logs. An online survey of employees (N=299, a 17.4% response rate) gathered information on stair use and attitudes and behaviors toward physical activity; interviews with key personnel identified major implementation issues. The skip-stop stair was used 33 times more than the enclosed stair of the traditional elevator core, with 72% of survey participants reporting daily stair use. Although implementation issues related to organizational objectives, costs, security, barrier-free accessibility, and building codes exist, the skip-stop feature offers a successful strategy for increasing stair use in workplaces.

Modeling the effect of bus stops on capacity of curb lane

NASA Astrophysics Data System (ADS)

Luo, Qingyu; Zheng, Tianyao; Wu, Wenjing; Jia, Hongfei; Li, Jin

With the increase of buses and bus lines, a negative effect on road section capacity is made by the prolonged delay and queuing time at bus stops. However, existing methods of measuring the negative effect pay little attention to different bus stop types in the curb lanes. This paper uses Gap theory and Queuing theory to build models for effect-time and potential capacity in different conditions, including curbside bus stops, bus bays with overflow and bus bays without overflow. In order to make the effect-time models accurate and reliable, two types of probabilities are introduced. One is the probability that the dwell time is less than the headway of curb lane at curbside bus stops; the other is the overflow probability at bus bays. Based on the fundamental road capacity model and effect-time models, potential capacity models of curb lane are designed. The new models are calibrated by the survey data from Changchun City, and verified by the simulation software of VISSIM. Furthermore, with different arrival rates of vehicles, the setting conditions of bus stops are researched. Results show that the potential capacity models have high precision. They can offer a reference for recognizing the effect of bus stops on the capacity of curb lane, which can provide a basis for planning, design and management of urban roads and bus stops.

Whole of Systems Trial of Prevention Strategies for Childhood Obesity: WHO STOPS Childhood Obesity.

PubMed

Allender, Steven; Millar, Lynne; Hovmand, Peter; Bell, Colin; Moodie, Marj; Carter, Rob; Swinburn, Boyd; Strugnell, Claudia; Lowe, Janette; de la Haye, Kayla; Orellana, Liliana; Morgan, Sue

2016-11-16

Background : Community-based initiatives show promise for preventing childhood obesity. They are characterized by community leaders and members working together to address complex local drivers of energy balance. Objectives : To present a protocol for a stepped wedge cluster randomized trial in ten communities in the Great South Coast Region of Victoria, Australia to test whether it is possible to: (1) strengthen community action for childhood obesity prevention, and (2) measure the impact of increased action on risk factors for childhood obesity. Methods: The WHO STOPS intervention involves a facilitated community engagement process that: creates an agreed systems map of childhood obesity causes for a community; identifies intervention opportunities through leveraging the dynamic aspects of the system; and, converts these understandings into community-built, systems-oriented action plans. Ten communities will be randomized (1:1) to intervention or control in year one and all communities will be included by year three. The primary outcome is childhood obesity prevalence among grade two (ages 7-8 y), grade four (9-10 y) and grade six (11-12 y) students measured using our established community-led monitoring system (69% school and 93% student participation rate in government and independent schools). An additional group of 13 external communities from other regions of Victoria with no specific interventions will provide an external comparison. These communities will also allow us to assess diffusion of the intervention to control communities during the first three years of the trial. Conclusion : This trial will test effectiveness, over a five-year period, of community-owned, -supported and -led strategies designed to address complex and dynamic causes of childhood obesity.

Dosimetric characteristics of electron beams produced by a mobile accelerator for IORT.

PubMed

Pimpinella, M; Mihailescu, D; Guerra, A S; Laitano, R F

2007-10-21

Energy and angular distributions of electron beams with different energies were simulated by Monte Carlo calculations. These beams were generated by the NOVAC7 system (Hitesys, Italy), a mobile electron accelerator specifically dedicated to intra-operative radiation therapy (IORT). The electron beam simulations were verified by comparing the measured dose distributions with the corresponding calculated distributions. As expected, a considerable difference was observed in the energy and angular distributions between the IORT beams studied in the present work and the electron beams produced by conventional accelerators for non-IORT applications. It was also found that significant differences exist between the IORT beams used in this work and other IORT beams with different collimation systems. For example, the contribution from the scattered electrons to the total dose was found to be up to 15% higher in the NOVAC7 beams. The water-to-air stopping power ratios of the IORT beams used in this work were calculated on the basis of the beam energy distributions obtained by the Monte Carlo simulations. These calculated stopping power ratios, s(w,air), were compared with the corresponding s(w,air) values recommended by the TRS-381 and TRS-398 IAEA dosimetry protocols in order to estimate the deviations between a dosimetry based on generic parameters and a dosimetry based on parameters specifically obtained for the actual IORT beams. The deviations in the s(w,air) values were found to be as large as up to about 1%. Therefore, we recommend that a preliminary analysis should always be made when dealing with IORT beams in order to assess to what extent the possible differences in the s(w,air) values have to be accounted for or may be neglected on the basis of the specific accuracy needed in clinical dosimetry.

Predicting clinical trial results based on announcements of interim analyses

PubMed Central

2014-01-01

Background Announcements of interim analyses of a clinical trial convey information about the results beyond the trial’s Data Safety Monitoring Board (DSMB). The amount of information conveyed may be minimal, but the fact that none of the trial’s stopping boundaries has been crossed implies that the experimental therapy is neither extremely effective nor hopeless. Predicting success of the ongoing trial is of interest to the trial’s sponsor, the medical community, pharmaceutical companies, and investors. We determine the probability of trial success by quantifying only the publicly available information from interim analyses of an ongoing trial. We illustrate our method in the context of the National Surgical Adjuvant Breast and Bowel (NSABP) trial, C-08. Methods We simulated trials based on the specifics of the NSABP C-08 protocol that were publicly available. We quantified the uncertainty around the treatment effect using prior weights for the various possibilities in light of other colon cancer studies and other studies of the investigational agent, bevacizumab. We considered alternative prior distributions. Results Subsequent to the trial’s third interim analysis, our predictive probabilities were: that the trial would eventually be successful, 48.0%; would stop for futility, 7.4%; and would continue to completion without statistical significance, 44.5%. The actual trial continued to completion without statistical significance. Conclusions Announcements of interim analyses provide information outside the DSMB’s sphere of confidentiality. This information is potentially helpful to clinical trial prognosticators. ‘Information leakage’ from standard interim analyses such as in NSABP C-08 is conventionally viewed as acceptable even though it may be quite revealing. Whether leakage from more aggressive types of adaptations is acceptable should be assessed at the design stage. PMID:24607270

The Ebola Spatial Care Path™: Accelerating point-of-care diagnosis, decision making, and community resilience in outbreaks.

PubMed

Kost, Gerald J; Ferguson, William J; Hoe, Jackie; Truong, Anh-Thu; Banpavichit, Arirat; Kongpila, Surin

2015-01-01

To present a vision where point-of-care testing (POCT) accelerates an Ebola Spatial Care Path™ (SCP) and future molecular diagnostics enable facilitated-access self-testing (FAST POC); to design an alternate care facility (ACF) for the SCP; to innovate an Ebola diagnostic center (DC); and to propel rapid POCT to the frontline to create resilience that stops future outbreaks. PubMed, literature, and web searches. Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), Medicine Without Frontiers, and World Health Organization (WHO) document analyses. Investigations in China, the Philippines, Thailand, and the United States. Review of SE Asia, US, and West Africa isolation-treatment centers. Innovation of a SCP, ACF, and DC suitable for American and other communities. The authors designed an ACF and DC to integrate SCP principles for urgent Ebola care. FDA emergency use authorizations for Ebola molecular diagnostics were discovered, but no portable, handheld, or self-contained molecular POC instruments are yet available, although feasible. The WHO initiated design criteria and an acceptance protocol for testing. Financial investment in POCT will downsize Ebola outbreaks. POCT is facilitating global health. Now, global health problems are elevating POCT to new levels of importance for accelerating diagnosis and evidence-based decision making during disease outbreaks. Authorities concur that rapid diagnosis has potential to stop disease spread. With embedded POCT, strategic SCPs planned by communities fulfill CDC recommendations. POC devices should consolidate multiplex test clusters supporting patients with Ebola in isolation. The ultimate future solution is FAST POC. New technologies offer minimally significant risks. Diagnostic centers in ACFs and transportable formats also will optimize Ebola SCPs.

Ecological Momentary Assessment and Smartphone Application Intervention in Adolescents with Substance Use and Comorbid Severe Psychiatric Disorders: Study Protocol.

PubMed

Benarous, Xavier; Edel, Yves; Consoli, Angèle; Brunelle, Julie; Etter, Jean-François; Cohen, David; Khazaal, Yasser

2016-01-01

Substance use disorders (SUDs) are highly prevalent among inpatient adolescents with psychiatric disorders. In this population, substance use and other psychiatric outcomes can reinforce one another. Despite the need for integrated interventions in youths with dual diagnoses, few specific instruments are available. App-based technologies have shown promising results to help reduce substance use in adolescents, but their applicability in youths with associated severe psychiatric disorders is poorly documented. We aim to evaluate the feasibility of an ecological momentary assessment (EMA) intervention for all substance users, and of a smartphone application for cannabis users (Stop-Cannabis), for outpatient treatment after hospital discharge. All inpatient adolescents with psychiatric disorders hospitalized between 2016 and 2018 in a university hospital will be systematically screened for SUD and, if positive, will be assessed by an independent specialist addiction team. Participants with confirmed SUDs will be invited and helped to download an EMA app and, if required, the Stop-Cannabis app, the week preceding hospital discharge. Information about the acceptability and use of both apps and the validity of EMA data in comparison to clinical assessments will be assessed after 6 months and 1 year. This research has been designed to raise specific issues for consideration regarding the sequence between substance use, contextual factors, and other psychiatric symptoms among adolescents with comorbid severe psychiatric disorders. A better understanding of the mechanisms involved will inform the development of integrated treatment for dual disorders at that age. The study has already been approved and granted. Dissemination will include presentations at international congresses as well as publications in peer-reviewed journals. European Clinical Trials Database: Number 2016-001999-30.

Whole of Systems Trial of Prevention Strategies for Childhood Obesity: WHO STOPS Childhood Obesity

PubMed Central

Allender, Steven; Millar, Lynne; Hovmand, Peter; Bell, Colin; Moodie, Marj; Carter, Rob; Swinburn, Boyd; Strugnell, Claudia; Lowe, Janette; de la Haye, Kayla; Orellana, Liliana; Morgan, Sue

2016-01-01

Background: Community-based initiatives show promise for preventing childhood obesity. They are characterized by community leaders and members working together to address complex local drivers of energy balance. Objectives: To present a protocol for a stepped wedge cluster randomized trial in ten communities in the Great South Coast Region of Victoria, Australia to test whether it is possible to: (1) strengthen community action for childhood obesity prevention, and (2) measure the impact of increased action on risk factors for childhood obesity. Methods: The WHO STOPS intervention involves a facilitated community engagement process that: creates an agreed systems map of childhood obesity causes for a community; identifies intervention opportunities through leveraging the dynamic aspects of the system; and, converts these understandings into community-built, systems-oriented action plans. Ten communities will be randomized (1:1) to intervention or control in year one and all communities will be included by year three. The primary outcome is childhood obesity prevalence among grade two (ages 7–8 y), grade four (9–10 y) and grade six (11–12 y) students measured using our established community-led monitoring system (69% school and 93% student participation rate in government and independent schools). An additional group of 13 external communities from other regions of Victoria with no specific interventions will provide an external comparison. These communities will also allow us to assess diffusion of the intervention to control communities during the first three years of the trial. Conclusion: This trial will test effectiveness, over a five-year period, of community-owned, -supported and -led strategies designed to address complex and dynamic causes of childhood obesity. PMID:27854354

Safety and effectiveness of antiretroviral drugs during pregnancy, delivery and breastfeeding for prevention of mother-to-child transmission of HIV-1: the Kesho Bora Multicentre Collaborative Study rationale, design, and implementation challenges.

PubMed

2011-01-01

To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). Copyright © 2010 Elsevier Inc. All rights reserved.

Extended treatment with pegylated interferon alfa/ribavirin in patients with genotype 2/3 chronic hepatitis C who do not achieve a rapid virological response: final analysis of the randomised N-CORE trial.

PubMed

Shiffman, Mitchell L; Cheinquer, Hugo; Berg, Christoph P; Berg, Thomas; de Figueiredo-Mendes, Cláudio; Dore, Gregory J; Ferraz, Maria Lúcia; Mendes-Corrêa, Maria Cássia; Lima, Maria Patelli; Parise, Edison R; Rios, Alma Minerva Perez; Reuter, Tania; Sanyal, Arun J; Shafran, Stephen D; Hohmann, Marc; Tatsch, Fernando; Bakalos, George; Zeuzem, Stefan

2014-10-01

The combination of pegylated interferon alfa/ribavirin will likely remain the treatment of choice for HCV genotype 2/3 patients in financially constrained countries for the foreseeable future. Patients with poor on-treatment response may benefit from treatment extension. This study examined the effect of 48 versus 24 weeks of peginterferon alfa-2a/ribavirin on the sustained virological response (SVR) in patients with HCV genotype 2/3 who did not achieve rapid virological response (RVR). N-CORE was a multicentre, randomised, phase III study. HCV genotype 2/3 patients receiving peginterferon alfa-2a/ribavirin without a rapid but with an early virological response were randomised at week 24 to stop treatment (Arm A) or continue to 48 weeks (Arm B). The primary efficacy endpoint was SVR. Two hundred thirty-five patients were enrolled. End of treatment response was similar in both treatment arms. SVR24 rates were not significantly greater in the extended treatment arm compared with the standard 24-week treatment in either the intention-to-treat or the per-protocol populations (61 vs. 52 %, p = 0.1934 and 63 vs. 52 %, p = 0.1461, respectively). Serious adverse events occurred more frequently in patients receiving extended treatment duration (12 %) versus 24-week therapy (4 %). It is unclear whether the extension of peginterferon alfa-2a/ribavirin treatment may benefit HCV genotype 2/3 patients who do not achieve RVR. The study was stopped early because recruitment was slower than anticipated, and this may have limited the statistical impact of these findings.

Determination of single-kidney glomerular filtration rate (GFR) with CT urography versus renal dynamic imaging Gates method.

PubMed

You, Shan; Ma, XianWu; Zhang, ChangZhu; Li, Qiang; Shi, WenWei; Zhang, Jing; Yuan, XiaoDong

2018-03-01

To present a single-kidney CT-GFR measurement and compare it with the renal dynamic imaging Gates-GFR. Thirty-six patients with hydronephrosis referred for CT urography and 99mTc-DTPA renal dynamic imaging were prospectively included. Informed consent was obtained from all patients. The CT urography protocol included non-contrast, nephrographic, and excretory phase imaging. The total CT-GFR was calculated by dividing the CT number increments of the total urinary system between the nephrographic and excretory phase by the products of iodine concentration in the aorta and the elapsed time, then multiplied by (1- Haematocrit). The total CT-GFR was then split into single-kidney CT-GFR by a left and right kidney proportionality factor. The results were compared with single-kidney Gates-GFR by using paired t-test, correlation analysis, and Bland-Altman plots. Paired difference between single-kidney CT-GFR (45.02 ± 13.91) and single-kidney Gates-GFR (51.21 ± 14.76) was 6.19 ± 5.63 ml/min, p<0.001, demonstrating 12.1% systematic underestimation with ±11.03 ml/min (±21.5%) measurement deviation. A good correlation was revealed between both measurements (r=0.87, p<0.001). The proposed single-kidney CT-GFR correlates and agrees well with the reference standard despite a systematic underestimation, therefore it could be a one-stop-shop for evaluating urinary tract morphology and split renal function. • A new CT method can assess split renal function • Only using images from CT urography and the value of haematocrit • A one-stop-shop CT technique without additional radiation dose.

Contingency management for tobacco smoking during opioid addiction treatment: a randomised pilot study.

PubMed

Ainscough, Tom Stephen; Brose, Leonie S; Strang, John; McNeill, Ann

2017-09-01

Smoking rates among individuals in treatment for opioid addiction are close to five times that of the general public. Moreover, drug-addicted smokers have a premature mortality rate four times greater than drug-addicted non-smokers. The aim of this pilot study was to investigate whether contingency management (CM) can be successfully added to evidence-based stop smoking treatment in individuals undergoing treatment for opioid addiction and assess preliminary evidence for its impact. Forty tobacco smokers currently undergoing treatment for opioid addiction. Escalating with reset CM as an adjunct to standard smoking cessation treatment. Financial incentives will be administered over a 5-week period for either biochemically verified abstinence from smoking or attendance at the clinic. Participants will be randomised to conditions stratified on current levels of smoking (high or low). To assess whether a CM intervention can be successfully added to standard stop smoking services treatment, in patients undergoing outpatient treatment for opioid addiction. This will be measured as the number of people completing the 5 weeks of the intervention. Ethics approval for the study was granted on the 16 June 2016 by the London-city and east (reference 16/LO/0990) ethics committee. The pilot study was retrospectively registered on clincaltrials.gov in January 2017 (ID: NCT03015597). A SPIRIT checklist and figure are available for this protocol. It is planned that the results of this study will be published in an academic journal. © 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.

Higgs and Z assisted stop searches at hadron colliders

NASA Astrophysics Data System (ADS)

Su, Shufang; Zhang, Huanian

2018-05-01

Current searches for the light top squark (stop) mostly focus on the decay channels of \\tilde{t}\\to t{χ}_1^0 or \\tilde{t}\\to b{χ}_1^{±}\\to bW{χ}_1^0 , leading to [InlineMediaObject not available: see fulltext.] final states for stop pair productions at the LHC. However, in supersymmetric scenarios with light neutralinos and charginos other than the neutralino lightest supersymmetric particle (LSP), more than one decay mode of the stop could be dominant. While those new decay modes could significantly weaken the current stop search limits at the LHC, they also offer alternative discovery channels for stop searches. In this paper, we studied the scenario with light Higgsino next-to-LSPs (NLSPs) and Bino LSP. The light stop decays primarily via {\\tilde{t}}_1\\to t{χ}_2^0/{χ}_3^0 , with the neutralinos subsequent decaying to a Z boson or a Higgs boson: χ 2 0 / χ 3 0 → χ 1 0 h/ Z. Pair production of light stops at the LHC leads to final states of [InlineMediaObject not available: see fulltext.] or [InlineMediaObject not available: see fulltext.] . We consider three signal regions: one charged lepton (1 ℓ), two opposite sign charged leptons (2 OS ℓ) and at least three charged leptons (≥3 ℓ). We found that the 1 ℓ signal region of channel [InlineMediaObject not available: see fulltext.] has the best reach sensitivity for light stop searches. For 14 TeV LHC with 300 fb-1 integrated luminosity, a stop mass up to 900 GeV can be discovered at 5 σ significance, or up to 1050 GeV can be excluded at 95% C.L. Combining all three decay channels for 1 ℓ signal region extends the reach for about 100-150 GeV. We also studied the stop reach at the 100 TeV pp collider with 3 ab-1 luminosity, with discovery and exclusion reach being 6 TeV and 7 TeV, respectively.

Second stop and sbottom searches with a stealth stop

NASA Astrophysics Data System (ADS)

Cheng, Hsin-Chia; Li, Lingfeng; Qin, Qin

2016-11-01

The top squarks (stops) may be the most wanted particles after the Higgs boson discovery. The searches for the lightest stop have put strong constraints on its mass. However, there is still a search gap in the low mass region if the spectrum of the stop and the lightest neutralino is compressed. In that case, it may be easier to look for the second stop since naturalness requires both stops to be close to the weak scale. The current experimental searches for the second stop are based on the simplified model approach with the decay modes {overset{˜ }{t}}_2to {overset{˜ }{t}}_1Z and {overset{˜ }{t}}_2to {overset{˜ }{t}}_1h . However, in a realistic supersymmetric spectrum there is always a sbottom lighter than the second stop, hence the decay patterns are usually more complicated than the simplified model assumptions. In particular, there are often large branching ratios of the decays {overset{˜ }{t}}_2to {overset{˜ }{b}}_1W and {overset{˜ }{b}}_1to {overset{˜ }{t}}_1W as long as they are open. The decay chains can be even more complex if there are intermediate states of additional charginos and neutralinos in the decays. By studying several MSSM benchmark models at the 14 TeV LHC, we point out the importance of the multi- W final states in the second stop and the sbottom searches, such as the same-sign dilepton and multilepton signals, aside from the traditional search modes. The observed same-sign dilepton excesses at LHC Run 1 and Run 2 may be explained by some of our benchmark models. We also suggest that the vector boson tagging and a new kinematic variable may help to suppress the backgrounds and increase the signal significance for some search channels. Due to the complex decay patterns and lack of the dominant decay channels, the best reaches likely require a combination of various search channels at the LHC for the second stop and the lightest sbottom.

Development and psychometric properties of the Suicidality: Treatment Occurring in Paediatrics (STOP) Suicidality Assessment Scale (STOP-SAS) in children and adolescents.

PubMed

Flamarique, I; Santosh, P; Zuddas, A; Arango, C; Purper-Ouakil, D; Hoekstra, P J; Coghill, D; Schulze, U; Dittmann, R W; Buitelaar, J K; Lievesley, K; Frongia, R; Llorente, C; Méndez, I; Sala, R; Fiori, F; Castro-Fornieles, J

2016-12-13

To create a self-reported, internet-based questionnaire for the assessment of suicide risk in children and adolescents. As part of the EU project 'Suicidality: Treatment Occurring in Paediatrics' (STOP project), we developed web-based Patient Reported Outcome Measures (PROMs) for children and adolescents and for proxy reports by parents and clinicians in order to assess suicidality. Based on a literature review, expert panels and focus groups of patients, we developed the items of the STOP Suicidality Assessment Scale (STOP-SAS) in Spanish and English, translated it into four more languages, and optimized it for web-based presentation using the HealthTracker TM platform. Of the total 19 questions developed for the STOP-SAS, four questions that assess low-level suicidality were identified as screening questions (three of them for use with children, and all four for use with adolescents, parents and clinicians). A total of 395 adolescents, 110 children, 637 parents and 716 clinicians completed the questionnaire using the HealthTracker TM , allowing us to evaluate the internal consistency and convergent validity of the STOP-SAS with the clinician-rated Columbia Suicide Severity Rating Scale (C-SSRS). Validity was also assessed with the receiver operating characteristic (ROC) area of the STOP-SAS with the C-SSRS. The STOP-SAS comprises 19 items in its adolescent, parent, and clinician versions, and 14 items in its children's version. Good internal consistency was found for adolescents (Cronbach's alpha: 0.965), children (Cronbach's alpha: 0.922), parents (Cronbach's alpha: 0.951) and clinicians (Cronbach's alpha: 0.955) versions. A strong correlation was found between the STOP-SAS and the C-SSRS for adolescents (r:0.670), parents (r:0.548), clinicians (r:0.863) and children (r:0.654). The ROC area was good for clinicians' (0.917), adolescents' (0.834) and parents' (0.756) versions but only fair (0.683) for children's version. The STOP-SAS is a comprehensive, web-based PROM developed on the HealthTracker TM platform, and co-designed for use by adolescents, children, parents and clinicians. It allows the evaluation of aspects of suicidality and shows good reliability and validity.

Mathematical modeling for optimizing skip-stop rail transit operation strategy using genetic algorithm.

DOT National Transportation Integrated Search

2012-03-01

"With skip-stop rail transit operation, transit agencies can reduce their operating costs and fleet size, : and passengers can experience reduced in-transit travel times without extra track and technological : improvement. However, since skip-stop op...

Survey on use of 4-way and reversed stop signs in residential areas.

DOT National Transportation Integrated Search

1977-01-01

A nationwide questionnaire survey on use of 4-way stop signs and reversed stop signs to reduce through traffic in residential areas elicited responses from 141 governmental agencies including state highway departments, urban counties containing citie...