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

PubMed

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

2016-02-01

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 Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events.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

An Exploratory Study of Emotional Affordance of a Massive Open Online Course

ERIC Educational Resources Information Center

Cheng, Jeremy C. Y.

2014-01-01

This exploratory study examines emotional affordance of a massive open online course (MOOC). Postings in a discussion forum of a MOOC in computer science are analysed following a research design informed by virtual ethnography. Emotional affordance is investigated, focusing on non-achievement emotions which are not directly linked to achievement…

FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study.

PubMed

Tedesco-Silva, H; Lorber, M I; Foster, C E; Sollinger, H W; Mendez, R; Carvalho, D B; Shapiro, R; Rajagopalan, P R; Mayer, H; Slade, J; Kahan, B D

2009-01-01

This exploratory, multicenter, open-label study evaluated the efficacy and safety of FTY720, as a part of an immunosuppressive regimen, in combination with everolimus and steroids in de novo renal transplant recipients at increased risk of delayed graft function (DGF). Patients received FTY720 (5 mg) and everolimus (4 mg) 2-12 h pre-transplantation, followed by 2.5 mg/d FTY720 and concentration-controlled everolimus (4-8 ng/mL) post-transplant for 12 months. Induction therapy was prohibited. After enrollment of 56 of the planned 200 patients between 2000 and 2002, the recruitment was terminated. The primary endpoint, rate of graft loss, or death at three months was 15.4% and the biopsy-confirmed acute rejection was 42.3%. Death or graft loss at 12 months in the DGF and non-DGF arms was 36.0% and 25.9%, respectively. The mean estimated creatinine clearance at three months was 63 and 55 mL/min in the non-DGF and DGF groups, respectively, while at 12 months it was 56 mL/min in both the groups. Although there was no comparator arm, the results from this exploratory study (compared with data from other phases II and III trials) indicated no apparent benefits of FTY720-based regimens for prevention of acute rejection and preservation of renal function in renal transplant recipients at high risk of DGF.

The Value of Learning Talk: Applying a Novel Dialogue Scoring Method to Inform Interaction Design in an Open-Ended, Embodied Museum Exhibit

ERIC Educational Resources Information Center

Roberts, Jessica; Lyons, Leilah

2017-01-01

Museum researchers have long acknowledged the importance of dialogue in informal learning, particularly for open-ended exploratory exhibits. Novel interaction techniques like full-body interaction are appealing for these exploratory exhibits, but designers have not had a metric for determining how their designs are supporting productive learning…

An Open-Label Exploratory Study with Memantine: Correlation between Proton Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate Alzheimer's Disease

PubMed Central

Gordon, Marc L.; Kingsley, Peter B.; Goldberg, Terry E.; Koppel, Jeremy; Christen, Erica; Keehlisen, Lynda; Kohn, Nina; Davies, Peter

2012-01-01

Aim To characterize progression of Alzheimer's disease (AD) using proton magnetic resonance spectroscopy (1H MRS). Methods Eleven subjects with mild to moderate AD underwent neurocognitive testing and single-voxel 1H MRS from the precuneus and posterior cingulate region at baseline, after 24 weeks of monotherapy with a cholinesterase inhibitor, and after another 24 weeks of combination therapy with open-label memantine and a cholinesterase inhibitor. Baseline metabolites [N-acetylaspartate (NAA), myo-inositol (mI), choline (Cho), and creatine (Cr)] and their ratios in AD subjects were compared with those of an age-matched control group of 28 cognitively normal subjects. Results AD subjects had significantly higher mI/Cr and lower NAA, NAA/Cr, NAA/Cho, and NAA/mI. Baseline Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores significantly correlated with NAA/Cr, mI/Cr, and NAA/mI. There was an increase in mI and a decrease in NAA/mI, but no significant change in other metabolites or ratios, or neurocognitive measures, when memantine was added to a cholinesterase inhibitor. Conclusion Metabolite ratios significantly differed between AD and control subjects. Baseline metabolite ratios correlated with function (ADCS-ADL). There was an increase in mI and a decrease in NAA/mI, but no changes in other metabolites, ratios, or cognitive measures, when memantine was added to a cholinesterase inhibitor. PMID:22962555

Changes in the pattern of exploratory behavior are associated with the emergence of social dominance relationships in male rats.

PubMed

Arakawa, Hiroyuki

2006-01-01

This study examined the effect of the establishment of dominance relationships and subordination on exploratory behavior for both postpubertal and adult male rats. Prior to an open field test, subjects were housed either in isolation (IS) or in littermate pairs (PS) with mild dominance relationships without overt victory or defeat, or in pairs with clear hierarchical relationships as dominants (DOM) or subordinates (SUB). Stretch-attend postures and entries into the center area of the open-field were measured as an index of passive and active exploratory behavior, respectively, and crossings in the peripheral area were counted as activity. SUB rats, both postpubertal and adult, displayed less activity and lower levels of active exploratory behavior, whereas adult IS rats showed higher levels of active exploratory behavior compared to the other groups. Furthermore, both DOM and PS rats exhibited a more passive pattern of exploratory behavior in adulthood than in postpuberty. Thus the results show that an increase in the active exploratory pattern is inhibited by the establishment of social relationships among adult rats, while a decrease in activity is a primarily effect of subordination. The capacity to change exploratory patterns following subordination is found even in the postpubertal stage when adultlike social relationships have not yet appeared. Copyright 2005 Wiley Periodicals, Inc.

Uridine monophosphate, folic acid and vitamin B12 in patients with symptomatic peripheral entrapment neuropathies.

PubMed

Negrão, Luis; Nunes, Paula

2016-01-01

Carpal tunnel syndrome is the most common type of peripheral entrapment neuropathy. We performed an exploratory, open-label, multicenter, observational study of 48 patients with peripheral entrapment neuropathy. Patients received a daily capsule of uridine monophosphate, folic acid + vitamin B12 for 2 months and were evaluated using the Pain DETECT questionnaire. The global score for pain decreased from 17.3 ± 5.9 at baseline to 10.3 ± 6.1 at the final evaluation (p < 0.001). Concomitant analgesic and anti-inflammatory treatment was stopped or the dose reduced in 77.4% of patients. Uridine monophosphate + folic acid + vitamin B12 reduced total pain score, intensity and characterization of pain and associated symptoms. These results should be tested in a well-designed, adequately powered randomized controlled trial.

Language Learning over 50 at the Open University in Poland: An Exploratory Study of Needs and Emotions

ERIC Educational Resources Information Center

Klimczak-Pawlak, Agata; Kossakowska-Pisarek, Sylwia

2018-01-01

This exploratory, retrospective study, which focuses on the needs, attitudes, and emotions of learners attending English as a foreign language courses at the Open University of the University of Warsaw is part of a larger scale project which aims at answering calls voiced, among others, by Boulton-Lewis (2010) to gather more data from older adults…

Exploratory Analysis of Fast-Food Chain Restaurant Menus Before and After Implementation of Local Calorie-Labeling Policies, 2005–2011

PubMed Central

Namba, Alexa; Leonberg, Beth L.; Wootan, Margo G.

2013-01-01

Introduction Since 2008, several states and municipalities have implemented regulations requiring provision of nutrition information at chain restaurants to address obesity. Although early research into the effect of such labels on consumer decisions has shown mixed results, little information exists on the restaurant industry’s response to labeling. The objective of this exploratory study was to evaluate the effect of menu labeling on fast-food menu offerings over 7 years, from 2005 through 2011. Methods Menus from 5 fast-food chains that had outlets in jurisdictions subject to menu-labeling laws (cases) were compared with menus from 4 fast-food chains operating in jurisdictions not requiring labeling (controls). A trend analysis assessed whether case restaurants improved the healthfulness of their menus relative to the control restaurants. Results Although the overall prevalence of “healthier” food options remained low, a noteworthy increase was seen after 2008 in locations with menu-labeling laws relative to those without such laws. Healthier food options increased from 13% to 20% at case locations while remaining static at 8% at control locations (test for difference in the trend, P = .02). Since 2005, the average calories for an à la carte entrée remained moderately high (approximately 450 kilocalories), with less than 25% of all entrées and sides qualifying as healthier and no clear systematic differences in the trend between chain restaurants in case versus control areas (P ≥ .50). Conclusion These findings suggest that menu labeling has thus far not affected the average nutritional content of fast-food menu items, but it may motivate restaurants to increase the availability of healthier options. PMID:23786908

Exploratory analysis of fast-food chain restaurant menus before and after implementation of local calorie-labeling policies, 2005-2011.

PubMed

Namba, Alexa; Auchincloss, Amy; Leonberg, Beth L; Wootan, Margo G

2013-06-20

Since 2008, several states and municipalities have implemented regulations requiring provision of nutrition information at chain restaurants to address obesity. Although early research into the effect of such labels on consumer decisions has shown mixed results, little information exists on the restaurant industry's response to labeling. The objective of this exploratory study was to evaluate the effect of menu labeling on fast-food menu offerings over 7 years, from 2005 through 2011. Menus from 5 fast-food chains that had outlets in jurisdictions subject to menu-labeling laws (cases) were compared with menus from 4 fast-food chains operating in jurisdictions not requiring labeling (controls). A trend analysis assessed whether case restaurants improved the healthfulness of their menus relative to the control restaurants. Although the overall prevalence of "healthier" food options remained low, a noteworthy increase was seen after 2008 in locations with menu-labeling laws relative to those without such laws. Healthier food options increased from 13% to 20% at case locations while remaining static at 8% at control locations (test for difference in the trend, P = .02). Since 2005, the average calories for an à la carte entrée remained moderately high (approximately 450 kilocalories), with less than 25% of all entrées and sides qualifying as healthier and no clear systematic differences in the trend between chain restaurants in case versus control areas (P ≥ .50). These findings suggest that menu labeling has thus far not affected the average nutritional content of fast-food menu items, but it may motivate restaurants to increase the availability of healthier options.

A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement

PubMed Central

Macchi, Zachary; Wang, Yunxia; Moore, Dan; Katz, Jonathan; Saperstein, David; Walk, David; Simpson, Ericka; Genge, Angela; Bertorini, Tulio; Fernandes, J Americo; Swenson, Andrea; Elman, Lauren; Dimachkie, Mazen; Herbelin, Laura; Miller, Joann; Lu, Jianghua; Wilkins, Heather; Swerdlow, Russell H; Statland, Jeffrey; Barohn, Richard

2015-01-01

OBJECTIVE Rasagiline, a monoamine oxidase B inhibitor, slowed disease progression in the SOD1 mouse, and in a case series of patients with amyotrophic lateral sclerosis (ALS). Here we determine whether rasagiline is safe and effective in ALS compared to historical placebo controls, and whether it alters mitochondrial biomarkers. METHODS We performed a prospective open-label, multicenter screening trial of 36 ALS patients treated with 2mg oral rasagiline daily for 12 months. Outcomes included the slope of deterioration of the revised ALS Functional Rating Scale (ALSFRS-R), adverse event monitoring, time to treatment failure, and exploratory biomarkers. RESULTS Participants experienced no serious drug-related adverse events, and the most common adverse event was nausea (11.1%). Rasagiline did not improve the rate of decline in the ALSFRS-R; however, differences in symptom duration compared to historical placebo controls differentially affected ALSFRS-R slope estimates. Rasagiline changed biomarkers over 12 months, such that the mitochondrial membrane potential increased (JC-1 red/green fluorescent ratio 1.92, P=0.0001) and apoptosis markers decreased (Bcl-2/Bax ratio 0.24, P<0.0001). CONCLUSION Engagement of exploratory biomarkers and questions about comparability of baseline characteristics lead us to recommend a further placebo-controlled trial. PMID:25832828

Effect of ketamine on exploratory behaviour in BALB/C and C57BL/6 mice.

PubMed

Akillioglu, Kubra; Melik, Emine Babar; Melik, Enver; Boga, Ayper

2012-01-01

In this study, we evaluated the effect of ketamine on exploratory locomotion behaviours in the Balb/c and C57BL/6 strains of mice, which differ in their locomotion behaviours. Intraperitoneal administration of ketamine at three different doses (1, 5 or 10 mg/kg, 0.1 ml/10 gr body weight) was performed on adult male Balb/c and C57BL/6 mice. The same volume of saline was applied to the control group. The open-field and elevated plus maze apparatus were used to evaluate exploratory locomotion. In the open-field test, Balb/c mice less spend time in the centre of the field and was decreased locomotor activity compared to C57BL/6 mice (p<0.01). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in locomotor activity and an increase in the amount of time spent in the centre in the open-field test, compared to the control group (p<0.05). In C57BL/6 mice, ketamine treatment (1 and 10 mg/kg) decreased locomotor activity (p<0.05). In C57BL/6 mice, the three different doses of ketamine application each caused a decrease in the frequency of centre crossing (p<0.001) and the spent time in the centre (p<0.05). In the elevated plus maze, the number of open-arm entries, the percentage of open-arm time and total arm entries were decreased in Balb/c mice compared to C57BL/6 mice (p<0.001). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in the open-arm activity (p<0.001). Ketamine application (10 mg/kg) decreased the open-arm activity in C57BL/6 mice (p<0.05). A subanaesthetic dose of ketamine increased exploratory locomotion in Balb/c mice. In contrast, a subanaesthetic dose of ketamine decreased exploratory locomotion in C57BL/6 mice. In conclusion, hereditary factors may play an important role in ketamine-induced responses. Copyright © 2011 Elsevier Inc. All rights reserved.

Older lesbian sexuality: identity, sexual behavior, and the impact of aging.

PubMed

Averett, Paige; Yoon, Intae; Jenkins, Carol L

2012-01-01

In response to the very limited and mostly outdated literature on older lesbian sexuality, this exploratory study examined older lesbian sexual identity, romantic relationships, the impact of aging, and experiences of discrimination within these contexts. Utilizing an online survey that recruited via numerous online lesbian communities and snowball sampling, 456 lesbians over the age of 50 responded to closed, Likert scale, and open-ended questions that provided a preliminary understanding of older lesbian sexuality. The results indicated that older lesbians have experienced fluidity in past romantic and sexual relationships, as well as in erotic fantasies, despite strong identification with being lesbian. The findings also indicate a decreased focus on sexuality in the context of relationships, with more focus on stability and continuity. Future research is needed that provides greater specificity and detail about older lesbian conceptions of sexual behavior and sexual identity labels, as well as specific sexual behaviors.

Open-label extension studies: do they provide meaningful information on the safety of new drugs?

PubMed

Day, Richard O; Williams, Kenneth M

2007-01-01

The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the time of entry into the open-label extension study. Negative aspects of open-label extension studies revolve around their use as a marketing tool, as they build a market for the drug and generate pressure for subsidised access to the drug from consumers and their physicians. Consumers, institutions where these studies are conducted and research ethics committees need to be convinced of the motives, as well as the quality, of the open-label extension study and its execution before supporting such studies. Open-label extension studies do have a legitimate but limited place in the clinical development of new medicines. The negative perceptions about these studies have arisen because of perversion of acceptable rationales for this type of study and a failure to recognise (or disclose) the limitations resulting from the inherent weaknesses in their design. Increased human exposure to a new medicine under reasonably controlled circumstances to increase confidence in the safety of the medicine is an acceptable rationale for an open-label extension study, and a useful activity to increase the knowledge of the safety profile of a new medicine. However, this goal is increasingly being achieved by means other than open-label extension studies.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study

PubMed Central

Douillard, J-Y; Ostoros, G; Cobo, M; Ciuleanu, T; McCormack, R; Webster, A; Milenkova, T

2014-01-01

Background: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Methods: Treatment: gefitinib 250 mg day−1 until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. Results: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8% adenocarcinoma 97.2% never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5–77.7), DCR 90.6% (95% CI 83.5–94.8), median PFS 9.7 months (95% CI 8.5–11.0), median OS 19.2 months (95% CI 17.0–NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15% SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8–74.7). Conclusion: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable. PMID:24263064

A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

PubMed

Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

2014-12-01

Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348. Copyright © 2014 Elsevier Inc. All rights reserved.

Exploratory behaviour in the open field test adapted for larval zebrafish: impact of environmental complexity.

PubMed

Ahmad, Farooq; Richardson, Michael K

2013-01-01

This study aimed to develop and characterize a novel (standard) open field test adapted for larval zebrafish. We also developed and characterized a variant of the same assay consisting of a colour-enriched open field; this was used to assess the impact of environmental complexity on patterns of exploratory behaviours as well to determine natural colour preference/avoidance. We report the following main findings: (1) zebrafish larvae display characteristic patterns of exploratory behaviours in the standard open field, such as thigmotaxis/centre avoidance; (2) environmental complexity (i.e. presence of colours) differentially affects patterns of exploratory behaviours and greatly attenuates natural zone preference; (3) larvae displayed the ability to discriminate colours. As reported previously in adult zebrafish, larvae showed avoidance towards blue and black; however, in contrast to the reported adult behaviour, larvae displayed avoidance towards red. Avoidance towards yellow and preference for green and orange are shown for the first time, (4) compared to standard open field tests, exposure to the colour-enriched open field resulted in an enhanced expression of anxiety-like behaviours. To conclude, we not only developed and adapted a traditional rodent behavioural assay that serves as a gold standard in preclinical drug screening, but we also provide a version of the same test that affords the possibility to investigate the impact of environmental stress on behaviour in larval zebrafish while representing the first test for assessment of natural colour preference/avoidance in larval zebrafish. In the future, these assays will improve preclinical drug screening methodologies towards the goal to uncover novel drugs. This article is part of a Special Issue entitled: insert SI title. Copyright © 2012 Elsevier B.V. All rights reserved.

A comparative study on the effects of systemic manual acupuncture, periauricular electroacupuncture, and digital electroacupuncture to treat tinnitus: A randomized, paralleled, open-labeled exploratory trial.

PubMed

Kim, Bong Hyun; Kim, Kyuseok; Nam, Hae Jeong

2017-01-31

Many previous studies of electroacupuncture used combined therapy of electroacupuncture and systemic manual acupuncture, so it was uncertain which treatment was effective. This study evaluated and compared the effects of systemic manual acupuncture, periauricular electroacupuncture and distal electroacupuncture for treating patients with tinnitus. A randomized, parallel, open-labeled exploratory trial was conducted. Subjects aged 20-75 years who had suffered from idiopathic tinnitus for > 2 weeks were recruited from May 2013 to April 2014. The subjects were divided into three groups by systemic manual acupuncture group (MA), periauricular electroacupuncture group (PE), and distal electroacupuncture group (DE). The groups were selected by random drawing. Nine acupoints (TE 17, TE21, SI19, GB2, GB8, ST36, ST37, TE3 and TE9), two periauricular acupoints (TE17 and TE21), and four distal acupoints (TE3, TE9, ST36, and ST37) were selected. The treatment sessions were performed twice weekly for a total of eight sessions over 4 weeks. Outcomes were the tinnitus handicap inventory (THI) score and the loud and uncomfortable visual analogue scales (VAS). Demographic and clinical characteristics of all participants were compared between the groups upon admission using one-way analysis of variance (ANOVA). One-way ANOVA was used to evaluate the THI, VAS loud , and VAS uncomfortable scores. The least significant difference test was used as a post-hoc test. Thirty-nine subjects were eligible and their data were analyzed. No difference in THI and VAS loudness scores was observed in between groups. The VAS uncomfortable scores decreased significantly in MA and DE compared with those in PE. Within the group, all three treatments showed some effect on THI, VAS loudness scores and VAS uncomfortable scores after treatment except DE in THI. There was no statistically significant difference between systemic manual acupuncture, periauricular electroacupuncture and distal electroacupuncture in tinnitus. However, all three treatments had some effect on tinnitus within the group before and after treatment. Systemic manual acupuncture and distal electroacupuncture have some effect on VAS uncomfortable . KCT0001991 by CRIS (Clinical Research Information Service), 2016-8-1, retrospectively registered.

The point of entry contributes to the organization of exploratory behavior of rats on an open field: an example of spontaneous episodic memory.

PubMed

Nemati, Farshad; Whishaw, Ian Q

2007-08-22

The exploratory behavior of rats on an open field is organized in that animals spend disproportionate amounts of time at certain locations, termed home bases, which serve as centers for excursions. Although home bases are preferentially formed near distinctive cues, including visual cues, animals also visit and pause and move slowly, or linger, at many other locations in a test environment. In order to further examine the organization of exploratory behavior, the present study examined the influence of the point of entry on animals placed on an open field table that was illuminated either by room light or infrared light (a wavelength in which they cannot see) and near which, or on which, distinctive cues were placed. The main findings were that in both room light and infrared light tests, rats visited and lingered at the point of entry significantly more often than comparative control locations. Although the rats also visited and lingered in the vicinity of salient visual cues, the point of entry still remained a focus of visits. Finally, the preference for the point of entry increased as a function of salience of the cues marking that location. That the point of entry influences the organization of exploratory behavior is discussed in relation to the idea that the exploratory behavior of the rat is directed toward optimizing security as well as forming a spatial representation of the environment.

Label-free serum ribonucleic acid analysis for colorectal cancer detection by surface-enhanced Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Chen, Yanping; Chen, Gang; Feng, Shangyuan; Pan, Jianji; Zheng, Xiongwei; Su, Ying; Chen, Yan; Huang, Zufang; Lin, Xiaoqian; Lan, Fenghua; Chen, Rong; Zeng, Haishan

2012-06-01

Studies with circulating ribonucleic acid (RNA) not only provide new targets for cancer detection, but also open up the possibility of noninvasive gene expression profiling for cancer. In this paper, we developed a surface-enhanced Raman scattering (SERS), platform for detection and differentiation of serum RNAs of colorectal cancer. A novel three-dimensional (3-D), Ag nanofilm formed by dry MgSO4 aggregated silver nanoparticles, Ag NP, as the SERS-active substrate was presented to effectively enhance the RNA Raman signals. SERS measurements were performed on two groups of serum RNA samples. One group from patients, n=55 with pathologically diagnosed colorectal cancer and the other group from healthy controls, n=45. Tentative assignments of the Raman bands in the normalized SERS spectra demonstrated that there are differential expressions of cancer-related RNAs between the two groups. Linear discriminate analysis, based on principal component analysis, generated features can differentiate the colorectal cancer SERS spectra from normal SERS spectra with sensitivity of 89.1 percent and specificity of 95.6 percent. This exploratory study demonstrated great potential for developing serum RNA SERS analysis into a useful clinical tool for label-free, noninvasive screening and detection of colorectal cancers.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy.

PubMed

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d'Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P; Büttner, Hartwig

2016-09-01

Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5mg once a day (OaD), tadalafil 20mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. The first decision-tree model (n=422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF-related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. ClinicalTrials.gov, NCT01026818. Copyright © 2016. Published by Elsevier B.V.

Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults with ADHD: Final Report of a 4-Year Study

ERIC Educational Resources Information Center

Adler, Lenard A.; Spencer, Thomas J.; Williams, David W.; Moore, Rodney J.; Michelson, David

2008-01-01

Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial…

Multi-walled carbon nanotubes increase anxiety levels in rats and reduce exploratory activity in the open field test.

PubMed

Sayapina, N V; Batalova, T A; Chaika, V V; Kuznetsov, V L; Sergievich, A A; Kolosov, V P; Perel'man, Yu M; Golokhvast, K S

2015-01-01

The results of the first study on the effects of multi-walled carbon nanotubes (MWNTs) on the exploratory activity and the emotional state in laboratory rats assessed by the open field test are reported. During three or ten days, rats received 8-10 nm MWNTs added to their food at a dose of 500 mg/kg. It was demonstrated that, in the group of rats which were fed with MWNTs, the integrated anxiety level index began to increase as early as the third day of the experiment; on the tenth day, it appeared to be twice increased. It was also demonstrated that MWNTs decreased the integrated exploratory activity index nearly twofold on the third day and nearly fourfold on the tenth day.

Infant titi monkey behavior in the open field test and the effect of early adversity

PubMed Central

Larke, Rebecca H.; Toubiana, Alice; Lindsay, Katrina A.; Mendoza, Sally P.; Bales, Karen L.

2017-01-01

The open field test is commonly used to measure anxiety-related behavior and exploration in rodents. Here, we used it as a standardized novel environment in which to evaluate the behavioral response of infant titi monkeys (Callicebus cupreus), to determine the effect of presence of individual family members, and to assess how adverse early experience alters infant behavior. Infants were tested in the open field for 5 days at ages 4 and 6 months in four successive 5 min trials on each day. A transport cage, which was situated on one side of the open field, was either empty (non-social control) or contained the father, mother, or sibling. Infant locomotor, vocalization, and exploratory behavior were quantified. Results indicated that age, sex, social condition, and early experience all had significant effects on infant behavior. Specifically, infants were generally more exploratory at 6 months and male infants were more exploratory than females. Infants distinguished between social and non-social conditions but made few behavioral distinctions between the attachment figure and other individuals. Infants which had adverse early life experience demonstrated greater emotional and physical independence, suggesting that early adversity led to resiliency in the novel environment. PMID:28605039

Aged women, witchcraft, and social relations among the Igbo in South-Eastern Nigeria.

PubMed

Atata, Scholastica Ngozi

2018-02-13

Belief in the existence of witchcraft has remained a social phenomenon in Igbo society, especially with aged women who are often labeled witches. This study is exploratory and explains the implication of labeling an aged woman a witch and social relations in Igbo society in South-Eastern Nigeria. Twenty interviews were conducted with aged women who are victims of the witchcraft label and their relatives using qualitative methods of data collection, key informant interviews, and in-depth interviews. Data collected were analyzed using ethnographic content analysis. Findings reveal different social views attached to witchcraft and how it relates to aged women.

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

PubMed

Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

2017-09-01

To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

Connectivism in Postsecondary Online Courses: An Exploratory Factor Analysis

ERIC Educational Resources Information Center

Hogg, Nanette; Lomicky, Carol S.

2012-01-01

This study explores 465 postsecondary students' experiences in online classes through the lens of connectivism. Downes' 4 properties of connectivism (diversity, autonomy, interactivity, and openness) were used as the study design. An exploratory factor analysis was performed. This study found a 4-factor solution. Subjects indicated that autonomy…

Open Access Theses in Institutional Repositories: An Exploratory Study of the Perceptions of Doctoral Students

ERIC Educational Resources Information Center

Stanton, Kate Valentine; Liew, Chern Li

2011-01-01

Introduction: We examine doctoral students' awareness of and attitudes to open access forms of publication. Levels of awareness of open access and the concept of institutional repositories, publishing behaviour and perceptions of benefits and risks of open access publishing were explored. Method: Qualitative and quantitative data were collected…

Safety and tolerability of varenicline tartrate (Champix(®)/Chantix(®)) for smoking cessation in HIV-infected subjects: a pilot open-label study.

PubMed

Cui, Qu; Robinson, Linda; Elston, Dawn; Smaill, Fiona; Cohen, Jeffrey; Quan, Corinna; McFarland, Nancy; Thabane, Lehana; McIvor, Andrew; Zeidler, Johannes; Smieja, Marek

2012-01-01

The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix(®), Pfizer, Saint-Laurent, QC, Canada or Chantix(®), Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p = 0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9-12 was 42% (95% confidence interval [CI]: 26-58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline.

Safety and Tolerability of Varenicline Tartrate (Champix®/Chantix®) for Smoking Cessation in HIV-Infected Subjects: A Pilot Open-Label Study

PubMed Central

Robinson, Linda; Elston, Dawn; Smaill, Fiona; Cohen, Jeffrey; Quan, Corinna; McFarland, Nancy; Thabane, Lehana; McIvor, Andrew; Zeidler, Johannes; Smieja, Marek

2012-01-01

Abstract The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix®, Pfizer, Saint-Laurent, QC, Canada or Chantix®, Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p=0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9–12 was 42% (95% confidence interval [CI]: 26–58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline. PMID:22007690

The Openness of the University of the Philippines Open University: Issues and Prospects

ERIC Educational Resources Information Center

Villamejor-Mendoza, Maria Fe

2013-01-01

This paper is a self-reflection on the state of openness of the University of the Philippines Open University (UPOU). An exploratory and descriptive study, it aims not only to define the elements of openness of UPOU, but also to unravel the causes and solutions to the issues and concerns that limit its options to becoming a truly open university.…

The effect of neonatal N-methyl-D-aspartate receptor blockade on exploratory and anxiety-like behaviors in adult BALB/c and C57BL/6 mice.

PubMed

Akillioglu, Kubra; Binokay, Secil; Kocahan, Sayad

2012-07-15

N-methyl-D-aspartate (NMDA) receptors play an important role in brain maturation and developmental processes. In our study, we evaluated the effects of neonatal NMDA receptor blockade on exploratory locomotion and anxiety-like behaviors of adult BALB/c and C57BL/6 mice. In this study, NMDA receptor hypofunction was induced 7-10 days after birth using MK-801 in BALB/c and C57BL/6 mice (0.25mg/kg twice a day for 4 days via intraperitoneal injection). The open-field (OF) and elevated plus maze (EPM) tests were used to evaluate exploratory locomotion and anxiety-like behaviors. In the OF, BALB/c mice spent less time in the center of the field (p<0.05) and had less vertical locomotor activity (p<0.01) compared to C57BL/6 mice. In BALB/c mice, MK-801 caused a decrease in vertical and horizontal locomotor activity in the OF test, compared to the control group (p<0.05). In C57BL/6 mice, MK-801 treatment increased horizontal locomotor activity and decreased time spent in the center in the OF test (p<0.05). In the EPM, the number of open-arm entries, the percentage of open-arm time (p<0.01) and total arm entries (p<0.05) were lower in BALB/c mice compared to C57BL/6 mice. In BALB/c mice, MK-801 caused an increase in the percentage of open-arm time compared to the control group (p<0.05). In C57BL/6 mice, MK-801 caused a decrease in the percentage of open-arm time compared to the control group (p<0.05). MK-801 decreased exploratory and anxiety-like behaviors in BALB/c mice. In contrast, MK-801 increased exploratory and anxiety-like behaviors in C57BL/6 mice. In conclusion, hereditary factors may play an important role in neonatal NMDA receptor blockade-induced responses. Copyright © 2012 Elsevier B.V. All rights reserved.

Differences in Spatio-Temporal Behavior of Zebrafish in the Open Tank Paradigm after a Short-Period Confinement into Dark and Bright Environments

PubMed Central

Rosemberg, Denis B.; Rico, Eduardo P.; Mussulini, Ben Hur M.; Piato, Ângelo L.; Calcagnotto, Maria E.; Bonan, Carla D.; Dias, Renato D.; Blaser, Rachel E.; Souza, Diogo O.; de Oliveira, Diogo L.

2011-01-01

The open tank paradigm, also known as novel tank diving test, is a protocol used to evaluate the zebrafish behavior. Several characteristics have been described for this species, including scototaxis, which is the natural preference for dark environments in detriment of bright ones. However, there is no evidence regarding the influence of “natural stimuli” in zebrafish subjected to novelty-based paradigms. In this report, we evaluated the spatio-temporal exploratory activity of the short-fin zebrafish phenotype in the open tank after a short-period confinement into dark/bright environments. A total of 44 animals were individually confined during a 10-min single session into one of three environments: black-painted, white-painted, and transparent cylinders (dark, bright, and transparent groups). Fish were further subjected to the novel tank test and their exploratory profile was recorded during a 15-min trial. The results demonstrated that zebrafish increased their vertical exploratory activity during the first 6-min, where the bright group spent more time and travelled a higher distance in the top area. Interestingly, all behavioral parameters measured for the dark group were similar to the transparent one. These data were confirmed by automated analysis of track and occupancy plots and also demonstrated that zebrafish display a classical homebase formation in the bottom area of the tank. A detailed spatio-temporal study of zebrafish exploratory behavior and the construction of representative ethograms showed that the experimental groups presented significant differences in the first 3-min vs. last 3-min of test. Although the main factors involved in these behavioral responses still remain ambiguous and require further investigation, the current report describes an alternative methodological approach for assessing the zebrafish behavior after a forced exposure to different environments. Additionally, the analysis of ethologically-relevant patterns across time could be a potential phenotyping tool to evaluate the zebrafish exploratory profile in the open tank task. PMID:21559304

Striatopallidal neurons control avoidance behavior in exploratory tasks.

PubMed

LeBlanc, Kimberly H; London, Tanisha D; Szczot, Ilona; Bocarsly, Miriam E; Friend, Danielle M; Nguyen, Katrina P; Mengesha, Marda M; Rubinstein, Marcelo; Alvarez, Veronica A; Kravitz, Alexxai V

2018-04-25

The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains unclear. We hypothesized that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested this hypothesis in two exploratory approach-avoidance conflict paradigms in mice: the elevated zero maze and open field. Genetic elimination of D2Rs on striatopallidal neurons (iMSNs), but not other neural populations, increased avoidance of the open areas in both tasks, in a manner that was dissociable from global changes in movement. Population calcium activity of dorsomedial iMSNs was disrupted in mice lacking D2Rs on iMSNs, suggesting that disrupted output of iMSNs contributes to heightened avoidance behavior. Consistently, artificial disruption of iMSN output with optogenetic stimulation heightened avoidance of open areas of these tasks, while inhibition of iMSN output reduced avoidance. We conclude that dorsomedial striatal iMSNs control approach-avoidance conflicts in exploratory tasks, and highlight this neural population as a potential target for reducing avoidance in anxiety disorders.

How informative are open-label studies for youth with bipolar disorder? A meta-analysis comparing open-label versus randomized, placebo-controlled clinical trials.

PubMed

Biederman, Joseph; Petty, Carter R; Woodworth, K Yvonne; Lomedico, Alexandra; O'Connor, Katherine B; Wozniak, Janet; Faraone, Stephen V

2012-03-01

To examine the informativeness of open-label trials toward predicting results in subsequent randomized, placebo-controlled clinical trials of psychopharmacologic treatments for pediatric bipolar disorder. We searched journal articles through PubMed at the National Library of Medicine using bipolar disorder, mania, pharmacotherapy, treatment and clinical trial as keywords. This search was supplemented with scientific presentations at national and international scientific meetings and submitted manuscripts from our group. Selection criteria included (1) enrollment of children diagnosed with DSM-IV bipolar disorder; (2) prospective assessment of at least 3 weeks; (3) monotherapy of a pharmacologic treatment for bipolar disorder; (4) use of a randomized placebo-controlled design or an open-label design for the same therapeutic compound; and (5) repeated use of the Young Mania Rating Scale (YMRS) as an outcome. The following information and data were extracted from 14 studies: study design, name of medication, class of medication, dose of medication, sample size, age, sex, trial length, and YMRS mean and standard deviation baseline and follow-up scores. For both study designs, the pooled effect size was statistically significant (open-label studies, z = 8.88, P < .001; randomized placebo-controlled studies, z = 13.75, P < .001), indicating a reduction in the YMRS from baseline to endpoint in both study designs. In a meta-analysis regression, study design was not a significant predictor of mean change in the YMRS. We found similarities in the treatment effects between open-label and randomized placebo-controlled studies in youth with bipolar disorder indicating that open-label studies are useful predictors of the potential safety and efficacy of a given compound in the treatment of pediatric bipolar disorder. © Copyright 2012 Physicians Postgraduate Press, Inc.

Adherence to Preexposure Prophylaxis: Current, Emerging, and Anticipated Bases of Evidence

PubMed Central

Amico, K. Rivet; Stirratt, Michael J.

2014-01-01

Despite considerable discussion and debate about adherence to preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV), scant data are available that characterize patterns of adherence to open-label PrEP. The current evidence base is instead dominated by research on adherence to placebo-controlled investigational drug by way of drug detection in active-arm participants of large randomized controlled trials (RCTs). Important differences between the context of blinded RCTs and open-label use suggest caution when generalizing from study product adherence to real-world PrEP use. Evidence specific to open-label PrEP adherence is presently sparse but will expand rapidly over the next few years as roll-out, demonstration projects, and more rigorous research collect and present findings. The current evidence bases established cannot yet predict uptake, adherence, or persistence with open-label effective PrEP. Emerging evidence suggests that some cohorts could execute better adherence in open-label use vs placebo-controlled research. Uptake of PrEP is presently slow in the United States; whether this changes as grassroots and community efforts increase awareness of PrEP as an effective HIV prevention option remains to be determined. As recommended by multiple guidelines for PrEP use, all current demonstration projects offer PrEP education and/or counseling. PrEP support approaches generally fall into community-based, technology, monitoring, and integrated sexual health promotion approaches. Developing and implementing research that moves beyond simple correlates of either study product use or open-label PrEP adherence toward more comprehensive models of sociobehavioral and socioecological adherence determinants would greatly accelerate progress. Intervention research is needed to identify effective models of support for open-label PrEP adherence. PMID:24926036

PKM[zeta] Inactivation Induces Spatial Familiarity

ERIC Educational Resources Information Center

Moncada, Diego; Viola, Haydee

2008-01-01

Spatial familiarization consists of a decrease in the exploratory activity over time after exposure to a place. Here, we show that a 30-min exposure to an open field led to a pronounced decrease in the exploratory behavior of rats, generating context familiarity. This behavioral output is associated with a selective decrease in hippocampal…

Examining Metacognitive Processes in Exploratory Computer-Based Learning Environments Using Activity Log Analysis

ERIC Educational Resources Information Center

Chang, Yoo Kyung

2010-01-01

Metacognition is widely studied for its influence on the effectiveness of learning. With Exploratory Computer-Based Learning Environments (ECBLE), metacognition is found to be especially important because these environments require adaptive metacognitive control by the learners due to their open-ended structure that allows for multiple learning…

The development of exploratory behaviour in the african striped mouse rhabdomys reflects a gene × environment compromise.

PubMed

Rymer, Tasmin L; Pillay, Neville

2012-09-01

Behaviour results from the interaction of an individual's genotype with prevailing environmental conditions, resulting in local adaptation to specific habitats. We investigated the development of exploratory behaviour in two closely-related species of African striped mice from the semi-arid Succulent Karoo (Rhabdomys pumilio) and moist grassland (R. dilectus chakae) localities. Irrespective of sex, R. pumilio displayed greater exploratory behaviour (open field) and greater use of the open arms of a modified plus maze, and thus were less anxious and bolder than R. d. chakae. When pups were cross-fostered between species, fostered individuals of both species showed an intermediate behavioural pattern between their foster and biological siblings: fostered R. pumilio explored more than their foster siblings but less than their biological siblings, whereas fostered R. d. chakae explored more than their biological siblings, but less than their foster siblings. Our study is one of the first to address how the underlying genotype and early postnatal experience interact to influence the expression of exploratory behaviour and personality. In particular, we showed that, in striped mice, the early postnatal environment shapes the anxiety responses and concomitant exploratory behaviour, but the genotype apparently modulates the phenotype and constrains the limit of behavioural flexibility.

Pharmacokinetic Analysis of Irinotecan Plus Bevacizumab in Patients with Advanced Solid Tumors

PubMed Central

Denlinger, Crystal S.; Blanchard, Rebecca; Xu, Lu; Bernaards, Coen; Litwin, Samuel; Spittle, Cynthia; Berg, Daniel J.; McLaughlin, Susan; Redlinger, Maryann; Dorr, Andrew; Hambleton, Julie; Holden, Scott; Kearns, Anne; Kenkare-Mitra, Sara; Lum, Bert; Meropol, Neal J.; O'Dwyer, Peter J.

2009-01-01

Purpose To evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted. Methods This was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3. Results Forty-five subjects were enrolled. No difference in dose-normalized AUC0-last for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected. Conclusion Bevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity. PMID:19415281

Infant titi monkey behavior in the open field test and the effect of early adversity.

PubMed

Larke, Rebecca H; Toubiana, Alice; Lindsay, Katrina A; Mendoza, Sally P; Bales, Karen L

2017-09-01

The open field test is commonly used to measure anxiety-related behavior and exploration in rodents. Here, we used it as a standardized novel environment in which to evaluate the behavioral response of infant titi monkeys (Callicebus cupreus), to determine the effect of presence of individual family members, and to assess how adverse early experience alters infant behavior. Infants were tested in the open field for 5 days at ages 4 and 6 months in four successive 5 min trials on each day. A transport cage, which was situated on one side of the open field, was either empty (non-social control) or contained the father, mother, or sibling. Infant locomotor, vocalization, and exploratory behavior were quantified. Results indicated that age, sex, social condition, and early experience all had significant effects on infant behavior. Specifically, infants were generally more exploratory at 6 months and male infants were more exploratory than females. Infants distinguished between social and non-social conditions but made few behavioral distinctions between the attachment figure and other individuals. Infants which had adverse early life experience demonstrated greater emotional and physical independence, suggesting that early adversity led to resiliency in the novel environment. © 2017 Wiley Periodicals, Inc.

Temporary Abdominal Closure Combined With an Irrigating System Utilizing Hypochlorous Acid Solution to Decrease Abdominal Mucopurulence

PubMed Central

Matthews, Marc R.; Quan, Asia N.; Weir, Alexandra S.; Foster, Kevin N.; Caruso, Daniel M.

2018-01-01

Introduction: Leaving the abdominal cavity open is a well-described and frequently utilized technique in the treatment of severe intra-abdominal sepsis. Irrigation through a negative pressure wound therapy device is a technique employed to assist in the closure of wounds as well as the reduction of bacterial contamination. Furthermore, hypochlorous acid has been found to be safe and effective in microorganismal elimination from extremity wounds. There is no literature regarding the infusion of hypochlorous solution into the abdominal cavity for intra-abdominal sepsis or mucopurulent abscesses or biofilm. Objectives: A 47-year-old man with granulomatosis polyangiitis was started on weekly rituximab. After 4 infusions, skin sloughing, ultimately diagnosed as toxic epidermal necrolysis, developed. During the hospital course, he developed sepsis and bowel perforation necessitating an exploratory laparotomy. The abdomen was left open with a temporary abdominal closure using the Abthera open abdomen negative wound therapy device; however, the abdomen remained infected with visually diffuse, thickening mucopurulence despite multiple washouts. Therefore, a VAC Vera-Flo irrigation device was combined with the Abthera open abdomen negative wound therapy device and cyclical irrigation of hypochlorous acid. After 72 hours, the purulence visually was improved and no adverse events were recorded with the placement of intra-abdominal hypochlorous acid. Conclusions: The combination of two medical devices for the intra-abdominal instillation of irrigation is considered “off-label use” from the manufacturer's recommendations. In addition, the repeated instillation of hypochlorous acid solution has not been described but was noted to have visually decreased the contaminated effluent within the intra-abdominal fluid. PMID:29527250

A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs. the reference formulation in subpopulations of kidney transplant patients.

PubMed

Bloom, R D; Trofe-Clark, J; Wiland, A; Alloway, R R

2013-01-01

An exploratory, post hoc analysis was performed using data from a prospective, multicenter, open-label, randomized, two-period (14 d per period), two-sequence, crossover, steady-state pharmacokinetic study comparing generic tacrolimus (Sandoz) vs. reference tacrolimus in stable renal transplant patients receiving their pre-study twice-daily dose. Pharmacokinetic parameters were compared in 68 patients according to gender, African American ethnicity, the presence or absence of diabetes, and use of steroids. The ratios of tacrolimus AUC0-12 h , Cmax , and C12 with generic vs. reference tacrolimus were calculated using the geometric mean (GM) of dose-normalized values at days 14 and 28. Mean (SD) tacrolimus dose at baseline was 5.7 (4.2) mg/d. There were no consistent differences in dose-normalized AUC0-12 h , C12 , Cmax, or tmax between the generic and reference preparations within subpopulations. The 90% confidence intervals (CI) for the ratios of dose-normalized AUC0-12 h and C12 with generic vs. reference tacrolimus were within 80-125% for all subpopulations, as were 90% CIs for Cmax other than for females, African Americans, and non-diabetics, which is not unexpected given the wide variability of tacrolimus Cmax and the small subpopulation sizes. These exploratory results suggest that this generic tacrolimus preparation would be expected to offer comparable bioavailability to the reference drug in these patient subpopulations. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ginkgo biloba special extract LI 1370 improves dual-task walking in patients with MCI: a randomised, double-blind, placebo-controlled exploratory study.

PubMed

Gschwind, Yves J; Bridenbaugh, Stephanie A; Reinhard, Sarah; Granacher, Urs; Monsch, Andreas U; Kressig, Reto W

2017-08-01

In patients with mild cognitive impairment (MCI), gait instability, particularly in dual-task situations, has been associated with impaired executive function and an increased fall risk. Ginkgo biloba extract (GBE) could be an effective mean to improve gait stability. This study investigated the effect of GBE on spatio-temporal gait parameters of MCI patients while walking under single and dual-task conditions. Fifty patients aged 50-85 years with MCI and associated dual-task-related gait impairment participated in this randomised, double-blind, placebo-controlled, exploratory phase IV drug trial. Intervention group (IG) patients received GBE (Symfona ® forte 120 mg) twice-daily for 6 months while control group (CG) patients received placebo capsules. A 6-month open-label phase with identical GBE dosage followed. Gait was quantified at months 0, 3, 6 and 12. After 6 months, dual-task-related cadence increased in the IG compared to the CG (p = 0.019, d = 0.71). No significant changes, but GBE-associated numerical non-significant trends were found after 6-month treatment for dual-task-related gait velocity and stride time variability. Findings suggest that 120 mg of GBE twice-daily for at least 6 months may improve dual-task-related gait performance in patients with MCI. The observed gait improvements add to the understanding of the self-reported unspecified improvements among MCI patients when treated with standardised GBE.

Teachers' Use of Dietary Recalls for Exploratory Dialogue in the Classroom

ERIC Educational Resources Information Center

Torres, Irene

2017-01-01

Objective: This study examines teachers' adoption and adaptation of 24-hour dietary recall technique for exploratory dialogue in the classroom with students aged 8-12 years. The focus is on the teachers' use of the information collected through the recall tool to pose open questions, recap, reformulate and elaborate collectively with the students…

Instructional Design, Facilitation, and Perceived Learning Outcomes: An Exploratory Case Study of a Human Trafficking MOOC for Attitudinal Change

ERIC Educational Resources Information Center

Watson, Sunnie Lee; Loizzo, Jamie; Watson, William R.; Mueller, Chad; Lim, Jieun; Ertmer, Peggy A.

2016-01-01

This exploratory case study describes the design and facilitation of a massive open online course (MOOC) for attitudinal change regarding human trafficking. It examines the course from the learners', instructor's, and instructional designer's perspectives. Two interviews with the instructor and instructional designer were conducted, and data from…

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy

PubMed Central

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d’Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P.; Büttner, Hartwig

2017-01-01

Background Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. Objective To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Design, setting, and participants Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Intervention Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5 mg once a day (OaD), tadalafil 20 mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Outcome measurements and statistical analysis Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. Results and limitations The first decision-tree model (n = 422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF–related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Conclusions Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Patient summary Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. Trial registration ClinicalTrials.gov, NCT01026818 PMID:26947602

Perceptions of Open Source versus Commercial Software: Is Higher Education Still on the Fence?

ERIC Educational Resources Information Center

van Rooij, Shahron Williams

2007-01-01

This exploratory study investigated the perceptions of technology and academic decision-makers about open source benefits and risks versus commercial software applications. The study also explored reactions to a concept for outsourcing campus-wide deployment and maintenance of open source. Data collected from telephone interviews were analyzed,…

Visual Culture in the Elementary-School Classroom: Moving from Box-Store Commodities to Out-of-the-Box Thinking

ERIC Educational Resources Information Center

Fattal, Laura Felleman

2017-01-01

The goal of the action research project on visual culture is to contribute to the dialogue on the exploratory ecology vs commodity culture of the elementary school classroom. Exploratory culture, unlike commodity culture, applauds open-ended thinking, inchoate imaginings, and critical thinking with its attachment to divergent paths to resolving…

Are Review Skills and Academic Writing Skills Related? An Exploratory Analysis via Multi Source Feedback Tools

ERIC Educational Resources Information Center

Razi, Salim

2016-01-01

Because students learn from each other as well as lecturers, it is important to create opportunities for collaboration in writing classes. Teachers now benefit from access to plagiarism detectors that can also provide feedback. This exploratory study considers the role of four review types, open and anonymous, involving the students themselves,…

Effects of beta-adrenergic antagonist, propranolol on spatial memory and exploratory behavior in mice.

PubMed

Sun, Huaying; Mao, Yu; Wang, Jianhong; Ma, Yuanye

2011-07-08

The beta-adrenergic system has been suggested to be involved in novelty detection and memory modulation. The present study aimed to investigate the role of beta-adrenergic receptors on novelty-based spatial recognition memory and exploratory behavior in mice using Y-maze test and open-field respectively. Mice were injected with three doses of beta-adrenergic receptor antagonist, propranolol (2, 10 and 20 mg/kg) or saline at three different time points (15 min prior to training, immediately after training and 15 min before test). The results showed that higher doses of propranolol (10 and 20 mg/kg) given before the training trial impaired spatial recognition memory while those injected at other two time points did not. A detailed analysis of exploratory behavior in open-field showed that lower dose (2 mg/kg) of propranolol reduced exploratory behavior of mice. Our findings indicate that higher dose of propranolol can impair acquisition of spatial information in the Y-maze without altering locomotion, suggesting that the beta-adrenergic system may be involved in modulating memory processes at the time of learning. Copyright © 2011. Published by Elsevier Ireland Ltd.

College Students Must Overcome Barriers to Use Calorie Labels in Fast-Food Restaurants.

PubMed

Stran, Kimberly A; Knol, Linda L; Turner, Lori W; Severt, Kimberly; McCallum, Debra M; Lawrence, Jeannine C

2016-02-01

To explore predictors of intention of college students to use calorie labels on fast-food menus and differences in calories ordered after viewing calorie information. Quasi-experimental design. Participants selected a meal from a menu without calorie labels, selected a meal from the same menu with calorie labels, and completed a survey that assessed demographics, dietary habits, Theory of Planned Behavior constructs, and potential barriers to use of calorie labeling. A southern university. Undergraduate university students (n = 97). Predictors of intention to use calorie labels and whether calories selected from the nonlabeled menu differed from the labeled menu. Confirmatory factor analysis, exploratory factor analysis, multiple regression, and paired t tests. Participants ordered significantly fewer calories (P = .02) when selecting from the labeled menu vs the menu without labels. Attitudes (P = .006), subjective norms (P < .001), and perceived behavioral control (P = .01) predicted intention to use calorie information but did not predict a difference in the calories ordered. Hunger (P = .03) and cost (P = .04) were barriers to using the calorie information. If students can overcome barriers, calorie labeling could provide information that college students need to select lower-calorie items at fast-food restaurants. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

An exploratory study of drinkers views of health information and warning labels on alcohol containers.

PubMed

Thomson, Lisa M; Vandenberg, Brian; Fitzgerald, John L

2012-03-01

To identify general and specific features of health information warning labels on alcohol beverage containers that could potentially inform the development and implementation of a new labelling regime in Australia. Mixed methods, including a cross-sectional population survey and a qualitative study of knowledge, attitudes and behaviours regarding alcohol beverage labelling. The population survey used computer-assisted telephone interviews of 1500 persons in Victoria, Australia to gauge the level of support for health information and warning labels. The qualitative study used six focus groups to test the suitability of 12 prototype labels that were placed in situ on a variety of alcohol beverage containers. The telephone survey found 80% to 90% support for a range of information that could potentially be mandated by government authorities for inclusion on labels (nutritional information, alcohol content, health warning, images). Focus group testing of the prototype label designs found that labels should be integrated with other alcohol-related health messages, such as government social advertising campaigns, and specific labels should be matched appropriately to specific consumer groups and beverage types. There are high levels of public support for health information and warning labels on alcohol beverages. This study contributes much needed empirical guidance for developing alcohol beverage labelling strategies in an Australian context. © 2011 Australasian Professional Society on Alcohol and other Drugs.

Effects of subchronic inhalation of vaporized plastic cement on exploratory behavior and Purkinje cell differentiation in the rat.

PubMed

Pascual, R; Salgado, C; Viancos, L; Figueroa, H R

1996-12-06

In the present study, the effects of preweaning cement vapor inhalation on exploratory behavior and cerebellar Purkinje cell differentiation were assessed. Sprague-Dawley albino rats were daily exposed to glue vapors between postnatal d 2 and 21. At postnatal d 22, all animals were submitted to the open-field test in order to evaluate their exploratory behavior. Then they were sacrificed, their brains dissected out, and cerebella stained according to the Golgi-Cox-Sholl procedure. Purkinje cells sampled from parasagittal sections of the cerebellar vermis were drawn under camera lucida and their dendritic domain was determined. The collected data indicate that glue solvent inhalation impairs both Purkinje cell differentiation and locomotor exploratory behavior.

Preliminary Investigation of a Stress Prevention and Mindfulness Group for Teachers

ERIC Educational Resources Information Center

Reiser, Jenson E.; McCarthy, Christopher J.

2018-01-01

This exploratory study evaluated a short-term (6-8 weeks) psychoeducation and support group for teachers focused on stress prevention and mindfulness (labeled SPAM group). A total of 4 groups were implemented in different schools, and evaluation was conducted with quantitative (pre- and post-measures of teacher vulnerability to stress, job…

Fruit and vegetables are similarly categorised by 8-13-year-old children

USDA-ARS?s Scientific Manuscript database

This exploratory study assessed how 8- to 13-year-old children categorized and labelled fruit and vegetables (FaV), and how these were influenced by child characteristics, to specify second-level categories in a hierarchical food search system for a computerised 24-h dietary recall (hdr). Two sets o...

Characterizing the EEG correlates of exploratory behavior.

PubMed

Bourdaud, Nicolas; Chavarriaga, Ricardo; Galan, Ferran; Millan, José Del R

2008-12-01

This study aims to characterize the electroencephalography (EEG) correlates of exploratory behavior. Decision making in an uncertain environment raises a conflict between two opposing needs: gathering information about the environment and exploiting this knowledge in order to optimize the decision. Exploratory behavior has already been studied using functional magnetic resonance imaging (fMRI). Based on a usual paradigm in reinforcement learning, this study has shown bilateral activation in the frontal and parietal cortex. To our knowledge, no previous study has been done on it using EEG. The study of the exploratory behavior using EEG signals raises two difficulties. First, the labels of trial as exploitation or exploration cannot be directly derived from the subject action. In order to access this information, a model of how the subject makes his decision must be built. The exploration related information can be then derived from it. Second, because of the complexity of the task, its EEG correlates are not necessarily time locked with the action. So the EEG processing methods used should be designed in order to handle signals that shift in time across trials. Using the same experimental protocol as the fMRI study, results show that the bilateral frontal and parietal areas are also the most discriminant. This strongly suggests that the EEG signal also conveys information about the exploratory behavior.

Early botulinum toxin treatment for spastic pes equinovarus--a randomized double-blind placebo-controlled study.

PubMed

Fietzek, U M; Kossmehl, P; Schelosky, L; Ebersbach, G; Wissel, J

2014-08-01

Spastic pes equinovarus is a frequent pathological posture of the lower extremity. Botulinum toxin (BoNT/A) has been successfully applied to treat lower limb spasticity. However, the best time to initiate treatment remains unclear. A beneficial effect of an early treatment has been suggested in previous studies. A single-centre double-blind randomized placebo-controlled trial was performed to investigate the efficacy of BoNT/A to reduce muscle hypertonicity at the ankle. Fifty-two patients with unilateral or bilateral spastic pes equinovarus with a modified Ashworth score (mAS) of at least 1+ after stroke, traumatic brain injury or hypoxic encephalopathy were allocated to receive either BoNT/A or placebo treatment. A second, open injection was optional at week 12. Patients received unilateral or bilateral injections with 230 or 460 U onabotulinumtoxinA, respectively. The course of the mAS was explored during the open study phase. Patients who had received BoNT/A treatment had lower mAS compared with placebo at week 12 (P < 0.01). During the open label phase, patients from the placebo group showed further deterioration of muscle tone despite starting from a similar baseline and receiving BoNT treatment. Spastic feet that had received BoNT/A in the first cycle had comparatively lower mAS scores over all follow-up data and at week 24 (P < 0.01). The study demonstrates a reduction of muscular hypertonicity in spastic pes equines with BoNT/A treatment given during the first 3 months after the lesion. Exploratory analyses of the course of muscular hypertonicity during the open phase favour earlier to later treatment. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

OpenMebius: an open source software for isotopically nonstationary 13C-based metabolic flux analysis.

PubMed

Kajihata, Shuichi; Furusawa, Chikara; Matsuda, Fumio; Shimizu, Hiroshi

2014-01-01

The in vivo measurement of metabolic flux by (13)C-based metabolic flux analysis ((13)C-MFA) provides valuable information regarding cell physiology. Bioinformatics tools have been developed to estimate metabolic flux distributions from the results of tracer isotopic labeling experiments using a (13)C-labeled carbon source. Metabolic flux is determined by nonlinear fitting of a metabolic model to the isotopic labeling enrichment of intracellular metabolites measured by mass spectrometry. Whereas (13)C-MFA is conventionally performed under isotopically constant conditions, isotopically nonstationary (13)C metabolic flux analysis (INST-(13)C-MFA) has recently been developed for flux analysis of cells with photosynthetic activity and cells at a quasi-steady metabolic state (e.g., primary cells or microorganisms under stationary phase). Here, the development of a novel open source software for INST-(13)C-MFA on the Windows platform is reported. OpenMebius (Open source software for Metabolic flux analysis) provides the function of autogenerating metabolic models for simulating isotopic labeling enrichment from a user-defined configuration worksheet. Analysis using simulated data demonstrated the applicability of OpenMebius for INST-(13)C-MFA. Confidence intervals determined by INST-(13)C-MFA were less than those determined by conventional methods, indicating the potential of INST-(13)C-MFA for precise metabolic flux analysis. OpenMebius is the open source software for the general application of INST-(13)C-MFA.

Implications of the University of South Africa's (UNISA) Shift to Open Distance e-Learning on Teacher Education

ERIC Educational Resources Information Center

Ngubane-Mokiwa, Sindile A.

2017-01-01

This conceptual and exploratory article seeks to explore the implications of the University of South Africa's (Unisa) shift from open distance learning (ODL) to open distance e-learning (ODeL) on Teacher Education. In addition, the article problematizes the shift as a policy imperative. Unisa's mandate to provide teacher education opportunities to…

The Use of Song to Open an Educational Development Workshop: Exploratory Analysis and Reflections

ERIC Educational Resources Information Center

Lesser, Lawrence; An, Song; Tillman, Daniel

2016-01-01

Song has been used by faculty of many disciplines in their classrooms and, to a lesser extent, by educational developers in workshops. This paper shares and discusses a new song (about an instructor's evolving openness to alternatives to lecture-only teaching) and its novel use to open an educational development workshop. Self-reported participant…

Identifying Facilitators and Barriers for Patient Safety in a Medicine Label Design System Using Patient Simulation and Interviews.

PubMed

Dieckmann, Peter; Clemmensen, Marianne Hald; Sørensen, Trine Kart; Kunstek, Pina; Hellebek, Annemarie

2016-12-01

Medicine label design plays an important role in improving patient safety. This study aimed at identifying facilitators and barriers in a medicine label system to prevent medication errors in clinical use by health care professionals. The study design is qualitative and exploratory, with a convenience sample of 10 nurses and 10 physicians from different acute care specialties working in hospitals in the Capital Region of Denmark. In 2 patient simulation scenarios and a sorting task, the participants selected the medicines from a range of ampules, vials, and infusion bags. After each scenario and in the end of the study, the participants were interviewed. Notes were validated with the participants, and content was analyzed. The label design benefited from the standardized construction of the labels, the clear layout and font, and some warning signs. The complexity of the system and some inconsistencies (different meaning of colors) posed challenges, when considered with the actual application context, in which there is little time to get familiar with the design features. For optimizing medicine labels and obtaining the full benefit of label design features on patient safety, it is necessary to consider the context in which they are used.

Prolonged Follow-Up of Patients in the U.S. Multicenter Trial of Ursodeoxycholic Acid for Primary Biliary Cirrhosis

PubMed Central

Combes, Burton; Luketic, Velimir A.; Peters, Marion G.; Zetterman, Rowen K.; Garcia-Tsao, Guadalupe; Munoz, Santiago J.; Lin, Danyu; Flye, Nancy; Carithers, Robert L.

2013-01-01

OBJECTIVE Randomized, double-blind, placebo-controlled trials of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) have not demonstrated improvement in survival during the placebo-controlled phases of these trials. Analyses purporting to demonstrate a survival advantage of UDCA are largely dependent on data obtained after the placebo phases were terminated, and placebo-treated patients were offered open-label UDCA. After completion of our 2-yr placebo-controlled trial of UDCA in which we observed no survival benefit for UDCA, we provided the patients with open-label UDCA to see if delay in providing UDCA for 2 yr had any effect on subsequent liver transplantation or death without liver transplantation. METHODS In our previously reported 2-yr placebo-controlled trial, 151 patients with PBC were randomized to receive either UDCA (n = 77) or placebo (n = 74). The number of patients who progressed to liver transplantation or death without transplantation were similar in both the groups, 12 (16%) in the UDCA-treated and 11 (15%) in placebo-treated patients. All the patients were then offered open-label UDCA, with 61 original UDCA and 56 original placebo-treated patients now taking UDCA in an extended open-label phase of the trial. RESULTS No significant differences were observed in the number of patients who underwent liver transplantation or died without liver transplantation in the open-label phase of the trial. Moreover, no difference in the time to these endpoints was seen over the period of observation of as long as 6 yr from the time of initial randomization. CONCLUSIONS Results of open-label extensions of previous conducted placebo-controlled trials of UDCA in PBC leave uncertain whether UDCA impacts significantly on liver transplantation and death without liver transplantation in patients with PBC. PMID:15046215

Effects of long-term treatment with rotigotine transdermal system on dyskinesia in patients with early-stage Parkinson's disease.

PubMed

Giladi, Nir; Ghys, Liesbet; Surmann, Erwin; Boroojerdi, Babak; Jankovic, Joseph

2014-12-01

In two 6-month, double-blind, placebo-controlled studies, rotigotine transdermal system was well-tolerated and efficacious monotherapy in early-stage PD. This post hoc analysis of the long-term open-label extensions (NCT00594165; NCT00599196) of these studies assessed incidence and severity of dyskinesia in participants treated with rotigotine, with or without concomitant levodopa, for up to 6 years. Open-label rotigotine was titrated to optimal dose (≤16 mg/24 h). Concomitant levodopa was permitted. Dyskinesia data, recorded using the Unified Parkinson's Disease Rating Scale Part IV, were pooled from the two open-label studies. Of 596 participants who received open-label rotigotine, 299 (50%) remained at trial closure; no patient discontinued due to dyskinesia. In the two studies, median exposure to rotigotine was 1910 days (∼5 years, 3 months), and 1564.5 days (∼4 years, 3 months). During up to 6 years of open-label rotigotine, 423/596 (71%) received levodopa. Dyskinesias were reported in 115/596 (19%) participants, 90/115 (78%) of who developed dyskinesia after levodopa was added; 25 reported dyskinesia in the absence of levodopa (includes patients who never received open-label levodopa, and those who reported dyskinesia before starting concomitant levodopa). Dyskinesia severity data were available for 107 of the 115 participants. In 56/107 (52%) participants, dyskinesia was considered 'not disabling' for all occurrences; the worst-case severity was 'mildly disabling' for 33/107 (31%), and 'moderately' or 'severely disabling' for 18/107 (17%; 3% of total participants). During treatment with rotigotine in patients with PD for up to 6 years the incidence of dyskinesia was low, and the dyskinesia was generally 'not disabling' or 'mildly disabling'. Copyright © 2014 Elsevier Ltd. All rights reserved.

AgRISTARS: Foreign commodity production forecasting. Minutes of the annual formal project manager's review, including preliminary technical review reports of FY80 experiments. [wheat/barley and corn/soybean experiments

NASA Technical Reports Server (NTRS)

1980-01-01

The U.S./Canada wheat/barley exploratory experiment is discussed with emphasis on labeling, machine processing using P1A, and the crop calendar. Classification and the simulated aggregation test used in the U.S. corn/soybean exploratory experiment are also considered. Topics covered regarding the foreign commodity production forecasting project include: (1) the acquisition, handling, and processing of both U.S. and foreign agricultural data, as well as meteorological data. The accuracy assessment methodology, multicrop sampling and aggregation technology development, frame development, the yield project interface, and classification for area estimation are also examined.

Pilot Study of Droxidopa With Carbidopa in Adults With ADHD.

PubMed

Adler, Lenard A; Gorny, Stephen W

2015-04-23

We conducted a two-period (open-label and double-blind) pilot investigation of droxidopa, with and without carbidopa, for ADHD. Twenty adult ADHD patients received open-label droxidopa titrated from 200 to 600 mg 3 times per day (TID; Weeks 1-3), then open-label droxidopa plus carbidopa titrated from 25 or 50 mg TID (Weeks 4-6). In Weeks 7 to 8, patients were randomized to continued co-treatment or matching placebo substitution. Improvements in mean total Adult ADHD Investigator Symptom Report Scale (AISRS) scores were seen at Week 1 (p < .0001) and Week 3 (p < .0001). Improvements were maintained but not increased with carbidopa. Thirteen of 20 patients completed open-label treatment. In the double-blind period, mean total AISRS scores were similar between the co-treatment (n = 6) and placebo (n = 5) groups. No serious adverse events were reported. These preliminary findings indicate that droxidopa can improve adult ADHD symptoms. Further studies are warranted to examine the efficacy and safety of droxidopa in ADHD. © 2015 SAGE Publications.

Learning, memory and exploratory similarities in genetically identical cloned dogs.

PubMed

Shin, Chi Won; Kim, Geon A; Park, Won Jun; Park, Kwan Yong; Jeon, Jeong Min; Oh, Hyun Ju; Kim, Min Jung; Lee, Byeong Chun

2016-12-30

Somatic cell nuclear transfer allows generation of genetically identical animals using donor cells derived from animals with particular traits. To date, few studies have investigated whether or not these cloned dogs will show identical behavior patterns. To address this question, learning, memory and exploratory patterns were examined using six cloned dogs with identical nuclear genomes. The variance of total incorrect choice number in the Y-maze test among cloned dogs was significantly lower than that of the control dogs. There was also a significant decrease in variance in the level of exploratory activity in the open fields test compared to age-matched control dogs. These results indicate that cloned dogs show similar cognitive and exploratory patterns, suggesting that these behavioral phenotypes are related to the genotypes of the individuals.

Supplemental US/Canada wheat and barley exploratory experiment implementation plan: Evaluation of a procedure 1A technology

NASA Technical Reports Server (NTRS)

1980-01-01

A plan is presented for a supplemental experiment to evaluate a sample allocation technique for selecting picture elements from remotely sensed multispectral imagery for labeling in connection with a new crop proportion estimation technique. The method of evaluating an improved allocation and proportion estimation technique is also provided.

Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases

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

Patt, Y.Z.; Lamki, L.M.; Shanken, J.

1990-07-01

We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 ofmore » the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti-CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer.« less

Medial septal GABAergic projection neurons promote object exploration behavior and type 2 theta rhythm

PubMed Central

Gangadharan, Gireesh; Shin, Jonghan; Kim, Seong-Wook; Kim, Angela; Paydar, Afshin; Kim, Duk-Soo; Miyazaki, Taisuke; Watanabe, Masahiko; Yanagawa, Yuchio; Kim, Jinhyun; Kim, Yeon-Soo; Kim, Daesoo; Shin, Hee-Sup

2016-01-01

Exploratory drive is one of the most fundamental emotions, of all organisms, that are evoked by novelty stimulation. Exploratory behavior plays a fundamental role in motivation, learning, and well-being of organisms. Diverse exploratory behaviors have been described, although their heterogeneity is not certain because of the lack of solid experimental evidence for their distinction. Here we present results demonstrating that different neural mechanisms underlie different exploratory behaviors. Localized Cav3.1 knockdown in the medial septum (MS) selectively enhanced object exploration, whereas the null mutant (KO) mice showed enhanced-object exploration as well as open-field exploration. In MS knockdown mice, only type 2 hippocampal theta rhythm was enhanced, whereas both type 1 and type 2 theta rhythm were enhanced in KO mice. This selective effect was accompanied by markedly increased excitability of septo-hippocampal GABAergic projection neurons in the MS lacking T-type Ca2+ channels. Furthermore, optogenetic activation of the septo-hippocampal GABAergic pathway in WT mice also selectively enhanced object exploration behavior and type 2 theta rhythm, whereas inhibition of the same pathway decreased the behavior and the rhythm. These findings define object exploration distinguished from open-field exploration and reveal a critical role of T-type Ca2+ channels in the medial septal GABAergic projection neurons in this behavior. PMID:27208094

Emotionality in growing pigs: is the open field a valid test?

PubMed

Donald, Ramona D; Healy, Susan D; Lawrence, Alistair B; Rutherford, Kenneth M D

2011-10-24

The ability to assess emotionality is important within animal welfare research. Yet, for farm animals, few tests of emotionality have been well validated. Here we investigated the construct validity of behavioural measures of pig emotionality in an open-field test by manipulating the experiences of pigs in three ways. In Experiment One (pharmacological manipulation), pigs pre-treated with Azaperone, a drug used to reduce stress in commercial pigs, were more active, spent more time exploring and vocalised less than control pigs. In Experiment Two (social manipulation), pigs that experienced the open-field arena with a familiar companion were also more exploratory, spent less time behaviourally idle, and were less vocal than controls although to a lesser degree than in Experiment One. In Experiment Three (novelty manipulation), pigs experiencing the open field for a second time were less active, explored less and vocalised less than they had done in the first exposure to the arena. A principal component analysis was conducted on data from all three trials. The first two components could be interpreted as relating to the form (cautious to exploratory) and magnitude (low to high arousal) of the emotional response to open-field testing. Based on these dimensions, in Experiment One, Azaperone pigs appeared to be less fearful than saline-treated controls. However, in Experiment Two, exposure to the arena with a conspecific did not affect the first two dimensions but did affect a third behavioural dimension, relating to oro-nasal exploration of the arena floor. In Experiment Three, repeat exposure altered the form but not the magnitude of emotional response: pigs were less exploratory in the second test. In conclusion, behavioural measures taken from pigs in an open-field test are sensitive to manipulations of their prior experience in a manner that suggests they reflect underlying emotionality. Behavioural measures taken during open-field exposure can be useful for making assessments of both pig emotionality and of their welfare. Copyright © 2011 Elsevier Inc. All rights reserved.

Does It Make a Sound: Are Open Access Monographs Discoverable in Library Catalogs?

ERIC Educational Resources Information Center

McCollough, Aaron

2017-01-01

This article describes an exploratory study examining the common perception among library-based publishers that open access academic publications (especially monographs) are not readily discoverable in library catalogs. Using titles from the Michigan Publishing imprint, digital culture books, the study provides an empirical basis for evaluating…

Designing a Virtual-Reality-Based, Gamelike Math Learning Environment

ERIC Educational Resources Information Center

Xu, Xinhao; Ke, Fengfeng

2016-01-01

This exploratory study examined the design issues related to a virtual-reality-based, gamelike learning environment (VRGLE) developed via OpenSimulator, an open-source virtual reality server. The researchers collected qualitative data to examine the VRGLE's usability, playability, and content integration for math learning. They found it important…

An open-label, prospective clinical study to evaluate the efficacy and safety of TLPL/AY/01/2008 in the management of functional constipation

PubMed Central

Munshi, Renuka; Bhalerao, Supriya; Rathi, Pravin; Kuber, V. V.; Nipanikar, S. U.; Kadbhane, K. P.

2011-01-01

Functional constipation is one of the most common gastrointestinal symptoms across the globe. Its high prevalence rate, economic burden, and adverse implications on the quality of life make constipation a major public health issue. Though various treatment options are available for the management of constipation, evidence for their efficacy and safety are limited. An open-label, prospective, interventional, and exploratory clinical trial was carried out to evaluate the efficacy and safety of “TLPL/AY/01/2008” in 34 patients suffering from functional constipation. “TLPL/AY/01/2008” is an Ayurvedic proprietary polyherbal formulation in powder form, containing Isabgol husk, Senna extract, and Triphala extract. Administration of “TLPL/AY/01/2008” for 14 days showed a significant increase in mean weekly bowel movements from 10.19 ± 05.64 to 18.29 ± 05.72 (P<0.05). The mean average time spent on toilet for bowel evacuation reduced significantly from 11.02 ± 05.43 minutes (baseline value) to 08.70 ± 04.72 minutes on day 14 (P<0.05). Mean stool form score assessed on Bristol stool form scale was improved from 02.97 ± 00.48 (baseline value) to 04.61 ± 00.84 (P<0.05) on day 14. A significant improvement (P<0.05) was also noted in straining during defecation, sensation of incomplete evacuation, sensation of anorectal blockage, and other associated symptoms of functional constipation. The significant improvement in most of the above symptoms was endured for a post-treatment observatory period of one week. All the study patients showed an excellent tolerability to the study drug. These findings suggest that “TLPL/AY/01/2008” is an effective, safe, and non-habit-forming herbal laxative formulation for the management of constipation. Comparative clinical studies with larger sample size would be able to confirm the above findings. PMID:22022157

A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer.

PubMed

Reynolds, Kerry Lynn; Bedard, Philippe L; Lee, Se-Hoon; Lin, Chia-Chi; Tabernero, Josep; Alsina, Maria; Cohen, Ezra; Baselga, José; Blumenschein, George; Graham, Donna M; Garrido-Laguna, Ignacio; Juric, Dejan; Sharma, Sunil; Salgia, Ravi; Seroutou, Abdelkader; Tian, Xianbin; Fernandez, Rose; Morozov, Alex; Sheng, Qing; Ramkumar, Thiruvamoor; Zubel, Angela; Bang, Yung-Jue

2017-09-12

Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. This open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling. Patients received LJM716 3-40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting >30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples. LJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing. Clinicaltrials.gov registry number NCT01598077 (registered on 4 May, 2012).

Double-blind, Randomized, 8-week Placebo-controlled followed by a 16-week open label extension study, with the LPA1 receptor antagonist SAR100842 for Patients With Diffuse Cutaneous Systemic Sclerosis.

PubMed

Allanore, Yannick; Distler, Oliver; Jagerschmidt, Alexandre; Illiano, Stephane; Ledein, Laetitia; Boitier, Eric; Agueusop, Inoncent; Denton, Christopher P; Khanna, Dinesh

2018-05-06

Preclinical studies suggest a role for lysophosphatidic acid (LPA) in the pathogenesis of systemic sclerosis (SSc). SAR100842, a potent selective oral antagonist of LPA1 receptor, was assessed for safety, biomarkers and clinical efficacy in patients with diffuse cutaneous SSc (dcSSc). An 8-week double-blind, randomized, placebo-controlled study followed by a 16-week open label extension with SAR100842 was performed in patients with early dcSSc and a baseline Rodnan skin score (mRSS) of at least 15. The primary endpoint was safety during the double-blind phase of the trial. Exploratory endpoints included the identification of a LPA-induced gene signature in patients 'skin. 17 of 32 subjects were randomized to placebo and 15 to SAR100842; 30 patients participated in the extension study. The most frequent adverse events reported for SAR100842 during the blinded phase were headache, diarrhea, nausea and fall and the safety profile was acceptable during the extension part. At Week 8, mean reduction in mRSS was numerically greater in the SAR100842 compared to placebo (mean change [SD]: -3.57 [4.18] versus -2.76 [4.85]; difference [95% CI]: -1.2 [-4.37 to 2.02], p=0.46). A greater reduction of LPA related genes was observed in skin of SAR100842 group at Week 8, indicating LPA 1 target engagement. SAR100842, a selective orally available LPA 1 receptor antagonist, was well tolerated in patients with dcSSc. MRSS improved during the study although not reaching significance, and additional gene signature analysis suggested target engagement. These results need to be confirmed in a larger controlled trial. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Efficacy and safety of dapagliflozin over 1 year as add-on to insulin therapy in Japanese patients with type 2 diabetes: the DAISY (Dapagliflozin Added to patients under InSulin therapY) trial.

PubMed

Araki, Eiichi; Onishi, Yukiko; Asano, Michiko; Kim, Hyosung; Yajima, Toshitaka

2017-04-01

To evaluate the efficacy and safety of dapagliflozin as add-on to insulin in Japanese patients with type 2 diabetes. Insulin-treated Japanese patients were randomized to 5 mg dapagliflozin or placebo during a 16-week double-blind treatment period. Both groups then received dapagliflozin 5 or 10 mg (the dose was increased at or after week 24 if glycated haemoglobin [HbA1c] at the previous visit was >7.5%) during a 36-week open-label extension period. The exploratory efficacy endpoint was to assess the maintenance efficacy of 5/10 mg dapagliflozin + insulin over 52 weeks of treatment. Safety was assessed in terms of adverse events, laboratory variables and vital signs. The changes in HbA1c from baseline to weeks 16 and 52 were -0.62% and -0.74%, respectively, in the dapagliflozin group, vs -0.08% and -0.83%, respectively, in the placebo-dapagliflozin group. Body weight decreased at both time points in the dapagliflozin group and after switching to open-label dapagliflozin in the placebo-dapagliflozin group. The total insulin dose decreased slightly after starting dapagliflozin. Adverse events occurred in 82.9% and 71.7% of patients in the dapagliflozin and placebo-dapagliflozin groups, respectively. Hypoglycaemia occurred in 35.0% and 41.7% of patients in the dapagliflozin and placebo-dapagliflozin groups, respectively, but the incidence was not increased by use of dapagliflozin in either trial period. Genital/urinary tract infections, renal impairment/failure, volume depletion, fracture and hepatic disorders occurred in ≤5% of patients. This trial showed that administration of dapagliflozin as an add-on to insulin therapy was effective, was well tolerated and had insulin-sparing effects in Japanese patients with type 2 diabetes. © 2016 John Wiley & Sons Ltd.

Open-Label Memantine in Fragile X Syndrome

ERIC Educational Resources Information Center

Erickson, Craig A.; Mullett, Jennifer E.; McDougle, Christopher J.

2009-01-01

Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). The purpose of this pilot study was to examine the effectiveness and tolerability of memantine for a number of target symptoms associated with FXS. Medical records describing open-label treatment with memantine in 6 patients with FXS and a comorbid…

Heart Rate Variability in Nonlinear Rats with Different Orientation and Exploratory Activity in the Open Field.

PubMed

Kur'yanova, E V; Teplyi, D L; Zhukova, Yu D; Zhukovina, N V

2015-12-01

The basic behavioral activity of nonlinear rats was evaluated from the sum of crossed peripheral and central squares and peripheral and central rearing postures in the open fi eld test. This index was low (<20 episodes), intermediate (20-29 episodes), or high (>30 episodes). Male rats with high score of orientation and exploratory activity were characterized by higher indexes of total heart rate variability than rats with low or intermediate activity. Specimens with a greater contribution of VLF waves into the total power spectrum of heart rate variability were shown to dominate among the rats with high behavioral activity. Our results are consistent with the notions of a suprasegmental nature of VLF waves.

Impairment of exploratory behavior and spatial memory in adolescent rats in lithium-pilocarpine model of temporal lobe epilepsy.

PubMed

Kalemenev, S V; Zubareva, O E; Frolova, E V; Sizov, V V; Lavrentyeva, V V; Lukomskaya, N Ya; Kim, K Kh; Zaitsev, A V; Magazanik, L G

2015-01-01

Cognitive impairment in six-week -old rats has been studied in the lithium-pilocarpine model of adolescent temporal lobe epilepsy in humans. The pilocarpine-treated rats (n =21) exhibited (a) a decreased exploratory activity in comparison with control rats (n = 20) in the open field (OP) test and (b) a slower extinction of exploratory behavior in repeated OP tests. The Morris Water Maze (MWM) test showed that the effect of training was less pronounced in the pilocarpine-treated rats, which demonstrated disruption of predominantly short-term memory. Therefore, our study has shown that lithium-pilocarpine seizures induce substantial changes in exploratory behavior and spatial memory in adolescent rats. OP and MWM tests can be used in the search of drugs reducing cognitive impairments associated with temporal lobe epilepsy.

The Development, Validity, and Reliability of the Barriers to Seeking Psychological Help Scale for College Students

ERIC Educational Resources Information Center

Topkaya, Nursel; Sahin, Ertugrul; Meydan, Betül

2017-01-01

The aim of this study was to develop a scale to determine the barriers affecting psychological help-seeking in college students. In line with this purpose, the validity and reliability of the scale were examined in five different studies. Exploratory factor analysis results suggested that the scale consists of five dimensions, labeled as…

Word, Thought, and Deed: The Role of Object Categories in Children's Inductive Inferences and Exploratory Play

ERIC Educational Resources Information Center

Schulz, Laura E.; Standing, Holly R.; Bonawitz, Elizabeth B.

2008-01-01

Previous research (e.g., S. A. Gelman & E. M. Markman, 1986; A. Gopnik & D. M. Sobel, 2000) suggests that children can use category labels to make inductive inferences about nonobvious causal properties of objects. However, such inductive generalizations can fail to predict objects' causal properties when (a) the property being projected varies…

Sentiments and Perspectives of Academics about Massive Open Online Courses (MOOCs)

ERIC Educational Resources Information Center

Fong, Jack

2017-01-01

Massive open online courses (MOOCs) have made a dramatic entry into higher education. Promising to provide an affordable, if not free, education, MOOCs are celebrated for promoting learning in lieu of the physical classroom. This exploratory study employs content analysis to make visible how MOOCs are viewed by academically oriented observers.…

Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice.

PubMed

Lau, Adeline A; Crawley, Allison C; Hopwood, John J; Hemsley, Kim M

2008-08-05

Mucopolysaccharidosis (MPS) IIIA, or Sanfilippo syndrome, is a lysosomal storage disorder characterized by severe and progressive neuropathology. Following an asymptomatic period, patients may present with sleep disturbances, cognitive decline, aggressive tendencies and hyperactivity. A naturally-occurring mouse model of MPS IIIA also exhibits many of these behavioral features and has been recently back-crossed onto a C57BL/6 genetic background. To more thoroughly characterize the behavioral phenotype of congenic MPS IIIA mice, we assessed exploratory activity and unconditioned anxiety-related behavior in the elevated plus maze (EPM) and open field locomotor activity. Although MPS IIIA male mice were less active in the EPM at 18 and 20 weeks of age, they were more likely to explore the open arms than their normal counter-parts suggesting reduced anxiety. Repeated EPM testing reduced exploration of the open arms in MPS IIIA mice. In the open field test, significant reductions in activity were evident in naïve-tested male MPS IIIA mice from 10 weeks of age. Female normal and MPS IIIA mice displayed similar exploratory activity in the open field test. These differences in anxiety and locomotor activity will allow us to evaluate the efficacy of therapeutic regimes for MPS IIIA as a forerunner to developing safe and effective therapies for Sanfilippo patients.

Open-Label, Prospective Trial of Olanzapine in Adolescents with Subaverage Intelligence and Disruptive Behavioral Disorders

ERIC Educational Resources Information Center

Handen, Benjamin L.; Hardan, Antonio Y.

2006-01-01

Objective: Olanzapine, an atypical antipsychotic, has been shown to be efficacious for treatment of psychotic and mood disorders in adults. This prospective, open-label study was conducted to examine the safety and usefulness of olanzapine in treating disruptive behavior disorders in adolescents with subaverage intelligence. Method: Sixteen…

Open-Label Trial of Atomoxetine Hydrochloride in Adults with ADHD

ERIC Educational Resources Information Center

Johnson, Mats; Cederlund, Mats; Rastam, Maria; Areskoug, Bjorn; Gillberg, Christopher

2010-01-01

Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary…

Age-dependent change in exploratory behavior of male rats following exposure to threat stimulus: effect of juvenile experience.

PubMed

Arakawa, Hiroyuki

2007-07-01

The ontogeny of exploratory behavior depending on the intensity of threat in a modified open-field was investigated in male rats aged 40, 65, and 130 days, by comparing with less threatening condition with no shock and more threatening condition where they were exposed to mild electric shock. The number of crossings in a dim peripheral alley was counted as the level of activity. The total duration of stay in the central area was measured as the level of exploration. The number of entries and stretch-attend postures into a bright center square were measured as active exploratory behavior and the risk assessment behavior, respectively. When exposed to mild shock prior to the test, 40-day-old rats decreased these exploratory behaviors, while 65- and 130-day-old rats increased active exploratory behavior (Experiment 1). A lower level of exploratory behavior following a mild shock was found in 65 and 130-day-old rats isolated during the juvenile stage, but not in rats isolated after puberty (Experiment 2). These findings suggest that the direction of changes in exploratory behavior of male rats following an increase in potential danger showed ontogenetic transition, which is mediated by social experiences as juveniles, but not as adults. This transition may be associated with the emergence of active exploratory behavior during the juvenile stage, which is activated by social interaction.

STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

ERIC Educational Resources Information Center

Erickson, Craig A.; Veenstra-Vanderweele, Jeremy M.; Melmed, Raun D.; McCracken, James T.; Ginsberg, Lawrence D.; Sikich, Linmarie; Scahill, Lawrence; Cherubini, Maryann; Zarevics, Peter; Walton-Bowen, Karen; Carpenter, Randall L.; Bear, Mark F.; Wang, Paul P.; King, Bryan H.

2014-01-01

STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32…

Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

ERIC Educational Resources Information Center

McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

2011-01-01

Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

Development of a PET Prostate-Specific Membrane Antigen Imaging Agent: Preclinical Translation for Future Clinical Application

DTIC Science & Technology

2016-10-01

small-molecule peptidomimetic imaging agents labeled with positron emitting fluorine- 18 . These data will enable the filing of an exploratory IND...outcome. 15. SUBJECT TERMS Prostate Cancer, Prostate Specific Membrane Antigen (PSMA), Fluorine- 18 , Molecular Imaging, Radiotracer, Automated...Synthesis, Phosphoramidate, Inhibitor, Peptide Mimic, Peptidomimetic 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a

A Surface-based Analysis of Language Lateralization and Cortical Asymmetry

PubMed Central

Greve, Douglas N.; Van der Haegen, Lise; Cai, Qing; Stufflebeam, Steven; Sabuncu, Mert R.; Fischl, Bruce; Bysbaert, Marc

2013-01-01

Among brain functions, language is one of the most lateralized. Cortical language areas are also some of the most asymmetrical in the brain. An open question is whether the asymmetry in function is linked to the asymmetry in anatomy. To address this question, we measured anatomical asymmetry in 34 participants shown with fMRI to have language dominance of the left hemisphere (LLD) and 21 participants shown to have atypical right hemisphere dominance (RLD). All participants were healthy and left-handed, and most (80%) were female. Gray matter (GM) volume asymmetry was measured using an automated surface-based technique in both ROIs and exploratory analyses. In the ROI analysis, a significant difference between LLD and RLD was found in the insula. No differences were found in planum temporale (PT), pars opercularis (POp), pars triangularis (PTr), or Heschl’s gyrus (HG). The PT, POp, insula, and HG were all significantly left lateralized in both LLD and RLD participants. Both the positive and negative ROI findings replicate a previous study using manually labeled ROIs in a different cohort [Keller, S. S., Roberts, N., Garcia-Finana, M., Mohammadi, S., Ringelstein, E. B., Knecht, S., et al. Can the language-dominant hemisphere be predicted by brain anatomy? Journal of Cognitive Neuroscience, 23, 2013–2029, 2011]. The exploratory analysis was accomplished using a new surface-based registration that aligns cortical folding patterns across both subject and hemisphere. A small but significant cluster was found in the superior temporal gyrus that overlapped with the PT. A cluster was also found in the ventral occipitotemporal cortex corresponding to the visual word recognition area. The surface-based analysis also makes it possible to disentangle the effects of GM volume, thickness, and surface area while removing the effects of curvature. For both the ROI and exploratory analyses, the difference between LLD and RLD volume laterality was most strongly driven by differences in surface area and not cortical thickness. Overall, there were surprisingly few differences in GM volume asymmetry between LLD and RLD indicating that gross morphometric asymmetry is only subtly related to functional language laterality. PMID:23701459

Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial.

PubMed

Malorni, L; Curigliano, G; Minisini, A M; Cinieri, S; Tondini, C A; D'Hollander, K; Arpino, G; Bernardo, A; Martignetti, A; Criscitiello, C; Puglisi, F; Pestrin, M; Sanna, G; Moretti, E; Risi, E; Biagioni, C; McCartney, A; Boni, L; Buyse, M; Migliaccio, I; Biganzoli, L; Di Leo, A

2018-06-11

The activity of palbociclib as a single agent in advanced breast cancer has not been extensively studied, with the only available clinical data limited to heavily pre-treated patients. Pre-clinical data suggests palbociclib may partially reverse endocrine resistance, though this hypothesis has not been evaluated in previous clinical studies. This phase II, open-label, multi-center study examined the activity of palbociclib monotherapy, as well as palbociclib given in combination with the same endocrine therapy (ET) that was received prior to disease progression, in post-menopausal women with moderately pre-treated, estrogen receptor-positive, HER2 negative advanced breast cancer. Eligible women with advanced disease which had progressed on one or two prior ETs were randomized 1:1 to receive either palbociclib alone, or palbociclib in combination with the ET as previously received. Primary endpoint was clinical benefit rate (CBR); secondary endpoints included progression-free survival (PFS). Between October 2012 and July 2016, a total of 115 patients were randomized. The CBR was 54% (95% CI 41.5 - 63.7) for combination therapy, and 60% (95% CI 47.8 - 72.9) for monotherapy. Median PFS was 10.8 months (95% CI 5.6 - 12.7) for combination therapy, and 6.5 months (95% CI, 5.4 to 8.5) for monotherapy (hazard ratio [HR] 0.69; 95% CI 0.4 - 1.1, exploratory P-value = 0.12). Exploratory analyses revealed the PFS advantage for combination therapy was seen in the subgroup of patients who received prior ET for >6 months (HR 0.53; 95% CI 0.3 - 0.9, exploratory P-value = 0.02), but not in those who received prior ET for ≤6 months. Palbociclib has clinical activity as a single agent in women with moderately pre-treated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET. NCT02549430.

Efficacy of heparinoid moisturizer as a prophylactic agent for radiation dermatitis following radiotherapy after breast-conserving surgery: a randomized controlled trial.

PubMed

Sekiguchi, Kenji; Akahane, Keiko; Ogita, Mami; Haga, Chiori; Ito, Ryoko; Arai, Satoru; Ishida, Yasushi; Tsukada, Yoichiro; Kawamori, Jiro

2018-05-01

The application of heparinoid moisturizer for 2 weeks following whole-breast radiotherapy (WBRT) was previously reported to significantly increase skin water content (WC) and help improve skin dryness and desquamation. The prospective open-label, randomized trial included an exploratory arm to investigate the preventive efficacy of heparinoid moisturizer for acute radiation dermatitis (ARD). Between April 2011 and April 2013, patients receiving WBRT were assigned (1:2:2) to receive either: moisturizer for prophylaxis (group P), moisturizer starting 2 weeks after WBRT for treatment (group M), and no moisturizer (group C). This paper presents the results of comparison between the exploratory arm and no moisturizer group. Skin WC was measured prior to WBRT, on the last day of WBRT, and 2 weeks, 4 weeks and 3 months following WBRT. Signs and symptoms were also assessed. Comparing two groups, WC values were significantly higher in group P until 4 weeks following WBRT. At 2 weeks following WBRT, mean WC values in group P and C were 38.5 ± 6.1 arbitrary units (a.u.) and 30.2 ± 7.8 a.u., respectively (P < 0.001). In group C, dryness was more severe at 2 and 4 weeks following WBRT and desquamation more severe until 3 months following WBRT. However, the erythema score showed no difference between the two groups. Regarding symptoms, group C pain scores on the last day of WBRT were significantly higher than in group P (P < 0.030). The preventive application of heparinoid moisturizer has the potential of reducing skin desquamation and dryness in patients receiving WBRT.

Exploratory trial of ombitasvir and ABT-450/r with or without ribavirin for HCV genotype 1, 2, and 3 infection.

PubMed

Lawitz, Eric; Sullivan, Greg; Rodriguez-Torres, Maribel; Bennett, Michael; Poordad, Fred; Kapoor, Mudra; Badri, Prajakta; Campbell, Andrew; Rodrigues, Lino; Hu, Yiran; Pilot-Matias, Tami; Vilchez, Regis A

2015-02-01

To examine the safety and efficacy of ombitasvir and ABT-450 with ritonavir (ABT-450/r) ± ribavirin (RBV) in treatment-naïve, non-cirrhotic adults with chronic HCV genotype 1-3 infection. Patients in this open-label, exploratory, phase 2, multicenter study received ombitasvir (25 mg QD) and ABT-450/r (200/100 mg QD) ± RBV for 12 weeks. Primary efficacy endpoint was HCV RNA < lower limit of quantitation (LLOQ) from week 4 through 12. Sustained virologic response 12 weeks post-treatment (SVR12) was a secondary endpoint. Sixty-one patients were enrolled. Among genotype 1-, 2-, and 3-infected patients, respectively, HCV RNA was

Nintedanib with Add-on Pirfenidone in Idiopathic Pulmonary Fibrosis. Results of the INJOURNEY Trial.

PubMed

Vancheri, Carlo; Kreuter, Michael; Richeldi, Luca; Ryerson, Christopher J; Valeyre, Dominique; Grutters, Jan C; Wiebe, Sabrina; Stansen, Wibke; Quaresma, Manuel; Stowasser, Susanne; Wuyts, Wim A

2018-02-01

Nintedanib and pirfenidone slow the progression of idiopathic pulmonary fibrosis (IPF), but the disease continues to progress. More data are needed on the safety and efficacy of combination therapy with nintedanib and add-on pirfenidone. To investigate safety, tolerability, and pharmacokinetic and exploratory efficacy endpoints in patients treated with nintedanib and add-on pirfenidone versus nintedanib alone. Patients with IPF and FVC greater than or equal to 50% predicted at screening who completed a 4- to 5-week run-in with nintedanib 150 mg twice daily without dose reduction or treatment interruption were randomized to receive nintedanib 150 mg twice daily with add-on pirfenidone (titrated to 801 mg three times daily) or nintedanib 150 mg twice daily alone in an open-label manner for 12 weeks. The primary endpoint was the percentage of patients with on-treatment gastrointestinal adverse events from baseline to Week 12. Analyses were descriptive and exploratory. On-treatment gastrointestinal adverse events were reported in 37 of 53 patients (69.8%) treated with nintedanib with add-on pirfenidone and 27 of 51 patients (52.9%) treated with nintedanib alone. Predose plasma trough concentrations of nintedanib were similar when it was administered alone or with add-on pirfenidone. Mean (SE) changes from baseline in FVC at Week 12 were -13.3 (17.4) ml and -40.9 (31.4) ml in patients treated with nintedanib with add-on pirfenidone (n = 48) and nintedanib alone (n = 44), respectively. Nintedanib with add-on pirfenidone had a manageable safety and tolerability profile in patients with IPF, in line with the adverse event profiles of each drug. These data support further research into combination regimens in the treatment of IPF. Clinical trial registered with www.clinicaltrials.gov (NCT02579603).

An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial.

PubMed

Khanna, Dinesh; Albera, Carlo; Fischer, Aryeh; Khalidi, Nader; Raghu, Ganesh; Chung, Lorinda; Chen, Dan; Schiopu, Elena; Tagliaferri, Margit; Seibold, James R; Gorina, Eduard

2016-09-01

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) shares a number of clinical features and pathogenic mechanisms with idiopathic pulmonary fibrosis (IPF). This study was designed to evaluate the tolerability of the IPF treatment pirfenidone in SSc-ILD. The known gastrointestinal, skin, and liver adverse events (AE) of pirfenidone are of importance given the involvement of these organs in SSc. All patients received pirfenidone and were randomized 1:1 to either a 2- or 4-week titration starting at 801 mg/day and finishing at a maintenance dose of 2403 mg/day. Patients received pirfenidone for 16 weeks in total. Assessments included treatment-emergent AE (TEAE) and exploratory disease outcomes. Sixty-three patients were randomized; 96.8% experienced a TEAE and more patients reported TEAE during the titration versus the maintenance period. The most commonly reported TEAE were consistent with those observed for pirfenidone in IPF (nausea, headache, fatigue) and were similar regardless of titration schedule. More patients discontinued treatment because of TEAE in the 2- versus 4-week titration group (5 vs 1, respectively); all discontinuation events occurred > 3 weeks after reaching the full dose of pirfenidone. Mycophenolate mofetil (MMF), taken by 63.5% of patients in addition to pirfenidone, did not appear to affect tolerability. Exploratory disease outcomes remained largely unchanged. Pirfenidone showed an acceptable tolerability profile in SSc-ILD, although a longer titration may be associated with better tolerability. Tolerability was not affected by concomitant MMF. The present findings support further investigation of pirfenidone in future clinical trials in patients with SSc-ILD. ClinicalTrials.gov; www.clinicaltrials.gov NCT01933334.

An Exploratory Investigation of the Role of Openness in Relationship Quality among Emerging Adult Chinese Couples

PubMed Central

Zhou, Yixin; Wang, Kexin; Chen, Shuang; Zhang, Jianxin; Zhou, Mingjie

2017-01-01

This study tested emerging adult couples’ openness and its fit effect on their romantic relationship quality using quadratic polynomial regression and response surface analysis. Participants were 260 emerging adult dyads. Both dyads’ openness and relationship quality were measured. The result showed that (1) female and male openness contribute differently to relationship quality; (2) couples with similar high openness could experience better relationship quality than those with similar low openness traits; and (3) when dyadic openness is dissimilar, it is better to be either relatively high or relatively low than to be moderate. These findings highlight the role of openness in emerging adults’ romantic relationships from a dyadic angle. PMID:28360875

An Open-Label Trial of Escitalopram in Pervasive Developmental Disorders.

ERIC Educational Resources Information Center

Owley, Thomas; Walton, Laura; Salt, Jeff; Guter, Stephen J., Jr.; Winnega, Marrea; Leventhal, Bennett L.; Cook, Edwin H., Jr.

2005-01-01

Objective: To assess the effect of escitalopram in the treatment of pervasive developmental disorders (PDDs). Method: This 10-week study had a forced titration, open-label design. Twenty-eight subjects (mean age 125.1 [+ or -] 33.5 months) with a PDD received escitalopram at a dose that increased weekly to a maximum dose of 20 mg as tolerated. The…

Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

ERIC Educational Resources Information Center

Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

2013-01-01

Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

An Open-Label Study of Lamotrigine Adjunct or Monotherapy for the Treatment of Adolescents with Bipolar Depression

ERIC Educational Resources Information Center

Chang, Kiki; Saxena, Kirti; Howe, Meghan

2006-01-01

Objective: The treatment of pediatric bipolar depression has not been well studied. The authors wished to prospectively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode. Method: This was an 8-week open-label trial of lamotrigine with 20 adolescents ages…

Linkage between Free Exploratory Movements and Subjective Tactile Ratings.

PubMed

Yokosaka, Takumi; Kuroki, Scinob; Watanabe, Junji; Nishida, Shinya

2017-01-01

We actively move our hands and eyes when exploring the external world and gaining information about object's attributes. Previous studies showing that how we touch might be related to how we felt led us to consider whether we could decode observers' subjective tactile experiences only by analyzing their exploratory movements without explicitly asking how they perceived. However, in those studies, explicit judgment tasks were performed about specific tactile attributes that were prearranged by experimenters. Here, we systematically investigated whether exploratory movements can explain tactile ratings even when participants do not need to judge any tactile attributes. While measuring both hand and eye movements, we asked participants to touch materials freely without judging any specific tactile attributes (free-touch task) or to evaluate one of four tactile attributes (roughness, hardness, slipperiness, and temperature). We found that tactile ratings in the judgment tasks correlated with exploratory movements even in the free-touch task and that eye movements as well as hand movements correlated with tactile ratings. These results might open up the possibility of decoding tactile experiences by exploratory movements.

Playful Collaboration (or Not): Using a Game to Grasp the Social Dynamics of Open Innovation in Innovation and Business Education

ERIC Educational Resources Information Center

Bogers, Marcel; Sproedt, Henrik

2012-01-01

This article explores how playing games can be used to teach intangible social interaction across boundaries, in particular within open collaborative innovation. We present an exploratory case study of how students learned from playing a board game in a graduate course of the international and interdisciplinary Innovation and Business master's…

Learning about Language Learning on a MOOC: How Massive, Open, Online and "Course"?

ERIC Educational Resources Information Center

Orsini-Jones, Marina; Pibworth-Dolinski, Laura; Cribb, Mike; Brick, Billy; Gazeley-Eke, Zoe; Leinster, Hannah; Lloyd, Elwyn

2015-01-01

This paper reports on an exploratory research project on the evaluation of the engagement with a Massive Open Online Course (MOOC) carried out by six members of staff and two "expert students" involved in the MA in English Language Teaching (ELT) in the Department of English and Languages at Coventry University (CU), United Kingdom,…

Establishing Influential Decision Making Factors for University Library Opening Hours: An Exploratory UK Regional Study

ERIC Educational Resources Information Center

Ravenwood, Clare; Stephens, Derek; Walton, Graham

2015-01-01

Many factors and pressures affect decisions made in UK university libraries on opening hours especially 24/7. This article reports on a project to examine the decision-making process, influential factors, and stakeholders. A workshop for senior library managers in the East Midlands was held to gather data and share experiences. From analysis of…

Socio-Technical Relations in the Creation of an Interest-Driven Open Course

ERIC Educational Resources Information Center

Ponti, Marisa

2011-01-01

The aim of this article is to present the findings from a small exploratory case study of an open course on cyberpunk literature conducted at the Peer 2 Peer University (P2PU), an online grass-roots organisation that runs non-accredited courses. Employing actor network theory to inform an ethnographic-inductive approach, the case study sought to…

Exploring the Relevance of Single-Gender Group Formation: What We Learn from a Massive Open Online Course (MOOC)

ERIC Educational Resources Information Center

Bayeck, Rebecca Yvonne; Hristova, Adelina; Jablokow, Kathryn W.; Bonafini, Fernanda

2018-01-01

This paper reports the results of an exploratory study on participants' perception of the importance of single-gender grouping in a massive open online course (MOOC) delivered through the Coursera platform. Findings reveal that female and male learners' perception of single-gender grouping differs. Female students more than males indicated less…

Affordable and Open Textbooks: An Exploratory Study of Faculty Attitudes. Research & Occasional Paper Series. CSHE.9.09

ERIC Educational Resources Information Center

Harley, Diane; Lawrence, Shannon; Acord, Sophia Krzys; Dixson, Jason

2009-01-01

The Student Public Interest Research Groups (Student PIRGs)--who have been at the forefront of raising awareness about textbook affordability for much of the past decade--launched a two-year campaign (MakeTextbooksAffordable.org/statement) in 2007 to drive mainstream faculty's acceptance of open textbooks and other affordable alternatives in place…

Automatic detection of adverse events to predict drug label changes using text and data mining techniques.

PubMed

Gurulingappa, Harsha; Toldo, Luca; Rajput, Abdul Mateen; Kors, Jan A; Taweel, Adel; Tayrouz, Yorki

2013-11-01

The aim of this study was to assess the impact of automatically detected adverse event signals from text and open-source data on the prediction of drug label changes. Open-source adverse effect data were collected from FAERS, Yellow Cards and SIDER databases. A shallow linguistic relation extraction system (JSRE) was applied for extraction of adverse effects from MEDLINE case reports. Statistical approach was applied on the extracted datasets for signal detection and subsequent prediction of label changes issued for 29 drugs by the UK Regulatory Authority in 2009. 76% of drug label changes were automatically predicted. Out of these, 6% of drug label changes were detected only by text mining. JSRE enabled precise identification of four adverse drug events from MEDLINE that were undetectable otherwise. Changes in drug labels can be predicted automatically using data and text mining techniques. Text mining technology is mature and well-placed to support the pharmacovigilance tasks. Copyright © 2013 John Wiley & Sons, Ltd.

Open-Label Uridine for Treatment of Depressed Adolescents with Bipolar Disorder

PubMed Central

Sung, Young-Hoon; Hellem, Tracy L.; Delmastro, Kristen K.; Jeong, Eun-Kee; Kim, Namkug; Shi, Xianfeng; Renshaw, Perry F.

2011-01-01

Abstract This report is an open-label case series of seven depressed adolescents with bipolar disorder treated with uridine for 6 weeks. Treatment response was measured with the Children's Depression Rating Scale-Revised and the Clinical Global Impressions scale. Uridine was associated with decreased depressive symptoms, and was well tolerated by study participants. Further systematic studies of uridine are warranted. PMID:21486171

Risperidone in Children with Disruptive Behavior Disorders and Subaverage Intelligence: A 1-Year, Open-Label Study of 504 Patients

ERIC Educational Resources Information Center

Croonenberghs, Jan; Fegert, Joerg M.; Findling, Robert L.; de Smedt, Goedele; van Dongen, Stefan

2005-01-01

Objective: To determine the long-term safety and effectiveness of risperidone for severe disruptive behaviors in children. Method: A multisite, 1-year, open-label study of patients aged 5 to 14 years with disruptive behaviors and subaverage intelligence was conducted. Results: Seventy-three percent of the 504 patients enrolled completed the study.…

No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a Phase I Open Label Study to assess safety, tolerability and cytokine responses

USDA-ARS?s Scientific Manuscript database

Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed since the mid 1990s by between 2 and 5 million people daily, the scientific literature lacks rigorous clinical trials that describe the potential harms of LGG, particularly in the elderly. The primary objective of this open label...

Atomoxetine and Methylphenidate Treatment in Children with ADHD: The Efficacy, Tolerability and Effects on Executive Functions

ERIC Educational Resources Information Center

Yildiz, Ozlem; Sismanlar, Sahika G.; Memik, Nursu Cakin; Karakaya, Isik; Agaoglu, Belma

2011-01-01

The aim of this study was to compare the safety, efficacy, tolerability, and the effects of atomoxetine and OROS-MPH on executive functions in children with ADHD. This study was an open-label study that only included two medication groups. Children were randomized to open-label atomoxetine or OROS-MPH for 12 weeks. Primary efficacy measures were…

16 CFR Figures 14 and 15 to Part 1633 - Label for Domestic Mattress Alone and with Foundation and Label for Imported Mattress Alone and...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Label for Domestic Mattress Alone and with Foundation and Label for Imported Mattress Alone and With Foundation 14 Figures 14 and 15 to Part 1633... FLAMMABILITY (OPEN FLAME) OF MATTRESS SETS Pt.1633, Figs. 14, 15 Figures 14 and 15 to Part 1633—Label for...

16 CFR Figures 14 and 15 to Part 1633 - Label for Domestic Mattress Alone and with Foundation and Label for Imported Mattress Alone and...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Label for Domestic Mattress Alone and with Foundation and Label for Imported Mattress Alone and With Foundation 14 Figures 14 and 15 to Part 1633... FLAMMABILITY (OPEN FLAME) OF MATTRESS SETS Pt.1633, Figs. 14, 15 Figures 14 and 15 to Part 1633—Label for...

Recognition of facial expressions of mixed emotions in school-age children exposed to terrorism.

PubMed

Scrimin, Sara; Moscardino, Ughetta; Capello, Fabia; Altoè, Gianmarco; Axia, Giovanna

2009-09-01

This exploratory study aims at investigating the effects of terrorism on children's ability to recognize emotions. A sample of 101 exposed and 102 nonexposed children (mean age = 11 years), balanced for age and gender, were assessed 20 months after a terrorist attack in Beslan, Russia. Two trials controlled for children's ability to match a facial emotional stimulus with an emotional label and their ability to match an emotional label with an emotional context. The experimental trial evaluated the relation between exposure to terrorism and children's free labeling of mixed emotion facial stimuli created by morphing between 2 prototypical emotions. Repeated measures analyses of covariance revealed that exposed children correctly recognized pure emotions. Four log-linear models were performed to explore the association between exposure group and category of answer given in response to different mixed emotion facial stimuli. Model parameters indicated that, compared with nonexposed children, exposed children (a) labeled facial expressions containing anger and sadness significantly more often than expected as anger, and (b) produced fewer correct answers in response to stimuli containing sadness as a target emotion.

Extraction and labeling high-resolution images from PDF documents

NASA Astrophysics Data System (ADS)

Chachra, Suchet K.; Xue, Zhiyun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.

2013-12-01

Accuracy of content-based image retrieval is affected by image resolution among other factors. Higher resolution images enable extraction of image features that more accurately represent the image content. In order to improve the relevance of search results for our biomedical image search engine, Open-I, we have developed techniques to extract and label high-resolution versions of figures from biomedical articles supplied in the PDF format. Open-I uses the open-access subset of biomedical articles from the PubMed Central repository hosted by the National Library of Medicine. Articles are available in XML and in publisher supplied PDF formats. As these PDF documents contain little or no meta-data to identify the embedded images, the task includes labeling images according to their figure number in the article after they have been successfully extracted. For this purpose we use the labeled small size images provided with the XML web version of the article. This paper describes the image extraction process and two alternative approaches to perform image labeling that measure the similarity between two images based upon the image intensity projection on the coordinate axes and similarity based upon the normalized cross-correlation between the intensities of two images. Using image identification based on image intensity projection, we were able to achieve a precision of 92.84% and a recall of 82.18% in labeling of the extracted images.

Six-month, open-label study of hydrocodone extended release formulated with abuse-deterrence technology: Safety, maintenance of analgesia, and abuse potential.

PubMed

Hale, Martin E; Ma, Yuju; Malamut, Richard

2016-01-01

To evaluate long-term safety, maintenance of analgesia, and aberrant drug-related behaviors of hydrocodone extended release (ER) formulated with CIMA® Abuse-Deterrence Technology. Phase 3, multicenter, open-label extension. Fifty-six US centers. Adults with chronic low back pain completing a 12-week placebocontrolled study of abuse-deterrent hydrocodone ER were eligible. One hundred eighty-two patients enrolled and received ≥1 dose of study drug, 170 entered openlabel treatment, and 136 completed the study. Patients receiving hydrocodone ER in the 12-week, placebo-controlled study continued their previous dose unless adjustment was needed; those previously receiving placebo (n=78) underwent dose titration/adjustment to an analgesic dose (15-90 mg every 12 hours). Patients received 22 weeks of open-label treatment. adverse events (AEs). Maintenance of analgesia: worst pain intensity (WPI) and average pain intensity (API) at each study visit. Aberrant drug behavior: study drug loss and diversion. AEs were reported for 65/182 (36 percent) patients during dose titration/ adjustment and 88/170 (52 percent) during open-label treatment. No treatmentrelated serious AEs were reported. There were no clinically meaningful trends in other safety assessments, including physical examinations and pure tone audiometry. One patient receiving hydrocodone ER 30 mg twice daily experienced a severe AE of neurosensory deafness that was considered treatment related. Mean WPI and API remained steady throughout open-label treatment. Six (3 percent) patients reported medication loss, and 5 (3 percent) reported diversion. Abuse-deterrent hydrocodone ER was generally well tolerated in patients with chronic low back pain, maintained efficacy, and was associated with low rates of loss and diversion.

Crowdsourcing quality control for Dark Energy Survey images

DOE PAGES

Melchior, P.

2016-07-01

We have developed a crowdsourcing web application for image quality control employed by the Dark Energy Survey. Dubbed the "DES exposure checker", it renders science-grade images directly to a web browser and allows users to mark problematic features from a set of predefined classes. Users can also generate custom labels and thus help identify previously unknown problem classes. User reports are fed back to hardware and software experts to help mitigate and eliminate recognized issues. We report on the implementation of the application and our experience with its over 100 users, the majority of which are professional or prospective astronomersmore » but not data management experts. We discuss aspects of user training and engagement, and demonstrate how problem reports have been pivotal to rapidly correct artifacts which would likely have been too subtle or infrequent to be recognized otherwise. We conclude with a number of important lessons learned, suggest possible improvements, and recommend this collective exploratory approach for future astronomical surveys or other extensive data sets with a sufficiently large user base. We also release open-source code of the web application and host an online demo versionat http://des-exp-checker.pmelchior.net« less

Crowdsourcing quality control for Dark Energy Survey images

NASA Astrophysics Data System (ADS)

Melchior, P.; Sheldon, E.; Drlica-Wagner, A.; Rykoff, E. S.; Abbott, T. M. C.; Abdalla, F. B.; Allam, S.; Benoit-Lévy, A.; Brooks, D.; Buckley-Geer, E.; Carnero Rosell, A.; Carrasco Kind, M.; Carretero, J.; Crocce, M.; D'Andrea, C. B.; da Costa, L. N.; Desai, S.; Doel, P.; Evrard, A. E.; Finley, D. A.; Flaugher, B.; Frieman, J.; Gaztanaga, E.; Gerdes, D. W.; Gruen, D.; Gruendl, R. A.; Honscheid, K.; James, D. J.; Jarvis, M.; Kuehn, K.; Li, T. S.; Maia, M. A. G.; March, M.; Marshall, J. L.; Nord, B.; Ogando, R.; Plazas, A. A.; Romer, A. K.; Sanchez, E.; Scarpine, V.; Sevilla-Noarbe, I.; Smith, R. C.; Soares-Santos, M.; Suchyta, E.; Swanson, M. E. C.; Tarle, G.; Vikram, V.; Walker, A. R.; Wester, W.; Zhang, Y.

2016-07-01

We have developed a crowdsourcing web application for image quality control employed by the Dark Energy Survey. Dubbed the "DES exposure checker", it renders science-grade images directly to a web browser and allows users to mark problematic features from a set of predefined classes. Users can also generate custom labels and thus help identify previously unknown problem classes. User reports are fed back to hardware and software experts to help mitigate and eliminate recognized issues. We report on the implementation of the application and our experience with its over 100 users, the majority of which are professional or prospective astronomers but not data management experts. We discuss aspects of user training and engagement, and demonstrate how problem reports have been pivotal to rapidly correct artifacts which would likely have been too subtle or infrequent to be recognized otherwise. We conclude with a number of important lessons learned, suggest possible improvements, and recommend this collective exploratory approach for future astronomical surveys or other extensive data sets with a sufficiently large user base. We also release open-source code of the web application and host an online demo version at http://des-exp-checker.pmelchior.net.

Crowdsourcing quality control for Dark Energy Survey images

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

Melchior, P.

We have developed a crowdsourcing web application for image quality control employed by the Dark Energy Survey. Dubbed the "DES exposure checker", it renders science-grade images directly to a web browser and allows users to mark problematic features from a set of predefined classes. Users can also generate custom labels and thus help identify previously unknown problem classes. User reports are fed back to hardware and software experts to help mitigate and eliminate recognized issues. We report on the implementation of the application and our experience with its over 100 users, the majority of which are professional or prospective astronomersmore » but not data management experts. We discuss aspects of user training and engagement, and demonstrate how problem reports have been pivotal to rapidly correct artifacts which would likely have been too subtle or infrequent to be recognized otherwise. We conclude with a number of important lessons learned, suggest possible improvements, and recommend this collective exploratory approach for future astronomical surveys or other extensive data sets with a sufficiently large user base. We also release open-source code of the web application and host an online demo versionat http://des-exp-checker.pmelchior.net« less

16 CFR 1633.12 - Labeling.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Labeling. 1633.12 Section 1633.12 Commercial... (OPEN FLAME) OF MATTRESS SETS Rules and Regulations § 1633.12 Labeling. (a) Each mattress set subject to... information (and no other information) in English: (1) Name of the manufacturer, or for imported mattress sets...

Brief review of published alprazolam clinical studies

PubMed Central

Straw, R. N.

1985-01-01

1 The clinical efficacy of alprazolam has been evaluated in both anxiety states and depressive disorders. In anxiety neurosis, studies have been conducted vs placebo and/or other benzodiazepine tranquilizers. Reports, to date, with regard to panic/phobia disorders have been limited to open-label studies and a single report from a placebo-controlled study. In depression, both open-label and double-blind studies (vs tricyclic antidepressants) have been published. PMID:2859879

Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

ERIC Educational Resources Information Center

Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

2011-01-01

Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

An Analysis of Patient Adherence to Treatment during a 1-Year, Open-Label Study of OROS[R] Methylphenidate in Children with ADHD

ERIC Educational Resources Information Center

Faraone, Stephen V.; Biederman, Joseph; Zimmerman, Brenda

2007-01-01

Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in…

Quantifying exploratory low dose compounds in humans with AMS

PubMed Central

Dueker, Stephen R.; Vuong, Le T.; Lohstroh, Peter N.; Giacomo, Jason A.; Vogel, John S.

2010-01-01

Accelerator Mass Spectrometry is an established technology whose essentiality extends beyond simply a better detector for radiolabeled molecules. Attomole sensitivity reduces radioisotope exposures in clinical subjects to the point that no population need be excluded from clinical study. Insights in human physiochemistry are enabled by the quantitative recovery of simplified AMS processes that provide biological concentrations of all labeled metabolites and total compound related material at non-saturating levels. In this paper, we review some of the exploratory applications of AMS 14C in toxicological, nutritional, and pharmacological research. This body of research addresses the human physiochemistry of important compounds in their own right, but also serves as examples of the analytical methods and clinical practices that are available for studying low dose physiochemistry of candidate therapeutic compounds, helping to broaden the knowledge base of AMS application in pharmaceutical research. PMID:21047543

Multi-atlas segmentation with joint label fusion and corrective learning—an open source implementation

PubMed Central

Wang, Hongzhi; Yushkevich, Paul A.

2013-01-01

Label fusion based multi-atlas segmentation has proven to be one of the most competitive techniques for medical image segmentation. This technique transfers segmentations from expert-labeled images, called atlases, to a novel image using deformable image registration. Errors produced by label transfer are further reduced by label fusion that combines the results produced by all atlases into a consensus solution. Among the proposed label fusion strategies, weighted voting with spatially varying weight distributions derived from atlas-target intensity similarity is a simple and highly effective label fusion technique. However, one limitation of most weighted voting methods is that the weights are computed independently for each atlas, without taking into account the fact that different atlases may produce similar label errors. To address this problem, we recently developed the joint label fusion technique and the corrective learning technique, which won the first place of the 2012 MICCAI Multi-Atlas Labeling Challenge and was one of the top performers in 2013 MICCAI Segmentation: Algorithms, Theory and Applications (SATA) challenge. To make our techniques more accessible to the scientific research community, we describe an Insight-Toolkit based open source implementation of our label fusion methods. Our implementation extends our methods to work with multi-modality imaging data and is more suitable for segmentation problems with multiple labels. We demonstrate the usage of our tools through applying them to the 2012 MICCAI Multi-Atlas Labeling Challenge brain image dataset and the 2013 SATA challenge canine leg image dataset. We report the best results on these two datasets so far. PMID:24319427

75 FR 72686 - Express Mail Open and Distribute and Priority Mail Open and Distribute

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... POSTAL SERVICE 39 CFR Part 111 Express Mail Open and Distribute and Priority Mail Open and... ``DB'' prefix along with new Tag 257, Tag 267, or Label 257S, on all Express Mail[supreg] Open and Distribute containers. The Postal Service is also revising the service commitment for Express Mail Open and...

The effect of physician and patient education when combined with vardenafil treatment in Canadian males with erectile dysfunction: an open-label, factorial-designed, cluster-randomized clinical trial.

PubMed

Brock, Gerald; Carrier, Serge; Alarie, Pierre; Pommerville, Peter; Casey, Richard; Harris, Stewart; Ward, Richard

2008-03-01

Studies evaluating the effect of education on treatment success with phosphodiesterase type 5 (PDE5) inhibitor therapy in men with erectile dysfunction (ED) are limited. Additional education of the primary care physician (PCP) and the patient are thought to optimize the treatment of ED. To assess the impact of education of the PCP or of the patient in the treatment of ED with vardenafil relative to usual care. In this 12-week, open-label, multicenter, factorial-designed, cluster-randomized Canadian study, 1,029 patients with ED were enrolled into four different education groups: usual care, patient education, PCP education, and both PCP and patient education. All groups started on vardenafil 10 mg, with the option to titrate at weeks 4 and 8. The primary efficacy measure was the difference at week 4 last observation carried forward (LOCF) in the overall improvement in erectile function (EF) as measured by the Global Assessment Question (GAQ), while on background vardenafil, between those receiving education vs. those who did not. Other secondary assessments included responses to diary questions regarding penetration (sexual encounter profile, SEP2) and erection maintenance (SEP3), and to questionnaires regarding treatment satisfaction (Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS]). A total of 956 patients were included in the intent-to-treat population. Mean baseline International Index of Erectile Function-EF domain score was 13. GAQ response rates at week 4 LOCF were high (>80%) for all groups, regardless of the education given. Mean per patient SEP2 and SEP3 rates at week 12 LOCF were 86-89% and 79-83%, respectively. In an exploratory analysis, a positive relationship between GAQ responses and EDITS scores was observed (P < or = 0.0007). Vardenafil was generally well tolerated. In men with moderate ED, vardenafil led to high success rates and satisfaction regardless of the education given. The benefits of education for PCP and patients in Canada were possibly masked by a ceiling effect in this study population.

Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma: Results From the Open-Label, Multicenter, Phase II DAWN Study.

PubMed

Gopal, Ajay K; Schuster, Stephen J; Fowler, Nathan H; Trotman, Judith; Hess, Georg; Hou, Jing-Zhou; Yacoub, Abdulraheem; Lill, Michael; Martin, Peter; Vitolo, Umberto; Spencer, Andrew; Radford, John; Jurczak, Wojciech; Morton, James; Caballero, Dolores; Deshpande, Sanjay; Gartenberg, Gary J; Wang, Shean-Sheng; Damle, Rajendra N; Schaffer, Michael; Balasubramanian, Sriram; Vermeulen, Jessica; Cheson, Bruce D; Salles, Gilles

2018-05-31

Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee-assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle 3) and cytokines/chemokines (baseline/cycle 2) were performed for available samples. Results Between March 2013 and May 2016, 110 patients with a median of three prior lines of therapy were enrolled. At median follow-up of 27.7 months, ORR was 20.9% (95% CI, 13.7% to 29.7%, which did not meet the 18% lower-bound threshold for the primary end point). Twelve patients achieved a complete response (11%; 95% CI, 5.8% to 18.3%). Median duration of response was 19.4 months (range, 1 to ≥ 33 months), with a median progression-free survival of 4.6 months and a 30-month overall survival of 61% (95% CI, 0.51% to 0.70%). Lymphoma symptoms resolved in 67%. Seven of 32 patients who experienced initial radiologic progression responded upon continuing therapy (pseudoprogression). The most common adverse events were diarrhea, fatigue, cough, and muscle spasms; 48.2% of patients reported serious adverse events. In patients who experienced a response, regulatory T cells were downregulated at C3D1 ( P = .02), and Th1-promoting (antitumor) cytokines interferon-γ and interleukin-12 increased ( P ≤ .035). Conclusion With an ORR of 20.9%, ibrutinib failed to meet its primary efficacy end point in chemoimmunotherapy in patients with relapsed/refractory FL, although responses were durable and associated with a reduction in regulatory T cells and increases in proinflammatory cytokines.

Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.

PubMed

Kang, Dae-Wook; Adams, James B; Gregory, Ann C; Borody, Thomas; Chittick, Lauren; Fasano, Alessio; Khoruts, Alexander; Geis, Elizabeth; Maldonado, Juan; McDonough-Means, Sharon; Pollard, Elena L; Roux, Simon; Sadowsky, Michael J; Lipson, Karen Schwarzberg; Sullivan, Matthew B; Caporaso, J Gregory; Krajmalnik-Brown, Rosa

2017-01-23

Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10 13 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. This trial was registered on the ClinicalTrials.gov, with the registration number  NCT02504554.

What Does It Mean to Assess Gifted Students' Perceptions of Giftedness Labels?

ERIC Educational Resources Information Center

Meadows, Bryan; Neumann, Jacob W.

2017-01-01

Measuring gifted and talented ("GT") students' perceptions of their "GT" label might seem to be a relatively straightforward affair. Most of this research uses survey methods that ask "GT" students to complete Likert scale or open-ended response questionnaires about their perceptions of the label and then presents…

A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

ERIC Educational Resources Information Center

Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

2013-01-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

An Open-Label Study of Risperidone in the Improvement of Quality of Life and Treatment of Symptoms of Violent and Self-Injurious Behaviour in Adults with Intellectual Disability

ERIC Educational Resources Information Center

Read, Stephen G.; Rendall, Maureen

2007-01-01

Background: We examined the benefits of risperidone, including quality of life (QoL), in the treatment of violent and self-injurious behaviour in adults with moderate, severe or profound intellectual disability. Methods: Twenty-four participants received open-label, oral, flexible-dose risperidone of 0.5-6 mg/day for 12 weeks. Efficacy was…

Automatic multi-label annotation of abdominal CT images using CBIR

NASA Astrophysics Data System (ADS)

Xue, Zhiyun; Antani, Sameer; Long, L. Rodney; Thoma, George R.

2017-03-01

We present a technique to annotate multiple organs shown in 2-D abdominal/pelvic CT images using CBIR. This annotation task is motivated by our research interests in visual question-answering (VQA). We aim to apply results from this effort in Open-iSM, a multimodal biomedical search engine developed by the National Library of Medicine (NLM). Understanding visual content of biomedical images is a necessary step for VQA. Though sufficient annotational information about an image may be available in related textual metadata, not all may be useful as descriptive tags, particularly for anatomy on the image. In this paper, we develop and evaluate a multi-label image annotation method using CBIR. We evaluate our method on two 2-D CT image datasets we generated from 3-D volumetric data obtained from a multi-organ segmentation challenge hosted in MICCAI 2015. Shape and spatial layout information is used to encode visual characteristics of the anatomy. We adapt a weighted voting scheme to assign multiple labels to the query image by combining the labels of the images identified as similar by the method. Key parameters that may affect the annotation performance, such as the number of images used in the label voting and the threshold for excluding labels that have low weights, are studied. The method proposes a coarse-to-fine retrieval strategy which integrates the classification with the nearest-neighbor search. Results from our evaluation (using the MICCAI CT image datasets as well as figures from Open-i) are presented.

Porosity estimation by semi-supervised learning with sparsely available labeled samples

NASA Astrophysics Data System (ADS)

Lima, Luiz Alberto; Görnitz, Nico; Varella, Luiz Eduardo; Vellasco, Marley; Müller, Klaus-Robert; Nakajima, Shinichi

2017-09-01

This paper addresses the porosity estimation problem from seismic impedance volumes and porosity samples located in a small group of exploratory wells. Regression methods, trained on the impedance as inputs and the porosity as output labels, generally suffer from extremely expensive (and hence sparsely available) porosity samples. To optimally make use of the valuable porosity data, a semi-supervised machine learning method was proposed, Transductive Conditional Random Field Regression (TCRFR), showing good performance (Görnitz et al., 2017). TCRFR, however, still requires more labeled data than those usually available, which creates a gap when applying the method to the porosity estimation problem in realistic situations. In this paper, we aim to fill this gap by introducing two graph-based preprocessing techniques, which adapt the original TCRFR for extremely weakly supervised scenarios. Our new method outperforms the previous automatic estimation methods on synthetic data and provides a comparable result to the manual labored, time-consuming geostatistics approach on real data, proving its potential as a practical industrial tool.

Four factors underlying mouse behavior in an open field

PubMed Central

Tanaka, Shoji; Young, Jared W.; Halberstadt, Adam L.; Masten, Virginia L.; Geyer, Mark A.

2012-01-01

The observation of the locomotor and exploratory behaviors of rodents in an open field is one of the most fundamental methods used in the field of behavioral pharmacology. A variety of behaviors can be recorded automatically and can readily generate a multivariate pattern of pharmacological effects. Nevertheless, the optimal ways to characterize observed behaviors and concomitant drug effects are still under development. The aim of this study was to extract meaningful behavioral factors that could explain variations in the observed variables from mouse exploration. Behavioral data were recorded from male C57BL/6J mice (n = 268) using the Behavioral Pattern Monitor (BPM). The BPM data were subjected to the exploratory factor analysis. The factor analysis extracted four factors: activity, sequential organization, diversive exploration, and inspective exploration. The activity factor and the two types of exploration factors correlated positively with one another, while the sequential organization factor negatively correlated with the remaining factors. The extracted factor structure constitutes a behavioral model of mouse exploration. This model will provide a platform on which one can assess the effects of psychoactive drugs and genetic manipulations on mouse exploratory behavior. Further studies are currently underway to examine the factor structure of similar multivariate data sets from humans tested in a human BPM. PMID:22569582

Four factors underlying mouse behavior in an open field.

PubMed

Tanaka, Shoji; Young, Jared W; Halberstadt, Adam L; Masten, Virginia L; Geyer, Mark A

2012-07-15

The observation of the locomotor and exploratory behaviors of rodents in an open field is one of the most fundamental methods used in the field of behavioral pharmacology. A variety of behaviors can be recorded automatically and can readily generate a multivariate pattern of pharmacological effects. Nevertheless, the optimal ways to characterize observed behaviors and concomitant drug effects are still under development. The aim of this study was to extract meaningful behavioral factors that could explain variations in the observed variables from mouse exploration. Behavioral data were recorded from male C57BL/6J mice (n=268) using the Behavioral Pattern Monitor (BPM). The BPM data were subjected to the exploratory factor analysis. The factor analysis extracted four factors: activity, sequential organization, diversive exploration, and inspective exploration. The activity factor and the two types of exploration factors correlated positively with one another, while the sequential organization factor negatively correlated with the remaining factors. The extracted factor structure constitutes a behavioral model of mouse exploration. This model will provide a platform on which one can assess the effects of psychoactive drugs and genetic manipulations on mouse exploratory behavior. Further studies are currently underway to examine the factor structure of similar multivariate data sets from humans tested in a human BPM. Copyright © 2012 Elsevier B.V. All rights reserved.

Safety, Tolerability, and Efficacy of Quetiapine in Youth with Schizophrenia or Bipolar I Disorder: A 26-Week, Open-Label, Continuation Study

PubMed Central

Pathak, Sanjeev; Earley, Willie R.; Liu, Sherry; DelBello, Melissa

2013-01-01

Abstract Objective The purpose of this study was to describe the safety, tolerability, and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with schizophrenia or bipolar I disorder. Methods Medically healthy boys and girls with a baseline Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) diagnosis of schizophrenia (ages 13–17 years) or a manic episode of bipolar I disorder (ages 10–17 years) who participated in one of two acute, double-blind, placebo-controlled studies of immediate-release quetiapine were potentially eligible to enroll in a 26-week, open-label study. During the open-label study, quetiapine was flexibly dosed at 400–800 mg/day, with options to reduce dosing to 200 mg/day based on tolerability. Safety and tolerability outcomes assessed from open-label baseline to week 26 included adverse events (AEs), metabolic/laboratory parameters, extrapyramidal symptoms, suicidality, and vital signs. Results Of 381 patients enrolled in the open-label study (n=176, schizophrenia; n=205, bipolar disorder diagnosis), 237 patients (62.2%) completed the 26-week study period (71.0%, schizophrenia; 54.6%, bipolar disorder). The most common AEs reported during the study included somnolence, headache, sedation, weight increase, and vomiting. A total of 14.9% of patients experienced a shift to potentially clinically significant low levels of high-density lipoprotein cholesterol and 10.2% of patients experienced a shift to potentially clinically significant high triglyceride levels. Weight gain ≥7% was reported in 35.6% of patients between open-label baseline and final visit. After adjustment for normal growth, 18.3% of study participants experienced clinically significant weight gain (i.e., increase in body mass index ≥0.5 standard deviations from baseline). Conclusions In this 26-week study, quetiapine flexibly dosed at 400–800 mg/day, with options to reduce dosing based on tolerability, was generally safe and well tolerated in youth. Clinicians should monitor lipid profiles and weight gain in youth with schizophrenia or bipolar disorder during treatment with quetiapine. Clinical trial registration information Quetiapine Fumarate (Seroquel) in the Treatment of Adolescent Patients With Schizophrenia and Bipolar I Disorder (ANCHOR 150). Available at: http://clinicaltrials.gov/ct2/show/NCT00227305 PMID:24024534

Impaired locomotor activity and exploratory behavior in mice lacking histamine H1 receptors

PubMed Central

Inoue, Isao; Yanai, Kazuhiko; Kitamura, Daisuke; Taniuchi, Ichiro; Kobayashi, Takashi; Niimura, Kaku; Watanabe, Takehiko; Watanabe, Takeshi

1996-01-01

From pharmacological studies using histamine antagonists and agonists, it has been demonstrated that histamine modulates many physiological functions of the hypothalamus, such as arousal state, locomotor activity, feeding, and drinking. Three kinds of receptors (H1, H2, and H3) mediate these actions. To define the contribution of the histamine H1 receptors (H1R) to behavior, mutant mice lacking the H1R were generated by homologous recombination. In brains of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. [3H]Doxepin has two saturable binding sites with higher and lower affinities in brains of wild-type mice, but H1R-deficient mice showed only the weak labeling of [3H]doxepin that corresponds to lower-affinity binding sites. Mutant mice develop normally, but absence of H1R significantly increased the ratio of ambulation during the light period to the total ambulation for 24 hr in an accustomed environment. In addition, mutant mice significantly reduced exploratory behavior of ambulation and rearings in a new environment. These results indicate that through H1R, histamine is involved in circadian rhythm of locomotor activity and exploratory behavior as a neurotransmitter. PMID:8917588

Thematic Analysis of Medical Notes Offers Preliminary Insight into Precipitants for Asian Suicide Attempters: An Exploratory Study.

PubMed

Choo, Carol C; Ho, Roger C; Burton, André A D

2018-04-20

One important dynamic risk factor for suicide assessment includes suicide precipitant. This exploratory study used a qualitative paradigm to look into the themes surrounding precipitants for suicide attempts in Singapore. Medical records related to suicide attempters who were admitted to the emergency department of a large teaching hospital in Singapore over a three year period were subjected to analysis. A total of 666 cases were examined (69.2% females; 63.8% Chinese, 15% Malays, 15.8% Indians), ages ranged from 10 years old to 85 years old (Mean = 29.7, Standard Deviation = 16.1). The thematic analysis process that was applied to the textual data elicited key concepts labelled as Relationship issues, Financial strain, Socio-legal-academic—environmental stress, and Physical and mental illness and pain. Interpreted with other recent local research on suicide attempters in Singapore, the findings have implications for informing suicide interventions.

Switching from adalimumab to tofacitinib in the treatment of patients with rheumatoid arthritis.

PubMed

Genovese, Mark C; van Vollenhoven, Ronald F; Wilkinson, Bethanie; Wang, Lisy; Zwillich, Samuel H; Gruben, David; Biswas, Pinaki; Riese, Richard; Takiya, Liza; Jones, Thomas V

2016-06-23

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The aim of this study was to explore the safety and efficacy of open-label tofacitinib following blinded treatment with adalimumab or tofacitinib for moderate to severe RA. Analyses included patients treated with adalimumab 40 mg once every 2 weeks or tofacitinib 10 mg twice daily (BID) with background methotrexate (MTX) in a 12-month randomized study (NCT00853385), who subsequently received tofacitinib 10 mg BID (with/without background MTX) in an open-label extension (NCT00413699). Patients with treatment-related serious adverse events (AEs) and serious or recurrent infections in the index study were excluded from the extension study. Exposure-adjusted incidence rates of safety-related events were assessed in 3-month and 12-month periods in the year before and in the year after switching. Efficacy was assessed 3 months before, at the time of, and 3 months after switching. There were 233 (107 adalimumab to tofacitinib 10 mg BID, 126 blinded to open-label tofacitinib 10 mg BID) patients included in these analyses. Patients in both treatment sequences had similar incidence rates (per 100 patient-years) of discontinuation due to AEs, serious AEs, and serious infections in the year before and in the year after switching. Incidence rates of AEs were increased in the first 3 months after switching compared with the last 3 months before switching in both treatment groups. Switching from either blinded adalimumab or tofacitinib to open-label tofacitinib resulted in numerically higher incidence of responders for signs and symptoms of disease and improved physical function. Treatment can be directly switched from adalimumab to tofacitinib. A similar safety and efficacy profile was seen when patients received open-label tofacitinib after receiving either blinded adalimumab or tofacitinib. ClinicalTrials.gov Identifiers: NCT00853385 , registered 27 February 2009; NCT00413699 , registered 18 December 2006.

Atomoxetine and Parent Training for Children With Autism and Attention-Deficit/Hyperactivity Disorder: A 24-Week Extension Study.

PubMed

Smith, Tristram; Aman, Michael G; Arnold, L Eugene; Silverman, Laura B; Lecavalier, Luc; Hollway, Jill; Tumuluru, Rameshwari; Hyman, Susan L; Buchan-Page, Kristin A; Hellings, Jessica; Rice, Robert R; Brown, Nicole V; Pan, Xueliang; Handen, Benjamin L

2016-10-01

The authors previously reported on a 2-by-2 randomized clinical trial of individual and combined treatment with atomoxetine (ATX) and parent training (PT) for attention-deficit/hyperactivity disorder (ADHD) symptoms and behavioral noncompliance in 128 5- to 14-year-old children with autism spectrum disorder. In the present report, they describe a 24-week extension of treatment responders and nonresponders. One-hundred seventeen participants from the acute trial (91%) entered the extension; 84 of these were in 2 subgroups: "treatment responders" (n = 43) from all 4 groups in the acute trial, seen monthly for 24 weeks, and "placebo nonresponders" (n = 41), treated with open-label ATX for 10 weeks. Participants originally assigned to PT continued PT during the extension; the remainder served as controls. Primary outcome measurements were the parent-rated Swanson, Nolan and Pelham ADHD scale and the Home Situations Questionnaire. Sixty percent (26 of 43) of treatment responders in the acute trial, including 68% of responders originally assigned to ATX, still met the response criteria at the end of the extension. The response rate of placebo nonresponders treated with 10-week open-label ATX was 37% (15 of 41), similar to the acute trial. Children receiving open-label ATX + PT were significantly more likely to be ADHD responders (53% versus 23%) and noncompliance responders (58% versus 14%) than those receiving open-label ATX alone. Most ATX responders maintained their responses during the extension. PT combined with ATX in the open-label trial appeared to improve ADHD and noncompliance outcomes more than ATX alone. Clinical trial registration information-Atomoxetine, Placebo and Parent Management Training in Autism (Strattera); http://clinicaltrials.gov; NCT00844753. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis.

PubMed

Ruperto, Nicolino; Lovell, Daniel J; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhães, Claudia; Chavez-Corrales, J; Huemer, Christian; Kivitz, Alan; Blanco, Francisco J; Foeldvari, Ivan; Hofer, Michael; Horneff, Gerd; Huppertz, Hans-Iko; Job-Deslandre, Chantal; Loy, Anna; Minden, Kirsten; Punaro, Marilynn; Nunez, Alejandro Flores; Sigal, Leonard H; Block, Alan J; Nys, Marleen; Martini, Alberto; Giannini, Edward H

2010-06-01

We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >or=21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008. Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

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

PubMed Central

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

2015-01-01

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

Randomized, Double-Blind, Placebo-Controlled Trial of Asenapine Maintenance Therapy in Adults With an Acute Manic or Mixed Episode Associated With Bipolar I Disorder.

PubMed

Szegedi, Armin; Durgam, Suresh; Mackle, Mary; Yu, Sung Yun; Wu, Xiao; Mathews, Maju; Landbloom, Ronald P

2018-01-01

The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder. Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this randomized, placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind randomized withdrawal period. The target asenapine dosage was 10 mg b.i.d. in the open-label period but could be titrated down to 5 mg b.i.d. After completing the open-label period, subjects meeting stabilization/stable-responder criteria were randomized to asenapine or placebo treatment in the double-blind period. The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period. Kaplan-Meier estimation was performed, and 95% confidence intervals were determined. Safety was assessed throughout. A total of 549 subjects entered the open-label period, of whom 253 enrolled in the double-blind randomized withdrawal period (127 in the placebo group; 126 in the asenapine group). Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects. In post hoc analyses, significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes. The most common treatment-emergent adverse events were somnolence (10.0%), akathisia (7.7%), and sedation (7.7%) in the open-label period and mania (11.9% of the placebo group compared with 4.0% of the asenapine group) and bipolar I disorder (6.3% compared with 1.6%) in the double-blind period. Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated.

Narrating personality change.

PubMed

Lodi-Smith, Jennifer; Geise, Aaron C; Roberts, Brent W; Robins, Richard W

2009-03-01

The present research investigated the longitudinal relations between personality traits and narratives. Specifically, the authors examined how individual differences in 170 college students' narratives of personality change (a) were predicted by personality traits at the beginning of college, (b) related to actual changes and perceived changes in personality traits during college, and (c) related to changes in emotional health during college. Individual differences in narratives of personality trait change told in the 4th year of college fell into 2 dimensions: affective processing, characterized by positive emotions, and exploratory processing, characterized by meaning making and causal processing. Conscientious, open, and extraverted freshmen told exploratory stories of change as seniors. Emotionally healthy freshmen told stories of change that were high in positive affect. Both positive affective and exploratory stories corresponded to change in emotional stability and conscientiousness during college above and beyond the effects of perceived changes in these traits. In addition, both positive affective and exploratory narratives corresponded to increases in emotional health during college independent of the effects of changes in personality traits. These findings improve our understanding of how individuals conceptualize their changing identity over time.

Narrating Personality Change

PubMed Central

Lodi-Smith, Jennifer; Geise, Aaron C.; Roberts, Brent W.; Robins, Richard W.

2009-01-01

The present research investigated the longitudinal relations between personality traits and narratives. Specifically, the authors examined how individual differences in 170 college students' narratives of personality change (a) were predicted by personality traits at the beginning of college, (b) related to actual changes and perceived changes in personality traits during college, and (c) related to changes in emotional health during college. Individual differences in narratives of personality trait change told in the 4th year of college fell into 2 dimensions: affective processing, characterized by positive emotions, and exploratory processing, characterized by meaning making and causal processing. Conscientious, open, and extraverted freshmen told exploratory stories of change as seniors. Emotionally healthy freshmen told stories of change that were high in positive affect. Both positive affective and exploratory stories corresponded to change in emotional stability and conscientiousness during college above and beyond the effects of perceived changes in these traits. In addition, both positive affective and exploratory narratives corresponded to increases in emotional health during college independent of the effects of changes in personality traits. These findings improve our understanding of how individuals conceptualize their changing identity over time. PMID:19254112

Otolith Dysfunction Alters Exploratory Movement in Mice

PubMed Central

Blankenship, Philip A.; Cherep, Lucia A.; Donaldson, Tia N.; Brockman, Sarah N.; Trainer, Alexandria D.; Yoder, Ryan M.; Wallace, Douglas G.

2017-01-01

The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system’s contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation. PMID:28235587

Alcohol consumers' attention to warning labels and brand information on alcohol packaging: Findings from cross-sectional and experimental studies.

PubMed

Kersbergen, Inge; Field, Matt

2017-01-26

Alcohol warning labels have a limited effect on drinking behavior, potentially because people devote minimal attention to them. We report findings from two studies in which we measured the extent to which alcohol consumers attend to warning labels on alcohol packaging, and aimed to identify if increased attention to warning labels is associated with motivation to change drinking behavior. Study 1 (N = 60) was an exploratory cross-sectional study in which we used eye-tracking to measure visual attention to brand and health information on alcohol and soda containers. In study 2 (N = 120) we manipulated motivation to reduce drinking using an alcohol brief intervention (vs control intervention) and measured heavy drinkers' attention to branding and warning labels with the same eye-tracking paradigm as in study 1. Then, in a separate task we experimentally manipulated attention by drawing a brightly colored border around health (or brand) information before measuring participants' self-reported drinking intentions for the subsequent week. Study 1 showed that participants paid minimal attention to warning labels (7% of viewing time). Participants who were motivated to reduce drinking paid less attention to alcohol branding and alcohol warning labels. Results from study 2 showed that the alcohol brief intervention decreased attention to branding compared to the control condition, but it did not affect attention to warning labels. Furthermore, the experimental manipulation of attention to health or brand information did not influence drinking intentions for the subsequent week. Alcohol consumers allocate minimal attention to warning labels on alcohol packaging and even if their attention is directed to these warning labels, this has no impact on their drinking intentions. The lack of attention to warning labels, even among people who actively want to cut down, suggests that there is room for improvement in the content of health warnings on alcohol packaging.

Interior of southeast gun chamber (labeled "Gun Turret No. Two), ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Interior of southeast gun chamber (labeled "Gun Turret No. Two), showing gun mounting pad, wall rings, small niche, and opening to outside - U.S. Naval Base, Pearl Harbor, Battery Adair, Princeton Place, Pearl City, Honolulu County, HI

An Open-Source Label Atlas Correction Tool and Preliminary Results on Huntingtons Disease Whole-Brain MRI Atlases

PubMed Central

Forbes, Jessica L.; Kim, Regina E. Y.; Paulsen, Jane S.; Johnson, Hans J.

2016-01-01

The creation of high-quality medical imaging reference atlas datasets with consistent dense anatomical region labels is a challenging task. Reference atlases have many uses in medical image applications and are essential components of atlas-based segmentation tools commonly used for producing personalized anatomical measurements for individual subjects. The process of manual identification of anatomical regions by experts is regarded as a so-called gold standard; however, it is usually impractical because of the labor-intensive costs. Further, as the number of regions of interest increases, these manually created atlases often contain many small inconsistently labeled or disconnected regions that need to be identified and corrected. This project proposes an efficient process to drastically reduce the time necessary for manual revision in order to improve atlas label quality. We introduce the LabelAtlasEditor tool, a SimpleITK-based open-source label atlas correction tool distributed within the image visualization software 3D Slicer. LabelAtlasEditor incorporates several 3D Slicer widgets into one consistent interface and provides label-specific correction tools, allowing for rapid identification, navigation, and modification of the small, disconnected erroneous labels within an atlas. The technical details for the implementation and performance of LabelAtlasEditor are demonstrated using an application of improving a set of 20 Huntingtons Disease-specific multi-modal brain atlases. Additionally, we present the advantages and limitations of automatic atlas correction. After the correction of atlas inconsistencies and small, disconnected regions, the number of unidentified voxels for each dataset was reduced on average by 68.48%. PMID:27536233

An Open-Source Label Atlas Correction Tool and Preliminary Results on Huntingtons Disease Whole-Brain MRI Atlases.

PubMed

Forbes, Jessica L; Kim, Regina E Y; Paulsen, Jane S; Johnson, Hans J

2016-01-01

The creation of high-quality medical imaging reference atlas datasets with consistent dense anatomical region labels is a challenging task. Reference atlases have many uses in medical image applications and are essential components of atlas-based segmentation tools commonly used for producing personalized anatomical measurements for individual subjects. The process of manual identification of anatomical regions by experts is regarded as a so-called gold standard; however, it is usually impractical because of the labor-intensive costs. Further, as the number of regions of interest increases, these manually created atlases often contain many small inconsistently labeled or disconnected regions that need to be identified and corrected. This project proposes an efficient process to drastically reduce the time necessary for manual revision in order to improve atlas label quality. We introduce the LabelAtlasEditor tool, a SimpleITK-based open-source label atlas correction tool distributed within the image visualization software 3D Slicer. LabelAtlasEditor incorporates several 3D Slicer widgets into one consistent interface and provides label-specific correction tools, allowing for rapid identification, navigation, and modification of the small, disconnected erroneous labels within an atlas. The technical details for the implementation and performance of LabelAtlasEditor are demonstrated using an application of improving a set of 20 Huntingtons Disease-specific multi-modal brain atlases. Additionally, we present the advantages and limitations of automatic atlas correction. After the correction of atlas inconsistencies and small, disconnected regions, the number of unidentified voxels for each dataset was reduced on average by 68.48%.

Deficits in novelty exploration after controlled cortical impact.

PubMed

Wagner, Amy K; Postal, Brett A; Darrah, Shaun D; Chen, Xiangbai; Khan, Amina S

2007-08-01

Experimental models of traumatic brain injury (TBI) have been utilized to characterize the behavioral derangements associated with brain trauma. Several studies exist characterizing motor function in the controlled cortical impact (CCI) injury model of TBI, but less research has focused on how CCI affects exploratory behavior. The goal of this study was to characterize deficits in three novelty exploration tasks after the CCI. Under anesthesia, 37 adult male Sprague Dawley rats received CCI (2.7 mm and 2.9 mm; 4 m/sec) over the right parietal cortex or sham surgery. For days 1-6 post-surgery, the beam balance and beam walking tasks were used to assess motor deficits. The Open Field, Y-Maze, and Free Choice Novelty (FCN) tasks were used to measure exploratory deficits from days 7-14 post-surgery. Injured rats displayed a significant, but transient, deficit on each motor task (p < 0.0001). Open Field results showed that injured rats had lower activity levels than shams (p < 0.0001), displayed less habituation to the task, and had more anxiety related behaviors (thigmotaxis) across days (p < 0.0001). Y-maze results suggest that injured rats spent less time in the novel arm versus the familiar arms when compared to shams (p < 0.0001). For FCN, injured rats were less active (p < 0.05) and spent less time and had fewer interactions with objects in the novel environment compared to shams (p < 0.05). These results suggest that several ethological factors contribute to exploratory deficits after CCI and can be effectively characterized with the behavioral tasks described. Future work will utilize these tasks to evaluate the neural substrates underlying exploratory deficits after TBI.

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

Woodson, W.R.; Handa, A.K.

Changes in proteins associated with senescence of the flowers of Hibiscus rosa-sinensis was studied using SDS-PAGE. Total extractable protein from petals decreased with senescence. Changes were noted in patterns of proteins from aging petals. Flower opening and senescence was associated with appearance and disappearance of several polypeptides. One new polypeptide with an apparent mw of 41 kd was first seen the day of flower opening and increased to over 9% of the total protein content of senescent petal tissue. Protein synthesis during aging was investigated by following uptake and incorporation of /sup 3/H-leucine into TCA-insoluble fraction of petal discs. Proteinmore » synthesis, as evidenced by the percent of label incorporated into the TCA-insoluble fraction, was greatest (32%) the day before flower opening. Senescent petal tissue incorporated 4% of label taken up into protein. Proteins were separated by SDS-PAGE and labelled polypeptides identified by fluorography. In presenescent petal tissue, radioactivity was distributed among several major polypeptides. In senescent tissue, much of the radioactivity was concentrated in the 41 kd polypeptide.« less

Indium-111 leukocyte scintigraphy in Wegener's granulomatosis involving the spleen

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

Morayati, S.J.; Fink-Bennett, D.

1986-12-01

Indium-111-labeled leukocyte scintigraphy was performed on a 44-yr-old man to exclude an occult abscess. Four- and twenty-four-hour images of the abdomen revealed splenic photopenia except for a rim of activity medially. A subsequent computed tomography (CT) study demonstrated necrosis or hemorrhage of the spleen except for a medial rim. Exploratory laparotomy demonstrated necrotizing vasculitis with granuloma formation consistent with Wegener's granulomatosis and a rim of viable splenic tissue corresponding to the radionuclide and CT studies.

The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial.

PubMed

Berk, Michael; Dean, Olivia; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa S; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Allwang, Christine; Cobb, Heidi; Bush, Ashley I; Schapkaitz, Ian; Dodd, Seetal; Malhi, Gin S

2011-12-01

Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need. This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder. In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 (SE=0.8). This reduction was statistically significant (p<0.001). Improvements in functioning and quality of life were similarly evident. These open label data demonstrate a robust decrement in depression scores with NAC treatment. Large placebo controlled trials of acute bipolar depression are warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities.

PubMed

Wasdell, Michael B; Jan, James E; Bomben, Melissa M; Freeman, Roger D; Rietveld, Wop J; Tai, Joseph; Hamilton, Donald; Weiss, Margaret D

2008-01-01

The purpose of this study was to determine the efficacy of controlled-release (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders. A randomized double-blind, placebo-controlled crossover trial of CR melatonin (5 mg) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects. Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs. Clinician rating of severity of the sleep disorder and improvement from baseline, along with caregiver ratings of global functioning and family stress were also obtained. Fifty-one children (age range 2-18 years) who did not respond to sleep hygiene intervention were enrolled. Fifty patients completed the crossover trial and 47 completed the open-label phase. Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min. Similarly, significant improvement was observed in clinician and parent ratings. There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase. Overall, the therapy improved the sleep of 47 children and was effective in reducing family stress. Children with neurodevelopmental disabilities, who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance, showed improvement in melatonin therapy.

A preliminary quality of life questionnaire-bronchiectasis: a patient-reported outcome measure for bronchiectasis.

PubMed

Quittner, Alexandra L; Marciel, Kristen K; Salathe, Matthias A; O'Donnell, Anne E; Gotfried, Mark H; Ilowite, Jonathan S; Metersky, Mark L; Flume, Patrick A; Lewis, Sandra A; McKevitt, Matthew; Montgomery, A Bruce; O'Riordan, Thomas G; Barker, Alan F

2014-08-01

The Quality of Life Questionnaire-Bronchiectasis (QOL-B) is the first disease-specific, patient-reported outcome measure for patients with bronchiectasis. Content validity, cognitive testing, responsivity to open-label treatment, and psychometric analyses are presented. Reviews of literature, existing measures, and physician input were used to generate the initial QOL-B. Modifications following preliminary cognitive testing (N = 35 patients with bronchiectasis) generated version (V) 1.0. An open-ended patient interview study (N = 28) provided additional information and was content analyzed to derive saturation matrices, which summarized all disease-related topics mentioned by each participant. This resulted in QOL-B V2.0. Psychometric analyses were carried out using results from an open-label phase 2 trial, in which 89 patients were enrolled and treated with aztreonam for inhalation solution. Responsivity to open-label treatment was observed. Additional analyses generated QOL-B V3.0, with 37 items on eight scales: respiratory symptoms; physical, role, emotional, and social functioning; vitality; health perceptions; and treatment burden. For each scale, scores are standardized on a 0-to-100-point scale; higher scores indicate better health-related quality of life. No total score is calculated. A final cognitive testing study (N = 40) resulted in a minor change to one social functioning scale item (QOL-B V3.1). Content validity, cognitive testing, responsivity to open-label treatment, and initial psychometric analyses supported QOL-B items and structure. This interim QOL-B is a promising tool for evaluating the efficacy of new therapies for patients with bronchiectasis and for measuring symptoms, functioning, and quality of life in these patients on a routine basis. A final psychometric validation study is needed and is forthcoming. ClinicalTrials.gov; No.: NCT00805025; URL: www.clinicaltrials.gov.

Pilot study of atomoxetine in patients with Parkinson's disease and dopa-unresponsive Freezing of Gait.

PubMed

Revuelta, Gonzalo J; Embry, Aaron; Elm, Jordan J; Gregory, Chris; Delambo, Amy; Kautz, Steve; Hinson, Vanessa K

2015-01-01

Freezing of gait (FoG) is a common and debilitating condition in Parkinson's disease (PD) associated with executive dysfunction. A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency. This pilot study explores the effects of atomoxetine on gait in PD patients with dopa-unresponsive FoG using a novel paradigm for objective gait assessment. Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study. Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning, while performing a dual task. Clinical, and subjective assessments of gait, quality of life, and safety were also administered. The primary outcome was a validated subjective assessment for FoG (FOG-Q). Atomoxetine was well tolerated, however, no significant change was observed in the primary outcome. The gait analysis protocol correlated well with clinical scales, but not with subjective assessments. DBS patients were more likely to increase gait velocity (p = 0.033), and improved in other clinical assessments. Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population, and may be superior correlates of FoG severity than subjective measures. These findings can inform future trials in this population.

Asthma control in patients on fixed dose combination evaluated with mannitol challenge test.

PubMed

Romberg, Kerstin A M; Berggren, Anna-Carin; Bjermer, Leif

2014-02-01

Asthma is often difficult to control and it is likely that not all patients are optimally treated. This study aimed to explore asthma control in adults receiving fixed dose combination (FDC) therapy. Control of asthma was assessed using the mannitol challenge test as a monitoring tool to see if this would give additional information compared to the asthma control test (ACT). The study was an open-label, prospective study on 98 adults prescribed with FDC therapies for at least three months. 74 patients considered that their asthma was well controlled. However, 60 patients had a positive mannitol challenge test (PD15 < 635 mg), and when those with a positive response to the short-acting β2-agonist (≥15%) after the mannitol challenge test were included, this increased to 64 patients (65%). Exploratory analysis determined that the spirometry parameters; FEV1/FVC and FEV1% of predicted, were statistically significant predictors of a positive mannitol challenge test. Co-morbid conditions such as concomitant upper airway involvement or eczema did not predict mannitol reactivity. Although most patients rated their asthma as well controlled, many provided a positive mannitol challenge test, suggesting the presence of underlying inflammation, despite treatment with fixed dose combination therapy. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

78 FR 37995 - Appliance Standards and Rulemaking Federal Advisory Committee: Notice of Open Teleconference/Webinar

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

...-2013-BT-NOC-0023] Appliance Standards and Rulemaking Federal Advisory Committee: Notice of Open...: Notice of open Teleconference/Webinar. SUMMARY: This document announces a meeting of the Appliance... appliances and commercial equipment, certification and enforcement of standards, and product labeling...

Principles Governing the Mechanics and Control of Snake Strikes

DTIC Science & Technology

2015-06-26

Zoo Atlanta. In this exploratory project we will monitor kinematics, ground reaction forces and strike forces in snakes to gain insight into common...species once Zoo Atlanta is again open for research collaboration; their renovation and expansion of herpetological facility has limited our

Predictors of relapse in patients with major depressive disorder in a 52-week, fixed dose, double blind, randomized trial of selegiline transdermal system (STS).

PubMed

Jang, Saeheon; Jung, Sungwon; Pae, Chiun; Kimberly, Blanchard Portland; Craig Nelson, J; Patkar, Ashwin A

2013-12-01

We investigated patient and disease characteristics predictive of relapse of MDD during a 52-week placebo controlled trial of selegiline transdermal system (STS) to identify patient characteristics relevant for STS treatment. After 10 weeks of open-label stabilization with STS, 322 remitted patients with MDD were randomized to 52-weeks of double-blind treatment with STS (6 mg/24h) or placebo (PLB). Relapse was defined as Hamilton Depression Rating Scale (HAMD-17) score of ≥ 14 and a CGI-S score of ≥ 3 with at least 2-point increase from the beginning of the double blind phase on 2 consecutive visits. Cox's proportional hazards regression was used to examine the effect of potential predictors (age, sex, age at onset of first MDD, early response pattern, number of previous antidepressant trials, severity of index episode, number of previous episodes, melancholic features, atypical features and anxious feature) on outcome. Exploratory analyses examined additional clinical variables (medical history, other psychiatric history, and individual items of HAM-D 28) on relapse. For all predictor variables analyzed, treatment Hazard Ratio (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than PLB). Age of onset was significantly predictive of relapse. Type, duration, and severity of depressive episodes, previous antidepressant trials, or demographic variables did not predict relapse. In additional exploratory analysis, eating disorder history and suicidal ideation were significant predictors of relapse after controlling for the effect of treatment in individual predictor analysis. While age of onset, eating disorder history and suicidal ideation were significant predictors, the majority of clinical and demographic variables were not predictive of relapse. Given the post-hoc nature of analysis, the findings need confirmation from a prospective study. It appears that selegiline transdermal system was broadly effective in preventing relapse across different subtypes and symptoms clusters of MDD. © 2013 Published by Elsevier B.V.

Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome.

PubMed

Berry-Kravis, Elizabeth; Sumis, Allison; Hervey, Crystal; Nelson, Michael; Porges, Stephen W; Weng, Ning; Weiler, Ivan Jeanne; Greenough, William T

2008-08-01

In fragile X syndrome (FXS), it is hypothesized that absence of the fragile X mental retardation protein (FMRP) disrupts regulation of group 1 metabotropic glutamate receptor (mGluR and mGluR5)-dependent translation in dendrites. Lithium reduces mGluR-activated translation and reverses phenotypes in the dfxr mutant fly and fmr1 knockout mouse. This pilot add-on trial was conducted to evaluate safety and efficacy of lithium in humans with FXS. Fifteen individuals with FXS, ages 6-23, received lithium titrated to levels of 0.8-1.2 mEq/L. The primary outcome measure, the Aberrant Behavior Checklist --Community Edition (ABC-C) Irritability Subscale, secondary outcome measures (other ABC-C subscales, clinical global improvement scale (CGI), visual analog scale for behavior (VAS), Vineland Adaptive Behavior Scale (VABS)), exploratory cognitive and psychophysiological measures and an extracellular signal-regulated kinase (ERK) activation assay were administered at baseline and 2 months of treatment. Side effects were quantified with a standardized checklist and lithium level, complete blood count (CBC), thyroid stimulating hormone (TSH), and chemistry screen were done at baseline, 2 weeks, 4 weeks and 2 months. The only significant treatment-related side effects were polyuria/polydipsia (n = 7) and elevated TSH (n = 4). Although the ABC-C Irritability Subscale showed only a trend toward improvement, there was significant improvement in the Total ABC-C score (p = 0.005), VAS (p = 0.003), CGI (p = 0.002), VABS Maladaptive Behavior Subscale (p = 0.007), and RBANS List Learning (p = 0.03) and an enhanced ERK activation rate (p = 0.007). Several exploratory tasks proved too difficult for lower-functioning FXS subjects. Results from this study are consistent with results in mouse and fly models of FXS, and suggest that lithium is well-tolerated and provides functional benefits in FXS, possibly by modifying the underlying neural defect. A placebo-controlled trial of lithium in FXS is warranted.

Long-term persistence of humoral and cellular immune responses induced by an AS03A-adjuvanted H1N1 2009 influenza vaccine: an open-label, randomized study in adults aged 18-60 years and older.

PubMed

Van Damme, Pierre; Kafeja, Froukje; Bambure, Vinod; Hanon, Emmanuel; Moris, Philippe; Roman, François; Gillard, Paul

2013-07-01

This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009 strain, six and 12 mo after adults received one dose (n = 138) or two doses (n = 102; 21 d apart) of a 3.75 µg Hemagglutinin antigen AS03-adjuvanted H1N1 2009 vaccine (NCT00968526). Two hundred forty subjects (18-60 y: 120;>60 y: 120) were vaccinated. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. Exploratory analyses assessed the cell-mediated immune response (CMI) up to Month 12 and the influence of previous influenza vaccination on persistence of immune response. At Month 6, the CHMP criteria were met in subjects aged 18-60 y who received one or two vaccine doses and in subjects aged>60 y who received two vaccine doses. At Month 12, the CHMP criteria were met only in subjects aged 18-60 y who received two vaccine doses. Persistence of HI immune response against the vaccine strain was higher in subjects without prior influenza vaccination. Exploratory analyses showed that two doses of the H1N1 2009 vaccine induced persistence of H1N1-specific CD4+ T cells up to Month 6 and memory B cells up to Month 12. In conclusion, HI immune responses persisted up to 12 mo after vaccination with one-dose and two-dose regimens of the AS03-adjuvanted 3.75 µg HA H1N1 2009 pandemic influenza vaccine, although not all three CHMP guidance criteria for both groups were met at Month 6 and Month 12. The CD4+ T cell and B cell responses also persisted up to Month 12.

Role of protein sulfation in vasodilation induced by minoxidil sulfate, a K+ channel opener

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

Meisheri, K.D.; Oleynek, J.J.; Puddington, L.

Evidence from contractile, radioisotope ion flux and electrophysiological studies suggest that minoxidil sulfate (MNXS) acts as a K+ channel opener in vascular smooth muscle. This study was designed to examine possible biochemical mechanisms by which MNXS exerts such an effect. Experiments performed in the isolated rabbit mesenteric artery (RMA) showed that MNXS, 5 microM, but not the parent compound minoxidil, was a potent vasodilator. Whereas the relaxant effects of an another K+ channel opener vasodilator, BRL-34915 (cromakalim), were removed by washing with physiological saline solution, the effects of MNXS persisted after repeated washout attempts. Furthermore, after an initial exposure ofmore » segments of intact RMA to (35S) MNXS, greater than 30% of the radiolabel was retained 2 hr after removal of the drug. In contrast, retention of radiolabel was not detected with either (3H)MNXS (label on the piperidine ring of MNXS) or (3H)minoxidil (each less than 3% after a 2-hr washout). These data suggested that the sulfate moiety from MNXS was closely associated with the vascular tissue. To determine if proteins were the acceptors of sulfate from MNXS, intact RMAs were incubated with (35S)MNXS, and then 35S-labeled proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by fluorography. Preferential labeling of a 116 kD protein was detected by 2 and 5 min of treatment. A 43 kD protein (resembling actin) also showed significant labeling. A similar profile of 35S-labeled proteins was observed in (35S) MNXS-treated A7r5 rat aortic smooth muscle cells, suggesting that the majority of proteins labeled by (35S)MNXS in intact RMA were components of smooth muscle cells.« less

Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

PubMed Central

Spellberg, Brad; Andes, David; Perez, Mario; Anglim, Anne; Bonilla, Hector; Mathisen, Glenn E.; Walsh, Thomas J.; Ibrahim, Ashraf S.

2009-01-01

We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis. PMID:19433555

Children's Well-Being in Day Care Centres: An Exploratory Empirical Study.

ERIC Educational Resources Information Center

Mayr, Toni; Ulich, Michaela

1999-01-01

Used educators' ratings to describe preschool children's well-being in day care centers. Identified 11 independent dimensions of well-being: empathic, prosocial behavior; social initiative and vitality; self-assertiveness, openness; pleasure in exploring; coping with stress; positive self-defense; pleasure in sensory experiences;…

High-Performance Computing in Neuroscience for Data-Driven Discovery, Integration, and Dissemination

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

Bouchard, Kristofer E.; Aimone, James B.; Chun, Miyoung

A lack of coherent plans to analyze, manage, and understand data threatens the various opportunities offered by new neuro-technologies. High-performance computing will allow exploratory analysis of massive datasets stored in standardized formats, hosted in open repositories, and integrated with simulations.

High-Performance Computing in Neuroscience for Data-Driven Discovery, Integration, and Dissemination

DOE PAGES

Bouchard, Kristofer E.; Aimone, James B.; Chun, Miyoung; ...

2016-11-01

A lack of coherent plans to analyze, manage, and understand data threatens the various opportunities offered by new neuro-technologies. High-performance computing will allow exploratory analysis of massive datasets stored in standardized formats, hosted in open repositories, and integrated with simulations.

Observing Protein & Energy Nutrition (OPEN) Study

Cancer.gov

The Observing Protein and Energy Nutrition (OPEN) Study was designed to assess dietary measurement error by comparing results from self-reported dietary intake data with four dietary biomarkers: doubly labeled water and urinary nitrogen, sodium, and potassium.

GO-PCA: An Unsupervised Method to Explore Gene Expression Data Using Prior Knowledge

PubMed Central

Wagner, Florian

2015-01-01

Method Genome-wide expression profiling is a widely used approach for characterizing heterogeneous populations of cells, tissues, biopsies, or other biological specimen. The exploratory analysis of such data typically relies on generic unsupervised methods, e.g. principal component analysis (PCA) or hierarchical clustering. However, generic methods fail to exploit prior knowledge about the molecular functions of genes. Here, I introduce GO-PCA, an unsupervised method that combines PCA with nonparametric GO enrichment analysis, in order to systematically search for sets of genes that are both strongly correlated and closely functionally related. These gene sets are then used to automatically generate expression signatures with functional labels, which collectively aim to provide a readily interpretable representation of biologically relevant similarities and differences. The robustness of the results obtained can be assessed by bootstrapping. Results I first applied GO-PCA to datasets containing diverse hematopoietic cell types from human and mouse, respectively. In both cases, GO-PCA generated a small number of signatures that represented the majority of lineages present, and whose labels reflected their respective biological characteristics. I then applied GO-PCA to human glioblastoma (GBM) data, and recovered signatures associated with four out of five previously defined GBM subtypes. My results demonstrate that GO-PCA is a powerful and versatile exploratory method that reduces an expression matrix containing thousands of genes to a much smaller set of interpretable signatures. In this way, GO-PCA aims to facilitate hypothesis generation, design of further analyses, and functional comparisons across datasets. PMID:26575370

GO-PCA: An Unsupervised Method to Explore Gene Expression Data Using Prior Knowledge.

PubMed

Wagner, Florian

2015-01-01

Genome-wide expression profiling is a widely used approach for characterizing heterogeneous populations of cells, tissues, biopsies, or other biological specimen. The exploratory analysis of such data typically relies on generic unsupervised methods, e.g. principal component analysis (PCA) or hierarchical clustering. However, generic methods fail to exploit prior knowledge about the molecular functions of genes. Here, I introduce GO-PCA, an unsupervised method that combines PCA with nonparametric GO enrichment analysis, in order to systematically search for sets of genes that are both strongly correlated and closely functionally related. These gene sets are then used to automatically generate expression signatures with functional labels, which collectively aim to provide a readily interpretable representation of biologically relevant similarities and differences. The robustness of the results obtained can be assessed by bootstrapping. I first applied GO-PCA to datasets containing diverse hematopoietic cell types from human and mouse, respectively. In both cases, GO-PCA generated a small number of signatures that represented the majority of lineages present, and whose labels reflected their respective biological characteristics. I then applied GO-PCA to human glioblastoma (GBM) data, and recovered signatures associated with four out of five previously defined GBM subtypes. My results demonstrate that GO-PCA is a powerful and versatile exploratory method that reduces an expression matrix containing thousands of genes to a much smaller set of interpretable signatures. In this way, GO-PCA aims to facilitate hypothesis generation, design of further analyses, and functional comparisons across datasets.

OpenCL based machine learning labeling of biomedical datasets

NASA Astrophysics Data System (ADS)

Amoros, Oscar; Escalera, Sergio; Puig, Anna

2011-03-01

In this paper, we propose a two-stage labeling method of large biomedical datasets through a parallel approach in a single GPU. Diagnostic methods, structures volume measurements, and visualization systems are of major importance for surgery planning, intra-operative imaging and image-guided surgery. In all cases, to provide an automatic and interactive method to label or to tag different structures contained into input data becomes imperative. Several approaches to label or segment biomedical datasets has been proposed to discriminate different anatomical structures in an output tagged dataset. Among existing methods, supervised learning methods for segmentation have been devised to easily analyze biomedical datasets by a non-expert user. However, they still have some problems concerning practical application, such as slow learning and testing speeds. In addition, recent technological developments have led to widespread availability of multi-core CPUs and GPUs, as well as new software languages, such as NVIDIA's CUDA and OpenCL, allowing to apply parallel programming paradigms in conventional personal computers. Adaboost classifier is one of the most widely applied methods for labeling in the Machine Learning community. In a first stage, Adaboost trains a binary classifier from a set of pre-labeled samples described by a set of features. This binary classifier is defined as a weighted combination of weak classifiers. Each weak classifier is a simple decision function estimated on a single feature value. Then, at the testing stage, each weak classifier is independently applied on the features of a set of unlabeled samples. In this work, we propose an alternative representation of the Adaboost binary classifier. We use this proposed representation to define a new GPU-based parallelized Adaboost testing stage using OpenCL. We provide numerical experiments based on large available data sets and we compare our results to CPU-based strategies in terms of time and labeling speeds.

Grains Are Similarly Categorized by 8- to 13-Year-Old Children

PubMed Central

Beltran, Alicia; Sepulveda, Karina Knight; Watson, Kathy; Baranowski, Tom; Baranowski, Janice; Islam, Noemi; Missaghian, Mariam

2009-01-01

This study assessed how 8- to 13-year-old children categorized and labeled grain foods and how these categories and labels were influenced by child characteristics. The main hypotheses were that children categorized foods in consistent ways and these food categories differed from the professional food categories. A set of 71 cards with pictures and names of grain foods from eight professionally denned food groups was sorted by each child into piles of similar foods. There were 149 8- to 13-year-old children (133 English-speaking, 16 Spanish-speaking) in this exploratory study. One-way analysis of variance and Robinson matrices for identification of clusters of food items were calculated. Children created a mean (± standard deviation) of 8.3±3.8 piles with 8.6±9.1 cards per pile. No substantial differences in Robinson clustering were detected across subcategories for each of the demographic characteristics. For the majority of the piles, children provided “taxonomic-professional” (34.5%) labels, such as bread for the professional category of breads, rolls, and tortillas, or “script” (26.1%) labels, such as breakfast for the professional category of pancakes, waffles, and flapjacks. These categories may be used to facilitate food search in a computerized 24-hour dietary recall for children in this age group. PMID:18954585

The relationship among expressions, labels, and descriptions of contempt.

PubMed

Matsumoto, David; Ekman, Paul

2004-10-01

This article reports 4 studies that demonstrate that the contempt expression is reliably associated with situations that elicit contempt and that the inability to label the contempt expression reflects a problem with its label or concept and not with the relationship between its expression and emotion. In Study I, the labeling of contempt in fixed-choice judgment tasks did not occur because of a process of elimination. In Studies 2 and 3, the contempt expression was associated with situations that elicit contempt, but participants did not label the situations in an open-ended response. In Study 3, participants also more reliably labeled the contempt expression with situations rather than with labels and did not generate contempt situations from labels. In Study 4, participants reported using, hearing, and reading about contempt the least among 7 emotions tested. (c) 2004 APA, all rights reserved

Repeat treatment with rifaximin improves irritable bowel syndrome-related quality of life: a secondary analysis of a randomized, double-blind, placebo-controlled trial.

PubMed

Cash, Brooks D; Pimentel, Mark; Rao, Satish S C; Weinstock, Leonard; Chang, Lin; Heimanson, Zeev; Lembo, Anthony

2017-09-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) impairs patient quality of life (QOL). Rifaximin is an oral, nonsystemic antibiotic indicated for IBS-D. The objective of this secondary analysis was to evaluate rifaximin retreatment on IBS-related QOL in patients with IBS-D. Patients received open-label rifaximin 550 mg three times daily for 2 weeks. Clinical responders [simultaneously meeting weekly response criteria for abdominal pain (⩾30% improvement from baseline in mean weekly pain score) and stool consistency (⩾50% decrease from baseline in number of days/week with Bristol Stool Scale (BSS) type 6 or 7 stools) during ⩾2 of first 4 weeks posttreatment] who relapsed during an up to 18-week treatment-free observation phase were randomly assigned to receive two 2-week courses of double-blind rifaximin or placebo, separated by 10 weeks. A validated 34-item IBS-QOL questionnaire examined patient responses in 8 domains. The 2579 patients receiving open-label rifaximin experienced a mean improvement from baseline in IBS-QOL overall score of 54.9%. Responders to open-label rifaximin ( n = 1074 of 2438 evaluable; 44.1%) had significantly greater improvement from baseline in IBS-QOL overall and all eight subdomain scores, including dysphoria, food avoidance, interference with activity, body image, and sexual function versus nonresponders at 4 weeks posttreatment ( n = 1364; p < 0.001 for all comparisons). A significantly greater percentage of responders to open-label rifaximin achieved the minimally clinically important difference (MCID; ⩾14-point improvement from baseline) in the overall IBS-QOL score versus nonresponders [ n = 561 (52.2%) versus n = 287 (21.0%); p < 0.0001]. Among 636 patients with IBS-D relapse, the MCID in the overall IBS-QOL score was achieved by a significantly greater percentage of patients receiving double-blind rifaximin versus placebo (38.6% versus 29.6%, respectively; p = 0.009). Open-label and blinded retreatment with a short course (2 weeks) of rifaximin improved IBS-QOL in patients with IBS-D [ClinicalTrials.gov identifier: NCT01543178].

The Reliability and Legality of Online Education

ERIC Educational Resources Information Center

Agbebaku, C. A.; Adavbiele, A. Justina

2016-01-01

Today, the classroom beyond the border through online Open University education in Nigeria has made it possible for many students to obtain university degrees. However, the reliability and legality of such degrees have become questionable. This paper is a descriptive exploratory case study regarding the public and private sector end-users, whose…

Enhancing Classroom Creativity. Premier PD

ERIC Educational Resources Information Center

Luna, Elizabeth; Ernst, Jeremy; Clark, Aaron; DeLuca, V. William; Kelly, Daniel

2018-01-01

Educators often hear about the need for students to be more creative, more free-thinking, and more exploratory throughout projects and class assignments. This article will highlight the importance of creating and implementing an open-classroom environment where students are confident in their ability to ask questions and capable of exploring a…

Male Teachers' Experiences of Own Aggression

ERIC Educational Resources Information Center

Botha, Johan; Myburgh, Chris; Poggenpoel, Marie

2013-01-01

We describe an exploratory, descriptive, and contextual study on the lived experiences of 17 male teachers' own aggression in the Gert Sibande district in Mpumalanga province. Individual phenomenological interviews were used to collect data from these volunteers for this qualitative research. The data were analysed by means of an open coding…

Open Crowdsourcing: Leveraging Community Software Developers for IT Projects

ERIC Educational Resources Information Center

Phair, Derek

2012-01-01

This qualitative exploratory single-case study was designed to examine and understand the use of volunteer community participants as software developers and other project related roles, such as testers, in completing a web-based application project by a non-profit organization. This study analyzed the strategic decision to engage crowd…

Students' Perceptions of Factors that Affect College Funding Decisions

ERIC Educational Resources Information Center

Porter, Julia Y.; Fossey, W. Richard; Davis, William E.; Burnett, Michael F.; Stuhlmann, Janice; Suchy, Patricia A.

2006-01-01

This exploratory study examines the factors that college students perceive are important in helping them make good financial decisions about paying for a college education. The study categorizes and summarizes students' self-reported responses to an open-ended survey question about recommendations for changes in financial aid counseling practices.…

An Exploratory Study of Taiwanese Mathematics Teachers' Conceptions of School Mathematics, School Statistics, and Their Differences

ERIC Educational Resources Information Center

Yang, Kai-Lin

2014-01-01

This study used phenomenography, a qualitative method, to investigate Taiwanese mathematics teachers' conceptions of school mathematics, school statistics, and their differences. To collect data, we interviewed five mathematics teachers by open questions. They also responded to statements drawn on mathematical/statistical conceptions and…

Students' Exploratory Thinking about a Nonroutine Calculus Task

ERIC Educational Resources Information Center

Nabb, Keith

2013-01-01

In this article on introductory calculus, intriguing questions are generated that can ignite an appreciation for the subject of mathematics. These questions open doors to advanced mathematical thinking and harness many elements of research-oriented mathematics. Such questions also offer greater incentives for students to think and reflect.…

Ubiquinol-10 supplementation improves autonomic nervous function and cognitive function in chronic fatigue syndrome.

PubMed

Fukuda, Sanae; Nojima, Junzo; Kajimoto, Osami; Yamaguti, Kouzi; Nakatomi, Yasuhito; Kuratsune, Hirohiko; Watanabe, Yasuyoshi

2016-07-08

The aim of this study was to evaluate the benefit of oral ubiquinol-10 supplementation in CFS patients using an open-label study and a randomized, double-blinded, placebo-controlled (RCT) study. Twenty patients with CFS were randomly enrolled in an 8-week open-label oral ubiquinol-10 (150 mg ubiquinol-10/day) study. The patients and the attending physicians were not blinded to the supplementation. Forty-three patients with CFS were randomly assigned to receive either ubiquinol-10 (150 mg/day) or placebo every day for 12 weeks. The patients and the attending physicians were blinded to the supplementation, and a total of 31 patients (N = 17 in the ubiquinol group and 14 in the placebo group) completed the study. The beneficial effects of ubiquinol-10 were observed in the open-label study we conducted prior to the RCT. The RCT results suggest that supplementation with ubiquinol-10 for 12 weeks is effective for improving several CFS symptoms. © 2016 BioFactors, 42(4):431-440, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

[Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis].

PubMed

Ershova, O B; Lesniak, O M; Belova, K Iu; Nazarova, A V; Manovitskaia, A V; Musaeva, T M; Musraev, R M; Nurlygaianov, R Z; Rozhinskaia, L Ia; Skripnikova, I A; Toroptsova, N V

2014-01-01

To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study. Patients aged 50 years or older with postmenopausal OP, who were treated with Prolia in clinical practice, were examined. The concentrations of the bone resorption (BR) marker of C-terminal telopeptide and other laboratory indicators (total serum calcium, total alkaline phosphatase, and creatinine) were measured following 3 months. Adverse drug reactions were recorded. Three months after initiation of the investigation, there was a significant decrease in the BR marker C-terminal telopeptide (by 89%; p<0.0001). There were rare adverse reactions: hypocalcemia in 3 (5.9%) patients, arthralgias in 2 (3.9%), and eczema in 1 (1.9%). There were neither serious adverse events nor study withdrawal cases. The preliminary results of the open-label study of Prolia in postmenopausal OP suggest that the significantly lower BR activity determines the efficacy of this drug and its high safety.

The "Trotter" Open-Air School, Milan (1922-1977): A City of Youth or Risky Business?

ERIC Educational Resources Information Center

Thyssen, Geert

2009-01-01

This article inserts the concept of risk in the context of open-air schools and investigates its implications, capacities and limits. It is contended that applying at-risk labels to pupils who attended open-air schools is itself a risky business. The category to some extent constitutes an anomaly within most open-air schools' histories, as much of…

Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, More than 8 Hours, 25 Foot Stack Height

EPA Pesticide Factsheets

This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks , 8 Hours or Less, 5 Foot Stack Height

EPA Pesticide Factsheets

This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, More than 8 Hours, 5 Foot Stack Height

EPA Pesticide Factsheets

This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, 8 Hours or Less, 10 Foot Stack Height

EPA Pesticide Factsheets

This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, 8 Hours or Less, 50 Foot Stack Height

EPA Pesticide Factsheets

This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, 8 Hours or Less, 25 Foot Stack Height

EPA Pesticide Factsheets

This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, More than 8 Hours, 50 Foot Stack Height

EPA Pesticide Factsheets

This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, More than 8 Hours, 10 Foot Stack Height

EPA Pesticide Factsheets

This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

New modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking

PubMed Central

Takatoh, Jun; Nelson, Anders; Zhou, Xiang; Bolton, M. McLean; Ehlers, Michael D.; Arenkiel, Benjamin R.; Mooney, Richard; Wang, Fan

2012-01-01

SUMMARY Rodents begin to use bilaterally coordinated, rhythmic sweeping of their vibrissae (“whisking”) for environmental exploration around two weeks after birth. Whether and how vibrissal control circuitry changes after birth is unknown, and relevant premotor circuitry remains poorly characterized. Using a modified rabies virus transsynaptic tracing strategy, we labeled neurons synapsing directly onto vibrissa facial motor neurons (vFMNs). Sources of potential excitatory, inhibitory, and modulatory vFMN premotor neurons, and differences between the premotor circuitry for vFMNs innervating intrinsic versus extrinsic vibrissal muscles, were systematically characterized. The emergence of whisking is accompanied by the addition of “new” sets of bilateral excitatory inputs to vFMNs from neurons in the lateral paragigantocellularis (LPGi). Furthermore, descending axons from the motor cortex directly innervate LPGi premotor neurons. Thus, neural modules well suited to facilitate the bilateral coordination and cortical control of whisking are added to premotor circuitry in parallel with the emergence of this exploratory behavior. PMID:23352170

Long-term use of a new topical formulation containing piroxicam 0.8% and sunscreen: efficacy and tolerability on actinic keratosis. A proof of concept study.

PubMed

Babino, Graziella; Diluvio, Laura; Bianchi, Luca; Orlandi, Augusto; Di Prete, Monia; Chimenti, Sergio; Milani, Massimo; Campione, Elena

2016-08-01

Cyclooxygenase (COX) 1 and 2 enzyme up-regulation is involved in the pathogenetic process of actinic keratosis (A.K.) and non-melanoma skin cancers. Diclofenac, a non-steroidal anti-inflammatory (N.S.A.I.D.) drug, is used as topical treatment of A.K. Piroxicam is a N.S.A.I.D. characterized by a high COX-1 inhibition activity. We conducted an 18 month exploratory open-label study on A.K., to assess the efficacy and tolerability of a new topical formulation of piroxicam and sunscreen in A.K. Enrolled subjects applied a galenic formulation of piroxicam 0.8%, vehiculated in a topical product containing sun filters with high (50+) and broad spectrum (UVA) actions, twice a day for 6 months. Subjects were then followed up for additional 12 months. Thirty-eight subjects with a total of 69 A.K. lesions participated in the trial. The primary outcome was the evolution of the Actinic Keratosis Erythema Scale Atrophy (A.K.E.S.A) score assessing erythema, scale, and atrophy of a target A.K. lesion. Secondary outcomes were the percentage of treated lesions with complete (100%) or partial (≥75%) clearance and the evaluation skin tolerability. A.K.E.S.A. mean (S.D.) score at baseline was 7.5 (1.2). After 6 months of treatment, A.K.E.S.A. score decreased to 0.9 (1.1), a -88% reduction versus baseline. At the end of follow-up, A.K.E.S.A. score was 0.8 (1.2). A complete response was achieved in 38 of the 69 lesions (55%, 95% C.I.: 43% to 66%) and clearance was maintained 1 year post-treatment. A partial clearance was observed in 57 of 69 treated lesions (83%, 95% C.I.: 73% to 91%). Adverse events were limited to mild local irritation. Our experience suggests that 6 month topical piroxicam 0.8% is efficacious and well tolerated in A.K. Clinical efficacy is maintained 1 year post-treatment. The main limitation of our study is that it was an open label non-controlled trial. Future controlled trials are warranted in order to compare the efficacy and tolerability of this topical piroxicam preparation with standard treatments in the management of A.K.

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

PubMed

Zdenkowski, N; Forbes, J F; Boyle, F M; Kannourakis, G; Gill, P G; Bayliss, E; Saunders, C; Della-Fiorentina, S; Kling, N; Campbell, I; Mann, G B; Coates, A S; Gebski, V; Davies, L; Thornton, R; Reaby, L; Cuzick, J; Green, M

2016-05-01

Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Dosing Strategies for Lithium Monotherapy in Children and Adolescents with Bipolar I Disorder

PubMed Central

Kafantaris, Vivian; Pavuluri, Mani; McNamara, Nora K.; McClellan, Jon; Frazier, Jean A.; Sikich, Linmarie; Kowatch, Robert; Lingler, Jacqui; Faber, Jon; Rowles, Brieana M.; Clemons, Traci E.; Taylor-Zapata, Perdita

2011-01-01

Abstract Objective The primary goal of this exploratory study was to obtain data that could lead to evidence-based dosing strategies for lithium in children and adolescents suffering from bipolar I disorder. Methods Outpatients aged 7–17 years meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition, diagnostic criteria for bipolar I disorder (manic or mixed) were eligible for 8 weeks of open label treatment with lithium in one of three dosing arms. In Arm I, participants began treatment at a dose of 300 mg of lithium twice daily. The starting dose of lithium in Arms II and III was 300 mg thrice daily. Patients in Arms I and II could have their dose increased by 300 mg/day, depending on clinical response, at weekly visits. Patients in Arm III also had mid-week telephone interviews after which they could also have their dose of lithium increased by 300 mg per day. Youths weighing <30 kg were automatically assigned to Arm I, whereas youths weighing ≥30 kg were randomly assigned to Arm I, II, or III. Randomization was balanced by age (7–11 years, 12–17 years) and sex in approximately equal numbers. A priori response criteria were defined as a Clinical Global Impressions-Improvement scale score of ≤2 and a 50% decrease from baseline on the Young Mania Rating Scale. Results Of the 61 youths [32 males (52.5%)] who received open-label lithium, 60 youths completed at least 1 week of treatment and returned for a postbaseline assessment. Most patients had a ≥50% improvement in Young Mania Rating Scale score, and more than half of the patients (58%) achieved response. Overall, lithium was well tolerated. All three treatment arms had similar effectiveness, side effect profiles, and tolerability of lithium. Conclusions On the basis of these results, a dosing strategy in which pediatric patients begin lithium at a dose of 300 mg thrice daily (with an additional 300 mg increase during the first week), followed by 300 mg weekly increases until a priori stopping criteria are met, will be used in an upcoming randomized, placebo-controlled trial. PMID:21663422

Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial.

PubMed

Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Jansa, Pavel; Kim, Nick H; Mayer, Eckhard; Pulido, Tomas; Wang, Chen; Colorado, Pablo; Fritsch, Arno; Meier, Christian; Nikkho, Sylvia; Hoeper, Marius M

2016-05-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years. Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429. 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events. Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers. Bayer Pharma AG. Copyright © 2016 Elsevier Ltd. All rights reserved.

A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

PubMed Central

2010-01-01

Background Oxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial. Methods The study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function. Results A significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression. Conclusion This study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT). Trial Registration Australian and New Zealand Clinical Trials Register: ACTRN12605000258651 PMID:20433711

Developing a framework of service convenience in health care: An exploratory study for a primary care provider.

PubMed

Tuzovic, Sven; Kuppelwieser, Volker

2016-01-01

From retail health clinics and online appointment scheduling to (mobile) kiosks that enable patient check-in and automate the collection of copays and open balances, convenience has become an important topic in the health care sector over the last few years. While service convenience has also gained much interest in academia, one common limitation is that authors have adopted a "goods-centered" perspective focusing primarily on retail settings. Results of this exploratory study reveal that health care service convenience encompasses seven different dimensions: decision, access, scheduling, registration and check-in, transaction, care delivery, and postconsultation convenience. Implications and future research suggestions are discussed.

Mesenchymal stem cells restore orientation and exploratory behavior of rats after brain injury.

PubMed

Sokolova, I B; Fedotova, O R; Tsikunov, S G; Polyntsev, D G

2011-05-01

We studied the effects of intravenous and intracerebral transplantation of MSC on restoration of orientation and exploratory behavior of Wistar-Kyoto rats after removal of the left motor cortex. Removal of the motor cortex led to a significant reduction of the number of behavioral acts in the open field test. Two weeks after removal of the motor cortex and intravenous transplantation, the animals were as inhibited as the controls, but during the next 10 weeks, the behavioral status of these rats remained unchanged, while controls exhibited further behavioral degradation. After injection of MSC into the brain, the behavior of rats with trauma did not change in comparison with intact rats over 10 weeks.

Characterization of the rat exploratory behavior in the elevated plus-maze with Markov chains.

PubMed

Tejada, Julián; Bosco, Geraldine G; Morato, Silvio; Roque, Antonio C

2010-11-30

The elevated plus-maze is an animal model of anxiety used to study the effect of different drugs on the behavior of the animal. It consists of a plus-shaped maze with two open and two closed arms elevated 50cm from the floor. The standard measures used to characterize exploratory behavior in the elevated plus-maze are the time spent and the number of entries in the open arms. In this work, we use Markov chains to characterize the exploratory behavior of the rat in the elevated plus-maze under three different conditions: normal and under the effects of anxiogenic and anxiolytic drugs. The spatial structure of the elevated plus-maze is divided into squares, which are associated with states of a Markov chain. By counting the frequencies of transitions between states during 5-min sessions in the elevated plus-maze, we constructed stochastic matrices for the three conditions studied. The stochastic matrices show specific patterns, which correspond to the observed behaviors of the rat under the three different conditions. For the control group, the stochastic matrix shows a clear preference for places in the closed arms. This preference is enhanced for the anxiogenic group. For the anxiolytic group, the stochastic matrix shows a pattern similar to a random walk. Our results suggest that Markov chains can be used together with the standard measures to characterize the rat behavior in the elevated plus-maze. Copyright © 2010 Elsevier B.V. All rights reserved.

The Ontogeny of Exploratory Behavior in Male and Female Adolescent Rats (Rattus norvegicus)

PubMed Central

Lynn, Debra A; Brown, Gillian R

2009-01-01

During adolescence, rats gain independence from their mothers and disperse from the natal burrow, with males typically dispersing further than females. We predicted that, if dispersal patterns are associated with responsiveness to novelty, exploratory behavior in novel environments would increase across adolescence, and males would explore more than females. Alternatively, females might explore more than males, if females are more motivated than males to learn about the immediate environment or if females have poorer spatial abilities than males. Twenty-five male and 21 female rats were exposed to two novel environments (open field and elevated plus-maze) during early, mid-, or late adolescence. Total locomotion and amount of exploration directed towards aversive areas increased across adolescence, even when body weight was included as a covariate. Female adolescents locomoted more and spent more time exploring aversive areas than males. Developmental changes in neural function potentially underlie age and sex differences in exploratory behavior. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 513–520, 2009. PMID:19582791

The ontogeny of exploratory behavior in male and female adolescent rats (Rattus norvegicus).

PubMed

Lynn, Debra A; Brown, Gillian R

2009-09-01

During adolescence, rats gain independence from their mothers and disperse from the natal burrow, with males typically dispersing further than females. We predicted that, if dispersal patterns are associated with responsiveness to novelty, exploratory behavior in novel environments would increase across adolescence, and males would explore more than females. Alternatively, females might explore more than males, if females are more motivated than males to learn about the immediate environment or if females have poorer spatial abilities than males. Twenty-five male and 21 female rats were exposed to two novel environments (open field and elevated plus-maze) during early, mid-, or late adolescence. Total locomotion and amount of exploration directed towards aversive areas increased across adolescence, even when body weight was included as a covariate. Female adolescents locomoted more and spent more time exploring aversive areas than males. Developmental changes in neural function potentially underlie age and sex differences in exploratory behavior. (c) 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 513-520, 2009.

Software LS-MIDA for efficient mass isotopomer distribution analysis in metabolic modelling.

PubMed

Ahmed, Zeeshan; Zeeshan, Saman; Huber, Claudia; Hensel, Michael; Schomburg, Dietmar; Münch, Richard; Eisenreich, Wolfgang; Dandekar, Thomas

2013-07-09

The knowledge of metabolic pathways and fluxes is important to understand the adaptation of organisms to their biotic and abiotic environment. The specific distribution of stable isotope labelled precursors into metabolic products can be taken as fingerprints of the metabolic events and dynamics through the metabolic networks. An open-source software is required that easily and rapidly calculates from mass spectra of labelled metabolites, derivatives and their fragments global isotope excess and isotopomer distribution. The open-source software "Least Square Mass Isotopomer Analyzer" (LS-MIDA) is presented that processes experimental mass spectrometry (MS) data on the basis of metabolite information such as the number of atoms in the compound, mass to charge ratio (m/e or m/z) values of the compounds and fragments under study, and the experimental relative MS intensities reflecting the enrichments of isotopomers in 13C- or 15 N-labelled compounds, in comparison to the natural abundances in the unlabelled molecules. The software uses Brauman's least square method of linear regression. As a result, global isotope enrichments of the metabolite or fragment under study and the molar abundances of each isotopomer are obtained and displayed. The new software provides an open-source platform that easily and rapidly converts experimental MS patterns of labelled metabolites into isotopomer enrichments that are the basis for subsequent observation-driven analysis of pathways and fluxes, as well as for model-driven metabolic flux calculations.

Improving Alcohol Screening for College Students: Screening for Alcohol Misuse amongst College Students with a Simple Modification to the CAGE Questionnaire

ERIC Educational Resources Information Center

Taylor, Purcell; El-Sabawi, Taleed; Cangin, Causenge

2016-01-01

Objective: To improve the CAGE (Cut down, Annoyed, Guilty, Eye opener) questionnaire's predictive accuracy in screening college students. Participants: The sample consisted of 219 midwestern university students who self-administered a confidential survey. Methods: Exploratory factor analysis, confirmatory factor analysis, receiver operating…

SOCR "Motion Charts": An Efficient, Open-Source, Interactive and Dynamic Applet for Visualizing Longitudinal Multivariate Data

ERIC Educational Resources Information Center

Al-Aziz, Jameel; Christou, Nicolas; Dinov, Ivo D.

2010-01-01

The amount, complexity and provenance of data have dramatically increased in the past five years. Visualization of observed and simulated data is a critical component of any social, environmental, biomedical or scientific quest. Dynamic, exploratory and interactive visualization of multivariate data, without preprocessing by dimensionality…

Principals' Perception and Self-Efficacy: Addressing Achievement in a Post Annual Yearly Progress Environment

ERIC Educational Resources Information Center

Staumont, John

2017-01-01

Purpose: The purpose of this single-case study was to explore principals' perceptions of self-efficacy beliefs as effective instructional leaders during a period of educational transition in a semiurban, unified school district in Southern California. Methodology: The researcher used exploratory case study, conducting semistructured, open-ended,…

Teachers' and School Leaders' Perceptions of Commercialisation in Australian Public Schools

ERIC Educational Resources Information Center

Hogan, Anna; Thompson, Greg; Sellar, Sam; Lingard, Bob

2018-01-01

This paper explores teachers' and school leaders' perceptions of commercialisation in Australian public schools, reporting on findings from an open-ended survey question from an exploratory study that sought to investigate teacher and school leader perceptions and experiences of commercialisation. Commercialisation, for the purposes of this paper,…

The Content of Beginning Special Educators' Conversations with Their Electronic Mentors

ERIC Educational Resources Information Center

Gentry, Roberta

2016-01-01

This exploratory study examined the frequency and content of text-based interactions between special education mentors (n = 22) and mentees (n = 50) within the Electronic Mentoring for Student Success Program (eMSS). Perceived outcomes of participants, based on an open ended survey question, were also analyzed. The Interstate Teacher Assessment…

Purposes and Effects of Lying.

ERIC Educational Resources Information Center

Hample, Dale

Three exploratory studies were aimed at describing the purposes of lies and the consequences of lying. Data were collected through a partly open-ended questionnaire, a content analysis of several tape-recorded interviews, and a large-scale survey. The results showed that two of every three lies were told for selfish reasons, while three of every…

Attitudes of Jordanian Society toward Wife Abuse

ERIC Educational Resources Information Center

Btoush, Rula; Haj-Yahia, Muhammad M.

2008-01-01

The authors conducted an exploratory study among a convenience sample of 260 Jordanian men and women, using self-administered open and closed questions to examine the participants' approach toward wife abuse. In general, there was high awareness of wife abuse and the different types of abuse (mainly physical and psychological), a general tendency…

Teachers' Use of YouTube in the United Arab Emirates: An Exploratory Study

ERIC Educational Resources Information Center

Tamim, Rana M.

2013-01-01

Teachers around the world are using YouTube movies for different purposes. This mixed-methods study was a preliminary investigation of United Arab Emirates teachers' perceptions about YouTube's advantages in the classroom, current practices, and major challenges faced. Forty-five teachers completed an open-ended questionnaire. Results indicated…

Learner-Controlled Scaffolding Linked to Open-Ended Problems in a Digital Learning Environment

ERIC Educational Resources Information Center

Edson, Alden Jack

2017-01-01

This exploratory study reports on how students activated learner-controlled scaffolding and navigated through sequences of connected problems in a digital learning environment. A design experiment was completed to (re)design, iteratively develop, test, and evaluate a digital version of an instructional unit focusing on binomial distributions and…

Using Web 2.0 to Design Meaningful Language Learning Environments

ERIC Educational Resources Information Center

Feng, Jiuguang; Wang, Wei

2012-01-01

This article reports on an exploratory study that examines how social networks can be used in foreign language teaching and learning. Qualitative data including interviews, online observations, and students' responses to open-ended survey questions was collected. The data suggests that there are both advantages and challenges associated with using…

Seizing Teachable Moments to Develop Integrative Middle Level Curriculum

ERIC Educational Resources Information Center

Virtue, David C.

2007-01-01

September 11, 2001, was a critical teachable moment that provided the author of this article and his team with an avenue to middle level curriculum that was relevant, challenging, integrative, and exploratory. Hurricane Katrina opened a similar window of opportunity for middle level educators to focus the minds of young adolescents on important…

EFL Writing Revision with Blind Expert and Peer Review Using a CMC Open Forum

ERIC Educational Resources Information Center

Wu, Wen-Chi Vivian; Petit, Emily; Chen, Ching-Huei

2015-01-01

This exploratory computer assisted-language learning (CALL) study used a computer-mediated communication (CMC) interface to allow English as a foreign language (EFL) writing students in classes at two universities to give each other anonymous peer feedback about essay-writing assignments reacting to selected news stories. Experts also provided…

Curriculum-Guided Crowd Sourcing of Assessments in a Developing Country

ERIC Educational Resources Information Center

Zualkernan, Imran A.; Raza, Anjana; Karim, Asad

2012-01-01

Success of Wikipedia has opened a number of possibilities for crowd sourcing learning resources. However, not all crowd sourcing initiatives are successful. For developing countries, adoption factors like lack of infrastructure and poor teacher training can have an impact on success of such systems. This paper presents an exploratory study to…

Using Spreadsheets to Discover Meaning for Parameters in Nonlinear Models

ERIC Educational Resources Information Center

Green, Kris H.

2008-01-01

This paper explores the use of spreadsheets to develop an exploratory environment where mathematics students can develop their own understanding of the parameters of commonly encountered families of functions: linear, logarithmic, exponential and power. The key to this understanding involves opening up the definition of rate of change from the…

Environmental Factors of Distance Learning: An Exploratory Study

ERIC Educational Resources Information Center

Klaus, Tim; Changchit, Chuleeporn

2014-01-01

The widespread use of the Internet has opened new avenues for learning in higher education. Distance education through the Internet has had a large increase over the last decade. This study focuses on examining factors of the online course environment that affect student satisfaction. The results identify factors that affect students' satisfaction…

Opening "The Door": An Evaluation of the Efficacy of a Problem-Based Learning Game

ERIC Educational Resources Information Center

Warren, Scott J.; Dondlinger, Mary Jo; McLeod, Julie; Bigenho, Chris

2012-01-01

As higher education institutions seek to improve undergraduate education, initiatives are underway to target instructional methods, re-examine curricula, and apply innovative technologies to better engage students with content. This article discusses the findings of an exploratory study focused on a course redesign that game elements, PBL methods,…

An Exploratory Study of Best Lean Sustainability Practices in Higher Education

ERIC Educational Resources Information Center

Comm, Clare L.; Mathaisel, Dennis F. X.

2005-01-01

Purpose: Because of the ever-expanding commercialization and marketing of higher education, a need now exists to apply the concepts of business process improvement to colleges and universities. Aims to explore this issue. Design/methodology/approach: An open-ended qualitative questionnaire was developed, administered to 18 public and private…

Placebo Effects and the Common Cold: A Randomized Controlled Trial

PubMed Central

Barrett, Bruce; Brown, Roger; Rakel, Dave; Rabago, David; Marchand, Lucille; Scheder, Jo; Mundt, Marlon; Thomas, Gay; Barlow, Shari

2011-01-01

PURPOSE We wanted to determine whether the severity and duration of illness caused by the common cold are influenced by randomized assignment to open-label pills, compared with conventional double-blind allocation to active and placebo pills, compared with no pills at all. METHODS We undertook a randomized controlled trial among a population with new-onset common cold. Study participants were allocated to 4 parallel groups: (1) those receiving no pills, (2) those blinded to placebo, (3) those blinded to echinacea, and (4) those given open-label echinacea. Primary outcomes were illness duration and area-under-the-curve global severity. Secondary outcomes included neutrophil count and interleukin 8 levels from nasal wash at intake and 2 days later. RESULTS Of 719 randomized study participants, 2 were lost and 4 exited early. Participants were 64% female, 88% white, and aged 12 to 80 years. Mean illness duration for each group was 7.03 days for those in the no-pill group, 6.87 days for those blinded to placebo, 6.34 days for those blinded to echinacea, and 6.76 days for those in the open-label echinacea group. Mean global severity scores for the 4 groups were no pills, 286; blinded to placebo, 264; blinded to echinacea, 236; and open-label echinacea, 258. Between-group differences were not statistically significant. Comparing the no-pill with blinded to placebo groups, differences (95% confidence interval [CI]) were −0.16 days (95% CI, −0.90 to 0.58 days) for illness duration and −22 severity points (95% CI, −70 to 26 points) for global severity. Comparing the group blinded to echinacea with the open-label echinacea group, differences were 0.42 days (95% CI, −0.28 to 1.12 days) and 22 severity points (95% CI, −19 to 63 points). Median change in interleukin 8 concentration and neutrophil cell count, respectively by group, were 30 pg/mL and 1 cell for the no-pill group, 39 pg/mL and 1 cell for the group binded to placebo, 58 pg/mL and 2 cells for the group blinded to echinacea, and 70 pg/mL and 1 cell for the group with open-label echinacea, also not statistically significant. Among the 120 participants who at intake rated echinacea’s effectiveness as greater than 50 on a 100-point scale for which 100 is extremely effective, illness duration was 2.58 days shorter (95% CI, −4.47 to −0.68 days) in those blinded to placebo rather than no pill, and mean global severity score was 26% lower but not significantly different (−97.0, 95% CI, −249.8 to 55.8 points). In this subgroup, neither duration nor severity differed significantly between the group blinded to echinacea and the open-label echinacea group. CONCLUSIONS Participants randomized to the no-pill group tended to have longer and more severe illnesses than those who received pills. For the subgroup who believed in echinacea and received pills, illnesses were substantively shorter and less severe, regardless of whether the pills contained echinacea. These findings support the general idea that beliefs and feelings about treatments may be important and perhaps should be taken into consideration when making medical decisions. PMID:21747102

Effects of the aqueous extract of Pimpinella anisum L. seeds on exploratory activity and emotional behavior in rats using the open field and elevated plus maze tests.

PubMed

Gamberini, Maria Thereza; Rodrigues, Domingos Sávio; Rodrigues, Daniela; Pontes, Victoria Bottino

2015-06-20

Pimpinella anisum L. is considered one of the first plants used for medicinal purposes. Pharmacological actions of the plant on the central nervous system have been proven but previous analyses have focused on anticonvulsant and neuroprotective actions. In traditional medicine worldwide, the use of Pimpinella is commonly recommended as a tranquilizer, although no scientific information supporting this use is available. Therefore, it was decided to investigate the central actions of the plant to observe behavioral responses, with an emphasis on the emotional component. To investigate the effects of the aqueous extract of Pimpinella seeds on exploratory activity and emotional behavior in rats using the open field and elevated plus maze tests. Seeds of Pimpinella were extracted with distilled water, concentrated and freeze-dried yielding the aqueous extract(AE). Rats were divided into four groups: control(water 5 mL/kg, p.o.) and AE 0.5, 1.0 and 2.0 g/kg, p.o. Individual observations were performed in an open field and the parameters locomotor activity, rearing, grooming and defecation were recorded. In elevated plus maze test, rats were divided into four groups: control(water 5 mL/kg, p.o.) and AE 0.5, 1.0 and 2.0 g/kg, p.o. The parameters arm entries, total time spent in open and closed arms; and total number of arrivals at the end of an open or closed arm were recorded for each rat. Among the parameters assessed with the open field test, only rearing was reduced in the AE 0.5 g/kg group. When AE 1.0 g/kg was administered, only the initiation of exploratory activity was delayed, without impairing the animals' general activity. The highest dose of AE (2.0 g/kg) induced a reduction in the animals' habituation during the open field test within the same session, as evidenced by the maintenance of high levels of peripheral locomotion and rearing throughout the test. On the elevated plus maze test, no alterations were observed in the responses of the animals relative to controls for all doses tested. These results failed to support anxiety-related central action of the aqueous extract of Pimpinella seeds, invalidating popular beliefs regarding a tranquilizing effect. However, a habituation-related central action of the extract was demonstrated, suggesting action of bioactive compounds on central learning-related areas. The characterization of effects that may interfere with cognitive processes reinforces caution regarding indiscriminate consumption of the plant, especially in individuals with deficits, such as Alzheimer's Disease patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Effects of Verbal Labels and Vocabulary Skill on Memory and Suggestibility

ERIC Educational Resources Information Center

Kulkofsky, Sarah

2010-01-01

The current study investigated the effectiveness of the verbal labels procedure (D. A. Brown & M. E. Pipe, 2003) to improve preschool children's responses to direct open-ended and misleading questions. Additionally, children's vocabulary skill was considered. Eighty-seven preschool children from diverse backgrounds were interviewed about a unique…

Ethnic Identity and Academic Achievement among Latino/a Adolescents

ERIC Educational Resources Information Center

Estela Zarate, Maria; Bhimji, Fazila; Reese, Leslie

2005-01-01

This study examines Latino/a adolescents' ethnic identities and academic achievement. In open-ended interviews, the high school aged youth employed cultural and nationality explanations for their ethnic label choices. In many cases, they did not commit to a specific label, employing instead language that indexed their fluid, border identities.…

Shelf Life of Food Products: From Open Labeling to Real-Time Measurements.

PubMed

Corradini, Maria G

2018-03-25

The labels currently used on food and beverage products only provide consumers with a rough guide to their expected shelf lives because they assume that a product only experiences a limited range of predefined handling and storage conditions. These static labels do not take into consideration conditions that might shorten a product's shelf life (such as temperature abuse), which can lead to problems associated with food safety and waste. Advances in shelf-life estimation have the potential to improve the safety, reliability, and sustainability of the food supply. Selection of appropriate kinetic models and data-analysis techniques is essential to predict shelf life, to account for variability in environmental conditions, and to allow real-time monitoring. Novel analytical tools to determine safety and quality attributes in situ coupled with modern tracking technologies and appropriate predictive tools have the potential to provide accurate estimations of the remaining shelf life of a food product in real time. This review summarizes the necessary steps to attain a transition from open labeling to real-time shelf-life measurements.

Safety and Durability of Effect with Long-Term, Open-Label Droxidopa Treatment in Patients with Symptomatic Neurogenic Orthostatic Hypotension (NOH303).

PubMed

Isaacson, Stuart; Shill, Holly A; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J

2016-10-19

Neurogenic orthostatic hypotension (nOH) is associated with insufficient norepinephrine release in response to postural change. The objective of this study was to evaluate the long-term safety and durability of efficacy of the norepinephrine precursor droxidopa in patients with symptomatic nOH. This multinational study consisted of 3 sequential phases: a 3-month open-label droxidopa treatment phase followed by a 2-week double-blind, placebo-controlled withdrawal phase, and a 9-month open-label extension phase in which all patients received droxidopa. Patients were adults diagnosed with symptomatic nOH associated with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Efficacy was evaluated using patient- and investigator-reported questionnaire responses and the orthostatic standing test. Safety was assessed through adverse event (AE) reports and vital signs. A total of 102 patients received treatment with droxidopa. Initial improvements from baseline in patient-reported nOH symptom severity and impact on daily activities, evaluated using the Orthostatic Hypotension Questionnaire, exceeded 50% and were maintained throughout the 12-month study. Decreased nOH severity was also reflected in clinician and patient ratings on the Clinical Global Impression questionnaire. Standing systolic and diastolic blood pressures were increased from baseline throughout the study with droxidopa treatment. The most frequently reported AEs were falls, urinary tract infection, and headache. There was a low incidence (≤2%) of cardiac AEs (eg, first-degree atrioventricular block, supraventricular extrasystoles). Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in nOH signs and symptoms.

An open-label, 12-week clinical and sleep EEG study of nefazodone in chronic combat-related posttraumatic stress disorder.

PubMed

Gillin, J C; Smith-Vaniz, A; Schnierow, B; Rapaport, M H; Kelsoe, J; Raimo, E; Marler, M R; Goyette, L M; Stein, M B; Zisook, S

2001-10-01

We examined the effects of nefazodone on polysomnographic sleep measures and subjective reports of sleep quality and nightmares. as well as other symptoms, in patients with chronic combat-related posttraumatic stress disorder (PTSD) during a 12-week, open-label clinical trial. To our knowledge, this is the first polysomnographic study of treatment in patients with PTSD. The subjects were 12 male veterans (mean age = 54 years) who met DSM-IV diagnostic criteria for PTSD (mean duration = 30 years). All but I patient also met DSM-IV criteria for major depressive disorder. Patients were evaluated weekly with clinical ratings in an open-label clinical trial. Polysomnographic recordings for 2 consecutive nights were obtained before treatment and at 2, 4, 8, and 12 weeks. The dose of nefazodone was adjusted according to individual clinical needs. Final mean daily dose was 441 mg. The patients reported significantly fewer nightmares and sleep problems during treatment. Nevertheless, contrary to studies in depressed patients, nefazodone did not significantly affect polysomnographic sleep measures compared with baseline. In addition, the patients showed significant improvement in the Clinical Global Impressions of PTSD symptoms (global score, hyperarousals and intrusions subscales), the Clinician-Administered PTSD Scale (global, hyperarousal, and intrusions subscales), the Hamilton Rating Scale for Depression (HAM-D). and the Beck Depression Inventory (BDI). These patients with chronic, treatment-resistant, combat-related PTSD showed significant improvement of subjective symptoms of nightmares and sleep disturbance, as well as depression and PTSD symptoms. in this 12-week open-label clinical trial. Nevertheless, objective polysomnographic sleep measures did not change. Further studies, including double-blind. placebo-controlled trials, are needed to extend these findings and to understand the relationships between the physiology of sleep and symptoms of poor sleep and nightmares.

Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay

PubMed Central

2013-01-01

Background Uncoating of the HIV-1 core plays a critical role during early post-fusion stages of infection but is poorly understood. Microscopy-based assays are unable to easily distinguish between intact and partially uncoated viral cores. Results In this study, we used 5-ethynyl uridine (EU) to label viral-associated RNA during HIV production. At early time points after infection with EU-labeled virions, the viral-associated RNA was stained with an EU-specific dye and was detected by confocal microscopy together with viral proteins. We observed that detection of the viral-associated RNA was specific for EU-labeled virions, was detected only after viral fusion with target cells, and occurred after an initial opening of the core. In vitro staining of cores showed that the opening of the core allowed the small molecule dye, but not RNase A or antibodies, inside. Also, staining of the viral-associated RNA, which is co-localized with nucleocapsid, decays over time after viral infection. The decay rate of RNA staining is dependent on capsid (CA) stability, which was altered by CA mutations or a small molecule inducer of HIV-1 uncoating. While the staining of EU-labeled RNA was not affected by inhibition of reverse transcription, the kinetics of core opening of different CA mutants correlated with initiation of reverse transcription. Analysis of the E45A CA mutant suggests that initial core opening is independent of complete capsid disassembly. Conclusions Taken together, our results establish a novel RNA accessibility-based assay that detects an early event in HIV-1 uncoating and can be used to further define this process. PMID:23835323

Prominin-1 Localizes to the Open Rims of Outer Segment Lamellae in Xenopus laevis Rod and Cone Photoreceptors

PubMed Central

Han, Zhou; Anderson, David W.

2012-01-01

Purpose. Prominin-1 expresses in rod and cone photoreceptors. Mutations in the prominin-1 gene cause retinal degeneration in humans. In this study, the authors investigated the expression and subcellular localization of xlProminin-1 protein, the Xenopus laevis ortholog of prominin-1, in rod and cone photoreceptors of this frog. Methods. Antibodies specific for xlProminin-1 were generated. Immunoblotting was used to study the expression and posttranslational processing of xlProminin-1 protein. Immunocytochemical light and electron microscopy and transgenesis were used to study the subcellular distribution of xlProminin-1. Results. xlProminin-1 is expressed and is subject to posttranslational proteolytic processing in the retina, brain, and kidney. xlProminin-1 is differently expressed and localized in outer segments of rod and cone photoreceptors of X. laevis. Antibodies specific for the N or C termini of xlProminin-1 labeled the open rims of lamellae of cone outer segments (COS) and the open lamellae at the base of rod outer segments (ROS). By contrast, anti–peripherin-2/rds antibody, Xper5A11, labeled the closed rims of cone lamellae adjacent to the ciliary axoneme and the rims of the closed ROS disks. The extent of labeling of the basal ROS by anti–xlProminin-1 antibodies varied with the light cycle in this frog. The entire ROS was also faintly labeled by both antibodies, a result that contrasts with the current notion that prominin-1 localizes only to the basal ROS. Conclusions. These findings suggest that xlProminin-1 may serve as an anti–fusogenic factor in the regulation of disk morphogenesis and may help to maintain the open lamellar structure of basal ROS and COS disks in X. laevis photoreceptors. PMID:22076989

Open-label, 9-month extension study investigating the uro-selective alpha-blocker silodosin in men with LUTS associated with BPH.

PubMed

Osman, Nadir I; Chapple, Christopher R; Tammela, Teuvo L; Eisenhardt, Andreas; Oelke, Matthias

2015-05-01

To evaluate the long-term safety (primary objective) and efficacy/impact on quality of life (QoL, secondary objectives) of silodosin 8 mg once daily in men with LUTS/BPH. Men who completed the 12-week double-blind study with silodosin 8 mg, tamsulosin 0.4 mg, or placebo were offered to continue with the 9-month open-label study during which all patients received silodosin 8 mg once daily. Safety was assessed by analysing vital signs, electrocardiograms, laboratory tests, and adverse events. Efficacy was evaluated with the International Prostate Symptom Score (IPSS), IPSS voiding and storage sub-scores, IPSS-QoL, and maximum urinary flow rate (Q max). A total of 500 patients (mean age 66 years) entered the 9-month open-label study. Treatment-emergent adverse events (TEAE) were experienced by 33.4% patients. Ejaculation dysfunction was the most common TEAE (9.0%) but led to study discontinuations in only 1.6% of patients. Dizziness without orthostatic hypotension occurred in 0.8%. A marked reduction in total IPSS (-2.7 ± 3.8) was documented at the first visit of this extension phase in patients having de novo silodosin compared with lesser improvement in patients previously treated with silodosin (-0.82 ± 4.2) or tamsulosin (-0.83 ± 3.8). Improvements were maintained throughout the open-label phase. QoL also improved, with the greatest improvement in de novo silodosin patients. No relevant changes in Q max occurred. Long-term treatment with silodosin was safe and efficacious. Abnormal ejaculation was the most common TEAE, but led to treatment discontinuation in only 1.6% of patients. Orthostatic hypotension was not seen, and only a few patients experienced dizziness.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis.

PubMed

Lichtenstein, Gary R; Travis, Simon; Danese, Silvio; D'Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J

2015-09-01

Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9 mg, 6 mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9 mg or placebo for 4 weeks, then open-label budesonide MMX 9 mg for 4 weeks]; and one open-label study [budesonide MMX 9 mg for 8 weeks] were pooled. Patients randomised to budesonide MMX 9 mg [n = 288], 6 mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9 mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Budesonide MMX 9 mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis

PubMed Central

Travis, Simon; Danese, Silvio; D’Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E. David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J.

2015-01-01

Background and aims: Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Methods: Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9mg, 6mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9mg or placebo for 4 weeks, then open-label budesonide MMX 9mg for 4 weeks]; and one open-label study [budesonide MMX 9mg for 8 weeks] were pooled. Results: Patients randomised to budesonide MMX 9mg [n = 288], 6mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Conclusions: Budesonide MMX 9mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. PMID:26094251

Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder.

PubMed

Wall, Christopher A; Croarkin, Paul E; Maroney-Smith, Mandie J; Haugen, Laura M; Baruth, Joshua M; Frye, Mark A; Sampson, Shirlene M; Port, John D

2016-09-01

Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression. Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6-8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods. Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment. Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study.

PubMed

Elmer, Lawrence W; Surmann, Erwin; Boroojerdi, Babak; Jankovic, Joseph

2012-06-01

This prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson's disease (PD). Patients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson's Disease Rating Scale (UPDRS) II+III total score. Of 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (≈ 5 years, 3 months; range 1-2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II+III total scores remained below double-blind baseline for up to 2 years of open-label treatment. This is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

[The influence of acute hypoxia on motility of rats in the open field test under the conditions of an altered photoperiod].

PubMed

Sopova, I Iu

2014-01-01

The influence of acute hypoxia on the motility of rats under the conditions of an altered photoperiod in the open field test was studied. Thus, keeping the animals in constant darkness after the modeling of acute hypoxia leads to the depression of locomotive and exploratory components of the behavior. At the same time the animals that were kept under the conditions of constant light show a change in the correlation between the components of motility after the action of hypoxia.

Exploratory behavior and recognition memory in medial septal electrolytic, neuro- and immunotoxic lesioned rats.

PubMed

Dashniani, M G; Burjanadze, M A; Naneishvili, T L; Chkhikvishvili, N C; Beselia, G V; Kruashvili, L B; Pochkhidze, N O; Chighladze, M R

2015-01-01

In the present study, the effect of the medial septal (MS) lesions on exploratory activity in the open field and the spatial and object recognition memory has been investigated. This experiment compares three types of MS lesions: electrolytic lesions that destroy cells and fibers of passage, neurotoxic - ibotenic acid lesions that spare fibers of passage but predominantly affect the septal noncholinergic neurons, and immunotoxin - 192 IgG-saporin infusions that only eliminate cholinergic neurons. The main results are: the MS electrolytic lesioned rats were impaired in habituating to the environment in the repeated spatial environment, but rats with immuno- or neurotoxic lesions of the MS did not differ from control ones; the MS electrolytic and ibotenic acid lesioned rats showed an increase in their exploratory activity to the objects and were impaired in habituating to the objects in the repeated spatial environment; rats with immunolesions of the MS did not differ from control rats; electrolytic lesions of the MS disrupt spatial recognition memory; rats with immuno- or neurotoxic lesions of the MS were normal in detecting spatial novelty; all of the MS-lesioned and control rats clearly reacted to the object novelty by exploring the new object more than familiar ones. Results observed across lesion techniques indicate that: (i) the deficits after nonselective damage of MS are limited to a subset of cognitive processes dependent on the hippocampus, (ii) MS is substantial for spatial, but not for object recognition memory - the object recognition memory can be supported outside the septohippocampal system; (iii) the selective loss of septohippocampal cholinergic or noncholinergic projections does not disrupt the function of the hippocampus to a sufficient extent to impair spatial recognition memory; (iv) there is dissociation between the two major components (cholinergic and noncholinergic) of the septohippocampal pathway in exploratory behavior assessed in the open field - the memory exhibited by decrements in exploration of repeated object presentations is affected by either electrolytic or ibotenic lesions, but not saporin.

pyQms enables universal and accurate quantification of mass spectrometry data.

PubMed

Leufken, Johannes; Niehues, Anna; Sarin, L Peter; Wessel, Florian; Hippler, Michael; Leidel, Sebastian A; Fufezan, Christian

2017-10-01

Quantitative mass spectrometry (MS) is a key technique in many research areas (1), including proteomics, metabolomics, glycomics, and lipidomics. Because all of the corresponding molecules can be described by chemical formulas, universal quantification tools are highly desirable. Here, we present pyQms, an open-source software for accurate quantification of all types of molecules measurable by MS. pyQms uses isotope pattern matching that offers an accurate quality assessment of all quantifications and the ability to directly incorporate mass spectrometer accuracy. pyQms is, due to its universal design, applicable to every research field, labeling strategy, and acquisition technique. This opens ultimate flexibility for researchers to design experiments employing innovative and hitherto unexplored labeling strategies. Importantly, pyQms performs very well to accurately quantify partially labeled proteomes in large scale and high throughput, the most challenging task for a quantification algorithm. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms.

PubMed

Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A

2016-04-14

Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with "open" digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions.

Recombinant human bone morphogenetic protein-2 use in the off-label treatment of nonunions and acute fractures: a retrospective review.

PubMed

Starman, James S; Bosse, Michael J; Cates, Casey A; Norton, H James

2012-03-01

Recombinant human bone morphogenetic protein-2 (BMP-2) is Food and Drug Administration-approved for use in acute open tibial shaft fractures. Some surgeons, however, also use BMP-2 in an "off-label" application for other acute fractures and for nonunion care. This retrospective study was performed to assess radiographic outcomes of off-label uses of BMP-2 for acute fractures and nonunions at our institution. All eligible off-label BMP-2 applications between 2004 and 2008 for acute fractures or nonunions were reviewed. Univariate and multivariate analyses were completed to identify patient and clinical factors that could predict radiographic success or failure of the procedure. One hundred sixteen of 145 BMP-2 applications in 104 of 128 patients met inclusion and exclusion criteria. The overall radiographic union rate was 66% (76 of 116). In the univariate analysis, five factors correlated with significantly higher union rate: volume of bone defect <4 cm3, >2 cortices in contact at the index procedure, male gender, body mass index <30, and history of closed fracture pattern. Within the multivariate analysis, factors independently predictive of radiographic union included open versus closed fracture, gender, and volume of bone defect. Off-label use of BMP-2 in acute fractures and nonunions resulted in a 66% success rate. It remains uncertain whether there is any clinical advantage to this approach, but it appears that female gender, open injury, and higher volumes of bone defect may be important negative prognostic factors for obtaining radiographic union. Appropriately powered prospective randomized trials are needed for further clarification, especially in light of the high cost of this treatment.

Determination of diffusivities in the Rustler Formation from exploratory-shaft construction at the Waste Isolation Pilot Plant in southeastern New Mexico

USGS Publications Warehouse

Stevens, Ken; Beyeler, Walt

1985-01-01

The construction of an exploratory shaft 12 feet in diameter into the Salado Formation (repository horizon for transuranic waste material) at the Waste Isolation Pilot Plant site in southeastern New Mexico affected water-levels in water-bearing zones above the repository horizon. By reading the construction history of the exploratory shaft, an approximation of construction-generated hydraulic stresses at the shaft was made. The magnitude of the construction-generated stresses was calibrated using the hydrographs from one hydrologic test pad. Whereas flow rates from the Magenta Dolomite and Culebra Dolomite Members in the Rustler Formation into the exploratory shaft were unknown, the ratio of transmissivity to storage (diffusivity) was determined by mathematically simulating the aquifers and the hydrologic stresses with flood-wave-response digital model. These results indicate that the Magenta Dolomite and Culebra Dolomite Members of the Rustler Formation can be modeled as homogeneous, isotropic, and confined water-bearing zones. One simple and consistent explanation, but by no means the only explanation, of the lack of a single diffusivity value in the Culebra aquifer is that the open-hole observation wells at the hydrologic test pads dampen the amplitude of water-level changes. (USGS)

Labelling and Marketing of Bivalve and Gastropod Molluscs Retailed in Sardinia, Italy Between 2009 and 2013.

PubMed

Meloni, Domenico

2015-05-28

The aim of the present survey was to investigate the correct enforcement of the Community rules on the labelling and marketing of bivalve and gastropod molluscs retailed in Sardinia, Italy between 2009 and 2013. A total of 1500 packages and labels for live bivalve and gastropod molluscs were considered. A total of 375 labels (25%) presented non-compliance concerning the wrong trade name and additional wrong or missing information. The highest percentage of anomalous labels has been detected in small-scale retail shops (35%) and open-air markets (25%) compared with the big retailing chains (20%). The 5% of packages were not in compliance with the European Community rules on packaging of bivalve and gastropod molluscs. The high percentage of non-compliance with the European regulations on labelling results is a strong limitation for the consumers and highlights the need to improve the control system about labelling of seafood products.

The interactive electrode localization utility: software for automatic sorting and labeling of intracranial subdural electrodes

PubMed Central

Tang, Wei; Peled, Noam; Vallejo, Deborah I.; Borzello, Mia; Dougherty, Darin D.; Eskandar, Emad N.; Widge, Alik S.; Cash, Sydney S.; Stufflebeam, Steven M.

2018-01-01

Purpose Existing methods for sorting, labeling, registering, and across-subject localization of electrodes in intracranial encephalography (iEEG) may involve laborious work requiring manual inspection of radiological images. Methods We describe a new open-source software package, the interactive electrode localization utility which presents a full pipeline for the registration, localization, and labeling of iEEG electrodes from CT and MR images. In addition, we describe a method to automatically sort and label electrodes from subdural grids of known geometry. Results We validated our software against manual inspection methods in twelve subjects undergoing iEEG for medically intractable epilepsy. Our algorithm for sorting and labeling performed correct identification on 96% of the electrodes. Conclusions The sorting and labeling methods we describe offer nearly perfect performance and the software package we have distributed may simplify the process of registering, sorting, labeling, and localizing subdural iEEG grid electrodes by manual inspection. PMID:27915398

The stress response and exploratory behaviour in Yucatan minipigs (Sus scrofa): Relations to sex and social rank.

PubMed

Adcock, Sarah J J; Martin, Gerard M; Walsh, Carolyn J

2015-12-01

According to the coping styles hypothesis, an individual demonstrates an integrated behavioural and physiological response to environmental challenge that is consistent over time and across situations. Individual consistency in behavioural responses to challenge has been documented across the animal kingdom. Comparatively few studies, however, have examined inter-individual variation in the physiological response, namely glucocorticoid and catecholamine levels, the stress hormones secreted by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, respectively. Variation in coping styles between individuals may be explained in part by differences in social rank and sex. Using 20 Yucatan minipigs (Sus scrofa) we: (1) investigated the existence of consistent inter-individual variation in exploratory behaviour and the hormonal stress response, and tested for correlations as predicted by the coping styles hypothesis; and (2) evaluated whether inter-individual behavioural and hormonal variation is related to social rank and sex. Salivary stress biomarkers (cortisol, alpha-amylase, chromogranin A) were assessed in the presence and absence of a stressor consisting of social isolation in a crate for 10 min. Principal components analysis on a set of behavioural variables revealed two traits, which we labelled exploratory tendency and neophobia. Neither exploratory tendency nor neophobia predicted the physiological stress response. Subordinate pigs exhibited higher catecholamine levels compared to dominant conspecifics. We observed sex differences in the repeatability of salivary stress markers and reactivity of the stress systems. The results do not provide support for the existence of behavioural-physiological coping styles in pigs. Sex is an important determinant of the physiological stress response and warrants consideration in research addressing behavioural and hormonal variation. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of conversion from calcineurin inhibitors to everolimus on hepatitis C viremia in adult kidney transplant recipients.

PubMed

Pacheco, Larissa Sgaria; Garcia, Valter Duro; Prá, Ronivan Luis Dal; Cardoso, Bruna Doleys; Rodrigues, Mariana Ferras; Zanetti, Helen Kris; Meinerz, Gisele; Neumann, Jorge; Gnatta, Diego; Keitel, Elizete

2018-05-14

Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors. Thirty patients were randomized and 28 were followed-up for 12 months (conversion group, Group 1 =15 and control group, Group 2 =13). RT-PCR HCV levels reported in log values were comparable in both groups and among patients in the same group. The statistical analysis showed no interaction effect between time and group (p value G*M= 0.852), overtime intra-groups (p-value M=0.889) and between group (p-value G=0.286). Group 1 showed a higher incidence of dyslipidemia (p=0.03) and proteinuria events (p=0.01), while no difference was observed in the incidence of anemia (p=0.17), new onset of post-transplant diabetes mellitus (p=1.00) or urinary tract infection (p=0.60). The mean eGFR was similar in both groups. Our study did not show viral load decrease after conversion to EVR with maintenance of antiproliferative therapy.

Phase II study of biweekly plitidepsin as second-line therapy for advanced or metastatic transitional cell carcinoma of the urothelium.

PubMed

Dumez, Herlinde; Gallardo, Enrique; Culine, Stephane; Galceran, Joan Carles; Schöffski, Patrick; Droz, Jean P; Extremera, Sonia; Szyldergemajn, Sergio; Fléchon, Aude

2009-09-16

The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m(2)) administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting > or = 6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

An open-label, randomized, four-treatment crossover study evaluating the effects of salt form, acetaminophen, and food on the pharmacokinetics of phenylephrine.

PubMed

Gelotte, Cathy K

2018-06-01

Phenylephrine hydrochloride (HCl) is a decongestant available in over-the-counter (OTC) medicines. Previously marketed prescription products contained phenylephrine tannate, an extended-release salt, which allowed dosing every 8-12 h. Given the regulatory history that cold medicines marketed before 1962 had limited supporting clinical data, and with widespread replacement of pseudoephedrine by phenylephrine in OTC products over the last ten years, the need for contemporary studies grew. This exploratory crossover study evaluated effects of salt form, acetaminophen, and food on phenylephrine pharmacokinetics and metabolites in healthy adults. Test treatments were 25 mg phenylephrine tannate (equivalent to 10 mg phenylephrine HCl) combined with 200 mg guaifenesin, fasted; 10 mg phenylephrine HCl combined with 650 mg acetaminophen, fasted; and 10 mg phenylephrine HCl, fed. The reference treatment was 10 mg phenylephrine HCl, fasted. Plasma phenylephrine pharmacokinetics and urine metabolites were determined. Although the tannate salt slowed phenylephrine absorption compared with the HCl salt, terminal concentrations were similar, suggesting that products containing the tannate salt should not be dosed less frequently than those containing the HCl salt. The premise that acetaminophen increases phenylephrine bioavailability by competition for presystemic sulfation was corroborated by increased phenylephrine sulfate in urine. Food delayed phenylephrine absorption, but not the total amount absorbed. Copyright © 2018. Published by Elsevier Inc.

Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome.

PubMed

Nagtegaal, Gijsbert J A; Pohl, Christoph; Wattjes, Mike P; Hulst, Hanneke E; Freedman, Mark S; Hartung, Hans-Peter; Miller, David; Montalban, Xavier; Kappos, Ludwig; Edan, Gilles; Pleimes, Dirk; Beckman, Karola; Stemper, Brigitte; Polman, Christoph H; Sandbrink, Rupert; Barkhof, Frederik

2014-02-01

Multiple sclerosis (MS) is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for patients with MS. To evaluate whether IFNB-1b in patients presenting with clinically isolated syndromes (CIS) prevented persisting T1 hypointensities on MRI (persistent black holes (PBHs)). In the placebo-controlled phase, patients (n = 468) were initially randomised to IFNB-1b (n = 292) or placebo (n = 176) for two years or clinically definite MS (CDMS). In the open-label phase (n = 418), both groups were offered IFNB-1b for up to five years. Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan (minimum time one year). A total of 435 patients were evaluable for analysis. The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases (.42 vs .71, p = .0102 and .70 vs 1.17, p = .0121). Exploratory analyses identified baseline characteristics that affected rate of conversion. Although the rate of lesions that converted to PBH showed no significant differences between groups, the numbers of PBHs per patient out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo. NCT00544037.

Feasibility of Autologous Cord Blood Cells for Infants with Hypoxic-Ischemic Encephalopathy

PubMed Central

Cotten, C. Michael; Murtha, Amy P.; Goldberg, Ronald N.; Grotegut, Chad A.; Smith, P. Brian; Goldstein, Ricki F.; Fisher, Kimberley A.; Gustafson, Kathryn E.; Waters-Pick, Barbara; Swamy, Geeta K.; Rattray, Benjamin; Tan, Siddhartha; Kurtzberg, Joanne

2014-01-01

Objective To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). Study design We enrolled infants in the Intensive Care Nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to four doses adjusted for volume and RBC content,1 – 5 × 107cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post- infusion vital signs. As exploratory analyses we compared cell recipients’ hospital outcomes (mortality, oral feeds at discharge) and one year survival with Bayley III scores ≥ 85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. Results Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 milliliters. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1 year outcomes survived with scores ≥ 85. Conclusions Collection, preparation and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed. PMID:24388332

The effect of brexpiprazole (OPC-34712) and aripiprazole in adult patients with acute schizophrenia: results from a randomized, exploratory study.

PubMed

Citrome, Leslie; Ota, Ai; Nagamizu, Kazuhiro; Perry, Pamela; Weiller, Emmanuelle; Baker, Ross A

2016-07-01

The aim of this study was to explore the effects of brexpiprazole and aripiprazole on efficacy, cognitive functioning, and safety in patients with acute schizophrenia. Patients who would benefit from hospitalization/continued hospitalization for acute relapse of schizophrenia were enrolled and randomized (2 : 1) to target doses of open-label brexpiprazole 3 mg/day or aripiprazole 15 mg/day for 6 weeks. Outcomes included change from baseline to week 6 in the Positive and Negative Syndrome Scale total score, Barratt Impulsiveness Scale 11-item score, and Cogstate computerized cognitive test battery scores. Patients treated with brexpiprazole (n=64) or aripiprazole (n=33) showed reductions in symptoms of schizophrenia as assessed by Positive and Negative Syndrome Scale total score (-22.9 and -19.4, respectively). A modest reduction in impulsivity was observed with brexpiprazole, but not aripiprazole (mean change in the Barratt Impulsiveness Scale 11-item total score: -2.7 and 0.1, respectively). No change in Cogstate scores was observed for either treatment. Brexpiprazole was well tolerated and the incidence of akathisia was lower in patients treated with brexpiprazole (9.4%) than aripiprazole (21.2%). Clinically relevant improvements in psychopathology were observed in patients with acute schizophrenia treated with brexpiprazole or aripiprazole. Brexpiprazole was well tolerated, with a lower incidence of akathisia than aripiprazole.

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study.

PubMed

Abujadi, Caio; Croarkin, Paul E; Bellini, Bianca B; Brentani, Helena; Marcolin, Marco A

2017-12-11

Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

Experiences with HPTN 067/ADAPT Study-Provided Open-Label PrEP Among Women in Cape Town: Facilitators and Barriers Within a Mutuality Framework.

PubMed

Amico, K Rivet; Wallace, Melissa; Bekker, Linda-Gail; Roux, Surita; Atujuna, Millicent; Sebastian, Elaine; Dye, Bonnie J; Elharrar, Vanessa; Grant, Robert M

2017-05-01

Placebo-controlled trials of pre-exposure prophylaxis (PrEP) have reported challenges with study-product uptake and use, with the greatest challenges reported in studies with young women in sub-Saharan Africa. We conducted a qualitative sub-study to explore experiences with open-label PrEP among young women in Cape Town, South Africa participating in HTPN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT). HPTN 067/ADAPT provided open label oral FTC/TDF PrEP to young women in Cape Town, South Africa who were randomized to daily and non-daily PrEP regimens. Following completion of study participation, women were invited into a qualitative sub-study including focus groups and in-depth interviews. Interviews and groups followed a semi-structured guide, were recorded, transcribed, and translated to English from isiXhosa, and coded using framework analysis. Sixty of the 179 women enrolled in HPTN 067/ADAPT participated in either a focus group (six groups for a total of 42 participants) or an in-depth interview (n = 18). This sample of mostly young, unmarried women identified facilitators of and barriers to PrEP use, as well as factors influencing study participation. Cross-cutting themes characterizing discourse suggested that women placed high value on contributing to the well-being of one's community (Ubuntu), experienced a degree of skepticism towards PrEP and the study more generally, and reported a wide range of approaches towards PrEP (ranging from active avoidance to high levels of persistence and adherence). A Mutuality Framework is proposed that identifies four dynamics (distrust, uncertainty, alignment, and mutuality) that represent distinct interactions between self, community and study and serve to contextualize women's experiences. Implications for better understanding PrEP use, and non-use, and intervention opportunities are discussed. In this sample of women, PrEP use in the context of an open-label research trial was heavily influenced by underlying beliefs about safety, reciprocity of contributions to community, and trust in transparency and integrity of the research. Greater attention to factors positioning women in the different dynamics of the proposed Mutuality Framework could direct intervention approaches in clinical trials, as well as open-label PrEP scale-up.

Labelling Polymers and Micellar Nanoparticles via Initiation, Propagation and Termination with ROMP

PubMed Central

Thompson, Matthew P.; Randolph, Lyndsay M.; James, Carrie R.; Davalos, Ashley N.; Hahn, Michael E.

2014-01-01

In this paper we compare and contrast three approaches for labelling polymers with functional groups via ring-opening metathesis polymerization (ROMP). We explored the incorporation of functionality via initiation, termination and propagation employing an array of novel initiators, termination agents and monomers. The goal was to allow the generation of selectively labelled and well-defined polymers that would in turn lead to the formation of labelled nanomaterials. Norbornene analogues, prepared as functionalized monomers for ROMP, included fluorescent dyes (rhodamine, fluorescein, EDANS, and coumarin), quenchers (DABCYL), conjugatable moieties (NHS esters, pentafluorophenyl esters), and protected amines. In addition, a set of symmetrical olefins for terminally labelling polymers, and for the generation of initiators in situ is described. PMID:24855496

Effects of interpretive nutrition labels on consumer food purchases: the Starlight randomized controlled trial.

PubMed

Ni Mhurchu, Cliona; Volkova, Ekaterina; Jiang, Yannan; Eyles, Helen; Michie, Jo; Neal, Bruce; Blakely, Tony; Swinburn, Boyd; Rayner, Mike

2017-03-01

Background: Nutrition labeling is a prominent policy to promote healthy eating. Objective: We aimed to evaluate the effects of 2 interpretive nutrition labels compared with a noninterpretive label on consumer food purchases. Design: In this parallel-group randomized controlled trial, we enrolled household shoppers across New Zealand who owned smartphones and were aged ≥18 y. Eligible participants were randomly assigned (1:1:1) to receive either traffic light labels (TLLs), Health Star Rating labels (HSRs), or a control [nutrition information panel (NIP)]. Smartphone technology allowed participants to scan barcodes of packaged foods and to receive allocated labels on their smartphone screens. The primary outcome was the mean healthiness of all packaged food purchases over the 4-wk intervention period, which was measured by using the Food Standards Australia New Zealand Nutrient Profiling Scoring Criterion (NPSC). Results: Between October 2014 and November 2015, 1357 eligible shoppers were randomly assigned to TLL ( n = 459), HSR ( n = 443), or NIP ( n = 455) labels. Overall difference in the mean transformed NPSC score for the TLL group compared with the NIP group was -0.20 (95% CI: -0.94, 0.54; P = 0.60). The corresponding difference for HSR compared with NIP was -0.60 (95% CI: -1.35, 0.15; P = 0.12). In an exploratory per-protocol analysis of participants who used the labeling intervention more often than average ( n = 423, 31%), those who were assigned to TLL and HSR had significantly better NPSC scores [TLL compared with NIP: -1.33 (95% CI: -2.63, -0.04; P = 0.04); HSR compared with NIP: -1.70 (95% CI: -2.97, -0.43; P = 0.01)]. Shoppers who were randomly assigned to HSR and TLL also found the labels significantly more useful and easy to understand than the NIP (all P values <0.001). Conclusions: At the relatively low level of use observed in this trial, interpretive nutrition labels had no significant effect on food purchases. However, shoppers who used interpretive labels found them to be significantly more useful and easy to understand, and compared with frequent NIP users, frequent TLL and HSR users had significantly healthier food purchases. This trial was registered at the Australian New Zealand Clinical Trials Registry (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366446&isReview=true) as ACTRN12614000644662. © 2017 American Society for Nutrition.

Continuing fascination of exploration in natural substances from microorganisms.

PubMed

Takahashi, Yoko

2017-01-01

In the search for novel organic compounds, I think it is of paramount importance not to overlook the pursuit of microorganism diversity and the abilities those microorganisms hold as a resource. In commemoration of Professor Satoshi Ōmura's Nobel Prize in Physiology or Medicine, I will briefly describe the microorganism that produces avermectin and then discuss how innovating isolation methods and pioneering isolation sources have opened the door to numerous new microorganism resources. Furthermore, as exploratory research of substances views the world from many different angles-from biological activity to a compound's physiochemical properties-it is possible to discover a novel compound from a well-known microorganism. Based on this, I will discuss the future prospects of exploratory research.

Anomalies in social behaviors and exploratory activities in an APPswe/PS1 mouse model of Alzheimer's disease.

PubMed

Filali, Mohammed; Lalonde, Robert; Rivest, Serge

2011-10-24

Alzheimer's disease is characterized by deficits in social communication, associated with generalized apathy or agitation, as well as social memory. To assess social behaviors in 6-month-old male APPswe/PS1 bigenics relative to non-transgenic controls, the 3-chamber test was used, together with open-field and elevated plus-maze tests of exploration. APPswe/PS1 mice were less willing to engage in social interaction than wild-type, avoiding an unfamiliar stimulus mouse, probably not due to generalized apathy because in both tests of exploratory activity the mutants were hyperactive. This study reveals reduced "sociability" combined with hyperactivity in an APPswe/PS1 mouse model of Alzheimer dementia. Copyright © 2011 Elsevier Inc. All rights reserved.

Landslide investigations, southern Cianjur Regency, West Java Province, Indonesia; a progress report

USGS Publications Warehouse

Ege, John R.

1983-01-01

Two landslide-monitoring sites have been established for a minimum 2-year investigation near the villages of Pasirpari and Cibacang in southern Cianjur Regency, West Java, Indonesia. Surveyed-in lines will measure amounts of surface movement and tilt, borings that produced exploratory cores now serve as slip-surface detectors and open-pipe piezometers, and rain gages will record rainfall at both sites. Exploratory cores and field observations located upper slip surfaces ranging in depth between 4 and 14 m. Rises of borehole-water levels of as much as 63 cm during drilling suggest that pore pressures exist at the inferred-slip surfaces. Sliding along slip surfaces and slope failures occurred during the rainy season between November 1980 and April 1981.

Role of thirst and visual barriers in the differential behavior displayed by streptozotocin-treated rats in the elevated plus-maze and the open field test.

PubMed

Rebolledo-Solleiro, Daniela; Crespo-Ramírez, Minerva; Roldán-Roldán, Gabriel; Hiriart, Marcia; Pérez de la Mora, Miguel

2013-08-15

Conflicting results have been obtained by several groups when studying the effects of streptozotocin (STZ)-treated rats in the elevated plus-maze (EPM). Since thirst is a prominent feature in STZ-induced diabetic-like condition, we studied whether the walls of the closed arms of the EPM, by limiting the search for water in the environment, may contribute to the observed differential behavioral outcomes. The aim of this study was to ascertain whether visual barriers within the EPM have an influence on the behavior of STZ-treated rats in this test of anxiety. A striking similarity between STZ-treated (50 mg/kg, i.p., in two consecutive days) and water deprived rats (72 h) was found in exploratory behavior in the EPM, showing an anxiolytic-like profile. However the anxiolytic response of STZ-treated rats exposed to the EPM shifts into an anxiogenic profile when they are subsequently tested in the open-field test, which unlike the EPM is devoid of visual barriers. Likewise, water deprived rats (72 h) also showed an anxiogenic profile when they were exposed to the open-field test. Our results indicate that experimental outcomes based on EPM observations can be misleading when studying physiological or pathological conditions, e.g. diabetes, in which thirst may increase exploratory behavior. © 2013.

The effects of N-Methyl-D-Aspartate receptor blockade during the early neurodevelopmental period on emotional behaviors and cognitive functions of adolescent Wistar rats.

PubMed

Kocahan, Sayad; Akillioglu, Kubra; Binokay, Secil; Sencar, Leman; Polat, Sait

2013-05-01

The N-Methyl-D-Aspartate (NMDA) receptor is expressed abundantly in the brain and plays an important role in neuronal development, learning and memory, neurodegenerative diseases, and neurogenesis. In this study, we evaluated the effects of NMDA receptor blockade during the early neurodevelopmental period on exploratory locomotion, anxiety-like behaviors and cognitive functions of adolescent Wistar rats. NMDA receptor hypofunction was induced 7-10 days after birth using MK-801 in rats (0.25 mg/kg twice a day for 4 days via intraperitoneal injection). The open-field (OF), elevated plus maze (EPM) and passive avoidance (PA) tests were used to evaluate exploratory locomotion, anxiety-like behaviors and cognitive functions. In the OF test, MK-801 caused an increase in locomotion behavior (p < 0.01) and in the frequency of rearing (p < 0.05). In the EPM test, MK-801 treatment increased the time spent in the open arms, the number of open arm entries and the amount of head dipping (p < 0.01). MK-801 treatment caused no statistical difference compared to the control group in the PA test (p > 0.05). Chronic NMDA receptor blockade during the critical period of maturation for the glutamatergic brain system (postnatal days 7-10) produces locomotor hyperactivity and decreased anxiety levels, but has no significant main effect on cognitive function during adolescence.

Effect of interleukin-1beta on the behavior of rats during mild stress in the open-field test.

PubMed

Pertsov, S S; Koplik, E V; Simbirtsev, A S; Kalinichenko, L S

2009-11-01

We studied the effect of interleukin-1beta on the behavior of rats with different individual typological characteristics during mild stress in the open-field test. Intraperitoneal injection of interleukin-1beta (5 microg/kg, 108 U/mg) was followed by a decrease in orientation and exploratory activity of passive and, particularly, of active animals in the open field. As differentiated from rats receiving physiological saline, the initial differences in behavioral characteristics of active and passive animals were not revealed in the repeated test after injection of interleukin-1beta. We conclude that interleukin-1beta abolishes the behavioral differences between active and passive specimens in the open field. These data suggest that administration of interleukin-1beta to rats leads to reorganization of the mechanisms for emotional evaluation of adverse emotiogenic factors under conditions of mild stress in the open-field test.

Social instability stress in adolescence increases anxiety and reduces social interactions in adulthood in male Long-Evans rats.

PubMed

Green, Matthew R; Barnes, Brittany; McCormick, Cheryl M

2013-12-01

We investigated the effects of social instability stress (daily 1-hr isolation, change of cage partner, postnatal day 30-45) in adolescence in male rats on open field exploration and social behavior in adulthood. Social stressed rats had longer latencies to enter the center of an open field and then took longer to approach an object placed in the center of the field. When another rat was placed in the open field, stressed rats spent less time in social interaction than control rats, particularly when paired with another stressed, rather than a control, rat. The groups did not differ in social approach tests (when a stimulus rat was separated by wire mesh) nor in novel object exploration (when controlling for open field anxiety). The results suggest social stress in adolescence increases open field anxiety while maintaining exploratory behavior, and alters social interactions in adulthood. © 2012 Wiley Periodicals, Inc.

An Exploration of Learners' Conceptions of Language, Culture, and Learning in Advanced-Level Spanish Courses

ERIC Educational Resources Information Center

Drewelow, Isabelle; Mitchell, Claire

2015-01-01

This article reports on an exploratory study, which examines learners' rating of culture in relation to other concepts in advanced Spanish courses and their justification of the ratings attributed. Open-ended responses, elicited from a questionnaire completed by 179 respondents, were analysed line by line using an interpretive approach. Data…

Questions about Answers: Probing Teachers' Awareness and Planned Remediation of Learners' Misconceptions about Electric Circuits

ERIC Educational Resources Information Center

Gaigher, Estelle

2014-01-01

This article reports an exploratory multi-case study on how science teachers understand and envisage addressing learners' misconceptions about electric circuits. Four teachers from schools in and around a large South African city participated in the study. An open-ended questionnaire was designed in a novel way, questioning teachers about wrong…

Versatility, Openness to Experience, and Topical Diversity in Creative Products: An Exploratory Historiometric Analysis of Scientists, Philosophers, and Writers

ERIC Educational Resources Information Center

Cassandro, Vincent J.; Simonton, Dean Keith

2010-01-01

Creative individuals are considered "versatile" when their achievements extend beyond their most commonly cited domain, thus indicating remarkable and varied interests and abilities. The present study examined the association between versatility and (a) the personalities of eminent creators and (b) the topical diversity of their creative products.…

Indigenous Crisis Counseling in Taiwan: An Exploratory Qualitative Case Study of an Expert Therapist

ERIC Educational Resources Information Center

Kuo, Ben C. H.; Hsu, Wei-Su; Lai, Nien-Hwa

2011-01-01

In this study, we adopted a single qualitative case study method to explore and examine indigenous approaches to crisis counseling in Taiwan, through the distinct lens of an expert Taiwanese counseling psychologist. In-depth, open-ended interviews were conducted with the psychologist (as the case) to document her lived clinical experiences…

Personal Learning Environments in the Workplace: An Exploratory Study into the Key Business Decision Factors

ERIC Educational Resources Information Center

Chatterjee, Arunangsu; Law, Effie Lai-Chong; Mikroyannidis, Alexander; Owen, Glyn; Velasco, Karen

2013-01-01

Personal Learning Environments (PLEs) have emerged as a solution to the need of learners for open and easily customisable learning environments. PLEs essentially hand complete control over the learning process to the learner. However, this learning model is not fully compatible with learning in the workplace, which is influenced by certain…

Sources of Stress among College Students--The Case of a Credit Transfer Program

ERIC Educational Resources Information Center

Ong, Bessie; Cheong, K. C.

2009-01-01

This exploratory study intends to identify the types and nature of stressor experienced by students in an American Degree Transfer Program at a private university college in Malaysia. Data collection was done by an open-ended questionnaire. The findings showed that the top five most frequently reported stressors were academic workload, too many…

Comparison of Wiltse's paraspinal approach and open book laminectomy for thoracolumbar burst fractures with greenstick lamina fractures: a randomized controlled trial.

PubMed

Chen, Zhi-da; Wu, Jin; Yao, Xiao-Tao; Cai, Tao-Yi; Zeng, Wen-Rong; Lin, Bin

2018-03-02

Posterior short-segment pedicle screw fixation is used to treat thoracolumbar burst fractures. However, no randomized controlled studies have compared the efficacy of the two approaches--the Wiltse's paraspinal approach and open book laminectomy in the treatment of thoracolumbar burst fractures with greenstick lamina fractures. Patients with burst fractures of the thoracolumbar spine without neurological deficit were randomized to receive either the Wiltse's paraspinal approach (group A, 24 patients) or open book laminectomy (group B, 23 patients). Patients were followed postoperatively for average of 27.4 months. Clinical and radiographic data of the two approaches were collected and compared. Our results showed the anterior segmental height, kyphotic angle, visual analog scale (VAS) score, and Smiley-Webster Scale (SWS) score significantly improved postoperatively in both groups, indicating that both the Wiltse's paraspinal approach and open book laminectomy can effectively treat thoracolumbar burst fractures with greenstick lamina fractures. The Wiltse's paraspinal approach was found to have significantly shorter operating time, less blood loss, and shorter length of hospital stay compared to open book laminectomy. However, there were two (2/24) patients in group A that had neurological deficits postoperatively and required a second exploratory operation. Dural tears and/or cauda equina entrapment were subsequently found in four patients in group B and all two patients of neurological deficits in group A during operation. No screw loosening, plate breakage, or other internal fixation failures were found at final follow-up. The results demonstrated that either of the two surgical approaches can achieve satisfactory results in treating thoracolumbar burst fractures in patients with greenstick lamina fractures. However, if there is any clinical or radiographic suspicion of a dural tear and/or cauda equina entrapment pre-operation, patients should receive an open book laminectomy to avoid a second exploratory operation. More research is still needed to optimize clinical decision-making regarding surgical approach.

46 CFR 194.10-35 - Labeling.

Code of Federal Regulations, 2011 CFR

2011-10-01

... DO NOT LIFT WITH CONTENTS (f) Control locations for magazine sprinkler systems, in addition to the... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY... conspicuous location, preferably the top, with the inscription: MAGAZINE CHEST KEEP OPEN LIGHTS AND FIRE AWAY...

46 CFR 194.10-35 - Labeling.

Code of Federal Regulations, 2010 CFR

2010-10-01

... DO NOT LIFT WITH CONTENTS (f) Control locations for magazine sprinkler systems, in addition to the... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY... conspicuous location, preferably the top, with the inscription: MAGAZINE CHEST KEEP OPEN LIGHTS AND FIRE AWAY...

46 CFR 194.10-35 - Labeling.

Code of Federal Regulations, 2014 CFR

2014-10-01

... DO NOT LIFT WITH CONTENTS (f) Control locations for magazine sprinkler systems, in addition to the... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY... conspicuous location, preferably the top, with the inscription: MAGAZINE CHEST KEEP OPEN LIGHTS AND FIRE AWAY...

46 CFR 194.10-35 - Labeling.

Code of Federal Regulations, 2013 CFR

2013-10-01

... DO NOT LIFT WITH CONTENTS (f) Control locations for magazine sprinkler systems, in addition to the... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY... conspicuous location, preferably the top, with the inscription: MAGAZINE CHEST KEEP OPEN LIGHTS AND FIRE AWAY...

46 CFR 194.10-35 - Labeling.

Code of Federal Regulations, 2012 CFR

2012-10-01

... DO NOT LIFT WITH CONTENTS (f) Control locations for magazine sprinkler systems, in addition to the... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY... conspicuous location, preferably the top, with the inscription: MAGAZINE CHEST KEEP OPEN LIGHTS AND FIRE AWAY...

Esophageal cancer detection based on tissue surface-enhanced Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan

2013-01-01

The capability of using silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) spectroscopy combined with principal component analysis (PCA) and linear discriminate analysis (LDA) to differentiate esophageal cancer tissue from normal tissue was presented. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues. PCA-LDA multivariate analysis of the measured tissue SERS spectra achieved diagnostic sensitivity of 90.9% and specificity of 97.8%. This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection.

77 FR 67013 - Blood Products Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-08

..., 2012, the Committee will meet in open session to discuss labeling of Red Blood Cells with historical...] Blood Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Blood...

Open-Minded Cognition.

PubMed

Price, Erika; Ottati, Victor; Wilson, Chase; Kim, Soyeon

2015-11-01

The present research conceptualizes open-minded cognition as a cognitive style that influences how individuals select and process information. An open-minded cognitive style is marked by willingness to consider a variety of intellectual perspectives, values, opinions, or beliefs-even those that contradict the individual's opinion. An individual's level of cognitive openness is expected to vary across domains (such as politics and religion). Four studies develop and validate a novel measure of open-minded cognition, as well as two domain-specific measures of religious and political open-minded cognition. Exploratory and confirmatory factor analysis (controlling for acquiescence bias) are used to develop the scales in Studies 1 to 3. Study 4 demonstrates that these scales possess convergent and discriminant validity. Study 5 demonstrates the scale's unique predictive validity using the outcome of Empathic Concern (Davis, 1980). Study 6 demonstrates the scale's unique predictive validity using the outcomes of warmth toward racial, religious, and sexual minorities. © 2015 by the Society for Personality and Social Psychology, Inc.

Spontaneous bleeding from liver after open heart surgery.

PubMed

Mir, Najeeb H; Shah, Mian T; Obeid, Mahmoud Ali; Gallo, Ricardo; Aliter, Hashem

2013-01-01

Intra-abdominal hemorrhage after open heart surgery is very uncommon in routine clinical practice. There are case reports of having bleeding from spleen or liver after starting low molecular weight heparin (LMWH) postoperatively. Our patient is a 58-year-old man with mitral valve regurgitation, who underwent mitral valve repair and developed intra-abdominal hemorrhage 8h after open heart surgery. The exploratory laparotomy revealed the source of bleeding from ruptured sub-capsular liver hematoma and oozing from raw areas of the liver surface. Liver packing was done to control the bleeding. The gastrointestinal complications after open heart surgery are rare and spontaneous bleeding from spleen has been reported. This is the first case from our hospital to have intra-abdominal hemorrhage after open heart surgery. Spontaneous bleeding from liver is a possible complication after open heart surgery. We submit the case for the academic interest and to discuss the possible cause of hemorrhage. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of New Antiviral Agent Camphecin on Behavior of Mice.

PubMed

Babina, A V; Lavrinenko, V A; Yarovaya, O I; Salakhutdinov, N F

2017-01-01

We studied the effect of camphecin (1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol) on mouse behavior in the open-field test. Camphecin possesses antiviral activity and inhibits viral replication, but its influence on the nervous system is poorly studied. Single camphecin injection produced no significant changes in behavioral patterns. Chronic camphecin administration (5 times over 2 weeks) to mice of different strains had no significant influence on open field behavior (motor, exploratory activity, anxiety, emotional state and vegetative functions). The findings are discussed in the context of neutral influence of camphecin on animal behavior.

Efficient Thread Labeling for Monitoring Programs with Nested Parallelism

NASA Astrophysics Data System (ADS)

Ha, Ok-Kyoon; Kim, Sun-Sook; Jun, Yong-Kee

It is difficult and cumbersome to detect data races occurred in an execution of parallel programs. Any on-the-fly race detection techniques using Lamport's happened-before relation needs a thread labeling scheme for generating unique identifiers which maintain logical concurrency information for the parallel threads. NR labeling is an efficient thread labeling scheme for the fork-join program model with nested parallelism, because its efficiency depends only on the nesting depth for every fork and join operation. This paper presents an improved NR labeling, called e-NR labeling, in which every thread generates its label by inheriting the pointer to its ancestor list from the parent threads or by updating the pointer in a constant amount of time and space. This labeling is more efficient than the NR labeling, because its efficiency does not depend on the nesting depth for every fork and join operation. Some experiments were performed with OpenMP programs having nesting depths of three or four and maximum parallelisms varying from 10,000 to 1,000,000. The results show that e-NR is 5 times faster than NR labeling and 4.3 times faster than OS labeling in the average time for creating and maintaining the thread labels. In average space required for labeling, it is 3.5 times smaller than NR labeling and 3 times smaller than OS labeling.

Psychometric Properties of Creative Self-Efficacy Inventory Among Distinguished Students in Saudi Arabian Universities.

PubMed

Alotaibi, Khaled N

2016-06-01

This study examined the psychometric properties of the Arabic version of Abbott's Creative Self-Efficacy inventory. Saudi honors students (157 men vs. 163 women) participated. These students are undergraduates (M age = 19.5 year, SD = 1.9) who complete 30 credit hours with a grade point average of no less than 4.5 out of 5. The results showed that the internal consistency (α = .87) and the test-retest reliabilities (r = .73) were satisfactory. The study sample was separated into two subsamples. The data from the first subsample (n = 60) were used to conduct an exploratory factor analysis, whereas the data from the second subsample (n = 260) were used to perform a confirmatory factor analysis. The results of exploratory factor analysis and confirmatory factor analysis indicated that creative self-efficacy was not a unidimensional construct but consisted of two factors labeled "creative thinking self-efficacy" and "creative performance self-efficacy." As expected, this two-factor model fit the data adequately, supporting prior research that treated creative self-efficacy as multidimensional construct. © The Author(s) 2016.

Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension.

PubMed

Suzuki, Katsuyoshi; Otsuka, Naomi; Hizaki, Hiroko; Hashimoto, Masayo; Kuwayama, Yasuaki

2018-06-05

This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM). This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire. In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n = 60) or LAT/TIM (n = 55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4-6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group. TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores. UMIN Clinical Trials Registry Identifier, UMIN000023862. Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Labelling and Marketing of Bivalve and Gastropod Molluscs Retailed in Sardinia, Italy Between 2009 and 2013

PubMed Central

2015-01-01

The aim of the present survey was to investigate the correct enforcement of the Community rules on the labelling and marketing of bivalve and gastropod molluscs retailed in Sardinia, Italy between 2009 and 2013. A total of 1500 packages and labels for live bivalve and gastropod molluscs were considered. A total of 375 labels (25%) presented non-compliance concerning the wrong trade name and additional wrong or missing information. The highest percentage of anomalous labels has been detected in small-scale retail shops (35%) and open-air markets (25%) compared with the big retailing chains (20%). The 5% of packages were not in compliance with the European Community rules on packaging of bivalve and gastropod molluscs. The high percentage of non-compliance with the European regulations on labelling results is a strong limitation for the consumers and highlights the need to improve the control system about labelling of seafood products. PMID:27800397

Virtual Reality Based Collaborative Design by Children with High-Functioning Autism: Design-Based Flexibility, Identity, and Norm Construction

ERIC Educational Resources Information Center

Ke, Fengfeng; Lee, Sungwoong

2016-01-01

This exploratory case study examined the process and potential impact of collaborative architectural design and construction in an OpenSimulator-based virtual reality (VR) on the social skills development of children with high-functioning autism (HFA). Two children with a formal medical diagnosis of HFA and one typically developing peer, aged…

Handwriting and Gender: A Multi-Use Data Set

ERIC Educational Resources Information Center

Bradley, Sean

2015-01-01

Can individuals guess the gender of a writer based on a sample of his or her handwriting? We administer an electronic survey twice to the same individuals to find out. The resulting data set is interesting to students, rich enough to be amenable to a wide array of activities, and open to a variety of exploratory tacks for statistics students and…

Primary School Pupils' Views of Characteristics of Good Primary School Teachers: An Exploratory, Open Approach for Investigating Pupils' Perceptions

ERIC Educational Resources Information Center

Bakx, Anouke; Koopman, Maaike; de Kruijf, Judith; den Brok, Perry

2015-01-01

This article reports on results of a study on pupils' perceptions on teacher quality in primary education. Pupils' perceptions of desired characteristics of good teachers in primary education were compared to results of research into teacher quality from different perspectives: (1) perception studies of ideal teaching-and-learning environments;…

White Teenage Girls and Affirmative Action in Higher Education in South Africa

ERIC Educational Resources Information Center

Botsis, H.

2010-01-01

This is an initial and exploratory comment on the pilot phase of a study into adolescent female white identity and socio-sexual desire in post-apartheid South Africa. In the course of this pilot it became apparent that historical issues of race and racism are openly discussed in these girls' classrooms. Yet, despite these everyday interactions the…

Agency capacity for recreation science and management: the case of the U.S. Forest Service.

Treesearch

Lee K. Cerveny; Clare M. Ryan

2008-01-01

This report examines the capacity of natural resource agencies to generate scientific knowledge and information for use by resource managers in planning and decisionmaking. This exploratory study focused on recreation in the U.S. Department of Agriculture, Forest Service. A semistructured, open-ended interview guide elicited insights from 58 managers and 28 researchers...

Exploratory Study of MOOC Learners' Demographics and Motivation: The Case of Students Involved in Groups

ERIC Educational Resources Information Center

Bayeck, Rebecca Yvonne

2016-01-01

This paper reports preliminary findings on students enrolled in a massive open online course, who were also assigned to work in groups. Part of a larger study on the effect of groups on retention and completion in MOOCs, the paper provides students' demographics (i.e., location, gender, education level, and employment status), and motivation for…

Social and Affective Concerns High-Ability Adolescents Indicate They Would Like to Discuss with a Caring Adult: Implications for Educators

ERIC Educational Resources Information Center

Jen, Enyi; Wu, Jiaxi; Gentry, Marcia

2016-01-01

This exploratory study investigated the social and affective concerns of 280 high-ability students in Grades 5 through 12 who participated in a summer residential program. Content analysis of responses from an open-ended survey indicated that high-ability adolescents expressed concerns regarding feelings and emotions, future aspirations, and…

Mixed Method Approaches in Open-Ended, Qualitative, Exploratory Research Involving People with Intellectual Disabilities: A Comparative Methods Study

ERIC Educational Resources Information Center

Ottmann, Goetz; Crosbie, Jenny

2013-01-01

People with intellectual disabilities and their families are increasingly being asked to provide input into the services they receive. Under the aegis of the United Nation Convention of the Rights of Persons with Disabilities, support plans crucially depend on a participant's articulation of his or her preferences and life goals. Yet, research…

Focus Group Guide

DTIC Science & Technology

2017-07-01

o Open-ended and exploratory questions. o Provide all an opportunity to participate. o Do not allow the group to get out of control . Manage...website under Assessment to Solutions at www.deomi.org. Focus Group Guide DEFENSE EQUAL OPPORTUNITY MANAGEMENT...www.deomi.org, provides a variety of tools and information to support conducting a focus group and the climate assessment process. Cover The cover

The Effect of Highly Scaffolded versus General Instruction on Students' Exploratory Behavior and Arousal

ERIC Educational Resources Information Center

Blikstein, Paulo; Gomes, July Silveira; Akiba, Henrique Teruo; Schneider, Bertrand

2017-01-01

Technology is changing the way students interact with knowledge, and open-ended activities are one of the main types of tasks that students engage with in technology-rich environments. However, the amount of guidance needed to promote learning in these environments remains unknown. We explore this issue by focusing on the effects of step-by-step…

Ruxolitinib reduces JAK2 p.V617F allele burden in patients with polycythemia vera enrolled in the RESPONSE study.

PubMed

Vannucchi, Alessandro Maria; Verstovsek, Srdan; Guglielmelli, Paola; Griesshammer, Martin; Burn, Timothy C; Naim, Ahmad; Paranagama, Dilan; Marker, Mahtab; Gadbaw, Brian; Kiladjian, Jean-Jacques

2017-07-01

In patients with polycythemia vera (PV), an elevated JAK2 p.V617F allele burden is associated with indicators of more severe disease (e.g., leukocytosis, splenomegaly, and increased thrombosis risk); however, correlations between allele burden reductions and clinical benefit in patients with PV have not been extensively evaluated in a randomized trial. This exploratory analysis from the multicenter, open-label, phase 3 Randomized Study of Efficacy and Safety in Polycythemia Vera With JAK Inhibitor INCB018424 Versus Best Supportive Care trial evaluated the long-term effect of ruxolitinib treatment on JAK2 p.V617F allele burden in patients with PV. Evaluable JAK2 p.V617F-positive patients randomized to ruxolitinib (n = 107) or best available therapy (BAT) who crossed over to ruxolitinib at week 32 (n = 97) had consistent JAK2 p.V617F allele burden reductions throughout the study. At all time points measured (up to weeks 208 [ruxolitinib-randomized] and 176 [ruxolitinib crossover]), mean changes from baseline over time in JAK2 p.V617F allele burden ranged from -12.2 to -40.0% (ruxolitinib-randomized) and -6.3 to -17.8% (ruxolitinib crossover). Complete or partial molecular response was observed in 3 patients (ruxolitinib-randomized, n = 2; ruxolitinib crossover, n = 1) and 54 patients (ruxolitinib-randomized, n = 33; ruxolitinib crossover, n = 20; BAT, n = 1), respectively. Among patients treated with interferon as BAT (n = 13), the mean maximal reduction in allele burden from baseline was 25.6% after crossover to ruxolitinib versus 6.6% before crossover. Collectively, the data from this exploratory analysis suggest that ruxolitinib treatment for up to 4 years provides progressive reductions in JAK2 p.V617F allele burden in patients with PV who are resistant to or intolerant of hydroxyurea. The relationship between allele burden changes and clinical outcomes in patients with PV remains unclear.

Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid-lowering component of ALLHAT

PubMed Central

Rahman, Mahboob; Baimbridge, Charles; Davis, Barry R.; Barzilay, Joshua I.; Basile, Jan N.; Henriquez, Mario A.; Huml, Anne; Kopyt, Nelson; Louis, Gail T.; Pressel, Sara L.; Rosendorff, Clive; Sastrasinh, Sithiporn; Stanford, Carol

2013-01-01

Background/Aims: The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). Methods: Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. Results: Through Year 6, total cholesterol declined in pravastatin (–20.7%) and usual-care groups (–11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory “as-treated” analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 – 0.85), p < 0.001) and lower CHD (HR = 0.84 (0.73 – 0.97), p = 0.01), but not combined cardiovascular disease (HR = 0.95 (0.88 – 1.04), p = 0.30). Total cholesterol reduction of 10 mg/dl from baseline to Year 2 was associated with 5% lower CHD risk. Conclusions: In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory “as-treated” analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy. PMID:23816477

Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study.

PubMed

Chandrashekara, S; Patted, Anand

2017-07-01

The aim of this exploratory study is to estimate the relationship between vitamin D (vit D) deficiency and active rheumatoid arthritis (RA), and the role of supplementation in improving disease activity. A randomized recruitment, consent screening, open-label interventional study was conducted in patients who fulfilled American College of Rheumatology/European League Against Rheumatism 2010 criteria for diagnosing RA and on stable disease-modifying anti-rheumatic drugs (DMARDs) for 3 months. Serum vit D levels and Disease Activity Score of 28 joints/C-reactive protein (DAS28-CRP) disease activity status were estimated at the first visit. Subjects with low vit D levels and DAS28-CRP > 2.6 were supplemented with vit D for 12 weeks, and were assessed for improvement in disease activity and serum vit D levels. One hundred and fifty RA patients of mean age 49 ± 12.1 years, mean duration of illness 78 ± 63 months, and on treatment with DMARDs for 44 ± 39 months were recruited for the study. Of these, 73 (49%) subjects were found to have DAS28-CRP > 2.6 and serum vit D below 20 ng/mL. The patients received vit D supplement of 60 000 IU/week for 6 weeks, followed by 60 000 IU/month for a total duration of 3 months. Disease activity and vit D status were assessed for 59 (80.8%) patients who reported at the end of 12 weeks of treatment. Mean DAS28-CRP of these patients showed a statistically significant improvement from 3.68 ± 0.93 at baseline to 3.08 ± 1.11 after supplementation (P = 0.002). Serum vit D levels improved from 10.05 ± 5.18 to 57.21 ± 24.77 ng/mL (P < 0.001) during the period. Supplementation of vit D in RA patients with persisting disease activity and vit D deficiency contributed to significant improvement in disease activity within a short duration. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Coping with daily thermal variability: behavioural performance of an ectotherm model in a warming world.

PubMed

Rojas, José M; Castillo, Simón B; Folguera, Guillermo; Abades, Sebastián; Bozinovic, Francisco

2014-01-01

Global climate change poses one of the greatest threats to species persistence. Most analyses of the potential biological impacts have focused on changes in mean temperature, but changes in thermal variance will also impact organisms and populations. We assessed the effects of acclimation to daily variance of temperature on dispersal and exploratory behavior in the terrestrial isopod Porcellio laevis in an open field. Acclimation treatments were 24 ± 0, 24 ± 4 and 24 ± 8 °C. Because the performance of ectotherms relates nonlinearly to temperature, we predicted that animals acclimated to a higher daily thermal variation should minimize the time exposed in the centre of open field, --i.e. increase the linearity of displacements. Consistent with our prediction, isopods acclimated to a thermally variable environment reduce their exploratory behaviour, hypothetically to minimize their exposure to adverse environmental conditions. This scenario as well as the long latency of animals after releases acclimated to variable environments is consistent with this idea. We suggested that to develop more realistic predictions about the biological impacts of climate change, one must consider the interactions between the mean and variance of environmental temperature on animals' performance.

Coping with Daily Thermal Variability: Behavioural Performance of an Ectotherm Model in a Warming World

PubMed Central

Rojas, José M.; Castillo, Simón B.; Folguera, Guillermo; Abades, Sebastián; Bozinovic, Francisco

2014-01-01

Global climate change poses one of the greatest threats to species persistence. Most analyses of the potential biological impacts have focused on changes in mean temperature, but changes in thermal variance will also impact organisms and populations. We assessed the effects of acclimation to daily variance of temperature on dispersal and exploratory behavior in the terrestrial isopod Porcellio laevis in an open field. Acclimation treatments were 24±0, 24±4 and 24±8°C. Because the performance of ectotherms relates nonlinearly to temperature, we predicted that animals acclimated to a higher daily thermal variation should minimize the time exposed in the centre of open field, – i.e. increase the linearity of displacements. Consistent with our prediction, isopods acclimated to a thermally variable environment reduce their exploratory behaviour, hypothetically to minimize their exposure to adverse environmental conditions. This scenario as well as the long latency of animals after releases acclimated to variable environments is consistent with this idea. We suggested that to develop more realistic predictions about the biological impacts of climate change, one must consider the interactions between the mean and variance of environmental temperature on animals' performance. PMID:25207653

SNARE-mediated Fusion of Single Proteoliposomes with Tethered Supported Bilayers in a Microfluidic Flow Cell Monitored by Polarized TIRF Microscopy

PubMed Central

Nikolaus, Joerg; Karatekin, Erdem

2016-01-01

In the ubiquitous process of membrane fusion the opening of a fusion pore establishes the first connection between two formerly separate compartments. During neurotransmitter or hormone release via exocytosis, the fusion pore can transiently open and close repeatedly, regulating cargo release kinetics. Pore dynamics also determine the mode of vesicle recycling; irreversible resealing results in transient, "kiss-and-run" fusion, whereas dilation leads to full fusion. To better understand what factors govern pore dynamics, we developed an assay to monitor membrane fusion using polarized total internal reflection fluorescence (TIRF) microscopy with single molecule sensitivity and ~15 msec time resolution in a biochemically well-defined in vitro system. Fusion of fluorescently labeled small unilamellar vesicles containing v-SNARE proteins (v-SUVs) with a planar bilayer bearing t-SNAREs, supported on a soft polymer cushion (t-SBL, t-supported bilayer), is monitored. The assay uses microfluidic flow channels that ensure minimal sample consumption while supplying a constant density of SUVs. Exploiting the rapid signal enhancement upon transfer of lipid labels from the SUV to the SBL during fusion, kinetics of lipid dye transfer is monitored. The sensitivity of TIRF microscopy allows tracking single fluorescent lipid labels, from which lipid diffusivity and SUV size can be deduced for every fusion event. Lipid dye release times can be much longer than expected for unimpeded passage through permanently open pores. Using a model that assumes retardation of lipid release is due to pore flickering, a pore "openness", the fraction of time the pore remains open during fusion, can be estimated. A soluble marker can be encapsulated in the SUVs for simultaneous monitoring of lipid and soluble cargo release. Such measurements indicate some pores may reseal after losing a fraction of the soluble cargo. PMID:27585113

A Review of Pharmacologic Treatment for Compulsive Buying Disorder.

PubMed

Soares, Célia; Fernandes, Natália; Morgado, Pedro

2016-04-01

At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder.

Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

PubMed

Husted, David S; Shapira, Nathan A; Murphy, Tanya K; Mann, Giselle D; Ward, Herbert E; Goodman, Wayne K

2007-01-01

Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

Development of a protocol for staining BrdU-labeled cells within cryosections of bovine mammary tissue that is suitable for subsequent transcriptome analysis

USDA-ARS?s Scientific Manuscript database

Bromodeoxyuridine (BrdU) is a thymidine analog that is incorporated into the DNA of proliferating cells. Immunostaining of BrdU-labeled cells within a histological section requires heat or chemical-mediated antigen retrieval to open the dsDNA and expose the BrdU antigen. We found that in cryosection...

Methylmercuric Chloride Induces Activation of Neuronal Stress Circuitry and Alters Exploratory Behavior in the Mouse

PubMed Central

Cooper, Joel F.

2007-01-01

Methylmercury (MeHg) is a well known neurotoxicant, responsible for neurological and cognitive alterations. However, there is very little information available on the effects of MeHg administration on activation of murine neuronal pathways involved in the stress response, and whether this is altered as a function of repeated exposure to MeHg. Moreover, interactions between MeHg and other psychogenic and inflammatory stressors have yet to be fully determined. Acute intraperitoneal (IP) exposure of male C57BL/6J mice to MeHg (2−8 mg/Kg) dose-dependently attenuated exploratory behavior in the open field in the presence and absence of a novel object. In addition, increased numbers of c-Fos immunoreactive cells appeared in response to acute IP and ICV MeHg within thalamic (PVA/PV), hypothalamic (PVN), central amygdaloid (CeC), septal and hippocampal (dentate gyrus) nuclei, medial bed nucleus (BSTm) and the locus coeruleus (Lc). The increase in c-Fos positive cells in response to acute IP and ICV MeHg did not appear to be influenced further by open field exposure. Repeated administration of MeHg led to an attenuation of most parameters of open field behavior altered by acute MeHg. However, increased c-Fos was significant in the CeC, Dg, supracapsular bed nucleus (BSTs), and Lc. Moreover, open field exposure after repeated treatments resulted in significant c-Fos responses in similar areas. Interestingly, 3 days after the final repeated MeHg dose (2 or 4 mg/kg) c-Fos increases to an immunogenic stressor (LPS) were not affected by MeHg pretreatment. These results demonstrate that systemic exposure to acute and repeated MeHg serves to activate the brain's stress circuitry, and furthermore appears to engage normal neuronal habituation processes. PMID:17764854

Assessment of mouse anxiety-like behavior in the light-dark box and open-field arena: role of equipment and procedure.

PubMed

Kulesskaya, Natalia; Voikar, Vootele

2014-06-22

Light-dark box and open field are conventional tests for assessment of anxiety-like behavior in the laboratory mice, based on approach-avoidance conflict. However, except the basic principles, variations in the equipment and procedures are very common. Therefore, contribution of certain methodological issues in different settings was investigated. Three inbred strains (C57BL/6, 129/Sv, DBA/2) and one outbred stock (ICR) of mice were used in the experiments. An effect of initial placement of mice either in the light or dark compartment was studied in the light-dark test. Moreover, two tracking systems were applied - position of the animals was detected either by infrared sensors in square box (1/2 dark) or by videotracking in rectangular box (1/3 dark). Both approaches revealed robust and consistent strain differences in the exploratory behavior. In general, C57BL/6 and ICR mice showed reduced anxiety-like behavior as compared to 129/Sv and DBA/2 strains. However, the latter two strains differed markedly in their behavior. DBA/2 mice displayed high avoidance of the light compartment accompanied by thigmotaxis, whereas the hypoactive 129 mice spent a significant proportion of time in risk-assessment behavior at the opening between two compartments. Starting from the light side increased the time spent in the light compartment and reduced the latency to the first transition. In the open field arena, black floor promoted exploratory behavior - increased time and distance in the center and increased rearing compared to white floor. In conclusion, modifications of the apparatus and procedure had significant effects on approach-avoidance behavior in general whereas the strain rankings remained unaffected. Copyright © 2014 Elsevier Inc. All rights reserved.

Professionals learning together with patients: An exploratory study of a collaborative learning Fellowship programme for healthcare improvement.

PubMed

Myron, Rowan; French, Catherine; Sullivan, Paul; Sathyamoorthy, Ganesh; Barlow, James; Pomeroy, Linda

2018-05-01

Improving the quality of healthcare involves collaboration between many different stakeholders. Collaborative learning theory suggests that teaching different professional groups alongside each other may enable them to develop skills in how to collaborate effectively, but there is little literature on how this works in practice. Further, though it is recognised that patients play a fundamental role in quality improvement, there are few examples of where they learn together with professionals. To contribute to addressing this gap, we review a collaborative fellowship in Northwest London, designed to build capacity to improve healthcare, which enabled patients and professionals to learn together. Using the lens of collaborative learning, we conducted an exploratory study of six cohorts of the year long programme (71 participants). Data were collected using open text responses from an online survey (n = 31) and semi-structured interviews (n = 34) and analysed using an inductive open coding approach. The collaborative design of the Fellowship, which included bringing multiple perspectives to discussions of real world problems, was valued by participants who reflected on the safe, egalitarian space created by the programme. Participants (healthcare professionals and patients) found this way of learning initially challenging yet ultimately productive. Despite the pedagogical and practical challenges of developing a collaborative programme, this study indicates that opening up previously restricted learning opportunities as widely as possible, to include patients and carers, is an effective mechanism to develop collaborative skills for quality improvement.

A Valepotriate Fraction of Valeriana glechomifolia Shows Sedative and Anxiolytic Properties and Impairs Recognition But Not Aversive Memory in Mice

PubMed Central

Maurmann, Natasha; Reolon, Gustavo Kellermann; Rech, Sandra Beatriz; Fett-Neto, Arthur Germano; Roesler, Rafael

2011-01-01

Plants of the genus Valeriana (Valerianaceae) are used in traditional medicine as a mild sedative, antispasmodic and tranquilizer in many countries. This study was undertaken to explore the neurobehavioral effects of systemic administration of a valepotriate extract fraction of known quantitative composition of Valeriana glechomifolia (endemic of southern Brazil) in mice. Adult animals were treated with a single intraperitoneal injection of valepotriate fraction (VF) in the concentrations of 1, 3 or 10 mg kg−1, or with vehicle in the pre-training period before each behavioral test. During the exploration of an open field, mice treated with 10 mg kg−1 of VF showed reduced locomotion and exploratory behavior. Although overall habituation sessions for locomotion and exploratory behavior among vehicle control and doses of VF were not affected, comparison between open-field and habituation sessions within each treatment showed that VF administration at 1 and 10 mg kg−1 impaired habituation. In the elevated plus-maze test, mice treated with VF (10 mg kg−1) showed a significant increase in the percentage of time spent in the open arms without significant effects in the number of total arm entries. VF at 3 mg kg−1 produced an impairment of novel-object recognition memory. In contrast, VF did not affect fear-related memory assessed in an inhibitory avoidance task. The results indicate that VF can have sedative effects and affect behavioral parameters related to recognition memory. PMID:20047889

Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.

PubMed

Rog, David J; Nurmikko, Turo J; Young, Carolyn A

2007-09-01

Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS. The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD (Sativex (R), GW Pharmaceuticals plc, Salisbury, United Kingdom) oromucosal spray in CNP associated with MS. This uncontrolled, open-label trial was an indefinite-duration extension of a previously reported 5-week randomized study in patients with MS and CNP. In the initial trial, patients were randomized to placebo or THC/CBD. Patients were only required to maintain their existing analgesia in the randomized study. In the open-label trial they could vary their other analgesia as required. All patients (placebo and THC/CBD) who completed the randomized trial commenced the open-label follow-up on THC/CBD (27 mg/mL: 25 mg/mL). Patients titrated their dosage, maintaining their existing analgesia. The primary end point of the trial was the number, frequency, and type of adverse events (AEs) reported by patients. Secondary end points included changes from baseline in 11-point numerical rating scale (NRS-11) neuropathic pain score, hematology and clinical chemistry test results, vital signs, trial drug usage, and intoxication visual analogue scale scores. Sixty-six patients were enrolled in the randomized trial; 64 (97%) completed the randomized trial and 63 (95%) entered the open-label extension (race, white, 100%; sex, male, 14 [22%]; mean [SD] age, 49 [8.4] years [range, 27-71 years[). The mean (SD) duration of open-label treatment was 463 (378) days (median, 638 days; range, 3-917 days), with 34 (54%) patients completing >1 year of treatment with THC/CBD and 28 (44%) patients completing the open-label trial with a mean (SD) duration of treatment of 839 (42) days (median, 845 days; range, 701-917 days). Mean NRS-11 pain scores in the final week of the randomized trial were 3.8 in the treatment group and 5.0 in the placebo group. In the 28 (44%) patients who completed the 2-year follow up, the mean (SD) NRS-11 pain score in the final week of treatment was 2.9 (2.0) (range, 0-8.0). Fifty-eight (92%) patients experienced > or =1 treatment-related AE. These AEs were rated by the investigator as mild in 47 (75%) patients, moderate in 49 (78%), and severe in 32 (51%). The most commonly reported AEs were dizziness (27%), nausea (18 %), and feeling intoxicated (11%). Two treatment-related serious AEs (ventricular bigeminy and circulatory collapse) were judged to be treatment-related. Both serious AEs occurred in the same patient and resolved completely following a period of discontinuation. Eleven (17%) patients experienced oral discomfort, 4 persistently. Regular oral examinations revealed that 7 (11%) patients developed white buccal mucosal patches and 2 (3%) developed red buccal mucosal patches; all cases were deemed mild and resolved. Seventeen (25%) patients withdrew due to AEs. The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial. THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment (n = 28). Ninety-two percent of patients experienced an AE, the most common of which were dizziness and nausea. The majority of AEs were deemed to be of mild to moderate severity by the investigators.

Brain histamine depletion enhances the behavioural sequences complexity of mice tested in the open-field: Partial reversal effect of the dopamine D2/D3 antagonist sulpiride.

PubMed

Santangelo, Andrea; Provensi, Gustavo; Costa, Alessia; Blandina, Patrizio; Ricca, Valdo; Crescimanno, Giuseppe; Casarrubea, Maurizio; Passani, M Beatrice

2017-02-01

Markers of histaminergic dysregulation were found in several neuropsychiatric disorders characterized by repetitive behaviours, thoughts and stereotypies. We analysed the effect of acute histamine depletion by means of i. c.v. injections of alpha-fluoromethylhistidine, a blocker of histidine decarboxylase, on the temporal organization of motor sequences of CD1 mice behaviour in the open-field test. An ethogram encompassing 9 behavioural components was employed. Durations and frequencies were only slightly affected by treatments. However, as revealed by multivariate t-pattern analysis, histamine depletion was associated with a striking increase in the number of behavioural patterns. We found 42 patterns of different composition occurring, on average, 520.90 ± 50.23 times per mouse in the histamine depleted (HD) group, whereas controls showed 12 different patterns occurring on average 223.30 ± 20.64 times. Exploratory and grooming behaviours clustered separately, and the increased pattern complexity involved exclusively exploratory patterns. To test the hypothesis of a histamine-dopamine interplay on behavioural pattern phenotype, non-sedative doses of the D2/D3 antagonist sulpiride (12.5-25-50 mg/kg) were additionally administered to different groups of HD mice. Sulpiride counterbalanced the enhancement of exploratory patterns of different composition, but it did not affect the mean number of patterns at none of the doses used. Our results provide new insights on the role of histamine on repetitive behavioural sequences of freely moving mice. Histamine deficiency is correlated with a general enhancement of pattern complexity. This study supports a putative involvement of histamine in the pathophysiology of tics and related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploratory Application of Augmented Reality/Mixed Reality Devices for Acute Care Procedure Training.

PubMed

Kobayashi, Leo; Zhang, Xiao Chi; Collins, Scott A; Karim, Naz; Merck, Derek L

2018-01-01

Augmented reality (AR), mixed reality (MR), and virtual reality devices are enabling technologies that may facilitate effective communication in healthcare between those with information and knowledge (clinician/specialist; expert; educator) and those seeking understanding and insight (patient/family; non-expert; learner). Investigators initiated an exploratory program to enable the study of AR/MR use-cases in acute care clinical and instructional settings. Academic clinician educators, computer scientists, and diagnostic imaging specialists conducted a proof-of-concept project to 1) implement a core holoimaging pipeline infrastructure and open-access repository at the study institution, and 2) use novel AR/MR techniques on off-the-shelf devices with holoimages generated by the infrastructure to demonstrate their potential role in the instructive communication of complex medical information. The study team successfully developed a medical holoimaging infrastructure methodology to identify, retrieve, and manipulate real patients' de-identified computed tomography and magnetic resonance imagesets for rendering, packaging, transfer, and display of modular holoimages onto AR/MR headset devices and connected displays. Holoimages containing key segmentations of cervical and thoracic anatomic structures and pathology were overlaid and registered onto physical task trainers for simulation-based "blind insertion" invasive procedural training. During the session, learners experienced and used task-relevant anatomic holoimages for central venous catheter and tube thoracostomy insertion training with enhanced visual cues and haptic feedback. Direct instructor access into the learner's AR/MR headset view of the task trainer was achieved for visual-axis interactive instructional guidance. Investigators implemented a core holoimaging pipeline infrastructure and modular open-access repository to generate and enable access to modular holoimages during exploratory pilot stage applications for invasive procedure training that featured innovative AR/MR techniques on off-the-shelf headset devices.

Exploratory Application of Augmented Reality/Mixed Reality Devices for Acute Care Procedure Training

PubMed Central

Kobayashi, Leo; Zhang, Xiao Chi; Collins, Scott A.; Karim, Naz; Merck, Derek L.

2018-01-01

Introduction Augmented reality (AR), mixed reality (MR), and virtual reality devices are enabling technologies that may facilitate effective communication in healthcare between those with information and knowledge (clinician/specialist; expert; educator) and those seeking understanding and insight (patient/family; non-expert; learner). Investigators initiated an exploratory program to enable the study of AR/MR use-cases in acute care clinical and instructional settings. Methods Academic clinician educators, computer scientists, and diagnostic imaging specialists conducted a proof-of-concept project to 1) implement a core holoimaging pipeline infrastructure and open-access repository at the study institution, and 2) use novel AR/MR techniques on off-the-shelf devices with holoimages generated by the infrastructure to demonstrate their potential role in the instructive communication of complex medical information. Results The study team successfully developed a medical holoimaging infrastructure methodology to identify, retrieve, and manipulate real patients’ de-identified computed tomography and magnetic resonance imagesets for rendering, packaging, transfer, and display of modular holoimages onto AR/MR headset devices and connected displays. Holoimages containing key segmentations of cervical and thoracic anatomic structures and pathology were overlaid and registered onto physical task trainers for simulation-based “blind insertion” invasive procedural training. During the session, learners experienced and used task-relevant anatomic holoimages for central venous catheter and tube thoracostomy insertion training with enhanced visual cues and haptic feedback. Direct instructor access into the learner’s AR/MR headset view of the task trainer was achieved for visual-axis interactive instructional guidance. Conclusion Investigators implemented a core holoimaging pipeline infrastructure and modular open-access repository to generate and enable access to modular holoimages during exploratory pilot stage applications for invasive procedure training that featured innovative AR/MR techniques on off-the-shelf headset devices. PMID:29383074

Effects of cholinergic system of dorsal hippocampus of rats on MK-801 induced anxiolytic-like behavior.

PubMed

Zarrindast, Mohammad Reza; Nasehi, Mohammad; Piri, Morteza; Heidari, Negar

2011-11-14

Some investigations have shown that the glutamate receptors play a critical role in cognitive processes such as learning and anxiety. The possible involvement of the cholinergic system of the dorsal hippocampus in the anxiolytic-like response induced by MK-801, NMDA receptor antagonist, was investigated in the present study. Male Wistar rats were used in the elevated plus maze apparatus to test the parameters: open arm time (%OAT), open arm entries (%OAE), close arm time (%CAT), close arm entries (%CAE) and other exploratory behaviors (locomotor activity, grooming, rearing and defecation) of anxiety-like response. The data indicated that intra-CA1 administration of MK-801 increased %OAT (2μg/rat) and %OAE (1 and 2μg/rat) while decreased %CAT and %CAE and did not alter other exploratory behaviors, indicating an anxiolytic-like effect. Moreover, intra-hippocampal injections of mecamylamine, a cholinergic receptor antagonists (2μg/rat) and scopolamine (4μg/rat), by themselves, 5min before testing, increased %OAT and %OAE but decreased %CAT and %CAE and did not alter locomotor activity and other exploratory behaviors, suggesting an anxiolytic-like effect. On the other hand, intra-CA1 co-administration of an ineffective dose of scopolamine (3μg/rat), but not mecamylamine (1μg/rat), with an ineffective dose of MK-801 (0.5μg/rat) increased %OAT and %OAE and decreased %CAT and %CAE. The data may indicate the possible involvement of the cholinergic system of the CA1 in the anxiolytic-like response induced by MK-801. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

68Ga-Labeled PSMA Uptake in Nonprostatic Malignancies: Has the Time Come to Remove "PS" From PSMA?

PubMed

Malik, Dharmender; Kumar, Rajender; Mittal, Bhagwant Rai; Singh, Harmandeep; Bhattacharya, Anish; Singh, Shrawan Kumar

2018-04-23

PET/CT with Ga-labeled prostate-specific membrane antigen (PSMA) is increasingly recognized as the best imaging modality for disease staging and detection of recurrent prostate cancer. Despite its name, PSMA expression has been reported in a number of nonprostatic benign and malignant pathologies. Apparently, angioneogenesis is the mechanism attributed to increased Ga-PSMA uptake at these sites. Here we illustrate the utility of Ga-PSMA in 5 nonprostatic malignancies that could open up new possibilities for diagnostics and theranostic concepts with PSMA labeled radioligands in nonprostate tumor entities.

Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders.

PubMed

Schneider, Patrick; Petzold, Sandra; Sommer, Angela; Nitsch, Robert; Schwegler, Herbert; Vogt, Johannes; Roskoden, Thomas

2018-01-15

Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1 -/- ) mice and PRG-1/LPA 2 -receptor double knockout (PRG-1 -/- /LPA 2 -/- ) mice in two open field settings of different size and assessing motor behavior in the Rota Rod test. PRG-1 -/- mice displayed significantly longer path lengths and higher running speed in both open field conditions. In addition, PRG-1 -/- mice spent significantly longer time in the larger open field and displayed rearing and self-grooming behavior. Furthermore PRG-1 -/- mice displayed stereotypical behavior resembling phenotypes of psychiatric disorders in the smaller sized open field arena. Altogether, this behavior is similar to the stereotypical behavior observed in animal models for psychiatric disease of autistic spectrum disorders which reflects a disrupted balance between glutamatergic and GABAergic synapses. These differences indicate an altered excitation/inhibition balance in neuronal circuits in PRG-1 -/- mice as recently shown in the somatosensory cortex [38]. In contrast, PRG-1 -/- /LPA 2 -/- did not show significant changes in behavior in the open field suggesting that these specific alterations were abolished when the LPA 2 -receptor was lacking. Our findings indicate that PRG-1 deficiency led to over-excitability caused by an altered LPA/LPA 2 -R signaling inducing a behavioral phenotype typically observed in animal models for psychiatric disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Variable stars around selected open clusters in the VVV area: Young Stellar Objects

NASA Astrophysics Data System (ADS)

Medina, Nicolas; Borissova, Jura; Bayo, Amelia; Kurtev, Radostin; Lucas, Philip

2017-09-01

Time-varying phenomena are one of the most substantial sources of astrophysical information, and led to many fundamental discoveries in modern astronomy. We have developed an automated tool to search and analyze variable sources in the near infrared Ks band, using the data from the Vista Variables in the Vía Láctea (VVV) ESO Public Survey ([5, 8]). One of our main goals is to investigate the Young Stellar Objects (YSOs) in the Galactic star forming regions, looking for: •Variability. •New pre-main sequence star clusters. Here we present the newly discovered YSOs within some selected stellar clusters in our Galaxy.

Pharmacokinetic and pharmacodynamic characterization of a new formulation containing synergistic proportions of interferons alpha-2b and gamma (HeberPAG®) in patients with mycosis fungoides: an open-label trial

PubMed Central

2012-01-01

Background The synergistic combination of interferon (IFN) alpha-2b and IFN gamma results in more potent in vitro biological effects mediated by both IFNs. The aim of this investigation was to evaluate by first time the pharmacokinetics and pharmacodynamics of this combination in patients with mycosis fungoides. Methods An exploratory, prospective, open-label clinical trial was conducted. Twelve patients, both genders, 18 to 75 years-old, with mycosis fungoides at stages IB to III, were eligible for the study. All of them received intramuscularly a single high dose (23 × 106 IU) of a novel synergistic IFN mixture (HeberPAG®) for pharmacokinetic and pharmacodynamic studies. Serum IFN alpha-2b and IFN gamma concentrations were measured during 96 hours by commercial enzyme immunoassays (EIA) specific for each IFN. Other blood IFN-inducible markers and laboratory variables were used as pharmacodynamics and safety criteria. Results The pharmacokinetic evaluation by EIA yielded a similar pattern for both IFNs that are also in agreement with the well-known described profiles for these molecules when these are administered separately. The average values for main parameters were: Cmax: 263 and 9.3 pg/mL; Tmax: 9.5 and 6.9 h; AUC: 4483 and 87.5 pg.h/mL, half-life (t1/2): 4.9 and 13.4 h; mean residence time (MRT): 13.9 and 13.5 h, for serum IFN alpha-2b and IFN gamma, respectively. The pharmacodynamic variables were strongly stimulated by simultaneous administration of both IFNs: serum neopterin and beta-2 microglobulin levels (β2M), and stimulation of 2’-5’ oligoadenylate synthetase (OAS1) mRNA expression. The most encouraging data was the high increment of serum neopterin, 8.0 ng/mL at 48 h, not been described before for any unmodified or pegylated IFN. Additionally, β2M concentration doubled the pre-dose value at 24–48 hours. For both variables the values remained clearly upper baseline levels at 96 hours. Conclusions HeberPAG®possesses improved pharmacodynamic properties that may be very useful in the oncologic setting. Efficacy trials can be carried out to confirm these findings. Trial registration Registro Público Cubano de Ensayos Clínicos RPCEC00000130 PMID:23272809

An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes.

PubMed

Ratliff, Joseph C; Palmese, Laura B; Reutenauer, Erin L; Tek, Cenk

2015-01-01

A possible mechanism of antipsychotic-induced weight gain is activation of hypothalamic monophosphate-dependent kinase (AMPK) mediated by histamine 1 receptors. Alpha-lipoic acid (ALA), a potent antioxidant, counteracts this effect and may be helpful in reducing weight for patients taking antipsychotics. The objective of this open-label study was to assess the efficacy of ALA (1,200 mg) on twelve non-diabetic schizophrenia patients over ten weeks. Participants lost significant weight during the intervention (-2.2 kg±2.5 kg). ALA was well tolerated and was particularly effective for individuals taking strongly antihistaminic antipsychotics (-2.9 kg±2.6 kg vs. -0.5 kg±1.0 kg). NCT01355952.

Role of ranitidine in negative symptoms of schizophrenia--an open label study.

PubMed

Mehta, Varun S; Ram, Daya

2014-12-01

In this open label study, 75 patients with a diagnosis of schizophrenia were randomized to three groups of 25 each, receiving 150mg/day ranitidine, 300mg/day ranitidine and receiving only olanzapine. They were rated on PANSS at baseline, 4 and 8 weeks. There was a significant reduction in the scores of negative scale in patients receiving 300mg/day ranitidine in comparison to patients not receiving ranitidine at the end of 4 weeks but was not seen again when assessed at the end of 8 weeks. Though effective in reducing the negative symptoms, the effect was not sustained due to the tolerance to the actions of ranitidine. Copyright © 2014 Elsevier B.V. All rights reserved.

Mysteries in the Night: An Exploratory Study of Student Use and Perceptions of 24/5 Hours

ERIC Educational Resources Information Center

Sowell, Steven L.; Nutefall, Jennifer E.

2014-01-01

The Oregon State University Valley Library has been open 24 hours per day, five days per week, during regular academic terms since 2010. The authors collected survey data during 2012 to explore how students used the hours and whether they perceived that the provision of 24/5 hours contributes to their academic success. Nearly 90% of the…

Use of Automated Scoring in Spoken Language Assessments for Test Takers with Speech Impairments. Research Report. ETS RR-17-42

ERIC Educational Resources Information Center

Loukina, Anastassia; Buzick, Heather

2017-01-01

This study is an evaluation of the performance of automated speech scoring for speakers with documented or suspected speech impairments. Given that the use of automated scoring of open-ended spoken responses is relatively nascent and there is little research to date that includes test takers with disabilities, this small exploratory study focuses…

10. COPY OF PHOTOGRAPH TAKEN SEPT. 21, 1926. LABELED 'MCKINNEY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. COPY OF PHOTOGRAPH TAKEN SEPT. 21, 1926. LABELED 'MCKINNEY STEEL PLANT.' PHOTO SHOWS THE ORIGINAL NUCLEUS OF CORRIGAN, MCKINNEY CO. STEEL PLANT: MIXER BUILDING, OPEN HEARTH BUILDING, 40-INCH BLOOMING MILL (21 inch and 18 inch SHEET BAR AND BILLET MILLS NOT VISIBLE.) VIEW LOOKING NORTH. PHOTO COURTESY THE CLEVELAND PLAIN DEALER. - Corrigan, McKinney Steel Company, 3100 East Forty-fifth Street, Cleveland, Cuyahoga County, OH

ESF GROUND SUPPORT - MATERIAL DEDICATION ANALYSIS FOR STRUCTURAL STEEL AND ACCESSORIES FROM A COMMERCIAL GRADE SOURCE

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

M.D. Stine

1996-01-23

The purpose of this analysis is to select the critical characteristics to be verified for steel sets and accessories and the verification methods to be implemented through a material dedication process for the procurement and use of commercial grade structural steel sets and accessories (which have a nuclear safety function) to be used in ground support (with the exception of alcove ground support and alcove opening framing, which are not addressed in this analysis) for the Exploratory Studies Facility (ESF) Topopah Spring (TS) Loop. The ESF TS Loop includes the North Ramp, Main Drift, and South Ramp underground openings.

Effect of vacuum-assisted closure combined with open bone grafting to promote rabbit bone graft vascularization.

PubMed

Hu, Chao; Zhang, Taogen; Ren, Bin; Deng, Zhouming; Cai, Lin; Lei, Jun; Ping, Ansong

2015-04-27

Patients with composite bone non-union and soft tissue defects are difficult to treat. Vacuum-assisted closure (VAC) combined with open bone grafting is one of the most effective treatments at present. The aim of the present study was to preliminarily investigate the effect and mechanism of VAC combined with open bone grafting to promote rabbit bone graft vascularization, and to propose a theoretical basis for clinical work. Twenty-four New Zealand white rabbits were randomly divided into an experimental and a control group. Allogeneic bones were grafted and banded with the proximal femur with a suture. The experimental group had VAC whereas the control group had normal wound closure. The bone vascularization rate was compared based on X-ray imaging, fluorescent bone labeling (labeled tetracycline hydrochloride and calcein), calcium content in the callus, and expression of fibroblast growth factor-2 (FGF-2) in bone allografts by Western blot analysis at the 4th, 8th, and 12th week after surgery. At the 4th, 8th, and 12th week after surgery, the results of the tests demonstrated that the callus was larger, contained more calcium (p<0.05), and expressed FGF-2 at higher levels (p<0.05) in the experimental group than in the control group. Fluorescent bone labeling showed the distance between the two fluorescent ribbons was significantly shorter in the control group than in the experimental group at the 8th and 12th week after surgery. VAC combined with open bone grafting promoted rabbit bone graft vascularization.

Ramelteon for Insomnia Symptoms in a Community Sample of Adults with Generalized Anxiety Disorder: An Open Label Study

PubMed Central

Gross, Paul K.; Nourse, Rosemary; Wasser, Thomas E.

2009-01-01

Objective: Prior research confirms the relationship between insomnia and psychiatric disorders, particularly anxiety and depression. The effectiveness and tolerability of ramelteon was examined in adult generalized anxiety disorder (GAD) patients with insomnia symptoms. Methods: Twenty-seven adults with sleep disturbance meeting DSM-IV diagnostic criteria for GAD and partially responsive on an SSRI or SNRI by randomization visit (as signified by a Hamilton Anxiety scale [HAMA] maximum score of 15 and minimum of 8, Clinical Global Impressions Severity of Illness [CGI-S] scale of ≤ 4 and ≥ 2 [measuring anxiety symptoms], CGI-S of ≥ 4 [measuring insomnia symptoms], ≥ 5 on the Pittsburgh Sleep Quality Index [PSQI], and ≥ 10 on the Epworth Sleepiness Scale [ESS]) were treated openly for 10 weeks on ramelteon 8 mg at bedtime. Analysis was conducted using repeated measures methodology. Patient reported sleep diaries were maintained throughout the study. Results: Significant symptom reduction was observed on all scales (HAMA, ESS, CGI-I, CGI-S), with subjects falling asleep faster and sleeping longer. Headache upon stopping ramelteon, daytime tiredness, agitation, and depression were the most commonly reported side effects and were cited as transient. Conclusion: Data from this 12-week open-label study suggests ramelteon is an effective and generally well tolerated treatment for insomnia symptoms in this community sample of adults with GAD. Citation: Gross PK; Nourse R; Wasser TE. Ramelteon for insomnia symptoms in a community sample of adults with generalized anxiety disorder: an open label study. J Clin Sleep Med 2009;5(1):28–33. PMID:19317378

Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2).

PubMed

Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Hoeper, Marius M; Jansa, Pavel; Kim, Nick H; Wang, Chen; Wilkins, Martin R; Fritsch, Arno; Davie, Neil; Colorado, Pablo; Mayer, Eckhard

2015-05-01

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1 baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year. Copyright ©ERS 2015.

The effects of apremilast on the QTc interval in healthy male volunteers: a formal, thorough QT study

PubMed Central

Palmisano, Maria; Wu, Anfan; Assaf, Mahmoud; Liu, Liangang; Park, C. Hyung; Savant, Ishani; Liu, Yong; Zhou, Simon

2016-01-01

Objective: This study was conducted to evaluate the effect of apremilast and its major metabolites on the placebo-corrected change-from-baseline QTc interval of an electrocardiogram (ECG). Materials and methods: Healthy male subjects received each of 4 treatments in a randomized, crossover manner. In the 2 active treatment periods, apremilast 30 mg (therapeutic exposure) or 50 mg (supratherapeutic exposure) was administered twice daily for 9 doses. A placebo control was used to ensure double-blind treatment of apremilast, and an open-label, single dose of moxifloxacin 400 mg was administered as a positive control. ECGs were measured using 24-hour digital Holter monitoring. Results: The two-sided 98% confidence intervals (CIs) for ΔΔQTcI of moxifloxacin completely exceeded 5 ms 2 – 4 hours postdose. For both apremilast dose studies, the least-squares mean ΔΔQTcI was < 1 ms at all time points, and the upper limit of two-sided 90% CIs was < 10 ms. There were no QT/QTc values > 480 ms or a change from baseline > 60 ms. Exploratory evaluation of pharmacokinetic/pharmacodynamic data showed no trend between the changes in QT/QTc interval and the concentration of apremilast or its major metabolites M12 and M14. Conclusions: Apremilast did not prolong the QT interval and appears to be safe and well tolerated up to doses of 50 mg twice daily. PMID:27285466

Sodium-glucose co-transporter-2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: A randomized, open-label, 3-arm parallel comparative, exploratory study.

PubMed

Yabe, Daisuke; Iwasaki, Masahiro; Kuwata, Hitoshi; Haraguchi, Takuya; Hamamoto, Yoshiyuki; Kurose, Takeshi; Sumita, Kiminobu; Yamazato, Hitoshi; Kanada, Shigeto; Seino, Yutaka

2017-05-01

This study investigated the safety and efficacy of the sodium-glucose co-transporter-2 (SGLT2) inhibitor luseogliflozin with differing carbohydrate intakes in Japanese individuals with type 2 diabetes (T2D). Participants were randomly assigned to 3 carbohydrate-adjusted meals for 14 days (days 1-14; a high carbohydrate [HC; 55% total energy carbohydrate] and high glycaemic index [HGI] meal; an HC [55% total energy carbohydrate] and low glycaemic index [LGI] meal; or a low carbohydrate [LC; 40% total energy carbohydrate] and HGI meal). All participants received luseogliflozin for the last 7 days (days 8-14), continuous glucose monitoring (CGM) before and after luseogliflozin treatment (days 5-8 and days 12-15) and blood tests on days 1, 8 and 15. Luseogliflozin significantly decreased the area under the curve and mean of CGM values in all 3 groups similarly. Fasting plasma glucose, insulin and glucagon were similar at all time points. Ketone bodies on day 15 were significantly higher in the LC-HGI group compared with the HC-HGI and HC-LGI groups. In conclusion, luseogliflozin has similar efficacy and safety in Japanese people with T2D when meals contain 40% to 55% total energy carbohydrate, but a strict LC diet on this class of drug should be avoided to prevent SGLT2 inhibitor-associated diabetic ketoacidosis. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Effects of yoga breathing exercises on pulmonary function in patients with Duchenne muscular dystrophy: an exploratory analysis*, **

PubMed Central

Rodrigues, Marcos Rojo; Carvalho, Celso Ricardo Fernandes; Santaella, Danilo Forghieri; Lorenzi-Filho, Geraldo; Marie, Suely Kazue Nagahashi

2014-01-01

OBJECTIVE: Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in children, and children with DMD die prematurely because of respiratory failure. We sought to determine the efficacy and safety of yoga breathing exercises, as well as the effects of those exercises on respiratory function, in such children. METHODS: This was a prospective open-label study of patients with a confirmed diagnosis of DMD, recruited from among those followed at the neurology outpatient clinic of a university hospital in the city of São Paulo, Brazil. Participants were taught how to perform hatha yoga breathing exercises and were instructed to perform the exercises three times a day for 10 months. RESULTS: Of the 76 patients who entered the study, 35 dropped out and 15 were unable to perform the breathing exercises, 26 having therefore completed the study (mean age, 9.5 ± 2.3 years; body mass index, 18.2 ± 3.8 kg/m2). The yoga breathing exercises resulted in a significant increase in FVC (% of predicted: 82.3 ± 18.6% at baseline vs. 90.3 ± 22.5% at 10 months later; p = 0.02) and FEV1 (% of predicted: 83.8 ± 16.6% at baseline vs. 90.1 ± 17.4% at 10 months later; p = 0.04). CONCLUSIONS: Yoga breathing exercises can improve pulmonary function in patients with DMD. PMID:24831396

Atmospheric scanning electron microscope observes cells and tissues in open medium through silicon nitride film.

PubMed

Nishiyama, Hidetoshi; Suga, Mitsuo; Ogura, Toshihiko; Maruyama, Yuusuke; Koizumi, Mitsuru; Mio, Kazuhiro; Kitamura, Shinichi; Sato, Chikara

2010-03-01

Direct observation of subcellular structures and their characterization is essential for understanding their physiological functions. To observe them in open environment, we have developed an inverted scanning electron microscope with a detachable, open-culture dish, capable of 8 nm resolution, and combined with a fluorescence microscope quasi-simultaneously observing the same area from the top. For scanning electron microscopy from the bottom, a silicon nitride film window in the base of the dish maintains a vacuum between electron gun and open sample dish while allowing electrons to pass through. Electrons are backscattered from the sample and captured by a detector under the dish. Cells cultured on the open dish can be externally manipulated under optical microscopy, fixed, and observed using scanning electron microscopy. Once fine structures have been revealed by scanning electron microscopy, their component proteins may be identified by comparison with separately prepared fluorescence-labeled optical microscopic images of the candidate proteins, with their heavy-metal-labeled or stained ASEM images. Furthermore, cell nuclei in a tissue block stained with platinum-blue were successfully observed without thin-sectioning, which suggests the applicability of this inverted scanning electron microscope to cancer diagnosis. This microscope visualizes mesoscopic-scale structures, and is also applicable to non-bioscience fields including polymer chemistry. (c) 2010 Elsevier Inc. All rights reserved.

An open treatment trial of venlafaxine for elderly patients with dysthymic disorder.

PubMed

Devanand, D P; Juszczak, Nicole; Nobler, Mitchell S; Turret, Nancy; Fitzsimons, Linda; Sackeim, Harold A; Roose, Steven P

2004-12-01

Treatment response and side effects of venlafaxine were evaluated in an open-label trial of elderly outpatients with dysthymic disorder (DD). Patients received flexible dose (up to 300 mg/d) venlafaxine (Effexor XR) for 12 weeks. Of 23 study patients, 18 completed the trial. Fourteen (60.9%) were responders in intent-to-treat analyses with the last observation carried forward, and 77.8% were responders in completer analyses. Nearly half the sample (47.8%) met criteria for remission. In the intent-to-treat sample, increased severity of depression at baseline was associated with superior response, and the presence of cardiovascular disease was associated with poorer response. Venlafaxine open-label treatment was associated with fairly high response rates and generally good tolerability in elderly patients with DD. These results indicate that in elderly patients with DD, placebo-controlled trials of a dual reuptake inhibitor such as venlafaxine would be needed to assess its efficacy or to compare its efficacy to that of other antidepressants.

Detection of Myoglobin with an Open-Cavity-Based Label-Free Photonic Crystal Biosensor.

PubMed

Zhang, Bailin; Tamez-Vela, Juan Manuel; Solis, Steven; Bustamante, Gilbert; Peterson, Ralph; Rahman, Shafiqur; Morales, Andres; Tang, Liang; Ye, Jing Yong

2013-01-01

The label-free detection of one of the cardiac biomarkers, myoglobin, using a photonic-crystal-based biosensor in a total-internal-reflection configuration (PC-TIR) is presented in this paper. The PC-TIR sensor possesses a unique open optical microcavity that allows for several key advantages in biomolecular assays. In contrast to a conventional closed microcavity, the open configuration allows easy functionalization of the sensing surface for rapid biomolecular binding assays. Moreover, the properties of PC structures make it easy to be designed and engineered for operating at any optical wavelength. Through fine design of the photonic crystal structure, biochemical modification of the sensor surface, and integration with a microfluidic system, we have demonstrated that the detection sensitivity of the sensor for myoglobin has reached the clinically significant concentration range, enabling potential usage of this biosensor for diagnosis of acute myocardial infarction. The real-time response of the sensor to the myoglobin binding may potentially provide point-of-care monitoring of patients and treatment effects.

An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women.

PubMed

Kious, Brent M; Sabic, Hana; Sung, Young-Hoon; Kondo, Douglas G; Renshaw, Perry

2017-10-01

Many women with major depressive disorder (MDD) respond inadequately to standard treatments. Augmentation of conventional antidepressants with creatine monohydrate and 5-hydroxytryptophan (5-HTP) could correct deficits in serotonin production and brain bioenergetics associated with depression in women, yielding synergistic benefit. We describe an open-label study of 5-HTP and creatine augmentation in women with MDD who had failed selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) monotherapy. Fifteen women who were adequately adherent to an SSRI or SNRI and currently experiencing MDD, with a 17-item Hamilton Depression Rating Scale (HAM-D) score of 16 or higher, were treated with 5 g of creatine monohydrate daily and 100 mg of 5-HTP twice daily for 8 weeks, with 4 weeks of posttreatment follow-up. The primary outcome was change in mean HAM-D scores. Mean HAM-D scores declined from 18.9 (SD, 2.5) at pretreatment visits to 7.5 (SD, 4.4) (P < 0.00001), a decrease of 60%. Participants did not experience any serious treatment-related adverse events. Combination treatment with creatine and 5-HTP may represent an effective augmentation strategy for women with SSRI- or SNRI-resistant depression. Given the limitations of this small, open-label trial, future study in randomized, placebo-controlled trials is warranted.

Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study

PubMed Central

Thonnard, Marie; Gosseries, Olivia; Demertzi, Athena; Lugo, Zulay; Vanhaudenhuyse, Audrey; Bruno, Marie-Aurélie; Chatelle, Camille; Thibaut, Aurore; Charland-Verville, Vanessa; Habbal, Dina; Schnakers, Caroline; Laureys, Steven

2013-01-01

Summary Zolpidem has been reported as an “awakening drug” in some patients with disorders of consciousness (DOC). We here present the results of a prospective open-label study in chronic DOC patients. Sixty patients (35±15 years; 18 females; mean time since insult ± SD: 4±5.5 years; 31 with traumatic etiology) with a diagnosis of vegetative state/unresponsive wakefulness syndrome (n=28) or minimally conscious state (n=32) were behaviorally assessed using the Coma Recovery Scale-Revised (CRS-R) before and one hour after administration of 10 mg of zolpidem. At the group level, the diagnosis did not change after intake of zolpidem (p=0.10) and CRS-R total scores decreased (p=0.01). Twelve patients (20%) showed improved behaviors and/or CRS-R total scores after zolpidem administration but in only one patient was the diagnosis after zolpidem intake found to show a significant improvement (functional object use), which suggested a change of diagnosis. However, in this patient, a double-blind placebo-controlled trial was performed in order to better specify the effects of zolpidem, but the patient, on this trial, failed to show any clinical improvements. The present open-label study therefore failed to show any clinically significant improvement (i.e., change of diagnosis) in any of the 60 studied chronic DOC patients. PMID:24598393

An open-label six-month extension study to investigate the safety and efficacy of an extract of Artemisia annua for managing pain, stiffness and functional limitation associated with osteoarthritis of the hip and knee.

PubMed

Hunt, Sheena; Stebbings, Simon; McNamara, Debra

2016-10-28

This six-month single-centre open-label extension study, conducted at the University of Otago, Dunedin, follows from a previously published 12-week pilot double-blind randomised placebo-controlled study of dietary supplement, Arthrem® (ART) in patients with osteoarthritis (OA) of the hip or knee. The pilot double-blind study showed that treatment with ART 150 mg twice-daily was associated with clinically relevant pain reduction. The extension study aims were to assess longer-term safety and efficacy during six months' treatment following the pilot trial. Patients who completed the pilot double-blind study had the option to continue on open-label treatment with ART for a further six months. Safety was assessed by adverse event monitoring and laboratory tests at three and six months. Efficacy was assessed at three and six months using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®). Thirty-four patients entered the optional extension and 28 completed six months' treatment. ART was well tolerated when taken for up to nine months. Improvements in WOMAC® efficacy parameters reported in the double-blind phase of the study were maintained over six months. ART appears to be a safe and effective alternative for managing the symptoms of OA over an extended period.

Efficacy and tolerability of quetiapine in the treatment of bipolar disorder: preliminary evidence from a 12-month open-label study.

PubMed

Altamura, A C; Salvadori, Daniele; Madaro, Donato; Santini, Annalisa; Mundo, Emanuela

2003-09-01

The literature on the use of quetiapine for the treatment of bipolar disorder (BD) is limited to case reports, and there are no systematic studies on the efficacy of quetiapine in the prophylactic treatment of BD. The aim of the present study was to compare the efficacy of flexible doses of quetiapine and well established mood stabilizers in the maintenance treatment of BD. Twenty-eight DSM-IV BD outpatients were consecutively recruited into the study and were randomized to receive one of two open-label treatments, with quetiapine or classical mood stabilizers at flexible doses for 12 months. Clinical assessment was carried out using BPRS, CGI, YMRS and the 21-item HAM-D at baseline (T0) and every 2 months until the end of the study. ANOVAs with repeated measures were applied to the rating scale scores considering the time and the treatment group as main factors. All patients experienced a significant improvement on the BPRS, CGI and HAM-D scores, with no significant side-effects and a good compliance. This study should be considered preliminary given the small sample size investigated and the open-label design. If these results will be replicated on larger samples and in controlled studies, there could be relevant implications for the use of quetiapine as an alternative maintenance treatment for BD.

Effects of aripiprazole once-monthly on symptoms of schizophrenia in patients switched from oral antipsychotics.

PubMed

Peters-Strickland, Timothy; Zhao, Cathy; Perry, Pamela P; Eramo, Anna; Salzman, Phyllis M; McQuade, Robert D; Johnson, Brian R; Sanchez, Raymond

2016-12-01

To assess the effects of aripiprazole once-monthly 400 mg (AOM 400) on clinical symptoms and global improvement in schizophrenia after switching from an oral antipsychotic. In a multicenter, open-label, mirror-image, naturalistic study in patients with schizophrenia (>1 year, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR] criteria), changes in efficacy measures were assessed during prospective treatment (6 months) with AOM 400 after switching from standard-of-care oral antipsychotics. During prospective treatment, patients were cross-titrated to oral aripiprazole monotherapy (1-4) weeks followed by open-label AOM 400 (24 weeks). Mean change from baseline of the open-label AOM 400 phase in Positive and Negative Syndrome Scale (PANSS) scores (total, positive and negative subscales) and Clinical Global Impression-Severity (CGI-S) scores; mean CGI-Improvement (CGI-I) score; and proportion of responders (≥30% decrease from baseline in PANSS total score or CGI-I score of 1 [very much improved] or 2 [much improved]) were assessed. PANSS and CGI-S scores improved from baseline (P<0.0001) and CGI-I demonstrated improvement at all time points. By the end of the study, 49.0% of patients were PANSS or CGI-I responders. In a community setting, patients with schizophrenia who were stabilized at baseline and switched to AOM 400 from oral antipsychotics showed clear improvements in clinical symptoms.

Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years.

PubMed

Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

2014-12-01

Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained. Copyright © 2014 Elsevier Inc. All rights reserved.

Wide brick tunnel randomization - an unequal allocation procedure that limits the imbalance in treatment totals.

PubMed

Kuznetsova, Olga M; Tymofyeyev, Yevgen

2014-04-30

In open-label studies, partial predictability of permuted block randomization provides potential for selection bias. To lessen the selection bias in two-arm studies with equal allocation, a number of allocation procedures that limit the imbalance in treatment totals at a pre-specified level but do not require the exact balance at the ends of the blocks were developed. In studies with unequal allocation, however, the task of designing a randomization procedure that sets a pre-specified limit on imbalance in group totals is not resolved. Existing allocation procedures either do not preserve the allocation ratio at every allocation or do not include all allocation sequences that comply with the pre-specified imbalance threshold. Kuznetsova and Tymofyeyev described the brick tunnel randomization for studies with unequal allocation that preserves the allocation ratio at every step and, in the two-arm case, includes all sequences that satisfy the smallest possible imbalance threshold. This article introduces wide brick tunnel randomization for studies with unequal allocation that allows all allocation sequences with imbalance not exceeding any pre-specified threshold while preserving the allocation ratio at every step. In open-label studies, allowing a larger imbalance in treatment totals lowers selection bias because of the predictability of treatment assignments. The applications of the technique in two-arm and multi-arm open-label studies with unequal allocation are described. Copyright © 2013 John Wiley & Sons, Ltd.

Augmentation in the treatment of restless legs syndrome with transdermal rotigotine.

PubMed

Beneš, Heike; García-Borreguero, Diego; Ferini-Strambi, Luigi; Schollmayer, Erwin; Fichtner, Andreas; Kohnen, Ralf

2012-06-01

To assess the risk of augmentation under treatment with the transdermally delivered dopamine agonist rotigotine for restless legs syndrome (RLS). Experts in RLS augmentation retrospectively reviewed data from two double-blind, placebo-controlled 6-month trials (745 rotigotine and 214 placebo subjects, NCT00136045 and NCT00135993) and from two open-label 1-year trials (620 rotigotine subjects, NCT00498108 and NCT00263068). All study visits were systematically evaluated applying the Max Planck Institute (MPI) criteria for the diagnosis of both augmentation and clinically relevant augmentation. MPI criteria for augmentation were met on at least one visit by 8.2% of all subjects in the double-blind trials with 12 subjects meeting the criteria for clinically relevant augmentation: 11 under rotigotine (1.5%) and one under placebo treatment. In the open-label trials, 9.7% of all subjects met the MPI criteria for augmentation and 2.9% met the criteria for clinically relevant augmentation. None of the patients treated with rotigotine for up to 1.5 years (double-blind plus open-label trial) discontinued prematurely owing to augmentation. Neither could dose-dependency or a time pattern for clinically relevant augmentation episodes be detected. Our analyses suggest that the risk for clinically relevant augmentation for the duration of up to 18 months of rotigotine treatment is low. Copyright © 2012 Elsevier B.V. All rights reserved.

Efficacy, safety and risk of augmentation of rotigotine for treating restless legs syndrome.

PubMed

Inoue, Yuichi; Hirata, Koichi; Hayashida, Kenichi; Hattori, Nobutaka; Tomida, Takayuki; Garcia-Borreguero, Diego

2013-01-10

The present study aimed to examine the long-term efficacy and safety of rotigotine treatment for restless legs syndrome (RLS), as well as the rate of clinically significant augmentation, in a 1-year open-label study of Japanese subjects. Japanese patients with RLS who had been treated with rotigotine or placebo in a double-blind trial were enrolled in a 1-year, open-label, uncontrolled extension study and treated with rotigotine at a dose of up to 3 mg/24 h after an 8-week titration phase. Outcomes included International Restless Legs Syndrome Study Group rating scale (IRLS scale), Pittsburgh Sleep Quality Index (PSQI), safety, and investigator-/expert panel-assessed augmentation (including Augmentation Severity Rating Scale). Overall, 185 patients entered the open-label study and 133 completed the study. IRLS and PSQI total scores improved throughout the 52-week treatment period (IRLS, from 23.2±5.1 to 7.8±7.6 and PSQI, from 8.0±3.1 to 5.0±2.9). Treatment-emergent adverse events were mild to moderate in severity, and included application site reactions (52.4%) and nausea (28.6%). Clinically significant augmentation occurred in five patients (2.7%). These results indicate a good long-term efficacy of rotigotine for treating RLS, with a relatively low risk of clinically significant augmentation. Copyright © 2012 Elsevier Inc. All rights reserved.

Lyophilized Kit for the Preparation of the PET Perfusion Agent [(68)Ga]-MAA.

PubMed

Amor-Coarasa, Alejandro; Milera, Andrew; Carvajal, Denny; Gulec, Seza; McGoron, Anthony J

2014-01-01

Rapid developments in the field of medical imaging have opened new avenues for the use of positron emitting labeled microparticles. The radioisotope used in our research was (68)Ga, which is easy to obtain from a generator and has good nuclear properties for PET imaging. Methods. Commercially available macroaggregated albumin (MAA) microparticles were suspended in sterile saline, centrifuged to remove the free albumin and stannous chloride, relyophilized, and stored for later labeling with (68)Ga. Labeling was performed at different temperatures and times. (68)Ga purification settings were also tested and optimized. Labeling yield and purity of relyophilized MAA microparticles were compared with those that were not relyophilized. Results. MAA particles kept their original size distribution after relyophilization. Labeling yield was 98% at 75°C when a (68)Ga purification system was used, compared to 80% with unpurified (68)Ga. Radiochemical purity was over 97% up to 4 hours after the labeling. The relyophilized MAA and labeling method eliminate the need for centrifugation purification of the final product and simplify the labeling process. Animal experiments demonstrated the high in vivo stability of the obtained PET agent with more than 95% of the activity remaining in the lungs after 4 hours.

Computing distance distributions from dipolar evolution data with overtones: RIDME spectroscopy with Gd(iii)-based spin labels.

PubMed

Keller, Katharina; Mertens, Valerie; Qi, Mian; Nalepa, Anna I; Godt, Adelheid; Savitsky, Anton; Jeschke, Gunnar; Yulikov, Maxim

2017-07-21

Extraction of distance distributions between high-spin paramagnetic centers from relaxation induced dipolar modulation enhancement (RIDME) data is affected by the presence of overtones of dipolar frequencies. As previously proposed, we account for these overtones by using a modified kernel function in Tikhonov regularization analysis. This paper analyzes the performance of such an approach on a series of model compounds with the Gd(iii)-PyMTA complex serving as paramagnetic high-spin label. We describe the calibration of the overtone coefficients for the RIDME kernel, demonstrate the accuracy of distance distributions obtained with this approach, and show that for our series of Gd-rulers RIDME technique provides more accurate distance distributions than Gd(iii)-Gd(iii) double electron-electron resonance (DEER). The analysis of RIDME data including harmonic overtones can be performed using the MATLAB-based program OvertoneAnalysis, which is available as open-source software from the web page of ETH Zurich. This approach opens a perspective for the routine use of the RIDME technique with high-spin labels in structural biology and structural studies of other soft matter.

Transfer of phloem-mobile substances from the host plants to the holoparasite Cuscuta sp.

PubMed

Birschwilks, Mandy; Haupt, Sophie; Hofius, Daniel; Neumann, Stefanie

2006-01-01

During the development of the haustorium, searching hyphae of the parasite and the host parenchyma cells are connected by plasmodesmata. Using transgenic tobacco plants expressing a GFP-labelled movement protein of the tobacco mosaic virus, it was demonstrated that the interspecific plasmodesmata are open. The transfer of substances in the phloem from host to the parasite is not selective. After simultaneous application of (3)H-sucrose and (14)C-labelled phloem-mobile amino acids, phytohormones, and xenobiotica to the host, corresponding percentages of the translocated compounds are found in the parasite. An open continuity between the host phloem and the Cuscuta phloem via the haustorium was demonstrated in CLSM pictures after application of the phloem-mobile fluorescent probes, carboxyfluorescein (CF) and hydroxypyrene trisulphonic acid (HPTS), to the host. Using a Cuscuta bridge (14)C-sucrose and the virus PVY(N) were transferred from one host plant to the another. The results of translocation experiments with labelled compounds, phloem-mobile dyes and the virus should be considered as unequivocal evidence for a symplastic transfer of phloem solutes between Cuscuta species and their compatible hosts.

"Miscommunication" and Undergraduate Women's Conceptualizations of Sexual Assault: A Qualitative Analysis.

PubMed

Dardis, Christina M; Kraft, Kathryn M; Gidycz, Christine A

2017-08-01

Approximately 60% of legally defined rape victims do not label their experiences as "rape," most of whom label the experience as "a serious miscommunication." However, little research has examined why women choose this label. Labeling rape as a miscommunication could be problematic if chosen due to stereotypical conceptions that one's experience is not "real" rape. The present study used a mixed-methodological approach to understand why women might refer to rape as a "miscommunication," and how their reasons for labeling might differ from those who label their experiences and those who are nonlabeled (i.e., unequivocally state that they were "not victimized"). Participants included 123 undergraduate women who experienced rape. Participants responded to how they labeled rape and answered questions regarding assault characteristics, disclosure, reporting, and self- and perpetrator blame. Chi-square analyses assessed labeling group differences. Responses to an open-ended question about factors contributing to their labeling decision were content analyzed. Whereas miscommunication-labeled and nonlabeled victims reported similar assault characteristics in the quantitative analyses, qualitative content analyses revealed varying reasons for labeling rape as miscommunication, not victimization, and rape. Over three quarters of miscommunication-labeled victims reported that one or more of the following factors influenced their labeling: victim and perpetrator substance use, sexual activity prior to the rape, and perceptions that one did not express nonconsent strongly enough and that the perpetrator "did not realize" their lack of desire. Whereas miscommunication-labeled and nonlabeled victims reported similar assault characteristics, the extent to which those assault characteristics affected their labeling differed. Those who labeled their experiences as miscommunication gave reasons for their label that centered on factors which reflect inconsistencies between their experiences and "stereotypical rape." Misperceptions of rape can be addressed via prevention programming and clinical work.

26. DETAIL OF THE NORTH SIDE OF A RECTANGULAR COKE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

26. DETAIL OF THE NORTH SIDE OF A RECTANGULAR COKE OVEN. THE OVENS ADDRESS, '140', APPEARS ABOVE THE CENTER OF THE OVEN. THE CUT STONES LINING THE OPENINGS ARE NUMBERED AND LABELED 'L' AND 'R', INDICATING THEIR PROPER PLACEMENT ALONG THE ARCH. THE CENTER STONE IS LABELED 'KEY.' - Tower Hill No. 2 Mine, Approximately 0.47 mile Southwest of intersection of Stone Church Road & Township Route 561, Hibbs, Fayette County, PA

Confronting the Impact of Alcohol Labeling and Marketing on Native American Health and Culture. Hearing before the Select Committee on Children, Youth and Families. House of Representatives, One Hundred Second Congress, Second Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Select Committee on Children, Youth, and Families.

A congressional hearing examined the effects of alcohol labeling and marketing on Native American health and culture. The focus of the hearing was on "Crazy Horse" malt liquor, a product named for the spiritual and political leader of the Native American Sioux. Following opening remarks by presiding committee chairwoman, Patricia…

Impact of methionine oxidation on calmodulin structural dynamics

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

McCarthy, Megan R.; Thompson, Andrew R.; Nitu, Florentin

2015-01-09

Highlights: • We measured the distance distribution between two spin labels on calmodulin by DEER. • Two structural states, open and closed, were resolved at both low and high Ca. • Ca shifted the equilibrium toward the open state by a factor of 13. • Methionine oxidation, simulated by glutamine substitution, decreased the Ca effect. • These results have important implications for aging in muscle and other tissues. - Abstract: We have used electron paramagnetic resonance (EPR) to examine the structural impact of oxidizing specific methionine (M) side chains in calmodulin (CaM). It has been shown that oxidation of eithermore » M109 or M124 in CaM diminishes CaM regulation of the muscle calcium release channel, the ryanodine receptor (RyR), and that mutation of M to Q (glutamine) in either case produces functional effects identical to those of oxidation. Here we have used site-directed spin labeling and double electron–electron resonance (DEER), a pulsed EPR technique that measures distances between spin labels, to characterize the structural changes resulting from these mutations. Spin labels were attached to a pair of introduced cysteine residues, one in the C-lobe (T117C) and one in the N-lobe (T34C) of CaM, and DEER was used to determine the distribution of interspin distances. Ca binding induced a large increase in the mean distance, in concert with previous X-ray crystallography and NMR data, showing a closed structure in the absence of Ca and an open structure in the presence of Ca. DEER revealed additional information about CaM’s structural heterogeneity in solution: in both the presence and absence of Ca, CaM populates both structural states, one with probes separated by ∼4 nm (closed) and another at ∼6 nm (open). Ca shifts the structural equilibrium constant toward the open state by a factor of 13. DEER reveals the distribution of interprobe distances, showing that each of these states is itself partially disordered, with the width of each population ranging from 1 to 3 nm. Both mutations (M109Q and M124Q) decrease the effect of Ca on the structure of CaM, primarily by decreasing the closed-to-open equilibrium constant in the presence of Ca. We propose that Met oxidation alters CaM’s functional interaction with its target proteins by perturbing this Ca-dependent structural shift.« less

An Open-Label Study of Controlled-Release Melatonin in Treatment of Sleep Disorders in Children with Autism

ERIC Educational Resources Information Center

Giannotti, F.; Cortesi, F.; Cerquiglini, A.; Bernabei, P.

2006-01-01

Long-term effectiveness of controlled-release melatonin in 25 children, aged 2.6-9.6 years with autism without other coexistent pathologies was evaluated openly. Sleep patterns were studied using Children's Sleep Habits Questionnaire (CSHQ) and sleep diaries at baseline, after 1-3-6 months melatonin treatment and 1 month after discontinuation.…

Fluoxetine for the Treatment of Childhood Anxiety Disorders: Open-Label, Long-Term Extension to a Controlled Trial

ERIC Educational Resources Information Center

Clark, Duncan B.; Birmaher, Boris; Axelson, David; Monk, Kelly; Kalas, Catherine; Ehmann, Mary; Bridge, Jeffrey; Wood, D. Scott; Muthen, Bengt; Brent, David

2005-01-01

Objective: To assess the efficacy of fluoxetine for the long-term treatment of children and adolescents with anxiety disorders, including generalized anxiety disorder, separation anxiety disorder, and/or social phobia. Method: Children and adolescents (7-17 years old) with anxiety disorders were studied in open treatment for 1 year after they…

Effect of the Jigsaw-Based Cooperative Learning Method on Student Performance in the General Certificate of Education Advanced-Level Psychology: An Exploratory Brunei Case Study

ERIC Educational Resources Information Center

Azmin, Nur Hafizah

2016-01-01

The mixed-methods study investigated the effect of the jigsaw cooperative learning method on student performance in psychology and their views towards it. Experimental data were obtained via pre-and-post tests and an open-ended questionnaire from 16 conveniently selected students at one Sixth Form College in Brunei. Moreover, the participants…

Students' Views regarding the Use of the First Language: An Exploratory Study in a Tertiary Context Maximizing Target Language Use

ERIC Educational Resources Information Center

Rolin-Ianziti, Jeanne; Varshney, Rachel

2008-01-01

The present study investigates the functions that language learners attribute to the first language (L1) within a teaching context that maximizes the target language (TL). Beginners of French in an Australian university (N = 52) completed a questionnaire consisting of 21 closed questions on their views on L1/TL use and two open questions on the…

Development and Preliminary Feasibility Study of a Brief Behavioral Activation Mobile Application (Behavioral Apptivation) to Be Used in Conjunction With Ongoing Therapy.

PubMed

Dahne, Jennifer; Kustanowitz, Jacob; Lejuez, C W

2018-02-01

Depressive symptoms are the most frequently treated psychiatric condition in the United States. Brief behavioral activation treatment for depression (BATD) is a popular, evidence-based psychotherapy with strong research support for the treatment of depression. In this paper, we describe the development and initial pilot feasibility testing of a BATD mobile application (Behavioral Apptivation) to be used by patients and therapists in conjunction with BATD therapy. We present information regarding the app development process as well as results from a small open-label feasibility trial of the app utilized in conjunction with individual BATD. We include a case series from the open-label trial highlighting how Behavioral Apptivation can be utilized in clinical practice.

An open-label naturalistic pilot study of acamprosate in youth with autistic disorder.

PubMed

Erickson, Craig A; Early, Maureen; Stigler, Kimberly A; Wink, Logan K; Mullett, Jennifer E; McDougle, Christopher J

2011-12-01

To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.

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

PubMed

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

2017-02-01

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

Vasoreactivity in CADASIL: Comparison to structural MRI and neuropsychology.

PubMed

Moreton, Fiona C; Cullen, Breda; Delles, Christian; Santosh, Celestine; Gonzalez, Rosario L; Dani, Krishna; Muir, Keith W

2018-06-01

Impaired cerebrovascular reactivity precedes histological and clinical evidence of CADASIL in animal models. We aimed to more fully characterise peripheral and cerebral vascular function and reactivity in a cohort of adult CADASIL patients, and explore the associations of these with conventional clinical, imaging and neuropsychological measures. A total of 22 adults with CADASIL gave informed consent to participate in an exploratory study of vascular function in CADASIL. Clinical assessment, comprehensive vascular assessment, MRI and neuropsychological testing were conducted. We measured cerebral vasoreactivity with transcranial Doppler and arterial spin labelling MRI with hypercapnia challenge. Number and volume of lacunes, subcortical hyperintensity volume, microbleeds and normalised brain volume were assessed on MRI. Analysis was exploratory and examined the associations between different markers. Cerebrovascular reactivity measured by ASL correlated with peripheral vasoreactivity measured by flow mediated dilatation. Subjects with ≥5 lacunes were older, with higher carotid intima-media thickness and had impaired cerebral and peripheral vasoreactivity. Subjects with depressive symptoms, disability or delayed processing speed also showed a trend to impaired vasoreactivity. Impaired vasoreactivity and vascular dysfunction may play a significant role in the pathophysiology of CADASIL, and vascular assessments may be useful biomarkers of severity in both longitudinal and clinical trials.

The Structure of The Extended Psychosis Phenotype in Early Adolescence—A Cross-sample Replication

PubMed Central

Wigman, Johanna T. W.; Vollebergh, Wilma A. M.; Raaijmakers, Quinten A. W.; Iedema, Jurjen; van Dorsselaer, Saskia; Ormel, Johan; Verhulst, Frank C.; van Os, Jim

2011-01-01

The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and structure of the extended psychosis phenotype was investigated. Positive psychotic experiences, broadly defined, were reported by the majority of adolescents. Exploratory analysis with Structural Equation Modelling (Exploratory Factor Analysis followed by Confirmatory Factor Analysis [CFA]) in sample 1 suggested that psychotic experiences were best represented by 5 underlying dimensions; CFA in sample 2 provided a replication of this model. Dimensions were labeled Hallucinations, Delusions, Paranoia, Grandiosity, and Paranormal beliefs. Prevalences differed strongly, Hallucinations having the lowest and Paranoia having the highest rates. Girls reported more experiences on all dimensions, except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations, Delusions, and Paranoia, but not Grandiosity and Paranormal beliefs, were associated with distress and general measures of psychopathology. Thus, only some of the dimensions of the extended psychosis phenotype in young people may represent a continuum with more severe psychopathology and predict later psychiatric disorder. PMID:20044595

A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia

PubMed Central

2013-01-01

Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was significantly greater in the SOC group at 24-week endpoint (P = .004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P = .444). Conclusion These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics. Trials registration A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia ClinicalTrials.gov identifier: NCT00845026. PMID:23694720

Towards Personalized Medicine: Leveraging Patient Similarity and Drug Similarity Analytics

PubMed Central

Zhang, Ping; Wang, Fei; Hu, Jianying; Sorrentino, Robert

2014-01-01

The rapid adoption of electronic health records (EHR) provides a comprehensive source for exploratory and predictive analytic to support clinical decision-making. In this paper, we investigate how to utilize EHR to tailor treatments to individual patients based on their likelihood to respond to a therapy. We construct a heterogeneous graph which includes two domains (patients and drugs) and encodes three relationships (patient similarity, drug similarity, and patient-drug prior associations). We describe a novel approach for performing a label propagation procedure to spread the label information representing the effectiveness of different drugs for different patients over this heterogeneous graph. The proposed method has been applied on a real-world EHR dataset to help identify personalized treatments for hypercholesterolemia. The experimental results demonstrate the effectiveness of the approach and suggest that the combination of appropriate patient similarity and drug similarity analytics could lead to actionable insights for personalized medicine. Particularly, by leveraging drug similarity in combination with patient similarity, our method could perform well even on new or rarely used drugs for which there are few records of known past performance. PMID:25717413

Rational dosages of nutrients have a prolonged effect on learning disabilities.

PubMed

Carlton, R M; Ente, G; Blum, L; Heyman, N; Davis, W; Ambrosino, S

2000-05-01

Reports that administration of nutrients has increased the academic performance of learning-disabled children exist in the literature. To document the effects of nutrients on learning-disabled children in a controlled study. A randomized, double-blind, placebo-controlled crossover trial, which followed 1 year of open-label nutrients. Children who improved in the open-label trial were eligible to enter the controlled phase of the study. Subjects were enrolled from the general community through advertisements. Twenty children met the criteria for being learning disabled. Each child was tried out on some (but not necessarily all) of the B vitamins and minerals used in this study. These were administered semi-blinded for the first year; double-blinded in crossover rotations during the second year; and open-label in the ensuing years. At various time points, school-certified psychologists administered psychoeducational tests. School report cards were evaluated at baseline and for all subsequent periods. Twenty learning-disabled children entered the study, but 1 dropped out because of nausea. The remaining 19 children showed significant academic and behavioral improvements within a few weeks or months of open-label treatment with nutrient supplements. Some children gained 3 to 5 years in reading comprehension within the first year of treatment; and all children in special education classes became mainstreamed, and their grades rose significantly. Twelve of the children completed the 1-year double-blind phase, after which approximately half of the children chose to remain on the nutrients for at least 2 additional years. For those who discontinued, it took at least 1 year to begin to see the first indications of decline in academic performance, and another year for their grades to drop significantly. In contrast, for children who remained on nutrients, the gains continued the upward trend; at the end of year 4, the difference in scores between the 2 groups had reached statistical significance (P < .01). The overall results of this study tentatively support the concept that learning disabilities may in some cases be a nutrient-responsive disorder.

Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

PubMed

Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

2009-01-01

The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

Early markers of retinal degeneration in rd/rd mice.

PubMed

Acosta, Monica L; Fletcher, Erica L; Azizoglu, Serap; Foster, Lisa E; Farber, Debora B; Kalloniatis, Michael

2005-09-06

In the rd/rd mouse, the cell death of rod photoreceptors has been correlated to abnormal levels of the cyclic nucleotide cGMP within photoreceptors. Given that cGMP is required for opening of the cationic channels, there is the possibility that a high cGMP concentration would maintain these channels open, at a high energy cost for the retina. We investigated whether cation channels were maintained in an open state in the rd/rd mouse retina by determining the labeling pattern of an organic cationic probe (agmatine, AGB) which selectively enters cells through open cationic channels. The metabolic activity of the rd/rd mice was measured by assaying lactate dehydrogenase (LDH) activity in several tissues and Na+/K+ ATPase activity was measured as a function of development and degeneration of the retina. AGB neuronal labeling showed a systematic increase consistent with the known neuronal functional maturation in the normal retina. There was a significant higher AGB labeling of photoreceptors in the rd/rd mouse retina from P6 supporting the possibility of open cationic channels from an early age. There were no changes in the LDH activity of tissues that contain PDE6 or that have a similar LDH distribution as the retina. However, LDH activity was significantly higher in the rd/rd mouse retina than in those of control mice from birth to P6, and it dramatically decreased from P9 as the photoreceptors degenerated. The predominant LDH isoenzyme changes and loss after degeneration appeared to be LDH5. ATPase activity increased with age, reaching adult levels by P16. Unlike LDH activity, there was no significant difference in Na+/K+ ATPase activity between control and rd/rd mice at any age examined. We conclude that AGB is a useful marker of photoreceptors destined to degenerate. We discard the possibility of a generalized metabolic effect in the rd/rd mice. However, the elevated LDH activity present before photoreceptor differentiation indicated altered retinal metabolic activity that could not be associated with open cationic channels alone. Therefore, altered metabolic activity as indicated by LDH measurements in the retina appeared to be the earliest sensitive sign of future photoreceptor dysfunction in the rd/rd mice.

Gaseous polycyclic aromatic hydrocarbon concentrations are higher in urban forests than adjacent open areas during summer but not in winter--Exploratory study.

PubMed

Viippola, Viljami; Rantalainen, Anna-Lea; Yli-Pelkonen, Vesa; Tervo, Peatta; Setälä, Heikki

2016-01-01

While the potential of plants to uptake polycyclic aromatic hydrocarbons (PAHs) is widely acknowledged, empirical evidence of the effects of this process on local atmospheric PAH concentrations and human health is tenuous. We measured gaseous PAH concentrations using passive samplers in urban tree-covered areas and adjacent open, treeless areas in a near-road environment in Finland to gain information on the ability of urban vegetation to improve air quality. The ability of urban, mostly deciduous, vegetation to affect PAHs was season dependent: during summer, concentrations were significantly higher in tree-covered areas, while in the fall, concentrations in open areas exceeded those in tree-covered areas. During winter, concentrations in tree-covered areas were either lower or did not differ from those in open areas. Results of this study imply that the commonly believed notion that trees unequivocally improve air quality does not apply to PAHs studied here. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reprint of: Atmospheric scanning electron microscope observes cells and tissues in open medium through silicon nitride film.

PubMed

Nishiyama, Hidetoshi; Suga, Mitsuo; Ogura, Toshihiko; Maruyama, Yuusuke; Koizumi, Mitsuru; Mio, Kazuhiro; Kitamura, Shinichi; Sato, Chikara

2010-11-01

Direct observation of subcellular structures and their characterization is essential for understanding their physiological functions. To observe them in open environment, we have developed an inverted scanning electron microscope with a detachable, open-culture dish, capable of 8 nm resolution, and combined with a fluorescence microscope quasi-simultaneously observing the same area from the top. For scanning electron microscopy from the bottom, a silicon nitride film window in the base of the dish maintains a vacuum between electron gun and open sample dish while allowing electrons to pass through. Electrons are backscattered from the sample and captured by a detector under the dish. Cells cultured on the open dish can be externally manipulated under optical microscopy, fixed, and observed using scanning electron microscopy. Once fine structures have been revealed by scanning electron microscopy, their component proteins may be identified by comparison with separately prepared fluorescence-labeled optical microscopic images of the candidate proteins, with their heavy-metal-labeled or stained ASEM images. Furthermore, cell nuclei in a tissue block stained with platinum-blue were successfully observed without thin-sectioning, which suggests the applicability of this inverted scanning electron microscope to cancer diagnosis. This microscope visualizes mesoscopic-scale structures, and is also applicable to non-bioscience fields including polymer chemistry. Copyright © 2010 Elsevier Inc. All rights reserved.

Bacterial Production of Site Specific 13C Labeled Phenylalanine and Methodology for High Level Incorporation into Bacterially Expressed Recombinant Proteins

PubMed Central

Ramaraju, Bhargavi; McFeeters, Hana; Vogler, Bernhard; McFeeters, Robert L.

2016-01-01

Nuclear magnetic resonance spectroscopy studies of ever larger systems have benefited from many different forms of isotope labeling, in particular, site specific isotopic labeling. Site specific 13C labeling of methyl groups has become an established means of probing systems not amenable to traditional methodology. However useful, methyl reporter sites can be limited in number and/or location. Therefore, new complementary site specific isotope labeling strategies are valuable. Aromatic amino acids make excellent probes since they are often found at important interaction interfaces and play significant structural roles. Aromatic side chains have many of the same advantages as methyl containing amino acids including distinct 13C chemical shifts and multiple magnetically equivalent 1H positions. Herein we report economical bacterial production and one-step purification of phenylalanine with 13C incorporation at the Cα, Cγ and Cε positions, resulting in two isolated 1H-13C spin systems. We also present methodology to maximize incorporation of phenylalanine into recombinantly overexpressed proteins in bacteria and demonstrate compatibility with ILV-methyl labeling. Inexpensive, site specific isotope labeled phenylalanine adds another dimension to biomolecular NMR, opening new avenues of study. PMID:28028744

Xray: N-dimensional, labeled arrays for analyzing physical datasets in Python

NASA Astrophysics Data System (ADS)

Hoyer, S.

2015-12-01

Efficient analysis of geophysical datasets requires tools that both preserve and utilize metadata, and that transparently scale to process large datas. Xray is such a tool, in the form of an open source Python library for analyzing the labeled, multi-dimensional array (tensor) datasets that are ubiquitous in the Earth sciences. Xray's approach pairs Python data structures based on the data model of the netCDF file format with the proven design and user interface of pandas, the popular Python data analysis library for labeled tabular data. On top of the NumPy array, xray adds labeled dimensions (e.g., "time") and coordinate values (e.g., "2015-04-10"), which it uses to enable a host of operations powered by these labels: selection, aggregation, alignment, broadcasting, split-apply-combine, interoperability with pandas and serialization to netCDF/HDF5. Many of these operations are enabled by xray's tight integration with pandas. Finally, to allow for easy parallelism and to enable its labeled data operations to scale to datasets that does not fit into memory, xray integrates with the parallel processing library dask.

Open science versus commercialization: a modern research conflict?

PubMed

Caulfield, Timothy; Harmon, Shawn He; Joly, Yann

2012-02-27

Efforts to improve research outcomes have resulted in genomic researchers being confronted with complex and seemingly contradictory instructions about how to perform their tasks. Over the past decade, there has been increasing pressure on university researchers to commercialize their work. Concurrently, they are encouraged to collaborate, share data and disseminate new knowledge quickly (that is, to adopt an open science model) in order to foster scientific progress, meet humanitarian goals, and to maximize the impact of their research. We present selected guidelines from three countries (Canada, United States, and United Kingdom) situated at the forefront of genomics to illustrate this potential policy conflict. Examining the innovation ecosystem and the messages conveyed by the different policies surveyed, we further investigate the inconsistencies between open science and commercialization policies. Commercialization and open science are not necessarily irreconcilable and could instead be envisioned as complementary elements of a more holistic innovation framework. Given the exploratory nature of our study, we wish to point out the need to gather additional evidence on the coexistence of open science and commercialization policies and on its impact, both positive and negative, on genomics academic research.

Interoperable Open-Source Sensor-Net Frameworks with Sensor-Package Workbench Capabilities: Motivation, Survey of Resources, and Exploratory Results

DTIC Science & Technology

2010-06-01

Military Scenario Definition Language (MSDL) for Nontraditional Warfare Scenarios," Paper 09S- SIW -001, Proceedings of the Spring Simulation...Update to the M&S Community," Paper 09S- SIW -002, Proceedings of the Spring Simulation Interoperability Workshop, Simulation Interoperability...Multiple Simulations: An Application of the Military Scenario Definition Language (MSDL)," Paper 09S- SIW -003, Proc. of the Spring Simulation

Lyophilized Kit for the Preparation of the PET Perfusion Agent [68Ga]-MAA

PubMed Central

Amor-Coarasa, Alejandro; Milera, Andrew; Gulec, Seza; McGoron, Anthony J.

2014-01-01

Rapid developments in the field of medical imaging have opened new avenues for the use of positron emitting labeled microparticles. The radioisotope used in our research was 68Ga, which is easy to obtain from a generator and has good nuclear properties for PET imaging. Methods. Commercially available macroaggregated albumin (MAA) microparticles were suspended in sterile saline, centrifuged to remove the free albumin and stannous chloride, relyophilized, and stored for later labeling with 68Ga. Labeling was performed at different temperatures and times. 68Ga purification settings were also tested and optimized. Labeling yield and purity of relyophilized MAA microparticles were compared with those that were not relyophilized. Results. MAA particles kept their original size distribution after relyophilization. Labeling yield was 98% at 75°C when a 68Ga purification system was used, compared to 80% with unpurified 68Ga. Radiochemical purity was over 97% up to 4 hours after the labeling. The relyophilized MAA and labeling method eliminate the need for centrifugation purification of the final product and simplify the labeling process. Animal experiments demonstrated the high in vivo stability of the obtained PET agent with more than 95% of the activity remaining in the lungs after 4 hours. PMID:24800071

The Near-Term Viability and Benefits of eLabels for Patients, Clinical Sites, and Sponsors.

PubMed

Smith-Gick, Jodi; Barnes, Nicola; Barone, Rocco; Bedford, Jeff; James, Jason R; Reisner, Stacy Frankovitz; Stephenson, Michael

2018-01-01

Current clinical trial labels are designed primarily to meet regulatory requirements. These labels have low patient and site utility, few are opened, and they have limited space and small fonts. As our world transitions from paper to electronic, an opportunity exists to provide patients with information about their investigational clinical trial product in a way that is more easily accessible, meets Health Authority requirements, and provides valuable additional information for the patient and caregiver. A TransCelerate initiative was launched to understand the current regulatory and technology landscape for the potential use an electronic label (eLabel) for investigational medicinal products (IMPs). Concepts and an example proof of concept were developed intended to show the "art of the possible" for a foundational eLabel and a "universal printed label." In addition, possible patient-centric enhancements were captured in the eLabel proof of concept. These concepts were shared with Health Authorities as well as patient and site advisory groups to gather feedback and subsequently enhance the concepts. Feedback indicated that the concept of an eLabel provides value and concepts should continue to be pursued. While the Health Authorities engaged with did not express issues with the use of an eLabel per se, the reduction in the content on the paper label is not possible in some geographic locations due to existing regulations. There is nothing that prevents transmitting the label electronically in conjunction with current conventional labeling. While there are still some regulatory barriers that need to be addressed for reducing what is on the paper label, advancement toward a more patient-centric approach benefits stakeholders and will enable a fully connected patient-centric experience. The industry must start now to build the foundation.

Tazemetostat Rollover Study (TRuST): An Open-Label Rollover Study

ClinicalTrials.gov

2018-06-05

Diffuse Large B-cell Lymphoma; Follicular Lymphoma; Malignant Rhabdoid Tumors (MRT); Rhabdoid Tumors of the Kidney (RTK); Atypical Teratoid Rhabdoid Tumors (ATRT); Synovial Sarcoma; Epitheliod Sarcoma; Mesothelioma; Advanced Solid Tumors

An Open-Label Naturalistic Pilot Study of Acamprosate in Youth with Autistic Disorder

PubMed Central

Early, Maureen; Stigler, Kimberly A.; Wink, Logan K.; Mullett, Jennifer E.; McDougle, Christopher J.

2011-01-01

Abstract To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration–approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects. PMID:22136091

Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder.

PubMed

Roitman, Pablo; Mechoulam, Raphael; Cooper-Kazaz, Rena; Shalev, Arieh

2014-08-01

Many patients with post-traumatic stress disorder (PTSD) achieve but partial remission with current treatments. Patients with unremitted PTSD show high rates of substance abuse. Marijuana is often used as compassion add-on therapy for treatment-resistant PTSD. This open-label study evaluates the tolerance and safety of orally absorbable Δ(9)-tetrahydrocannabinol (THC) for chronic PTSD. Ten outpatients with chronic PTSD, on stable medication, received 5 mg of Δ(9)-THC twice a day as add-on treatment. There were mild adverse effects in three patients, none of which led to treatment discontinuation. The intervention caused a statistically significant improvement in global symptom severity, sleep quality, frequency of nightmares, and PTSD hyperarousal symptoms. Orally absorbable Δ(9)-THC was safe and well tolerated by patients with chronic PTSD.

Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension.

PubMed

Kadowaki, Takashi; Muto, Satsuki; Ouchi, Yoshiumi; Shimazaki, Ryutaro; Seino, Yutaka

2017-12-01

We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus. We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint. At Week 16, the adjusted change in HbA1c from baseline increased by 0.51% with placebo and decreased by 0.40% with saxagliptin (difference -0.92% [95% confidence interval -1.07%, -0.76%; p < 0.001]). In patients receiving saxagliptin, reductions in HbA1c at Week 16 were maintained to Week 52, while switching from placebo to saxagliptin resulted in a similar reduction in HbA1c. The incidence of hypoglycemia was not markedly increased with saxagliptin versus placebo in the double-blind period and did not increase substantially during the open-label extension period. The efficacy and safety of saxagliptin was similar between the elderly and non-elderly patient groups. Adding saxagliptin to ongoing insulin therapy improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes.

Cardiovascular Safety of Droxidopa in Patients With Symptomatic Neurogenic Orthostatic Hypotension.

PubMed

White, William B; Hauser, Robert A; Rowse, Gerald J; Ziemann, Adam; Hewitt, L Arthur

2017-04-01

The norepinephrine prodrug droxidopa improves symptoms of neurogenic orthostatic hypotension, a condition that is associated with diseases of neurogenic autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure). These conditions are more prevalent in older patients who also have cardiovascular co-morbidities. Hence, we evaluated the cardiovascular safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension who participated in randomized controlled studies (short-term studies of 1 to 2 weeks and an intermediate 8- to 10-week study) and long-term open-label studies. Rates of cardiovascular adverse events (AEs) for patients treated with droxidopa were 4.4% in the intermediate study and 10.8% in the long-term open-label studies. Adjusting for exposure time, cardiovascular AE rates were 0.30 events/patient-year in the short-term and intermediate studies and 0.15 events/patient-year in the long-term open-label studies. The incidence of treatment discontinuation due to blood pressure-related events was approximately 2.5%. Among patients with a history of cardiac disorders at baseline, the rates of cardiovascular-related and blood pressure-related AEs were nominally higher with droxidopa compared to placebo. Most of these events were minor atrial arrhythmias; none were major adverse cardiovascular events or deaths. In conclusion, small increases in cardiovascular AEs were observed with droxidopa compared to placebo; this was most evident in patients with preexisting cardiac disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.

PubMed

Berk, Michael; Dean, Olivia M; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Moss, Kirsteen; Allwang, Christine; Schapkaitz, Ian; Cobb, Heidi; Bush, Ashley I; Dodd, Seetal; Malhi, Gin S

2012-08-14

N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

A cascade autocatalytic strand displacement amplification and hybridization chain reaction event for label-free and ultrasensitive electrochemical nucleic acid biosensing.

PubMed

Chen, Zhiqiang; Liu, Ying; Xin, Chen; Zhao, Jikuan; Liu, Shufeng

2018-08-15

Herein, an autocatalytic strand displacement amplification (ASDA) strategy was proposed for the first time, which was further ingeniously coupled with hybridization chain reaction (HCR) event for the isothermal, label-free and multiple amplification toward nucleic acid detection. During the ASDA module, the target recognition opens the immobilized hairpin probe (IP) and initiates the annealing of the auxiliary DNA strand (AS) with the opened IP for the successive polymerization and nicking reaction in the presence of DNA polymerase and nicking endonuclease. This induces the target recycling and generation of a large amount of intermediate DNA sequences, which can be used as target analogy to execute the autocatalytic strand displacement amplification. Simultaneously, the introduced AS strand can propagate the HCR between two hairpins (H1 and H2) to form a linear DNA concatamer with cytosine (C)-rich loop region, which can facilitate the in-situ synthesis of silver nanoclusters (AgNCs) as electrochemical tags for further amplification toward target responses. With current cascade ASDA and HCR strategy, the detection of target DNA could be achieved with a low detection limit of about 0.16 fM and a good selectivity. The developed biosensor also exhibits the distinct advantages of flexibility and simplicity in probe design and biosensor fabrication, and label-free electrochemical detection, thus opens a promising avenue for the detection of nucleic acid with low abundance in bioanalysis and clinical biomedicine. Copyright © 2018 Elsevier B.V. All rights reserved.

Doxycycline for prevention of erlotinib-induced rash in patients with non-small-cell lung cancer (NSCLC) after failure of first-line chemotherapy: A randomized, open-label trial.

PubMed

Deplanque, Gaël; Gervais, Radj; Vergnenegre, Alain; Falchero, Lionel; Souquet, Pierre-Jean; Chavaillon, Jean-Michel; Taviot, Bruno; Fraboulet, Ghislaine; Saal, Hakim; Robert, Caroline; Chosidow, Olivier

2016-06-01

Rash is a common epidermal growth factor receptor inhibitor-induced toxicity that can impair quality of life and treatment compliance. We sought to evaluate the efficacy of doxycycline in preventing erlotinib-induced rash (folliculitis) in patients with non-small-cell lung cancer. This open-label, randomized, prospective, phase II trial was conducted in 147 patients with locally advanced or metastatic non-small-cell lung cancer progressing after first-line chemotherapy, randomized for 4 months with erlotinib alone 150 mg/d per os (control arm) or combined with doxycycline 100 mg/d (doxycycline arm). Incidence and severity of rash, compliance, survival, and safety were assessed. Baseline characteristics of the 147 patients were well balanced in the intent-to-treat population. Folliculitis occurred in 71% of patients in the doxycycline arm and 81% in the control arm (P = .175). The severity of folliculitis and other skin lesions was lower in the doxycycline arm compared with the control arm. Other adverse events were reported at a similar frequency across arms. There was no significant difference in survival between treatment arms. The open-label design of the study and the duration of the treatment with doxycycline are limitations. Doxycycline did not reduce the incidence of erlotinib-induced folliculitis, but significantly reduced its severity. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Baicalin supplementation reduces serum biomarkers of skeletal muscle wasting and may protect against lean body mass reduction in cancer patients: Results from a pilot open-label study.

PubMed

Emanuele, Enzo; Bertona, Marco; Pareja-Galeano, Helios; Fiuza-Luces, Carmen; Morales, Javier Salvador; Sanchis-Gomar, Fabian; Lucia, Alejandro

2016-07-01

Muscle wasting in patients with cancer has been linked to an increased activity of nuclear factor κB (NF-κB) and higher circulating levels of activin-A (ActA), a negative growth factor for muscle mass. Baicalin is a natural flavonoid that can reduce skeletal muscle atrophy in animal models of cancer cachexia by inhibiting NF-κB. This pilot open-label study assessed the effects of baicalin supplementation (50 mg daily for 3 months) in cancer patients who showed involuntary weight loss >5% over the past 6 months. A total of 20 patients were investigated. Participants were evaluated at baseline and at the end of the 3-month study period for the following endpoints: 1) changes from baseline in serum NF-κB and ActA levels; and 2) change from baseline in lean body mass (LBM). We observed significant reduction in both NF-κB (p<0.05) and ActA (p<0.05) serum levels from baseline to 3 months. At 3 months, patients also showed a significant mean increase in LBM (+0.8 kg, p<0.05 compared with baseline). Our pilot open-label data suggest that baicalin supplementation is potentially useful for contrasting lean body mass reduction in cancer patients with involuntary weight loss, an effect which is likely mediated by the inhibition of negative growth factors for muscle mass.

A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders.

PubMed

McDougle, C J; Holmes, J P; Carlson, D C; Pelton, G H; Cohen, D J; Price, L H

1998-07-01

Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures. Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.

Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study.

PubMed

2008-12-01

To determine whether ethyl-eicosapentaenoic acid (ethyl-EPA), an omega-3 fatty acid, improves the motor features of Huntington disease. Six-month multicenter, randomized, double-blind, placebo-controlled trial followed by a 6-month open-label phase without disclosing initial treatment assignments. Forty-one research sites in the United States and Canada. Three hundred sixteen adults with Huntington disease, enriched for a population with shorter trinucleotide (cytosine-adenine-guanine) repeat length expansions. Random assignment to placebo or ethyl-EPA, 1 g twice a day, followed by open-label treatment with ethyl-EPA. Six-month change in the Total Motor Score 4 component of the Unified Huntington's Disease Rating Scale analyzed for all research participants and those with shorter cytosine-adenine-guanine repeat length expansions (<45). At 6 months, the Total Motor Score 4 point change for patients receiving ethyl-EPA did not differ from that for those receiving placebo. No differences were found in measures of function, cognition, or global impression. Before public disclosure of the 6-month placebo-controlled results, 192 individuals completed the open-label phase. The Total Motor Score 4 change did not worsen for those who received active treatment for 12 continuous months compared with those who received active treatment for only 6 months (2.0-point worsening; P=.02). Ethyl-EPA was not beneficial in patients with Huntington disease during 6 months of placebo-controlled evaluation. Clinical Trial Registry clinicaltrials.gov Identifier: NCT00146211.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients: a multicenter, open-label, phase III study.

PubMed

Zeng, Meng-Su; Ye, Hui-Yi; Guo, Liang; Peng, Wei-Jun; Lu, Jian-Ping; Teng, Gao-Jun; Huan, Yi; Li, Ping; Xu, Jian-Rong; Liang, Chang-Hong; Breuer, Josy

2013-12-01

Contrast agents help to improve visibility in magnetic resonance (MR) imaging. However, owing to the large interstitial spaces of the liver, there is a reduction in the natural contrast gradient between lesions and healthy tissue. This study was undertaken to evaluate the efficacy and safety of the liver-specific MR imaging contrast agent gadoxetate disodium (Gd-EOB-DTPA) in Chinese patients. This was a single-arm, open-label, multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging. MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA (0.025 mmol/kg body weight). Images were evaluated by clinical study investigators and three independent, blinded radiologists. The primary efficacy endpoint was sensitivity in lesion detection. Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46% compared with pre-contrast imaging for the average of the three blinded readers (94.78% vs 85.32% for Gd-EOB-DTPA vs pre-contrast, respectively). Improvements in detection were more pronounced in lesions less than 1 cm. Gd-EOB-DTPA improved diagnostic accuracy in lesion classification. This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions, particularly in those smaller than 1 cm. Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification, and furthermore, Gd-EOB-DTPA is safe in Chinese patients with liver lesions.

Automated selected reaction monitoring software for accurate label-free protein quantification.

PubMed

Teleman, Johan; Karlsson, Christofer; Waldemarson, Sofia; Hansson, Karin; James, Peter; Malmström, Johan; Levander, Fredrik

2012-07-06

Selected reaction monitoring (SRM) is a mass spectrometry method with documented ability to quantify proteins accurately and reproducibly using labeled reference peptides. However, the use of labeled reference peptides becomes impractical if large numbers of peptides are targeted and when high flexibility is desired when selecting peptides. We have developed a label-free quantitative SRM workflow that relies on a new automated algorithm, Anubis, for accurate peak detection. Anubis efficiently removes interfering signals from contaminating peptides to estimate the true signal of the targeted peptides. We evaluated the algorithm on a published multisite data set and achieved results in line with manual data analysis. In complex peptide mixtures from whole proteome digests of Streptococcus pyogenes we achieved a technical variability across the entire proteome abundance range of 6.5-19.2%, which was considerably below the total variation across biological samples. Our results show that the label-free SRM workflow with automated data analysis is feasible for large-scale biological studies, opening up new possibilities for quantitative proteomics and systems biology.

[Not quite the same: illness beliefs regarding burnout and depression among the general population].

PubMed

Bahlmann, Johannes; Schomerus, Georg; Angermeyer, Matthias C

2015-11-01

This study examined illness beliefs of the lay public associated with the diagnostic labels burnout and depression. Representative population survey in Germany 2011, using unlabelled case vignettes of a person suffering from depression. Following presentation of the vignette, respondents were asked openly how they would call the problem described. Agreement with various illness beliefs was elicited with Likert-scaled items. Seeing the problem as inherited predicted use of the label depression (OR 1.29, p < 0.001), while stress at work as a perceived cause was associated with use of the label burnout (OR 1.56, p < 0.001). Belief that the problem described resembled everyday experiences (belief in a symptom continuum) also predicted using the label burnout instead of depression (OR 1.31, p < 0.05). Although overlapping with beliefs about depression, the diagnostic label burnout is also associated with specific illness beliefs among the general public. © Georg Thieme Verlag KG Stuttgart · New York.

A molecular beacon microarray based on a quantum dot label for detecting single nucleotide polymorphisms.

PubMed

Guo, Qingsheng; Bai, Zhixiong; Liu, Yuqian; Sun, Qingjiang

2016-03-15

In this work, we report the application of streptavidin-coated quantum dot (strAV-QD) in molecular beacon (MB) microarray assays by using the strAV-QD to label the immobilized MB, avoiding target labeling and meanwhile obviating the use of amplification. The MBs are stem-loop structured oligodeoxynucleotides, modified with a thiol and a biotin at two terminals of the stem. With the strAV-QD labeling an "opened" MB rather than a "closed" MB via streptavidin-biotin reaction, a sensitive and specific detection of label-free target DNA sequence is demonstrated by the MB microarray, with a signal-to-background ratio of 8. The immobilized MBs can be perfectly regenerated, allowing the reuse of the microarray. The MB microarray also is able to detect single nucleotide polymorphisms, exhibiting genotype-dependent fluorescence signals. It is demonstrated that the MB microarray can perform as a 4-to-2 encoder, compressing the genotype information into two outputs. Copyright © 2015 Elsevier B.V. All rights reserved.

Developmental subchronic exposure to diphenylarsinic acid induced increased exploratory behavior, impaired learning behavior, and decreased cerebellar glutathione concentration in rats.

PubMed

Negishi, Takayuki; Matsunaga, Yuki; Kobayashi, Yayoi; Hirano, Seishiro; Tashiro, Tomoko

2013-12-01

In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0-6 weeks of age] and/or late period [7-12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA.

Second-Order Moller-Plesset Perturbation Theory for Molecular Dirac-Hartree-Fock Wave Functions

NASA Technical Reports Server (NTRS)

Dyall, Kenneth G.; Arnold, James O. (Technical Monitor)

1994-01-01

Moller-Plesset perturbation theory is developed to second order for a selection of Kramers restricted Dirac-Hartree-Fock closed and open-shell reference wave functions. The open-shell wave functions considered are limited to those with no more than two electrons in open shells, but include the case of a two-configuration SCF reference. Denominator shifts are included in the style of Davidson's OPT2 method. An implementation which uses unordered integrals with labels is presented, and results are given for a few test cases.

The exploratory behaviour of rats in the hole-board apparatus: Is head-dipping a valid measure of neophilia?

PubMed Central

Brown, Gillian R.; Nemes, Christopher

2008-01-01

The exploratory behaviour of laboratory rodents is of interest within a number of areas of behavioural pharmacology. However, how best to measure exploratory behaviour in rodents remains a contentious issue. Many unconditioned tests, such as the open field, potentially confound general locomotor activity with exploration. The hole-board apparatus appears to avoid this confound, as head-dipping into holes in the floor is assumed to be a valid measure of the subject's attraction towards novelty (neophilia). This study aimed to investigate whether head-dipping should be considered a valid measure of neophilia by comparing performance of adult male and female Lister hooded rats on the hole-board task (a) over repeated sessions and (b) when novel objects were absent or present underneath the holes. The results show that head-dipping initially decreased across repeated exposures, while time spent in the aversive central area increased. No change in head-dipping was seen in response to objects being placed underneath the holes. Rather than being a measure of neophilia, these results support the hypothesis that head-dipping represents an escape response, which declines as the subject becomes less fearful. These results are compared with previous studies of repeated exposure to other novel environments. PMID:18406075

The validity of three tests of temperament in guppies (Poecilia reticulata).

PubMed

Burns, James G

2008-11-01

Differences in temperament (consistent differences among individuals in behavior) can have important effects on fitness-related activities such as dispersal and competition. However, evolutionary ecologists have put limited effort into validating their tests of temperament. This article attempts to validate three standard tests of temperament in guppies: the open-field test, emergence test, and novel-object test. Through multiple reliability trials, and comparison of results between different types of test, this study establishes the confidence that can be placed in these temperament tests. The open-field test is shown to be a good test of boldness and exploratory behavior; the open-field test was reliable when tested in multiple ways. There were problems with the emergence test and novel-object test, which leads one to conclude that the protocols used in this study should not be considered valid tests for this species. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Chronic methylphenidate-effects over circadian cycle of young and adult rats submitted to open-field and object recognition tests.

PubMed

Gomes, Karin M; Souza, Renan P; Valvassori, Samira S; Réus, Gislaine Z; Inácio, Cecília G; Martins, Márcio R; Comim, Clarissa M; Quevedo, João

2009-11-01

In this study age-, circadian rhythm- and methylphenidate administration- effect on open field habituation and object recognition were analyzed. Young and adult male Wistar rats were treated with saline or methylphenidate 2.0 mg/kg for 28 days. Experiments were performed during the light and the dark cycle. Locomotor activity was significantly altered by circadian cycle and methylphenidate treatment during the training session and by drug treatment during the testing session. Exploratory activity was significantly modulated by age during the training session and by age and drug treatment during the testing session. Object recognition memory was altered by cycle at the training session; by age 1.5 h later and by cycle and age 24 h after the training session. These results show that methylphenidate treatment was the major modulator factor on open-field test while cycle and age had an important effect on object recognition experiment.

Efficacy and tolerability of fixed-combination brinzolamide/timolol in Latin American patients with open-angle glaucoma or ocular hypertension previously on brimonidine/timolol fixed combination.

PubMed

Alezzandrini, Arturo; Hubatsch, Douglas; Alfaro, Rene

2014-09-01

Fixed-combination glaucoma medications are commonly used to achieve target intraocular pressure (IOP) reduction in patients uncontrolled with monotherapy; however, ocular discomfort associated with eye drops can decrease adherence. This study assessed the efficacy and tolerability of twice-daily fixed-combination brinzolamide 1%/timolol 0.5% (BRINZ/TIM-FC) in Latin American patients transitioned from fixed-combination brimonidine 0.2%/timolol 0.5% (BRIM/TIM-FC) because of insufficient IOP control or treatment intolerance. This 8-week, open-label, prospective study was conducted at six sites in Argentina, Chile, and Mexico. Enrolled patients were aged ≥18 years with open-angle glaucoma (including primary, exfoliative, or pigment-dispersion glaucoma) or ocular hypertension with IOP of 19-35 mmHg in ≥1 eye at baseline (on BRIM/TIM-FC). Patients self-administered BRINZ/TIM-FC to both eyes at 8 a.m. and 8 p.m. daily for 8 weeks. The primary and secondary efficacy endpoints were mean IOP change from baseline at week 8 and percentage of patients achieving target IOP (≤18 mmHg) at week 8, respectively. Exploratory endpoints included patient and investigator preference for treatment at week 8. Adverse events (AEs) were assessed as the safety endpoint. Fifty patients (mean ± SD age, 66.7 ± 11.5 years) received BRINZ/TIM-FC, and 49 were included in the intent-to-treat population. Mean ± SD IOP was significantly reduced from baseline after 8 weeks of treatment with BRINZ/TIM-FC (-3.6 ± 3.0 mmHg; P < 0.0001, Wilcoxon signed-rank test; 17.1% reduction). Overall, 55.3% of patients achieved IOP ≤18 mmHg at week 8. Significantly more patients (89.4%) and investigators (95.7%) preferred BRINZ/TIM-FC to BRIM/TIM-FC (both P < 0.0001, exact binomial test). Of the 13 AEs observed, 8 were related to BRINZ/TIM-FC; the most common treatment-related AEs were eye irritation (n = 4) and abnormal sensation in the eye (n = 2). BRINZ/TIM-FC provides an effective and well-tolerated treatment option for patients transitioned from BRIM/TIM-FC.

Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia

ClinicalTrials.gov

2016-08-01

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

The ultrastructure of subgingival dental plaque, revealed by high-resolution field emission scanning electron microscopy.

PubMed

Holliday, Richard; Preshaw, Philip M; Bowen, Leon; Jakubovics, Nicholas S

2015-01-01

To explore the ultrastructure of subgingival dental plaque using high-resolution field emission scanning electron microscopy (FE-SEM) and to investigate whether extracellular DNA (eDNA) could be visualised in ex vivo samples. Ten patients were recruited who fulfilled the inclusion criteria (teeth requiring extraction with radiographic horizontal bone loss of over 50% and grade II/III mobility). In total, 12 teeth were extracted using a minimally traumatic technique. Roots were sectioned using a dental air turbine handpiece, under water cooling to produce 21 samples. Standard fixation and dehydration protocols were followed. For some samples, gold-labelled anti-DNA antibodies were applied before visualising biofilms by FE-SEM. High-resolution FE-SEMs of subgingival biofilm were obtained in 90% of the samples. The sectioning technique left dental plaque biofilms undisturbed. Copious amounts of extracellular material were observed in the plaque, which may have been eDNA as they had a similar appearance to labelled eDNA from in vitro studies. There was also evidence of membrane vesicles and open-ended tubular structures. Efforts to label eDNA with immune-gold antibodies were unsuccessful and eDNA was not clearly labelled. High-resolution FE-SEM images were obtained of undisturbed subgingival ex vivo dental plaque biofilms. Important structural features were observed including extracellular polymeric material, vesicles and unusual open tubule structures that may be remnants of lysed cells. The application of an eDNA immune-gold-labelling technique, previously used successfully in in vitro samples, did not clearly identify eDNA in ex vivo samples. Further studies are needed to characterise the molecular composition of the observed extracellular matrix material.

The ultrastructure of subgingival dental plaque, revealed by high-resolution field emission scanning electron microscopy

PubMed Central

Holliday, Richard; Preshaw, Philip M; Bowen, Leon; Jakubovics, Nicholas S

2015-01-01

Objectives/Aims: To explore the ultrastructure of subgingival dental plaque using high-resolution field emission scanning electron microscopy (FE-SEM) and to investigate whether extracellular DNA (eDNA) could be visualised in ex vivo samples. Materials and Methods: Ten patients were recruited who fulfilled the inclusion criteria (teeth requiring extraction with radiographic horizontal bone loss of over 50% and grade II/III mobility). In total, 12 teeth were extracted using a minimally traumatic technique. Roots were sectioned using a dental air turbine handpiece, under water cooling to produce 21 samples. Standard fixation and dehydration protocols were followed. For some samples, gold-labelled anti-DNA antibodies were applied before visualising biofilms by FE-SEM. Results: High-resolution FE-SEMs of subgingival biofilm were obtained in 90% of the samples. The sectioning technique left dental plaque biofilms undisturbed. Copious amounts of extracellular material were observed in the plaque, which may have been eDNA as they had a similar appearance to labelled eDNA from in vitro studies. There was also evidence of membrane vesicles and open-ended tubular structures. Efforts to label eDNA with immune-gold antibodies were unsuccessful and eDNA was not clearly labelled. Conclusions: High-resolution FE-SEM images were obtained of undisturbed subgingival ex vivo dental plaque biofilms. Important structural features were observed including extracellular polymeric material, vesicles and unusual open tubule structures that may be remnants of lysed cells. The application of an eDNA immune-gold-labelling technique, previously used successfully in in vitro samples, did not clearly identify eDNA in ex vivo samples. Further studies are needed to characterise the molecular composition of the observed extracellular matrix material. PMID:29607057

Assessing Insecticide Hazard to Bumble Bees Foraging on Flowering Weeds in Treated Lawns

PubMed Central

Larson, Jonathan L.; Redmond, Carl T.; Potter, Daniel A.

2013-01-01

Maintaining bee-friendly habitats in cities and suburbs can help conserve the vital pollination services of declining bee populations. Despite label precautions not to apply them to blooming plants, neonicotinoids and other residual systemic insecticides may be applied for preventive control of lawn insect pests when spring-flowering weeds are present. Dietary exposure to neonicotinoids adversely affects bees, but the extent of hazard from field usage is controversial. We exposed colonies of the bumble bee Bombus impatiens to turf with blooming white clover that had been treated with clothianidin, a neonicotinoid, or with chlorantraniliprole, the first anthranilic diamide labeled for use on lawns. The sprays were applied at label rate and lightly irrigated. After residues had dried, colonies were confined to forage for six days, and then moved to a non-treated rural site to openly forage and develop. Colonies exposed to clothianidin-treated weedy turf had delayed weight gain and produced no new queens whereas those exposed to chlorantraniliprole-treated plots developed normally compared with controls. Neither bumble bees nor honey bees avoided foraging on treated white clover in open plots. Nectar from clover blooms directly contaminated by spray residues contained 171±44 ppb clothianidin. Notably, neither insecticide adversely impacted bee colonies confined on the treated turf after it had been mown to remove clover blooms present at the time of treatment, and new blooms had formed. Our results validate EPA label precautionary statements not to apply neonicotinoids to blooming nectar-producing plants if bees may visit the treatment area. Whatever systemic hazard through lawn weeds they may pose appears transitory, however, and direct hazard can be mitigated by adhering to label precautions, or if blooms inadvertently are contaminated, by mowing to remove them. Chlorantraniliprole usage on lawns appears non-hazardous to bumble bees. PMID:23776667

Assessing insecticide hazard to bumble bees foraging on flowering weeds in treated lawns.

PubMed

Larson, Jonathan L; Redmond, Carl T; Potter, Daniel A

2013-01-01

Maintaining bee-friendly habitats in cities and suburbs can help conserve the vital pollination services of declining bee populations. Despite label precautions not to apply them to blooming plants, neonicotinoids and other residual systemic insecticides may be applied for preventive control of lawn insect pests when spring-flowering weeds are present. Dietary exposure to neonicotinoids adversely affects bees, but the extent of hazard from field usage is controversial. We exposed colonies of the bumble bee Bombus impatiens to turf with blooming white clover that had been treated with clothianidin, a neonicotinoid, or with chlorantraniliprole, the first anthranilic diamide labeled for use on lawns. The sprays were applied at label rate and lightly irrigated. After residues had dried, colonies were confined to forage for six days, and then moved to a non-treated rural site to openly forage and develop. Colonies exposed to clothianidin-treated weedy turf had delayed weight gain and produced no new queens whereas those exposed to chlorantraniliprole-treated plots developed normally compared with controls. Neither bumble bees nor honey bees avoided foraging on treated white clover in open plots. Nectar from clover blooms directly contaminated by spray residues contained 171±44 ppb clothianidin. Notably, neither insecticide adversely impacted bee colonies confined on the treated turf after it had been mown to remove clover blooms present at the time of treatment, and new blooms had formed. Our results validate EPA label precautionary statements not to apply neonicotinoids to blooming nectar-producing plants if bees may visit the treatment area. Whatever systemic hazard through lawn weeds they may pose appears transitory, however, and direct hazard can be mitigated by adhering to label precautions, or if blooms inadvertently are contaminated, by mowing to remove them. Chlorantraniliprole usage on lawns appears non-hazardous to bumble bees.

A reverse-translational study of dysfunctional exploration in psychiatric disorders: from mice to men.

PubMed

Perry, William; Minassian, Arpi; Paulus, Martin P; Young, Jared W; Kincaid, Meegin J; Ferguson, Eliza J; Henry, Brook L; Zhuang, Xiaoxi; Masten, Virginia L; Sharp, Richard F; Geyer, Mark A

2009-10-01

Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, which raises the question of whether they are the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these 2 disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. To quantify the exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Static group comparison by the use of a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM). Psychiatric hospital. Fifteen patients with bipolar mania and 16 patients with schizophrenia were compared with 26 healthy volunteers in the human BPM. The effects of amphetamine sulfate, the selective dopamine transporter inhibitor GBR12909, and the genetic knockdown of the dopamine transporter were compared with controls in the mouse BPM. The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Patients with bipolar mania demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Patients with schizophrenia did not show the expected habituation of motor activity. Selective genetic or pharmacologic inhibition of the dopamine transporter matched the mania phenotype better than the effects of amphetamine, which has been the criterion standard for animal models of mania. These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from those of schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to the identification of the neurobiological underpinnings of neuropsychiatric disorders.

A reverse translational study of dysfunctional exploration in psychiatric disorders: from mice to men

PubMed Central

Perry, William; Minassian, Arpi; Paulus, Martin P.; Young, Jared W.; Kincaid, Meegin J.; Ferguson, Eliza J.; Henry, Brook L.; Zhuang, Xiaoxi; Masten, Virginia L.; Sharp, Richard F.; Geyer, Mark A.

2009-01-01

Context Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, raising the question of whether they are in fact the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these two disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. Objective We used a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM), to quantify exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Design Static group comparison. Setting Psychiatric hospital. Participants 15 bipolar mania and 16 schizophrenia subjects were compared to 26 healthy volunteers in the human BPM. The effects of amphetamine, the selective dopamine transporter (DAT) inhibitor GBR12909, and genetic knockdown of the DAT were compared to controls in the mouse BPM. Measures The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Results Bipolar manic subjects demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Schizophrenia subjects did not show the expected habituation of motor activity. Selective genetic or pharmacological inhibition of the DAT matched the mania phenotype better than the “gold standard” model of mania (amphetamine). Conclusion These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to identify neurobiological underpinnings of neuropsychiatric disorders. PMID:19805697

Quantitative phosphoproteomics using acetone-based peptide labeling: Method evaluation and application to a cardiac ischemia/reperfusion model

PubMed Central

Wijeratne, Aruna B.; Manning, Janet R.; Schultz, Jo El J.; Greis, Kenneth D.

2013-01-01

Mass spectrometry (MS) techniques to globally profile protein phosphorylation in cellular systems that are relevant to physiological or pathological changes have been of significant interest in biological research. In this report, an MS-based strategy utilizing an inexpensive acetone-based peptide labeling technique known as reductive alkylation by acetone (RABA) for quantitative phosphoproteomics was explored to evaluate its capacity. Since the chemistry for RABA-labeling for phosphorylation profiling had not been previously reported, it was first validated using a standard phosphoprotein and identical phosphoproteomes from cardiac tissue extracts. A workflow was then utilized to compare cardiac tissue phosphoproteomes from mouse hearts not expressing FGF2 vs. hearts expressing low molecular weight fibroblast growth factor-2 (LMW FGF2) to relate low molecular weight fibroblast growth factor-2 (LMW FGF2) mediated cardioprotective phenomena induced by ischemia/reperfusion (I/R) injury of hearts, with downstream phosphorylation changes in LMW FGF2 signaling cascades. Statistically significant phosphorylation changes were identified at 14 different sites on 10 distinct proteins including some with mechanisms already established for LMW FGF2-mediated cardioprotective signaling (e.g. connexin-43), some with new details linking LMW FGF2 to the cardioprotective mechanisms (e.g. cardiac myosin binding protein C or cMyBPC), and also several new downstream effectors not previously recognized for cardio-protective signaling by LMW FGF2. Additionally, one of the phosphopeptides, cMyBPC/pSer-282, identified was further verified with site-specific quantification using an SRM (selected reaction monitoring)-based approach that also relies on isotope labeling of a synthetic phosphopeptide with deuterated acetone as an internal standard. Overall, this study confirms that the inexpensive acetone-based peptide labeling can be used in both exploratory and targeted quantification phosphoproteomic studies to identify and verify biologically-relevant phosphorylation changes in whole tissues. PMID:24016359

The Stigma of Mental Illness as a Barrier to Self Labeling as Having a Mental Illness.

PubMed

Stolzenburg, Susanne; Freitag, Simone; Evans-Lacko, Sara; Muehlan, Holger; Schmidt, Silke; Schomerus, Georg

2017-12-01

The aim of this study was to investigate whether personal stigma decreases self-identification as having a mental illness in individuals with untreated mental health problems. We interviewed 207 persons with a currently untreated mental health problem as confirmed by a structured diagnostic interview. Measures included symptom appraisal, self-identification as having a mental illness (SELFI), self-labeling (open-ended question on the nature of their problem) stigma-related variables (explicit and implicit), as well as sociodemographics, current symptom severity, and previous treatment. Support for discrimination and implicit stigmatizing attitude were both associated with lower likelihood of self-identification. More social distance and support for discrimination were associated with less self-labeling. Previous treatment was the strongest predictor of symptom appraisal, SELFI, and self-labeling. Destigmatizing mental illness could increase awareness of personal mental health problems, potentially leading to lower rates of untreated mental illness.

Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

NASA Technical Reports Server (NTRS)

Higuchi, Yoshinori; Nelson, Gregory A.; Vazquez, Marcelo; Laskowitz, Daniel T.; Slater, James M.; Pearlstein, Robert D.

2002-01-01

Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. METHODS: Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. ROTAROD TEST: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. OPEN FIELD TEST: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. MORRIS WATER MAZE: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. CONCLUSIONS: These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the CNS. ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process.

Measurement invariance of big-five factors over the life span: ESEM tests of gender, age, plasticity, maturity, and la dolce vita effects.

PubMed

Marsh, Herbert W; Nagengast, Benjamin; Morin, Alexandre J S

2013-06-01

This substantive-methodological synergy applies evolving approaches to factor analysis to substantively important developmental issues of how five-factor-approach (FFA) personality measures vary with gender, age, and their interaction. Confirmatory factor analyses (CFAs) conducted at the item level often do not support a priori FFA structures, due in part to the overly restrictive assumptions of CFA models. Here we demonstrate that exploratory structural equation modeling (ESEM), an integration of CFA and exploratory factor analysis, overcomes these problems with the 15-item Big Five Inventory administered as part of the nationally representative British Household Panel Study (N = 14,021; age: 15-99 years, Mage = 47.1). ESEM fitted the data substantially better and resulted in much more differentiated (less correlated) factors than did CFA. Methodologically, we extended ESEM (introducing ESEM-within-CFA models and a hybrid of multiple groups and multiple indicators multiple causes models), evaluating full measurement invariance and latent mean differences over age, gender, and their interaction. Substantively the results showed that women had higher latent scores for all Big Five factors except for Openness and that these gender differences were consistent over the entire life span. Substantial nonlinear age effects led to the rejection of the plaster hypothesis and the maturity principle but did support a newly proposed la dolce vita effect in old age. In later years, individuals become happier (more agreeable and less neurotic), more self-content and self-centered (less extroverted and open), more laid back and satisfied with what they have (less conscientious, open, outgoing and extroverted), and less preoccupied with productivity. PsycINFO Database Record (c) 2013 APA, all rights reserved

Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD.

PubMed

Pergola, Pablo E; Krauth, Melissa; Huff, J Warren; Ferguson, Deborah A; Ruiz, Stacey; Meyer, Colin J; Warnock, David G

2011-01-01

Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules. This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes. Patients received 25 mg of bardoxolone methyl daily for 28 days, followed by 75 mg daily for another 28 days. The study achieved its primary efficacy endpoint, as demonstrated by a significant increase from baseline in estimated glomerular filtration rate (eGFR) of 7.2 ml/min/1.73 m2 (p < 0.001). Improvements were seen in approximately 90% of patients and showed a dose- and time-dependent increase in eGFR. The eGFR change paralleled a significant reduction in serum creatinine (-0.3 mg/dl) and blood urea nitrogen (-4.9 mg/dl), along with an increase in creatinine clearance (+14.6 ml/min/1.73 m2), without a change in the 24-hour creatinine excretion rate. Markers of vascular injury and inflammation were improved by treatment with bardoxolone. No life-threatening adverse events or drug-related serious adverse events were reported. The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function. Copyright © 2011 S. Karger AG, Basel.

Long-chain omega-3 fatty acids in aneurysmal subarachnoid hemorrhage: A randomized pilot trial of pharmaconutrition.

PubMed

Saito, Geisi; Zapata, Rodrigo; Rivera, Rodrigo; Zambrano, Héctor; Rojas, David; Acevedo, Hernán; Ravera, Franco; Mosquera, John; Vásquez, Juan E; Mura, Jorge

2017-01-01

Functional recovery after aneurysmal subarachnoid hemorrhage (SAH) remains a significant problem. We tested a novel therapeutic approach with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) to assess the safety and feasibility of an effectiveness trial. We conducted a multicentre, parallel, randomized, open-label pilot trial. Patients admitted within 72 hours after SAH with modified Fisher scale scores of 3 or 4 who were selected for scheduled aneurysm clipping were allocated to receive either n-3 PUFA treatment (parenteral perioperative: 5 days; oral: 8 weeks) plus usual care or usual care alone. Exploratory outcome measures included major postoperative intracranial bleeding complications (PIBCs), cerebral infarction caused by delayed cerebral ischemia, shunt-dependent hydrocephalus, and consent rate. The computed tomography evaluator was blinded to the group assignment. Forty-one patients were randomized, but one patient had to be excluded after allocation. Twenty patients remained for intention to treat analysis in each trial arm. No PIBs (95% confidence interval [CI]: 0.00 to 0.16) or other unexpected harm were observed in the intervention group (IG). No patient suspended the intervention due to side effects. There was a trend towards improvements in all benefit-related outcomes in the IG. The overall consent rate was 0.91 (95% CI: 0.78 to 0.96), and there was no consent withdrawal. Although the balance between the benefit and harm of the intervention appears highly favourable, further testing on SAH patients is required. We recommend proceeding with amendments in a dose-finding trial to determine the optimal duration of parenteral treatment.

Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities.

PubMed

Soler, Joaquim; Elices, Matilde; Franquesa, Alba; Barker, Steven; Friedlander, Pablo; Feilding, Amanda; Pascual, Juan C; Riba, Jordi

2016-03-01

Ayahuasca is a psychotropic plant tea used for ritual purposes by the indigenous populations of the Amazon. In the last two decades, its use has expanded worldwide. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested its therapeutic potential, reporting that its use has helped individuals abandon the consumption of addictive drugs. Furthermore, recent open-label studies in patients with treatment-resistant depression found that a single ayahuasca dose induced a rapid antidepressant effect that was maintained weeks after administration. Here, we conducted an exploratory study of the psychological mechanisms that could underlie the beneficial effects of ayahuasca. We assessed a group of 25 individuals before and 24 h after an ayahuasca session using two instruments designed to measure mindfulness capacities: The Five Facets Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ). Ayahuasca intake led to significant increases in two facets of the FFMQ indicating a reduction in judgmental processing of experiences and in inner reactivity. It also led to a significant increase in decentering ability as measured by the EQ. These changes are classic goals of conventional mindfulness training, and the scores obtained are in the range of those observed after extensive mindfulness practice. The present findings support the claim that ayahuasca has therapeutic potential and suggest that this potential is due to an increase in mindfulness capacities.

fMRI brain activation changes following treatment of a first bipolar manic episode.

PubMed

Strakowski, Stephen M; Fleck, David E; Welge, Jeffrey; Eliassen, James C; Norris, Matthew; Durling, Michelle; Komoroski, Richard A; Chu, Wen-Jang; Weber, Wade; Dudley, Jonathan A; Blom, Thomas J; Stover, Amanda; Klein, Christina; Strawn, Jeffrey R; DelBello, Melissa P; Lee, Jing-Huei; Adler, Caleb M

2016-09-01

We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would normalize - i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status, potentially identifying neuroanatomic treatment response markers. Forty-two participants with bipolar I disorder were recruited during their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as potential measures of treatment response. ROI data were reduced using exploratory factor analysis, which identified five factors that were organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general, treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors. These findings provide evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pegaptanib sodium as maintenance therapy in neovascular age-related macular degeneration: the LEVEL study.

PubMed

Friberg, Thomas R; Tolentino, Michael; Weber, Pamela; Patel, Sunil; Campbell, Scott; Goldbaum, Mauro

2010-12-01

To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy. A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30-120 days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275 μm or less or thinning of 100 μm or more (optical coherence tomography); visual acuity (VA) 20/20-20/400. Intravitreal pegaptanib 0.3 mg was administered as maintenance every 6 weeks for 48 weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration. Of 568 enrolled subjects, 86% completed 1 year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20 μm increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147 days after maintenance initiation). An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD.

Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy.

PubMed

Chiriboga, Claudia A; Swoboda, Kathryn J; Darras, Basil T; Iannaccone, Susan T; Montes, Jacqueline; De Vivo, Darryl C; Norris, Daniel A; Bennett, C Frank; Bishop, Kathie M

2016-03-08

To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMNRx), an antisense oligonucleotide designed to alter splicing of SMN2 mRNA, in patients with childhood spinal muscular atrophy (SMA). Nusinersen was delivered by intrathecal injection to medically stable patients with type 2 and type 3 SMA aged 2-14 years in an open-label phase 1 study and its long-term extension. Four ascending single-dose levels (1, 3, 6, and 9 mg) were examined in cohorts of 6-10 participants. Participants were monitored for safety and tolerability, and CSF and plasma pharmacokinetics were measured. Exploratory efficacy endpoints included the Hammersmith Functional Motor Scale Expanded (HFMSE) and Pediatric Quality of Life Inventory. A total of 28 participants enrolled in the study (n = 6 in first 3 dose cohorts; n = 10 in the 9-mg cohort). Intrathecal nusinersen was well-tolerated with no safety/tolerability concerns identified. Plasma and CSF drug levels were dose-dependent, consistent with preclinical data. Extended pharmacokinetics indicated a prolonged CSF drug half-life of 4-6 months after initial clearance. A significant increase in HFMSE scores was observed at the 9-mg dose at 3 months postdose (3.1 points; p = 0.016), which was further increased 9-14 months postdose (5.8 points; p = 0.008) during the extension study. Results from this study support continued development of nusinersen for treatment of SMA. This study provides Class IV evidence that in children with SMA, intrathecal nusinersen is not associated with safety or tolerability concerns. © 2016 American Academy of Neurology.

Phase I/II evaluation of RV1001, a novel PI3Kδ inhibitor, in spontaneous canine lymphoma.

PubMed

Gardner, Heather L; Rippy, Sarah B; Bear, Misty D; Cronin, Kim L; Heeb, Heather; Burr, Holly; Cannon, Claire M; Penmetsa, Kumar V; Viswanadha, Srikant; Vakkalanka, Swaroop; London, Cheryl A

2018-01-01

RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL). Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy. The objective response rate was 62% (complete response (CR) n = 3; partial response (PR) n = 10), and responses were observed in both naïve and chemotherapy-resistant B and T cell NHL. This study provided the recommended starting dose for a phase II, non-pivotal, exploratory, open label multi-centered clinical trial in 35 dogs with naïve and drug resistant T and B-cell NHL, to further define the efficacy and safety profile of RV1001. The objective response rate in the phase II study was 77% (CR n = 1; PR n = 26). Clinical toxicities were primarily hepatobiliary and gastrointestinal, and were responsive to dose modifications and/or temporary drug discontinuation. Hepatotoxicity was the primary dose limiting toxicity. RV1001 exhibits good oral bioavailability, an acceptable safety profile, and biologic activity with associated inhibition of pAKT in dogs with B and T cell NHL. Data from these studies can be leveraged to help inform the design of future studies involving isoform-selective PI3K inhibitors in humans.

Gene expression associated with suicide attempts in US veterans (Open Access)

DTIC Science & Technology

2017-09-05

schizophrenia who had died from suicide. This gene codes for a cytokine that is part of the tumor necrosis factor family. In addition, the PIK3C3...expression level of eIF2 (and mTOR and WNT) was downregulated in one published report examining post- mortem tissue in people who had a schizophrenia ...HK. Suicide candidate genes associated with bipolar disorder and schizophrenia : an exploratory gene expression profiling analysis of post-mortem

Advanced thermally stable jet fuels: Technical progress report, October 1994--December 1994

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

Schobert, H.H.; Eser, S.; Song, C.

There are five tasks within this project on thermally stable coal-based jet fuels. Progress on each of the tasks is described. Task 1, Investigation of the quantitative degradation chemistry of fuels, has 5 subtasks which are described: Literature review on thermal stability of jet fuels; Pyrolytic and catalytic reactions of potential endothermic fuels: cis- and trans-decalin; Use of site specific {sup 13}C-labeling to examine the thermal stressing of 1-phenylhexane: A case study for the determination of reaction kinetics in complex fuel mixtures versus model compound studies; Estimation of critical temperatures of jet fuels; and Surface effects on deposit formation inmore » a flow reactor system. Under Task 2, Investigation of incipient deposition, the subtask reported is Uncertainty analysis on growth and deposition of particles during heating of coal-derived aviation gas turbine fuels; under Task 3, Characterization of solid gums, sediments, and carbonaceous deposits, is subtask, Studies of surface chemistry of PX-21 activated carbon during thermal degradation of jet A-1 fuel and n-dodecane; under Task 4, Coal-based fuel stabilization studies, is subtask, Exploratory screening and development potential of jet fuel thermal stabilizers over 400 C; and under Task 5, Exploratory studies on the direct conversion of coal to high quality jet fuels, are 4 subtasks: Novel approaches to low-severity coal liquefaction and coal/resid co-processing using water and dispersed catalysts; Shape-selective naphthalene hydrogenation for production of thermally stable jet fuels; Design of a batch mode and a continuous mode three-phase reactor system for the liquefaction of coal and upgrading of coal liquids; and Exploratory studies on coal liquids upgrading using mesopores molecular sieve catalysts. 136 refs., 69 figs., 24 tabs.« less

Tissue organ distribution and behavioral effects of platinum following acute and repeated exposure of the mouse to platinum sulfate.

PubMed Central

Lown, B A; Morganti, J B; Stineman, C H; D'Agostino, R B; Massaro, E J

1980-01-01

Platinum sulfate was administered intragastrically (IG) to adult male Swiss mice in a single dose at the 7 day LD5 or LD25 level. Control groups received 0.25M H2SO4 (pH 0.85) or 0.14M NaCl. Open field behavior (ambulations, rearings) was measured, and tissue/organ Pt levels determined at 4 hr, or 1, 3, or 7 days post administration. At all times, the LD25 depressed ambulations significantly and rearings marginally. It did not effect exploratory ("hole-in-board") behavior. The LD25 resulted in disproportionately high tissue Pt levels relateive to the LD5. There were significant inverse correlations between behavior and tissue Pt levels for most tissues, but not for brain. In related experiments, adult male mice were subjected to repeated IG administration of Pt(SO4)2 at the LD1 level (one dose every 72 hr for up to 10 doses). Three days after administration of the final dose of each series, open-field and exploratory performance were measured and tissue/organ Pt levels determined. Tissue/organ Pt levels were variable but generally increased with dose number. No Pt was detected in the brain. Activity and explorations were marginally depressed. Only rearings correlated significantly with tissue Pt levels. PMID:7389684

Phase I, open-cycle absorption solar cooling. Part IV. Executive summary analysis and resolution of critical issues and recommendations for Phase II. Final report

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

Wood, B.D.

The objective of this project is to advance lower cost solar cooling technology with the feasibility analysis, design and evaluation of proof-of-concept open cycle solar cooling concepts. The work is divided into three phases, with planned completion of each phase before proceeding with the following phase: Phase I - performance/economic/environmental related analysis and exploratory studies; Phase II - design and construction of an experimental system, including evaluative testing; Phase III - extended system testing during operation and engineering modifications as required. For Phase I, analysis and resolution of critical issues were completed with the objective of developing design specifications formore » an improved prototype OCA system.« less

Exploring social support and job satisfaction among associate degree program directors in California.

PubMed

Mintz-Binder, Ronda D; Fitzpatrick, Joyce J

2009-01-01

A troubling trend noted in California has been an increase in the number of open positions for program directors of associate degree registered nursing (ADRN) programs. Positions remain open for extended periods of time, and the number of qualified applicants for such positions is insufficient. The loss of and ensuing slow replacement of ADRN program directors can put these programs in jeopardy of student admission suspension, or, worse yet, closure by the state nursing board. In this exploratory study, variables of social support and job satisfaction were studied. Variables were found to be limited opportunities for peer interaction, expressed discontent, and retention concerns. A significant positive relationship between job satisfaction and social support was noted. Recommendations for future research are offered.

Entrepreneurship in Nursing: overview of companies in the State of São Paulo.

PubMed

Andrade, Andréia de Carvalho; Dal Ben, Luiza Watanabe; Sanna, Maria Cristina

2015-01-01

The present study aimed to identify and characterize nursing companies managed by entrepreneur nurses registered at the Commercial Registry of São Paulo by 2011. It's a descriptive, exploratory study, whose data collection, made throughout January 2012, was carried out on the Commercial Registry of Sao Paulo website. This non-governmental body has the function of registering the opening of companies and supervising their trade situation. This study allowed us to identify that the entrepreneur nurse is a growing reality through the identification of 196 companies opened by these professionals. Afterwards, it was analyzed their time of functioning, the main economic activity of the company, capital value, percentage of nurse partners and the distribution of companies by region of Sao Paulo State.

A machine learning pipeline for automated registration and classification of 3D lidar data

NASA Astrophysics Data System (ADS)

Rajagopal, Abhejit; Chellappan, Karthik; Chandrasekaran, Shivkumar; Brown, Andrew P.

2017-05-01

Despite the large availability of geospatial data, registration and exploitation of these datasets remains a persis- tent challenge in geoinformatics. Popular signal processing and machine learning algorithms, such as non-linear SVMs and neural networks, rely on well-formatted input models as well as reliable output labels, which are not always immediately available. In this paper we outline a pipeline for gathering, registering, and classifying initially unlabeled wide-area geospatial data. As an illustrative example, we demonstrate the training and test- ing of a convolutional neural network to recognize 3D models in the OGRIP 2007 LiDAR dataset using fuzzy labels derived from OpenStreetMap as well as other datasets available on OpenTopography.org. When auxiliary label information is required, various text and natural language processing filters are used to extract and cluster keywords useful for identifying potential target classes. A subset of these keywords are subsequently used to form multi-class labels, with no assumption of independence. Finally, we employ class-dependent geometry extraction routines to identify candidates from both training and testing datasets. Our regression networks are able to identify the presence of 6 structural classes, including roads, walls, and buildings, in volumes as big as 8000 m3 in as little as 1.2 seconds on a commodity 4-core Intel CPU. The presented framework is neither dataset nor sensor-modality limited due to the registration process, and is capable of multi-sensor data-fusion.

Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

PubMed

Provenzano, Robert; Besarab, Anatole; Wright, Steven; Dua, Sohan; Zeig, Steven; Nguyen, Peter; Poole, Lona; Saikali, Khalil G; Saha, Gopal; Hemmerich, Stefan; Szczech, Lynda; Yu, K H Peony; Neff, Thomas B

2016-06-01

Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. Short treatment duration and small sample size. In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study.

PubMed

Vakhapova, Veronika; Cohen, Tzafra; Richter, Yael; Herzog, Yael; Kam, Yossi; Korczyn, Amos D

2014-01-01

The present study is an open-label extension (OLE) aimed at evaluating the effect of 100 mg/day of phosphatidylserine enriched with docosahexaenoic acid (PS-DHA) on cognitive performance in nondemented elderly individuals with memory complaints. From the participants who completed the core study, 122 continued with a 15-week OLE. Efficacy was assessed using a computerized tool and the Clinical Global Impression of Change (CGI-C) rating scale. A significant improvement in sustained attention and memory recognition was observed in the PS-DHA naïve group, while the PS-DHA continuers maintained their cognitive status. Additionally, a significant improvement in CGI-C was observed in the naïve group. The results demonstrate that consumption of 100 mg/day of PS-DHA might be associated with improving or maintaining cognitive status in elderly subjects with memory complaints.

Open-label trial of atomoxetine hydrochloride in adults with ADHD.

PubMed

Johnson, Mats; Cederlund, Mats; Råstam, Maria; Areskoug, Björn; Gillberg, Christopher

2010-03-01

While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Ten patients met primary efficacy criteria at 10 weeks. Only one patient completed the whole study. Six patients discontinued before 10 weeks and thirteen at 10 weeks or later, mainly because of side-effects (aggression, depressed mood, raised liver enzymes, thyroid hormones, diastolic blood pressure), decreasing efficacy or non-compliance. Fifty percent responded to treatment, but only one patient (5%) felt sufficient improvement to continue for one year. Dosage may have been too low, and baseline impairment too high, for atomoxetine to have sufficient effect on ADHD symptoms in our group of adults. The majority had few side-effects, but several terminated treatment because of adverse effects.

HCP: A Flexible CNN Framework for Multi-label Image Classification.

PubMed

Wei, Yunchao; Xia, Wei; Lin, Min; Huang, Junshi; Ni, Bingbing; Dong, Jian; Zhao, Yao; Yan, Shuicheng

2015-10-26

Convolutional Neural Network (CNN) has demonstrated promising performance in single-label image classification tasks. However, how CNN best copes with multi-label images still remains an open problem, mainly due to the complex underlying object layouts and insufficient multi-label training images. In this work, we propose a flexible deep CNN infrastructure, called Hypotheses-CNN-Pooling (HCP), where an arbitrary number of object segment hypotheses are taken as the inputs, then a shared CNN is connected with each hypothesis, and finally the CNN output results from different hypotheses are aggregated with max pooling to produce the ultimate multi-label predictions. Some unique characteristics of this flexible deep CNN infrastructure include: 1) no ground-truth bounding box information is required for training; 2) the whole HCP infrastructure is robust to possibly noisy and/or redundant hypotheses; 3) the shared CNN is flexible and can be well pre-trained with a large-scale single-label image dataset, e.g., ImageNet; and 4) it may naturally output multi-label prediction results. Experimental results on Pascal VOC 2007 and VOC 2012 multi-label image datasets well demonstrate the superiority of the proposed HCP infrastructure over other state-of-the-arts. In particular, the mAP reaches 90.5% by HCP only and 93.2% after the fusion with our complementary result in [44] based on hand-crafted features on the VOC 2012 dataset.

Single Particle Differentiation through 2D Optical Fiber Trapping and Back-Scattered Signal Statistical Analysis: An Exploratory Approach

PubMed Central

Ribeiro, Rita S. R.; Cunha, João P. S.; Rosa, Carla C.; Jorge, Pedro A. S.

2018-01-01

Recent trends on microbiology point out the urge to develop optical micro-tools with multifunctionalities such as simultaneous manipulation and sensing. Considering that miniaturization has been recognized as one of the most important paradigms of emerging sensing biotechnologies, optical fiber tools, including Optical Fiber Tweezers (OFTs), are suitable candidates for developing multifunctional small sensors for Medicine and Biology. OFTs are flexible and versatile optotools based on fibers with one extremity patterned to form a micro-lens. These are able to focus laser beams and exert forces onto microparticles strong enough (piconewtons) to trap and manipulate them. In this paper, through an exploratory analysis of a 45 features set, including time and frequency-domain parameters of the back-scattered signal of particles trapped by a polymeric lens, we created a novel single feature able to differentiate synthetic particles (PMMA and Polystyrene) from living yeasts cells. This single statistical feature can be useful for the development of label-free hybrid optical fiber sensors with applications in infectious diseases detection or cells sorting. It can also contribute, by revealing the most significant information that can be extracted from the scattered signal, to the development of a simpler method for particles characterization (in terms of composition, heterogeneity degree) than existent technologies. PMID:29495502

School Motivation Questionnaire for the Portuguese population: structure and psychometric studies.

PubMed

Cordeiro, Pedro Miguel Gomes; Figueira, Ana Paula Couceiro; da Silva, José Tomás; Matos, Lennia

2012-11-01

It is presented the structure and psychometric studies of the "School Motivation Questionnaire". The SMQ is a self-report questionnaire with 101 items, organized in sixteen scales that measure the students' goal orientations, the perceived classroom goal structures, the perceived teacher's autonomy support and the use of learning strategies. Twelve scales are adapted from the "Learning Climate Questionnaire", "Perceptions of Instrumentality" and "Cuestionário a Estudiantes". Four scales and five additional items are created new. The psychometric studies rely on a convenience sample consisting of 9th and 12th grade students (N = 485) of Portuguese schools. The factorial and construct validity, verified through several exploratory factorial analyses to the data, presents a final solution of six factors, labelled Strategies (F1), Teacher Extrinsic Goals (F2), Student Extrinsic Goals, Externally Regulated (F3) Teacher Intrinsic Goals (F4), Student Extrinsic Goals, Internally Regulated (F5), and Student Intrinsic Goals (F6). The six-factor solution explains a significant variance of the scale results (53.95%). Good coefficients of internal consistency are obtained for all factors, never below (.858; F6). In sum there is strong evidence to support the multi-dimensionality of SMQ, upholding that the data obtained is exploratory and applies for future validation studies.

The Nursing Performance Instrument: Exploratory and Confirmatory Factor Analyses in Registered Nurses.

PubMed

Sagherian, Knar; Steege, Linsey M; Geiger-Brown, Jeanne; Harrington, Donna

2018-04-01

The optimal performance of nurses in healthcare settings plays a critical role in care quality and patient safety. Despite this importance, few measures are provided in the literature that evaluate nursing performance as an independent construct from competencies. The nine-item Nursing Performance Instrument (NPI) was developed to fill this gap. The aim of this study was to examine and confirm the underlying factor structure of the NPI in registered nurses. The design was cross-sectional, using secondary data collected between February 2008 and April 2009 for the "Fatigue in Nursing Survey" (N = 797). The sample was predominantly dayshift female nurses working in acute care settings. Using Mplus software, exploratory and confirmatory factor analyses were applied to the NPI data, which were divided into two equal subsamples. Multiple fit indices were used to evaluate the fit of the alternative models. The three-factor model was determined to fit the data adequately. The factors that were labeled as "physical/mental decrements," "consistent practice," and "behavioral change" were moderately to strongly intercorrelated, indicating good convergent validity. The reliability coefficients for the subscales were acceptable. The NPI consists of three latent constructs. This instrument has the potentialto be used as a self-monitoring instrument that addressesnurses' perceptions of performance while providing patient care.

Single Particle Differentiation through 2D Optical Fiber Trapping and Back-Scattered Signal Statistical Analysis: An Exploratory Approach.

PubMed

Paiva, Joana S; Ribeiro, Rita S R; Cunha, João P S; Rosa, Carla C; Jorge, Pedro A S

2018-02-27

Recent trends on microbiology point out the urge to develop optical micro-tools with multifunctionalities such as simultaneous manipulation and sensing. Considering that miniaturization has been recognized as one of the most important paradigms of emerging sensing biotechnologies, optical fiber tools, including Optical Fiber Tweezers (OFTs), are suitable candidates for developing multifunctional small sensors for Medicine and Biology. OFTs are flexible and versatile optotools based on fibers with one extremity patterned to form a micro-lens. These are able to focus laser beams and exert forces onto microparticles strong enough (piconewtons) to trap and manipulate them. In this paper, through an exploratory analysis of a 45 features set, including time and frequency-domain parameters of the back-scattered signal of particles trapped by a polymeric lens, we created a novel single feature able to differentiate synthetic particles (PMMA and Polystyrene) from living yeasts cells. This single statistical feature can be useful for the development of label-free hybrid optical fiber sensors with applications in infectious diseases detection or cells sorting. It can also contribute, by revealing the most significant information that can be extracted from the scattered signal, to the development of a simpler method for particles characterization (in terms of composition, heterogeneity degree) than existent technologies.

Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial.

PubMed

Phyo, Aung Pyae; Jittamala, Podjanee; Nosten, François H; Pukrittayakamee, Sasithon; Imwong, Mallika; White, Nicholas J; Duparc, Stephan; Macintyre, Fiona; Baker, Mark; Möhrle, Jörg J

2016-01-01

Artefenomel (OZ439) is a novel synthetic trioxolane with improved pharmacokinetic properties compared with other antimalarial drugs with the artemisinin pharmacophore. Artefenomel has been generally well tolerated in volunteers at doses up to 1600 mg and is being developed as a partner drug in an antimalarial combination treatment. We investigated the efficacy, tolerability, and pharmacokinetics of artefenomel at different doses in patients with Plasmodium falciparum or Plasmodium vivax malaria. This phase 2a exploratory, open-label trial was done at the Hospital for Tropical Diseases, Bangkok, and the Shoklo Malaria Research Unit in Thailand. Adult patients with acute, uncomplicated P falciparum or P vivax malaria received artefenomel in a single oral dose (200 mg, 400 mg, 800 mg, or 1200 mg). The first cohort received 800 mg. Testing of a new dose of artefenomel in a patient cohort was decided on after safety and efficacy assessment of the preceding cohort. The primary endpoint was the natural log parasite reduction per 24 h. Definitive oral treatment was given at 36 h. This trial is registered with ClinicalTrials.gov, number NCT01213966. Between Oct 24, 2010, and May 25, 2012, 82 patients were enrolled (20 in each of the 200 mg, 400 mg, and 800 mg cohorts, and 21 in the 1200 mg cohort). One patient withdrew consent (before the administration of artefenomel) but there were no further dropouts. The parasite reduction rates per 24 h ranged from 0·90 to 1·88 for P falciparum, and 2·09 to 2·53 for P vivax. All doses were equally effective in both P falciparum and P vivax malaria, with median parasite clearance half-lives of 4·1 h (range 1·3-6·7) to 5·6 h (2·0-8·5) for P falciparum and 2·3 h (1·2-3·9) to 3·2 h (0·9-15·0) for P vivax. Maximum plasma concentrations, dose-proportional to 800 mg, occurred at 4 h (median). The estimated elimination half-life was 46-62 h. No serious drug-related adverse effects were reported; other adverse effects were generally mild and reversible, with the highest number in the 1200 mg cohort (17 [81%] patients with at least one adverse event). The most frequently reported adverse effect was an asymptomatic increase in plasma creatine phosphokinase concentration (200 mg, n=5; 400 mg, n=3; 800 mg, n=1; 1200 mg, n=3). Artefenomel is a new synthetic antimalarial peroxide with a good safety profile that clears parasitaemia rapidly in both P falciparum and P vivax malaria. Its long half-life suggests a possible use in a single-dose treatment in combination with other drugs. Bill & Melinda Gates Foundation, Wellcome Trust, and UK Department for International Development. Copyright © 2016 Phyo et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.

Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

PubMed

Smith, Deidre J; Sarris, Jerome; Dowling, Nathan; O'Connor, Manjula; Ng, Chee H

2018-04-01

Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P < 0.05). Despite a significant reduction in the HAM-D score for middle insomnia (P = 0.02), the reduction in excessive daytime somnolence on the total Epworth Sleepiness Scale (ESS) did not reach significance. No significant adverse reactions to DHA were found. Within the major limits of this open-label pilot study, the results suggest that DHA may provide additional adjunctive benefits in patients with mild- to -moderate depression.

Design, objectives, execution and reporting of published open-label extension studies.

PubMed

Megan, Bowers; Pickering, Ruth M; Weatherall, Mark

2012-04-01

Open-label extension (OLE) studies following blinded randomized controlled trials (RCTs) of pharmaceuticals are increasingly being carried out but do not conform to regulatory standards and questions surround the validity of their evidence. OLE studies are usually discussed as a homogenous group, yet substantial differences in study design still meet the definition of an OLE. We describe published papers reporting OLE studies focussing on stated objectives, design, conduct and reporting. A search of Embase and Medline databases for 1996 to July 2008 revealed 268 papers reporting OLE studies that met our eligibility criteria. A random sample of 50 was selected for detailed review. Over 80% of the studies had efficacy stated as an objective. The most common methods of allocation at the start of the OLE were for all RCT participants to switch to one active treatment or for only participants on the new drug to continue, but in three studies all participants were re-randomized at the start of the OLE. Eligibility criteria and other selection factors resulted in on average of 74% of participants in the preceding RCT(s) enrolling in the OLE and only 57% completed it. Published OLE studies do not form a homogenous group with respect to design or retention of participants, and thus the validity of evidence from an OLE should be judged on an individual basis. The term 'open label' suggests bias through lack of blinding, but slippage in relation to the sample randomized in the preceding RCT may be the more important threat to validity. © 2010 Blackwell Publishing Ltd.

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

PubMed Central

2012-01-01

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493). PMID:22891797

Randomized open-label trial of baclofen for relapse prevention in alcohol dependence.

PubMed

Gupta, Manushree; Verma, Pankaj; Rastogi, Rajesh; Arora, Sheetal; Elwadhi, Deeksha

2017-05-01

Alcohol dependence is a progressive chronic disorder characterized by narrowing of the drinking repertoire, salience of drinking, tolerance and withdrawal phenomenon, compulsion to drink, and frequent relapses. Baclofen has been shown to promote abstinence, to reduce craving, and to reduce anxiety in alcohol-dependent individuals, and it promises to be a useful agent, although clinical data are limited at present. The current study aimed to test the utility of baclofen, a GABA agonist, in improving the relapse rates in alcohol-dependent subjects. A total of 122 alcohol-dependent subjects were randomized into two groups. Groups were administered baclofen (30 mg/day) or benfothiamine (a nutritional supplement) using an open label design. Both groups received brief motivational intervention. Subjects were assessed at 0, 2, 4, 8, and 12 weeks for the primary outcome measures: time to first relapse, heavy drinking days, cumulative abstinence duration, and craving (measured by the Obsessive Compulsive Drinking Scale (OCDS)). Seventy-two participants received baclofen, and 50 received benfothiamine. Participants receiving baclofen remained abstinent for significantly more days than the benfothiamine group (p < 0.05). The percentage of heavy drinking days was significantly lower in the baclofen group (p = 0.001). Craving and anxiety scores (Hamilton Anxiety Rating Scale) were also significantly decreased in the baclofen group relative to the control group (p = 0.001). Time to first relapse was similar in both groups. In this open-label trial, alcohol-dependent participants receiving baclofen showed significant improvements in drinking outcomes compared with participants receiving benfothiamine. This study provides further evidence that baclofen is useful for the treatment of alcohol dependence.

Defining success in clinical trials--profiling pregabalin, the newest AED.

PubMed

Ryvlin, P

2005-11-01

The efficacy and safety of pregabalin as adjunctive therapy for patients with partial epilepsy with or without secondary generalization has been established by four randomized, 12-week, double-blind, placebo-controlled trials (n = 1396) and four long-term open-label studies (n = 1480). Patients in the three fixed-dose trials were >/=12 years of age, had >/=6 partial seizures and no 4-week seizure-free period during the 8-week baseline period. Seventy-three per cent of patients were taking >/=2 concomitant antiepileptic drugs. Responder rates across the effective doses (150-600 mg/day) ranged from 14% to 51% and demonstrated a significant dose-response relationship. The most common adverse events were central nervous system related, generally mild or moderate, transient, and tended to be dose related. The fourth placebo-controlled trial compared a fixed dose of pregabalin 600 mg/day with a flexible-dose regimen (150-600 mg/day). Responder rates were greater for both the fixed dose (45.3%, P < 0.001) and flexible dose (31.3%, P < 0.001) when compared with placebo (11.0%). Compared with the fixed-dose group, the flexible-dose patients had a lower incidence of adverse events and study discontinuations. In long-term open-label trials, the efficacy of pregabalin was maintained with respect to 50% responder rates suggesting no obvious tolerance developing over 2 years. Seizure-free rates were 8.9% and 5.8% for the last 6 months and 1 year of pregabalin treatment, respectively. Long-term open-label pregabalin treatment was well tolerated.

IGF-1 in autosomal dominant cerebellar ataxia - open-label trial.

PubMed

Sanz-Gallego, Irene; Rodriguez-de-Rivera, Francisco J; Pulido, Irene; Torres-Aleman, Ignacio; Arpa, Javier

2014-01-01

The objective of this clinical open-label trial was to test the safety, tolerability and efficacy of IGF-1 therapy for autosomal dominant cerebellar ataxia (ADCA) patients. A total of 19 molecularly confirmed patients with SCA3, 1 patient with SCA6 and 6 patients with SCA7 completed our study. They were 8 females and 18 males, 28 to 74 years of age (average ± SD: 49.3 ± 14.1). Patients were treated with IGF-1 therapy with a dosage of 50 μg/kg twice a day for 12 months. The efficacy of this therapy was assessed by change from baseline on the scale for the assessment and rating of ataxia (SARA). Ten patients, consecutively selected, continued their assigned dosages in a second year open-label extension trial. A statistically significant improvement in SARA scores was observed for patients with SCA3, patients with SCA7 and all patients grouped together after the first year of IGF-1 therapy, while a stabilization of the disease was confirmed during the second year (extension study). The single patient with SCA6 showed 3 improvement points in SARA score after 3 four-month periods of IGF-1 therapy when compared with baseline measurements. Our data indicate that IGF-1 is safe and well tolerated in general. Our data, in comparison with results from previous cohorts, indicate a trend for IGF-1 treatment to stabilize the disease progression for patients with SCA, indicating that IGF-1 therapy is able to decrease the progressivity of ADCA.

Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy.

PubMed

Waddington Cruz, Márcia; Amass, Leslie; Keohane, Denis; Schwartz, Jeffrey; Li, Huihua; Gundapaneni, Balarama

2016-09-01

Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and -7.8 (-44.3, 28.8) kg/m 2 × g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis. ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002.

An open-label study of sodium oxybate in Spasmodic dysphonia.

PubMed

Rumbach, Anna F; Blitzer, Andrew; Frucht, Steven J; Simonyan, Kristina

2017-06-01

Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. Open-label study. We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of sodium oxybate (Xyrem), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration. Sodium oxybate significantly improved voice symptoms (P = .001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium oxybate further showed a trend for improving VT symptoms (P = .03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug's effects were observed approximately 30 to 40 minutes after its intake and lasted about 3.5 to 4 hours. Our study demonstrated that sodium oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of sodium oxybate in SD and SD/VT may be linked to that of alcohol, and as such, sodium oxybate might be beneficial for alcohol-responsive SD and SD/VT patients. 4 Laryngoscope, 127:1402-1407, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy.

PubMed

Sadun, Alfredo A; Chicani, Carlos Filipe; Ross-Cisneros, Fred N; Barboni, Piero; Thoolen, Martin; Shrader, William D; Kubis, Kenneth; Carelli, Valerio; Miller, Guy

2012-03-01

To evaluate the safety and efficacy of a new therapeutic agent, EPI-743, in Leber hereditary optic neuropathy (LHON) using standard clinical, anatomic, and functional visual outcome measures. Open-label clinical trial. University medical center. Patients  Five patients with genetically confirmed LHON with acute loss of vision were consecutively enrolled and treated with the experimental therapeutic agent EPI-743 within 90 days of conversion. Intervention  During the course of the study, 5 consecutive patients received EPI-743, by mouth, 3 times daily (100-400 mg per dose). Treatment effect was assessed by serial measurements of anatomic and functional visual indices over 6 to 18 months, including Snellen visual acuity, retinal nerve fiber layer thickness measured by optical coherence tomography, Humphrey visual fields (mean decibels and area with 1-log unit depression), and color vision. Treatment effect in this clinical proof of principle study was assessed by comparison of the prospective open-label treatment group with historical controls. Of 5 subjects treated with EPI-743, 4 demonstrated arrest of disease progression and reversal of visual loss. Two patients exhibited a total recovery of visual acuity. No drug-related adverse events were recorded. In a small open-label trial, EPI-743 arrested disease progression and reversed vision loss in all but 1 of the 5 consecutively treated patients with LHON. Given the known natural history of acute and rapid progression of LHON resulting in chronic and persistent bilateral blindness, these data suggest that the previously described irreversible priming to retinal ganglion cell loss may be reversed.

Value, Cost, and Sharing: Open Issues in Constrained Clustering

NASA Technical Reports Server (NTRS)

Wagstaff, Kiri L.

2006-01-01

Clustering is an important tool for data mining, since it can identify major patterns or trends without any supervision (labeled data). Over the past five years, semi-supervised (constrained) clustering methods have become very popular. These methods began with incorporating pairwise constraints and have developed into more general methods that can learn appropriate distance metrics. However, several important open questions have arisen about which constraints are most useful, how they can be actively acquired, and when and how they should be propagated to neighboring points. This position paper describes these open questions and suggests future directions for constrained clustering research.

A combined analysis of the Frost Multidimensional Perfectionism Scale (FMPS), Child and Adolescent Perfectionism Scale (CAPS), and Almost Perfect Scale-Revised (APS-R): Different perfectionist profiles in adolescent high school students.

PubMed

Sironic, Amanda; Reeve, Robert A

2015-12-01

To investigate differences and similarities in the dimensional constructs of the Frost Multidimensional Perfectionism Scale (FMPS; Frost, Marten, Lahart, & Rosenblate, 1990), Child and Adolescent Perfectionism Scale (CAPS; Flett, Hewitt, Boucher, Davidson, & Munro, 2000), and Almost Perfect Scale-Revised (APS-R; Slaney, Rice, Mobley, Trippi, & Ashby, 2001), 938 high school students completed the 3 perfectionism questionnaires, as well as the Depression Anxiety Stress Scales (DASS; Lovibond & Lovibond, 1995). Preliminary analyses revealed commonly observed factor structures for each perfectionism questionnaire. Exploratory factor analysis of item responses from the questionnaires (combined) yielded a 4-factor solution (factors were labeled High Personal Standards, Concerns, Doubts and Discrepancy, Externally Motivated Perfectionism, and Organization and Order). A latent class analysis of individuals' mean ratings on each of the 4 factors yielded a 6-class solution. Three of the 6 classes represented perfectionist subgroups (labeled adaptive perfectionist, externally motivated maladaptive perfectionist, and mixed maladaptive perfectionist), and 3 represented nonperfectionist subgroups (labeled nonperfectionist A, nonperfectionist B, and order and organization nonperfectionist). Each of the 6 subgroups was meaningfully associated with the DASS. Findings showed that 3 out of 10 students were classified as maladaptive perfectionists, and maladaptive perfectionists were more prevalent than adaptive perfectionists. In sum, it is evident that combined ratings from the FMPS, CAPS, and APS-R offer a meaningful characterization of perfectionism. (c) 2015 APA, all rights reserved).

Delivery of cyclodextrin polymers to bacterial biofilms - An exploratory study using rhodamine labelled cyclodextrins and multiphoton microscopy.

PubMed

Thomsen, Hanna; Benkovics, Gábor; Fenyvesi, Éva; Farewell, Anne; Malanga, Milo; Ericson, Marica B

2017-10-15

Cyclodextrin (CD) polymers are interesting nanoparticulate systems for pharmaceutical delivery; however, knowledge regarding their applications towards delivery into complex microbial biofilm structures is so far limited. The challenge is to demonstrate penetration and transport through the biofilm and its exopolysaccharide matrix. The ideal functionalization for penetration into mature biofilms is unexplored. In this paper, we present a novel set of rhodamine labelled βCD-polymers, with different charge moieties, i.e., neutral, anionic, and cationic, and explore their potential delivery into mature Staphylococcus epidermidis biofilms using multiphoton laser scanning microscopy (MPM). The S. epidermidis biofilms, being a medically relevant model organism, were stained with SYTO9. By using MPM, three-dimensional imaging and spectral investigation of the distribution of the βCD-polymers could be obtained. It was found that the cationic βCD-polymers showed significantly higher integration into the biofilms, compared to neutral and anionic functionalized βCDs. None of the carriers presented any inherent toxicity to the biofilms, meaning that the addition of rhodamine moiety does not affect the inertness of the delivery system. Taken together, this study demonstrates a novel approach by which delivery of fluorescently labelled CD nanoparticles to bacterial biofilms can be explored using MPM. Future studies should be undertaken investigating the potential in using cationic functionalization of CD based delivery systems for targeting anti-microbial effects in biofilms. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Developmental Subchronic Exposure to Diphenylarsinic Acid Induced Increased Exploratory Behavior, Impaired Learning Behavior, and Decreased Cerebellar Glutathione Concentration in Rats

PubMed Central

Negishi, Takayuki; Matsunaga, Yuki

2013-01-01

In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0–6 weeks of age] and/or late period [7–12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA. PMID:24008832

Lipopolysaccharide affects exploratory behaviors toward novel objects by impairing cognition and/or motivation in mice: Possible role of activation of the central amygdala.

PubMed

Haba, Ryota; Shintani, Norihito; Onaka, Yusuke; Wang, Hyper; Takenaga, Risa; Hayata, Atsuko; Baba, Akemichi; Hashimoto, Hitoshi

2012-03-17

Lipopolysaccharide (LPS) produces a series of systemic and psychiatric changes called sickness behavior. In the present study, we characterized the LPS-induced decrease in novel object exploratory behaviors in BALB/c mice. As already reported, LPS (0.3-5 μg/mouse) induced dose- and time-dependent decreases in locomotor activity, food intake, social interaction, and exploration for novel objects, and an increase in immobility in the forced-swim test. Although the decrease in locomotor activity was ameliorated by 10h postinjection, novel object exploratory behaviors remained decreased at 24h and were observed even with the lowest dose of LPS. In an object exploration test, LPS shortened object exploration time but did not affect moving time or the frequency of object exploration. Although pre-exposure to the same object markedly decreased the duration of exploration and LPS did not change this reduction, LPS significantly impaired the exploration of a novel object that replaced the familiar one. LPS did not affect anxiety-like behaviors in open-field and elevated plus-maze tests. An LPS-induced increase in the number of c-Fos-immunoreactive cells was observed in several brain regions within 6h of LPS administration, but the number of cells quickly returned to control levels, except in the central amygdala where the increase continued for 24h. These results suggest that LPS most prominently affects object exploratory behaviors by impairing cognition and/or motivation including continuous attention and curiosity toward objects, and that this may be associated with activation of brain nuclei such as the central amygdala. Copyright © 2012 Elsevier B.V. All rights reserved.

Alcohol hangover: type and time-extension of motor function impairments.

PubMed

Karadayian, Analía G; Cutrera, Rodolfo A

2013-06-15

Alcohol hangover is defined as the unpleasant next-day state following an evening of excessive alcohol consumption. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. During hangover cognitive functions and subjective capacities are affected along with inefficiency, reduced productivity, absenteeism, driving impairments, poor academic achievement and reductions in motor coordination. The aim of this work was to study the type and length of motor and exploratory functions from the beginning to the end of the alcohol hangover. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Motor performance, walking deficiency, motor strength, locomotion and exploratory activity were evaluated at a basal point (ZT0) and every 2 h up to 20 h after blood alcohol levels were close to zero (hangover onset). Motor performance was 80% decreased at the onset of hangover (p<0.001). Hangover mice exhibited a reduced motor performance during the next 16 h (p<0.01). Motor function was recovered 20 h after hangover onset. Hangover mice displayed walking deficiencies from the beginning to 16 h after hangover onset (p<0.05). Moreover, mice suffering from a hangover, exhibited a significant decrease in neuromuscular strength during 16 h (p<0.001). Averaged speed and total distance traveled in the open field test and the exploratory activity on T-maze and hole board tests were reduced during 16 h after hangover onset (p<0.05). Our findings demonstrate a time-extension between 16 to 20 h for hangover motor and exploratory impairments. As a whole, this study shows the long lasting effects of alcohol hangover. Copyright © 2013 Elsevier B.V. All rights reserved.

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

PubMed

Flores-Montoya, Mayra Gisel; Sobin, Christina

2015-07-01

Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). Copyright © 2014 John Wiley & Sons, Ltd.

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

PubMed Central

Flores-Montoya, Mayra Gisel; Sobin, Christina

2014-01-01

Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 μg dl−1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 μg dl−1. PMID:25219894

An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension.

PubMed

Riedl, Marc A; Bernstein, Jonathan A; Craig, Timothy; Banerji, Aleena; Magerl, Markus; Cicardi, Marco; Longhurst, Hilary J; Shennak, Mustafa M; Yang, William H; Schranz, Jennifer; Baptista, Jovanna; Busse, Paula J

2017-01-01

Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study ("rollover patients") and those who did not participate in the double-blind study ("non-rollover patients"), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient's first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up. Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT02741596.

Video Object Segmentation through Spatially Accurate and Temporally Dense Extraction of Primary Object Regions (Open Access)

DTIC Science & Technology

2013-10-03

fol- low the setup in the literature ([13, 14]), and use 5 (birdfall, cheetah , girl, monkeydog and parachute) of the videos for evaluation (since the...segmentation labeling results of the method, GT is the ground-truth labeling of the video, and F is the (a) Birdfall (b) Cheetah (c) Girl (d) Monkeydog...Video Ours [14] [13] [20] [6] birdfall 155 189 288 252 454 cheetah 633 806 905 1142 1217 girl 1488 1698 1785 1304 1755 monkeydog 365 472 521 563 683

Labelling Facial Affect in Context in Adults with and without TBI

PubMed Central

Turkstra, Lyn S.; Kraning, Sarah G.; Riedeman, Sarah K.; Mutlu, Bilge; Duff, Melissa; VanDenHeuvel, Sara

2017-01-01

Recognition of facial affect has been studied extensively in adults with and without traumatic brain injury (TBI), mostly by asking examinees to match basic emotion words to isolated faces. This method may not capture affect labelling in everyday life when faces are in context and choices are open-ended. To examine effects of context and response format, we asked 148 undergraduate students to label emotions shown on faces either in isolation or in natural visual scenes. Responses were categorised as representing basic emotions, social emotions, cognitive state terms, or appraisals. We used students’ responses to create a scoring system that was applied prospectively to five men with TBI. In both groups, over 50% of responses were neither basic emotion words nor synonyms, and there was no significant difference in response types between faces alone vs. in scenes. Adults with TBI used labels not seen in students’ responses, talked more overall, and often gave multiple labels for one photo. Results suggest benefits of moving beyond forced-choice tests of faces in isolation to fully characterise affect recognition in adults with and without TBI. PMID:29093643

An observational study of consumer use of fast-food restaurant drive-through lanes: implications for menu labelling policy.

PubMed

Roberto, Christina A; Hoffnagle, Elena; Bragg, Marie A; Brownell, Kelly D

2010-11-01

Some versions of restaurant menu labelling legislation do not require energy information to be posted on menus for drive-through lanes. The present study was designed to quantify the number of customers who purchase fast food through drive-in windows as a means of informing legislative labelling efforts. This was an observational study. The study took place at two McDonald's and Burger King restaurants, and single Dairy Queen, Kentucky Fried Chicken, Taco Bell and Wendy's restaurants. The number of customers entering the chain restaurants and purchasing food via the drive-through lane were recorded. A total of 3549 patrons were observed. The percentage of customers who made their purchases at drive-throughs was fifty-seven. The overall average (57 %) is likely a conservative estimate because some fast-food restaurants have late-night hours when only the drive-throughs are open. Since nearly six in ten customers purchase food via the drive-through lanes, menu labelling legislation should mandate the inclusion of menu labels on drive-through menu boards to maximise the impact of this public health intervention.

Incorporation of {sup 13}C-labeled intermediates into developing lignin revealed by analytical pyrolysis and CuO oxidation in combination with IRM-GC-MS

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

Eglinton, T.I.; Goni, M.A.; Boon, J.J.

1995-12-31

Tissue samples from Ginkgo shoots (Ginkgo biloba L.) and Rice grass (Oryzasitiva sp.) incubated in the presence of {sup 13}C-labeled substrates such as coniferin (postulated to be biosynthetic intermediates in lignin biosynthesis) were studied using thermal and chemical dissociation methods in combination with molecular-level isotopic measurements. The aim of the study was (1) to investigate dissociation mechanisms, and (2) to examine and quantify the proportions of labeled material incorporated within each sample. Isotopic analysis of specific dissociation products revealed the presence of the label in its original positions, and only within lignin-derived (phenolic) products. Moreover, the distribution and isotopic compositionmore » of the dissociation products strongly suggest an origin from newly-formed lignin. These results clearly indicate that there is no {open_quotes}scrambling{close_quotes} of carbon atoms as a result of the dissociation process, thereby lending support to this analytical approach. In addition, the data provide confidence in the selective labeling approach for elucidation of the structure and biosynthesis of lignin.« less

Magnetic tagging of cell-derived microparticles: new prospects for imaging and manipulation of these mediators of biological information.

PubMed

Vats, Nidhi; Wilhelm, Claire; Rautou, Pierre-Emmanuel; Poirier-Quinot, Marie; Péchoux, Christine; Devue, Cécile; Boulanger, Chantal M; Gazeau, Florence

2010-07-01

Submicron membrane fragments termed microparticles (MPs), which are released by apoptotic or activated cells, are newly considered as vectors of biological information and actors of pathology development. We propose the tagging of MPs with magnetic nanoparticles as a new approach allowing imaging, manipulation and targeting of cell-derived MPs. MPs generated in vitro from human endothelial cells or isolated from atherosclerotic plaques were labeled using citrate-coated 8 nm iron-oxide nanoparticles. MPs were tagged with magnetic nanoparticles on their surface and detected as Annexin-V positive by flow cytometry. Labeled MPs could be mobilized, isolated and manipulated at a distance in a magnetic field gradient. Magnetic mobility of labeled MPs was quantified by micromagnetophoresis. Interactions of labeled MPs with endothelial cells could be triggered and modulated by magnetic guidance. Nanoparticles served as tracers at different scales: at the subcellular level by electron microscopy, at the cellular level by histology and at the macroscopic level by MRI. Magnetic labeling of biogenic MPs opens new prospects for noninvasive monitoring and distal manipulations of these biological effectors.

ALE: automated label extraction from GEO metadata.

PubMed

Giles, Cory B; Brown, Chase A; Ripperger, Michael; Dennis, Zane; Roopnarinesingh, Xiavan; Porter, Hunter; Perz, Aleksandra; Wren, Jonathan D

2017-12-28

NCBI's Gene Expression Omnibus (GEO) is a rich community resource containing millions of gene expression experiments from human, mouse, rat, and other model organisms. However, information about each experiment (metadata) is in the format of an open-ended, non-standardized textual description provided by the depositor. Thus, classification of experiments for meta-analysis by factors such as gender, age of the sample donor, and tissue of origin is not feasible without assigning labels to the experiments. Automated approaches are preferable for this, primarily because of the size and volume of the data to be processed, but also because it ensures standardization and consistency. While some of these labels can be extracted directly from the textual metadata, many of the data available do not contain explicit text informing the researcher about the age and gender of the subjects with the study. To bridge this gap, machine-learning methods can be trained to use the gene expression patterns associated with the text-derived labels to refine label-prediction confidence. Our analysis shows only 26% of metadata text contains information about gender and 21% about age. In order to ameliorate the lack of available labels for these data sets, we first extract labels from the textual metadata for each GEO RNA dataset and evaluate the performance against a gold standard of manually curated labels. We then use machine-learning methods to predict labels, based upon gene expression of the samples and compare this to the text-based method. Here we present an automated method to extract labels for age, gender, and tissue from textual metadata and GEO data using both a heuristic approach as well as machine learning. We show the two methods together improve accuracy of label assignment to GEO samples.

Study and development of label-free optical biosensors for biomedical applications

NASA Astrophysics Data System (ADS)

Choi, Charles J.

For the majority of assays currently performed, fluorescent or colorimetric chemical labels are commonly attached to the molecules under study so that they may be readily visualized. The methods of using labels to track biomolecular binding events are very sensitive and effective, and are employed as standardized assay protocol across research labs worldwide. However, using labels induces experimental uncertainties due to the effect of the label on molecular conformation, active binding sites, or inability to find an appropriate label that functions equivalently for all molecules in an experiment. Therefore, the ability to perform highly sensitive biochemical detection without the use of fluorescent labels would further simplify assay protocols and would provide quantitative kinetic data, while removing experimental artifacts from fluorescent quenching, shelf-life, and background fluorescence phenomena. In view of the advantages mentioned above, the study and development of optical label-free sensor technologies have been undertaken here. In general, label-free photonic crystal (PC) biosensors and metal nanodome array surface-enhanced Raman scattering (SERS) substrates, both of which are fabricated by nanoreplica molding process, have been used as the method to attack the problem. Chapter 1 shows the work on PC label-free biosensor incorporated microfluidic network for bioassay performance enhancement and kinetic reaction rate constant determination. Chapter 2 describes the work on theoretical and experimental comparison of label-free biosensing in microplate, microfluidic, and spot-based affinity capture assays. Chapter 3 shows the work on integration of PC biosensor with actuate-to-open valve microfluidic chip for pL-volume combinatorial mixing and screening application. In Chapter 4, the development and characterization of SERS nanodome array is shown. Lastly, Chapter 5 describes SERS nanodome sensor incorporated tubing for point-of-care monitoring of intravenous drugs and metabolites.

Relations between open-field, elevated plus-maze, and emergence tests in C57BL/6JIco and BALB/cAnN@Ico mice injected with ethanol.

PubMed

Lalonde, R; Strazielle, C

2012-04-01

The effects of ethanol were examined on three tests of exploratory activity in two mouse strains. Although ethanol reduced open-field rearing in both strains, it increased ambulation only in the less active BALB/cAnN@Ico strain, not in the C57BL/6JIco strain. Likewise, ethanol increased open and enclosed arm entries in the elevated plus-maze only in the more anxious BALB/cAnN@Ico strain. However, both strains injected with ethanol emerged faster than placebo from a small chamber at doses not affecting behaviors in the other two tests. Significant correlations were found between emergence latencies on one hand and either slow stereotyped movements or open and enclosed arm entries on the other. The strain-specific effects may be attributable to differences in GABA(A) -related receptor binding or catalase activity. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Evaluation of the procedure 1A component of the 1980 US/Canada wheat and barley exploratory experiment

NASA Technical Reports Server (NTRS)

Chapman, G. M. (Principal Investigator); Carnes, J. G.

1981-01-01

Several techniques which use clusters generated by a new clustering algorithm, CLASSY, are proposed as alternatives to random sampling to obtain greater precision in crop proportion estimation: (1) Proportional Allocation/relative count estimator (PA/RCE) uses proportional allocation of dots to clusters on the basis of cluster size and a relative count cluster level estimate; (2) Proportional Allocation/Bayes Estimator (PA/BE) uses proportional allocation of dots to clusters and a Bayesian cluster-level estimate; and (3) Bayes Sequential Allocation/Bayesian Estimator (BSA/BE) uses sequential allocation of dots to clusters and a Bayesian cluster level estimate. Clustering in an effective method in making proportion estimates. It is estimated that, to obtain the same precision with random sampling as obtained by the proportional sampling of 50 dots with an unbiased estimator, samples of 85 or 166 would need to be taken if dot sets with AI labels (integrated procedure) or ground truth labels, respectively were input. Dot reallocation provides dot sets that are unbiased. It is recommended that these proportion estimation techniques are maintained, particularly the PA/BE because it provides the greatest precision.

Alcohol Warnings and Moderate Drinking Patterns among Italian University Students: An Exploratory Study

PubMed Central

Annunziata, Azzurra; Vecchio, Riccardo; Mariani, Angela

2017-01-01

The introduction of health warnings on labels to correct externalities associated with alcohol consumption is heavily debated and has been explored from different perspectives. The current paper aims to analyse the interest and attitudes of Italian university students regarding health warnings on alcoholic beverages and to verify the existence of segments that differ in terms of attitudes towards such warnings. Our results show that young consumers consider health warnings quite important, although the degree of perceived utility differs in relation to the type of warning. Cluster analysis shows the existence of three groups of young consumers with different degrees of attention and perceived utility of warnings on alcoholic beverages, but also in relation to drinking behaviour and awareness of social and health risks related to alcohol consumption. In brief, Italian young adults with moderate consumption behaviour view label warnings positively, while this attitude is weaker among younger adults and those with riskier consumption behaviours. Our findings, albeit limited and based on stated and not revealed data, support the need for appropriate tools to improve the availability of information among young adults on the risks of excessive alcohol consumption and increased awareness of the importance of moderate drinking. PMID:28629138

Translating knowledge into practice: An exploratory study of dementia-specific training for community-based service providers.

PubMed

O'Sullivan, Grace; Hocking, Clare; McPherson, Kathryn

2017-08-01

Objective To develop, deliver, and evaluate dementia-specific training designed to inform service delivery by enhancing the knowledge of community-based service providers. Methods This exploratory qualitative study used an interdisciplinary, interuniversity team approach to develop and deliver dementia-specific training. Participants included management, care staff, and clients from three organizations funded to provide services in the community. Data on the acceptability, applicability, and perceived outcomes of the training were gathered through focus group discussions and individual interviews. Transcripts were analyzed to generate open codes which were clustered into themes and sub-themes addressing the content, delivery, and value of the training. Findings Staff valued up-to-date knowledge and "real stories" grounded in practice. Clients welcomed the strengths-based approach. Contractual obligations impact on the application of knowledge in practice. Implications The capacity to implement new knowledge may be limited by the legislative policies which frame service provision, to the detriment of service users.

Brain-computer interface using wavelet transformation and naïve bayes classifier.

PubMed

Bassani, Thiago; Nievola, Julio Cesar

2010-01-01

The main purpose of this work is to establish an exploratory approach using electroencephalographic (EEG) signal, analyzing the patterns in the time-frequency plane. This work also aims to optimize the EEG signal analysis through the improvement of classifiers and, eventually, of the BCI performance. In this paper a novel exploratory approach for data mining of EEG signal based on continuous wavelet transformation (CWT) and wavelet coherence (WC) statistical analysis is introduced and applied. The CWT allows the representation of time-frequency patterns of the signal's information content by WC qualiatative analysis. Results suggest that the proposed methodology is capable of identifying regions in time-frequency spectrum during the specified task of BCI. Furthermore, an example of a region is identified, and the patterns are classified using a Naïve Bayes Classifier (NBC). This innovative characteristic of the process justifies the feasibility of the proposed approach to other data mining applications. It can open new physiologic researches in this field and on non stationary time series analysis.

Ghanaian youth and festive transvestism.

PubMed

Geoffrion, Karine

2013-01-01

'Festive transvestism' is an increasingly visible cross-dressing practice performed by young people in the Southern parts of contemporary Ghana. Based on participant observation in four cross-dressing events, 15 individual interviews and a focus-group discussion, festive cross-dressing is understood as a contemporary ritual that mainly serves the purpose of reinforcing and reproducing gender binaries as well as heteronormativity in Ghanaian society. Nevertheless cross-dressing events also provide a subjective, creative and exploratory space--although temporary and circumscribed--for the transvestites as well as for the spectators to deconstruct sex, gender and sexuality through the performativity of transvestism. The opening of this exploratory space is made possible by the liminality of the social category of youth in Ghana, which grants young people, especially young men, more liberty and (gender) flexibility. Finally, the paper challenges the widely spread Western perception that feminine men and cross-dressers are necessarily homosexual by resituating the concept of homosexuality within the context of Ghanaian society, where it has recently started to occupy the public space.

Self-esteem in adolescent patients with attention-deficit/hyperactivity disorder during open-label atomoxetine treatment: psychometric evaluation of the Rosenberg Self-Esteem Scale and clinical findings.

PubMed

Dittmann, Ralf W; Wehmeier, Peter M; Schacht, Alexander; Lehmann, Martin; Lehmkuhl, Gerd

2009-12-01

To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12-17 years), treated in an open-label study for 24 weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous structure of the SES could be confirmed. Reliability and internal consistency were moderate to excellent. Highest coefficients were found for the correlation between SES and GIPD scores. Self-esteem significantly increased over time, accompanied by an improvement of ADHD symptoms and related perceived difficulties. The Rosenberg SES was shown to be internally consistent, reliable, and sensitive to treatment-related changes of self-esteem. According to these findings, self-esteem may be an important individual patient outcome beyond the core symptoms of ADHD. © The Author(s) 2009. This article is published with open access at Springerlink.com

The effects of varenicline on sensory gating and exploratory behavior with pretreatment with nicotinic or 5-HT3A receptor antagonists.

PubMed

Kucinski, Aaron; Wersinger, Scott; Stachowiak, Ewa K; Becker, Chani; Lippiello, Pat; Bencherif, Merouane; Stachowiak, Michal K

2015-02-01

Individuals with schizophrenia smoke at high frequency relative to the general population. Despite the harmful effects of cigarette smoking, smoking among schizophrenic patients improves cognitive impairments not addressed or worsened by common neuroleptics. Varenicline, a nonselective neuronal nicotinic receptor (NNR) agonist and full agonist of 5-HT3A receptors, helps reduce smoking among schizophrenic patients. To determine whether varenicline also improves a cognitive symptom of schizophrenia, namely, impaired sensory gating, a transgenic mouse with schizophrenia, th-fgfr1(tk-), was used. Varenicline dose-dependently increased prepulse inhibition (PPI) of the startle response, a measure of sensory gating, in th-fgfr1(tk-) mice and normalized PPI deficits relative to nontransgenic controls. With the highest dose (10 mg/kg), however, there was a robust elevation of PPI and startle response, as well as reduced exploratory behavior in the open field and elevated plus maze. Pretreatment with the nonspecific NNR antagonist mecamylamine attenuated the exaggerated PPI response and, similar to the 5-HT3A receptor antagonist ondansetron, it prevented the reduction in exploratory behavior. Collectively, these results indicate that varenicline at low-to-moderate doses may be beneficial against impaired sensory gating in schizophrenia; however, higher doses may induce anxiogenic effects, which can be prevented with antagonists of NNRs or 5-HT3A receptors.

SOCR Motion Charts: An Efficient, Open-Source, Interactive and Dynamic Applet for Visualizing Longitudinal Multivariate Data

PubMed Central

Al-Aziz, Jameel; Christou, Nicolas; Dinov, Ivo D.

2011-01-01

The amount, complexity and provenance of data have dramatically increased in the past five years. Visualization of observed and simulated data is a critical component of any social, environmental, biomedical or scientific quest. Dynamic, exploratory and interactive visualization of multivariate data, without preprocessing by dimensionality reduction, remains a nearly insurmountable challenge. The Statistics Online Computational Resource (www.SOCR.ucla.edu) provides portable online aids for probability and statistics education, technology-based instruction and statistical computing. We have developed a new Java-based infrastructure, SOCR Motion Charts, for discovery-based exploratory analysis of multivariate data. This interactive data visualization tool enables the visualization of high-dimensional longitudinal data. SOCR Motion Charts allows mapping of ordinal, nominal and quantitative variables onto time, 2D axes, size, colors, glyphs and appearance characteristics, which facilitates the interactive display of multidimensional data. We validated this new visualization paradigm using several publicly available multivariate datasets including Ice-Thickness, Housing Prices, Consumer Price Index, and California Ozone Data. SOCR Motion Charts is designed using object-oriented programming, implemented as a Java Web-applet and is available to the entire community on the web at www.socr.ucla.edu/SOCR_MotionCharts. It can be used as an instructional tool for rendering and interrogating high-dimensional data in the classroom, as well as a research tool for exploratory data analysis. PMID:21479108

Enduring effects of post-weaning rearing condition on depressive- and anxiety-like behaviors and motor activity in male rats.

PubMed

Mosaferi, Belal; Babri, Shirin; Ebrahimi, Hadi; Mohaddes, Gisou

2015-04-01

Environmental manipulation at early critical periods could have long-lasting effects. In spite of the great interest in the biological effects of the environmental condition so far, its long-lasting effects are less documented. This study looks at the enduring effects of rearing condition on tasks that measure affective responses and exploratory behavior in male Wistar rats. The animals were reared from weaning to adulthood in an enriched environment, standard laboratory condition, or isolated condition. Then, all rats were housed in standard laboratory cages to provide a common environment, and successively exposed to different tests between 0 and 11 weeks post-manipulation. The open field test indicated a more efficient exploratory behavior in the enriched group, and an enhanced spontaneous motor activity in both standard and isolated groups. In addition, rats reared in standard condition showed heightened motor activity in forced swimming test and elevated plus maze. Forced swimming test showed an antidepressive-like effect in the enriched environment group by increased climbing behavior. In respect to the anxiety behavior, environmental enrichment improved threat detection ability. It is concluded that rearing condition from weaning to adulthood has important and long-lasting effects on depressive- and anxiety-like and exploratory behaviors as well as motor activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Structural analysis of N-glycans by the glycan-labeling method using 3-aminoquinoline-based liquid matrix in negative-ion MALDI-MS.

PubMed

Nishikaze, Takashi; Kaneshiro, Kaoru; Kawabata, Shin-ichirou; Tanaka, Koichi

2012-11-06

Negative-ion fragmentation of underivatized N-glycans has been proven to be more informative than positive-ion fragmentation. Fluorescent labeling via reductive amination is often employed for glycan analysis, but little is known about the influence of the labeling group on negative-ion fragmentation. We previously demonstrated that the on-target glycan-labeling method using 3-aminoquinoline/α-cyano-4-hydroxycinnamic acid (3AQ/CHCA) liquid matrix enables highly sensitive, rapid, and quantitative N-glycan profiling analysis. The current study investigates the suitability of 3AQ-labeled N-glycans for structural analysis based on negative-ion collision-induced dissociation (CID) spectra. 3AQ-labeled N-glycans exhibited simple and informative CID spectra similar to those of underivatized N-glycans, with product ions due to cross-ring cleavages of the chitobiose core and ions specific to two antennae (D and E ions). The interpretation of diagnostic fragment ions suggested for underivatized N-glycans could be directly applied to the 3AQ-labeled N-glycans. However, fluorescently labeled N-glycans by conventional reductive amination, such as 2-aminobenzamide (2AB)- and 2-pyrydilamine (2PA)-labeled N-glycans, exhibited complicated CID spectra consisting of numerous signals formed by dehydration and multiple cleavages. The complicated spectra of 2AB- and 2PA-labeled N-glycans was found to be due to their open reducing-terminal N-acetylglucosamine (GlcNAc) ring, rather than structural differences in the labeling group in the N-glycan derivative. Finally, as an example, the on-target 3AQ labeling method followed by negative-ion CID was applied to structurally analyze neutral N-glycans released from human epidermal growth factor receptor type 2 (HER2) protein. The glycan-labeling method using 3AQ-based liquid matrix should facilitate highly sensitive quantitative and qualitative analyses of glycans.

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

PubMed

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

2014-12-01

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

Mangifera indica extract (Vimang) impairs aversive memory without affecting open field behaviour or habituation in rats.

PubMed

Preissler, Thales; Martins, Márcio Rodrigo; Pardo-Andreu, Gilberto L; Henriques, João Antônio Pêgas; Quevedo, João; Delgado, Rene; Roesler, Rafael

2009-06-01

Vimang is an aqueous extract of Mangifera indica L, used in Cuba for the treatment of immunopathological disorders. Increasing evidence from preclinical studies indicates that Vimang displays antioxidant, antiallergic, analgesic and antiinflammatory actions. The present study investigated the effects of systemic administration of Vimang on behavioural outcomes of neurological function in rats. A single oral administration of Vimang produced an impairment of short- and long-term retention of memory for aversive training when given either 1 h pretraining or immediately posttraining, but not 8 h posttraining. Vimang did not affect open field behaviour or habituation. The results indicate that Vimang might induce deficits of emotionally motivated memory without affecting nonassociative memory, locomotion, exploratory behaviour or anxiety. (c) 2008 John Wiley & Sons, Ltd.

Structure preserving noise and dissipation in the Toda lattice

NASA Astrophysics Data System (ADS)

Arnaudon, Alexis

2018-05-01

In this paper, we use Flaschka’s change of variables of the open Toda lattice and its interpretation in terms of the group structure of the LU factorisation as a coadjoint motion on a certain dual of the Lie algebra to implement a structure preserving noise and dissipation. Both preserve the structure of the coadjoint orbit, that is the space of symmetric tri-diagonal matrices and arise as a new type of multiplicative noise and nonlinear dissipation of the Toda lattice. We investigate some of the properties of these deformations and, in particular, the continuum limit as a stochastic Burger equation with a nonlinear viscosity. This work is meant to be exploratory, and open more questions that we can answer with simple mathematical tools and without numerical simulations.

A Bayesian Markov-chain-based heteroscedastic regression model for the analysis of 18O-labeled mass spectra.

PubMed

Zhu, Qi; Burzykowski, Tomasz

2011-03-01

To reduce the influence of the between-spectra variability on the results of peptide quantification, one can consider the (18)O-labeling approach. Ideally, with such labeling technique, a mass shift of 4 Da of the isotopic distributions of peptides from the labeled sample is induced, which allows one to distinguish the two samples and to quantify the relative abundance of the peptides. It is worth noting, however, that the presence of small quantities of (16)O and (17)O atoms during the labeling step can cause incomplete labeling. In practice, ignoring incomplete labeling may result in the biased estimation of the relative abundance of the peptide in the compared samples. A Markov model was developed to address this issue (Zhu, Valkenborg, Burzykowski. J. Proteome Res. 9, 2669-2677, 2010). The model assumed that the peak intensities were normally distributed with heteroscedasticity using a power-of-the-mean variance funtion. Such a dependence has been observed in practice. Alternatively, we formulate the model within the Bayesian framework. This opens the possibility to further extend the model by the inclusion of random effects that can be used to capture the biological/technical variability of the peptide abundance. The operational characteristics of the model were investigated by applications to real-life mass-spectrometry data sets and a simulation study. © American Society for Mass Spectrometry, 2011

Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes.

PubMed

Hackett, Geoffrey; Cole, Nigel; Bhartia, Mithun; Kennedy, David; Raju, Jessie; Wilkinson, Peter

2013-06-01

Sexual dysfunction, particularly erectile dysfunction (ED), is common in men with type 2 diabetes, occurring in up to 75% of cases. The prevalence of hypogonadism is also high in men with diabetes and low testosterone is associated with both sexual dysfunction and a reduced response to oral therapy for ED. This study aimed to determine the effect of testosterone replacement with long-acting Testosterone Undecanoate (TU) on sexual function, mood and quality of life vs. placebo over a treatment period of 30 weeks followed by 52 weeks of open-label medication. The study was conducted in a primary care population of men with type 2 diabetes attending their primary care physician for routine visits. The male diabetic populations of seven general practices were screened at routine diabetes visits to detect symptomatic men with total testosterone levels of 12 nmol/L or less or with free testosterones of 250 pmol/L or less. Two hundred eleven men were screened. A double-blind placebo-controlled study was conducted in 199 men with type 2 diabetes and hypogonadism treated for 30 weeks with either 1,000 mg of TU or matching placebo followed by 52-week open-label follow on. The primary outcome measure, International Index of Erectile Function (IIEF), was used to evaluate sexual dysfunction, and the Ageing Male Symptom (AMS), Hospital Anxiety and Depression Scale, and Global Efficacy Question were used as secondary outcome measures to assess mood and self-reported quality of life. Testosterone replacement therapy with long-acting TU improved all domains of sexual function at 30 weeks (erectile function [EF], P = 0.005; intercourse satisfaction, P = 0.015; sexual desire, P = 0.001; overall satisfaction, P = 0.05; and orgasm, P = 0.04), with benefit as early as 6 weeks. Improvements in AMS score were significant in men without depression (P = 0.02) and the presence of depression at baseline was associated with marked reduction in response to both sexual function and psychological scores. All responses in sexual function continued to improve significantly up to 18 months with an improvement in EF score of 4.31 from baseline. In a small cohort of 35 men taking phosphodiesterase type 5 inhibitors, there was no change during the double-blind phase but a nine-point improvement in EF domain during 52-week open-label treatment. After 30 weeks, 46% vs. 17% of patients on active therapy vs. placebo felt that the treatment had improved their health, reaching 70% after open-label therapy. Less obese and older patients responded better to testosterone therapy. There were no significant adverse events. TU significantly improved all domains of the IIEF and patient reported quality of life at 30 weeks and more significantly after 52-week open-label extension. Improvement was most marked in less obese patient and those without coexisting depression. In men with type 2 diabetes, trials of therapy may need to be given for much longer than 3-6 months suggested in current guidelines. © 2013 International Society for Sexual Medicine.

Dynamic nano-imaging of label-free living cells using electron beam excitation-assisted optical microscope

PubMed Central

Fukuta, Masahiro; Kanamori, Satoshi; Furukawa, Taichi; Nawa, Yasunori; Inami, Wataru; Lin, Sheng; Kawata, Yoshimasa; Terakawa, Susumu

2015-01-01

Optical microscopes are effective tools for cellular function analysis because biological cells can be observed non-destructively and non-invasively in the living state in either water or atmosphere condition. Label-free optical imaging technique such as phase-contrast microscopy has been analysed many cellular functions, and it is essential technology for bioscience field. However, the diffraction limit of light makes it is difficult to image nano-structures in a label-free living cell, for example the endoplasmic reticulum, the Golgi body and the localization of proteins. Here we demonstrate the dynamic imaging of a label-free cell with high spatial resolution by using an electron beam excitation-assisted optical (EXA) microscope. We observed the dynamic movement of the nucleus and nano-scale granules in living cells with better than 100 nm spatial resolution and a signal-to-noise ratio (SNR) around 10. Our results contribute to the development of cellular function analysis and open up new bioscience applications. PMID:26525841

Dynamic nano-imaging of label-free living cells using electron beam excitation-assisted optical microscope.

PubMed

Fukuta, Masahiro; Kanamori, Satoshi; Furukawa, Taichi; Nawa, Yasunori; Inami, Wataru; Lin, Sheng; Kawata, Yoshimasa; Terakawa, Susumu

2015-11-03

Optical microscopes are effective tools for cellular function analysis because biological cells can be observed non-destructively and non-invasively in the living state in either water or atmosphere condition. Label-free optical imaging technique such as phase-contrast microscopy has been analysed many cellular functions, and it is essential technology for bioscience field. However, the diffraction limit of light makes it is difficult to image nano-structures in a label-free living cell, for example the endoplasmic reticulum, the Golgi body and the localization of proteins. Here we demonstrate the dynamic imaging of a label-free cell with high spatial resolution by using an electron beam excitation-assisted optical (EXA) microscope. We observed the dynamic movement of the nucleus and nano-scale granules in living cells with better than 100 nm spatial resolution and a signal-to-noise ratio (SNR) around 10. Our results contribute to the development of cellular function analysis and open up new bioscience applications.

A multi-center study benchmarks software tools for label-free proteome quantification

PubMed Central

Gillet, Ludovic C; Bernhardt, Oliver M.; MacLean, Brendan; Röst, Hannes L.; Tate, Stephen A.; Tsou, Chih-Chiang; Reiter, Lukas; Distler, Ute; Rosenberger, George; Perez-Riverol, Yasset; Nesvizhskii, Alexey I.; Aebersold, Ruedi; Tenzer, Stefan

2016-01-01

The consistent and accurate quantification of proteins by mass spectrometry (MS)-based proteomics depends on the performance of instruments, acquisition methods and data analysis software. In collaboration with the software developers, we evaluated OpenSWATH, SWATH2.0, Skyline, Spectronaut and DIA-Umpire, five of the most widely used software methods for processing data from SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra), a method that uses data-independent acquisition (DIA) for label-free protein quantification. We analyzed high-complexity test datasets from hybrid proteome samples of defined quantitative composition acquired on two different MS instruments using different SWATH isolation windows setups. For consistent evaluation we developed LFQbench, an R-package to calculate metrics of precision and accuracy in label-free quantitative MS, and report the identification performance, robustness and specificity of each software tool. Our reference datasets enabled developers to improve their software tools. After optimization, all tools provided highly convergent identification and reliable quantification performance, underscoring their robustness for label-free quantitative proteomics. PMID:27701404

A multicenter study benchmarks software tools for label-free proteome quantification.

PubMed

Navarro, Pedro; Kuharev, Jörg; Gillet, Ludovic C; Bernhardt, Oliver M; MacLean, Brendan; Röst, Hannes L; Tate, Stephen A; Tsou, Chih-Chiang; Reiter, Lukas; Distler, Ute; Rosenberger, George; Perez-Riverol, Yasset; Nesvizhskii, Alexey I; Aebersold, Ruedi; Tenzer, Stefan

2016-11-01

Consistent and accurate quantification of proteins by mass spectrometry (MS)-based proteomics depends on the performance of instruments, acquisition methods and data analysis software. In collaboration with the software developers, we evaluated OpenSWATH, SWATH 2.0, Skyline, Spectronaut and DIA-Umpire, five of the most widely used software methods for processing data from sequential window acquisition of all theoretical fragment-ion spectra (SWATH)-MS, which uses data-independent acquisition (DIA) for label-free protein quantification. We analyzed high-complexity test data sets from hybrid proteome samples of defined quantitative composition acquired on two different MS instruments using different SWATH isolation-window setups. For consistent evaluation, we developed LFQbench, an R package, to calculate metrics of precision and accuracy in label-free quantitative MS and report the identification performance, robustness and specificity of each software tool. Our reference data sets enabled developers to improve their software tools. After optimization, all tools provided highly convergent identification and reliable quantification performance, underscoring their robustness for label-free quantitative proteomics.

Reactivity assay of surface carboxyl chain-ends of poly(ethylene terephthalate) (PET) film and track-etched microporous membranes using fluorine labelled- and/or 3H-labelled derivatization reagents: tandem analysis by X-ray photoelectron spectroscopy (XPS) and liquid scintillation counting (LSC)

NASA Astrophysics Data System (ADS)

Deldime, Michèle; Dewez, Jean-Luc; Schneider, Yves-Jacques; Marchand-Brynaert, Jacqueline

1995-09-01

Poly(ethylene terephthalate) (PET) films and track-etched microporous membranes of two different porosities were pretreated by hydrolysis and/or oxidation in order to enhance the amount of carboxyl chain-ends displayed on their surface. The reactivity of these carboxyl functions was determined by derivatization assays in which the reactions were carried out under conditions likely to be encountered in the coupling of water-soluble biochemical signals on the surface of biomaterials. Original reagents, fluorine-labelled and/or 3H-labelled aminoacid compounds, were used. The derivatized PET samples were examined by X-ray photoelectron spectroscopy (XPS) to characterize their apparent surfaces, and by liquid scintillation counting (LSC) to quantify the amount of tags fixed on their open surfaces. Using this dual assay technique, we analyzed the surface of microporous membranes which are currently used as substrates for cell culture systems.

Dynamic nano-imaging of label-free living cells using electron beam excitation-assisted optical microscope

NASA Astrophysics Data System (ADS)

Fukuta, Masahiro; Kanamori, Satoshi; Furukawa, Taichi; Nawa, Yasunori; Inami, Wataru; Lin, Sheng; Kawata, Yoshimasa; Terakawa, Susumu

2015-11-01

Optical microscopes are effective tools for cellular function analysis because biological cells can be observed non-destructively and non-invasively in the living state in either water or atmosphere condition. Label-free optical imaging technique such as phase-contrast microscopy has been analysed many cellular functions, and it is essential technology for bioscience field. However, the diffraction limit of light makes it is difficult to image nano-structures in a label-free living cell, for example the endoplasmic reticulum, the Golgi body and the localization of proteins. Here we demonstrate the dynamic imaging of a label-free cell with high spatial resolution by using an electron beam excitation-assisted optical (EXA) microscope. We observed the dynamic movement of the nucleus and nano-scale granules in living cells with better than 100 nm spatial resolution and a signal-to-noise ratio (SNR) around 10. Our results contribute to the development of cellular function analysis and open up new bioscience applications.

Do Emotions Spark Interest in Alternative Tobacco Products?

PubMed

Popova, Lucy; So, Jiyeon; Sangalang, Angeline; Neilands, Torsten B; Ling, Pamela M

2017-08-01

Exposure to advertisements for tobacco products and tobacco warning labels evokes emotions. This study evaluated the association of discrete positive and negative emotions with interest in alternative tobacco products. In 2013, 1,226 U.S. adult nonsmokers and current smokers viewed advertisements for moist snuff, snus, and electronic cigarettes (e-cigarettes) with various warning labels and then indicated their emotional responses in terms of anger, anxiety, sadness, guilt, disgust, discouragement, hope, and contentment. Outcomes were openness to using moist snuff, snus, and e-cigarettes in the future and interest in a free sample of each product. Data were analyzed in 2016. Hope was positively associated with openness and interest across all alternative tobacco products as was contentment for moist snuff and snus. Anger was negatively associated with openness to moist snuff and e-cigarettes, disgust negatively to moist snuff and snus, and anxiety negatively to e-cigarettes. Being a current smoker, ever trying a corresponding product, being male, and younger age were associated with greater openness to and interest in moist snuff and snus. For e-cigarettes, being a current smoker, ever trying e-cigarettes, and being female were associated with greater openness, and being a current smoker was associated with greater odds of selecting a free sample. Positive emotions, particularly hope, were consistently positively associated with interest in alternative tobacco products. Hope is widely used by tobacco and e-cigarette companies to advertise their products. Antitobacco messages should aim to lower hope associated with tobacco products but increase hope for cessation or life without tobacco.

An evaluation of open set recognition for FLIR images

NASA Astrophysics Data System (ADS)

Scherreik, Matthew; Rigling, Brian

2015-05-01

Typical supervised classification algorithms label inputs according to what was learned in a training phase. Thus, test inputs that were not seen in training are always given incorrect labels. Open set recognition algorithms address this issue by accounting for inputs that are not present in training and providing the classifier with an option to reject" unknown samples. A number of such techniques have been developed in the literature, many of which are based on support vector machines (SVMs). One approach, the 1-vs-set machine, constructs a slab" in feature space using the SVM hyperplane. Inputs falling on one side of the slab or within the slab belong to a training class, while inputs falling on the far side of the slab are rejected. We note that rejection of unknown inputs can be achieved by thresholding class posterior probabilities. Another recently developed approach, the Probabilistic Open Set SVM (POS-SVM), empirically determines good probability thresholds. We apply the 1-vs-set machine, POS-SVM, and closed set SVMs to FLIR images taken from the Comanche SIG dataset. Vehicles in the dataset are divided into three general classes: wheeled, armored personnel carrier (APC), and tank. For each class, a coarse pose estimate (front, rear, left, right) is taken. In a closed set sense, we analyze these algorithms for prediction of vehicle class and pose. To test open set performance, one or more vehicle classes are held out from training. By considering closed and open set performance separately, we may closely analyze both inter-class discrimination and threshold effectiveness.

Neuroanatomical pathways underlying the effects of hypothalamo-hypophysial-adrenal hormones on exploratory activity.

PubMed

Lalonde, Robert; Strazielle, Catherine

2017-07-26

When injected via the intracerebroventricular route, corticosterone-releasing hormone (CRH) reduced exploration in the elevated plus-maze, the center region of the open-field, and the large chamber in the defensive withdrawal test. The anxiogenic action of CRH in the elevated plus-maze also occurred when infused in the basolateral amygdala, ventral hippocampus, lateral septum, bed nucleus of the stria terminalis, nucleus accumbens, periaqueductal grey, and medial frontal cortex. The anxiogenic action of CRH in the defensive withdrawal test was reproduced when injected in the locus coeruleus, while the amygdala, hippocampus, lateral septum, nucleus accumbens, and lateral globus pallidus contribute to center zone exploration in the open-field. In addition to elevated plus-maze and open-field tests, the amygdala appears as a target region for CRH-mediated anxiety in the elevated T-maze. Thus, the amygdala is the principal brain region identified with these three tests, and further research must identify the neural circuits underlying this form of anxiety.

Involvement of Family Members and Professionals in Older Women's Post-Fall Decision Making.

PubMed

Bergeron, Caroline D; Hilfinger Messias, DeAnne K; Friedman, Daniela B; Spencer, S Melinda; Miller, Susan C

2018-03-01

This exploratory, descriptive study examined involvement of family members and professionals in older women's post-fall decision making. We conducted semistructured interviews with 17 older women who had recently fallen and 11 individuals these women identified as being engaged in their post-fall decision-making processes. Qualitative data analysis involved open and axial coding and development of themes. After experiencing a fall, these older women's openness to others' opinions and advice; their assessments of types and credibility of potential information sources; and the communication practices they established with these sources influenced how they accessed, accepted, or rejected information from family members and professionals. Increased awareness of the involvement of others in post-fall decision making could enhance communication with older women who fall. Developing and implementing practical strategies to help family members and professionals initiate and engage in conversations about falls and their consequences could lead to more open decision making and improved post-fall quality of life among older women.

Exposure-related effects of Pseudomonas fluorescens, strain CL145A, on coldwater, coolwater, and warmwater fish

USGS Publications Warehouse

Luoma, James A.; Weber, Kerry L.; Denise A. Mayer,

2015-01-01

Further investigations to evaluate the SDP-exposure related effects on freshwater fish at the maximum approved open-water label concentration and exposure duration (100 mg/L for 8 hours) and using the expected lentic application technique (static application) are warranted. The variation in tolerance to P. fluorescens, strain CL145A, exposure observed in this study indicates that fish species community composition should be considered before SDP is applied in open-water environments.

Pyridostigmine in the treatment of orthostatic intolerance.

PubMed

Gales, Barry J; Gales, Mark A

2007-02-01

To review the efficacy of pyridostigmine bromide for the treatment of orthostatic intolerance. MEDLINE and International Pharmaceutical Abstracts were searched (1966-December 2006) using the terms pyridostigmine, acetylcholinesterase inhibitor, orthostatic intolerance, orthostatic hypotension, neurogenic orthostatic hypotension, postural tachycardia syndrome, tachycardia, and orthostatic tachycardia. Pertinent English-language human clinical trials, case reports, and background material were evaluated for safety and efficacy data. The references of reviewed articles were reviewed and used to identify additional sources. Pyridostigmine bromide has been associated with improved baroreceptor sensitivity and presents a novel approach to treatment of orthostatic intolerance. Four single-dose trials and a follow-up survey encompassing a total of 106 patients were identified. One open-label and one placebo-controlled single-dose trial in patients with neurogenic orthostatic hypotension (NOH) found statistically significant improvement in standing diastolic blood pressures (DBP). Absolute improvements in standing DBP were 3.7 and 6.4 mm Hg in the open-label and controlled trials, respectively. Long-term data consist of a single survey of patients receiving open-label pyridostigmine bromide. Twenty-nine percent of patients who initiated maintenance pyridostigmine bromide discontinued therapy. Concomitant NOH medications were taken by 75% of patients, and 85% of patients reported receiving benefit from pyridostigmine bromide. When evaluated for postural tachycardia syndrome, pyridostigmine bromide significantly reduced standing heart rate (10%). Pyridostigmine bromide significantly reduced symptom scores when compared with baseline but not placebo. The majority of patients included in these trials did not have supine hypertension. Single doses of pyridostigmine bromide produced modest but statistically significant improvements in hemodynamic measurements. At this time, long-term data are insufficient to support recommending the routine use of pyridostigmine bromide for treatment of orthostatic intolerance.

Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial.

PubMed

Murrough, James W; Wade, Elizabeth; Sayed, Sehrish; Ahle, Gabriella; Kiraly, Drew D; Welch, Alison; Collins, Katherine A; Soleimani, Laili; Iosifescu, Dan V; Charney, Dennis S

2017-08-15

At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion. There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t 19 =5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t 19 =4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively. Open-label, proof-of-concept design. Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Open-label dose optimization of methylphenidate modified release long acting (MPH-LA): a post hoc analysis of real-life titration from a 40-week randomized trial.

PubMed

Huss, Michael; Ginsberg, Ylva; Arngrim, Torben; Philipsen, Alexandra; Carter, Katherine; Chen, Chien-Wei; Gandhi, Preetam; Kumar, Vinod

2014-09-01

In the management of attention-deficit hyperactivity disorder (ADHD) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses. Studies with methylphenidate modified release long acting (MPH-LA) in children have reported the need for treatment optimization for improved outcomes. We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized, placebo-controlled, multicenter 40-week study (9-week double-blind dose confirmation phase, 5-week open-label dose optimization phase, and 26-week double-blind maintenance of effect phase). Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day; up/down titrated to their optimal dose (at which there was balance between control of symptoms and side effects) of 40, 60, or 80 mg/day in increments of 20 mg/week by week 12 or 13. Safety was assessed by monitoring the adverse events (AEs) and serious AEs. Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Attention-Deficit Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores. At the end of the dose confirmation phase, similar numbers of patients were treated optimally with each of the 40, 60, and 80 mg/day doses (152, 177, and 160, respectively) for MPH-LA. Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 ± 9.90 and 9.7 ± 7.36, respectively. Dose optimization with MPH-LA (40, 60, or 80 mg/day) improved treatment outcomes and was well-tolerated in adult ADHD patients.