Treatment Groups (treatment + groups)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Treatment Groups

  • active treatment groups
  • different treatment groups
  • experimental treatment groups
  • other treatment groups


  • Selected Abstracts


    Conflict resolution and bully prevention: Skills for school success

    CONFLICT RESOLUTION QUARTERLY, Issue 1 2006
    Roberta A. Heydenberk
    In a two-year study, 673 elementary students participated in a bully prevention program that included seven training sessions introducing affective vocabulary, social and emotional literacy, and Conflict resolution skills. Treatment groups showed statistically significant gains on the Conflict resolution subscale of the standardized instrument employed. No gains were found in the comparison groups. A decrease in bullying and an increased sense of safety were indicated from student and staff questionnaire responses. [source]


    A 3-year comparison of dental anxiety treatment outcomes: hypnosis, group therapy and individual desensitization vs. no specialist treatment

    EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2002
    Rod Moore
    Outcomes of hypnotherapy (HT), group therapy (GT) and individual systematic desensitization (SD) on extreme dental anxiety in adults aged 19,65 yr were compared by regular attendance behaviors, changes in dental anxiety and changes in beliefs about dentists and treatment after 3 yr. Treatment groups were comparable with a static reference control group of 65 anxious patients (Dental Anxiety Scale ,,15) who were followed for a mean of nearly 6 yr. After 3 yr, 54.5% of HT patients, 69.6% of GT patients and 65.5% of SD patients were maintaining regular dental care habits. This was better than the 46.1% of the reference group, who reported going regularly to the dentist again within the cohort follow-up period, and 38.9% of a control subgroup with observation for 3 yr. Women were better regular attenders than men at 3 yr. Specialist-treated regular attenders were significantly less anxious and had more positive beliefs than regular attenders from reference groups. There were few differences between HT, GT and SD after 3 yr. It was concluded that many patients can, on their own, successfully start and maintain regular dental treatment habits with dentists despite years of avoidance associated with phobic or extreme anxiety. However, it also appears that these patients had less success in reducing dental anxiety and improving beliefs about dentists long-term than did patients who were treated at the specialist clinic with psychological strategies. [source]


    Effect of IL-2-Bax, a novel interleukin-2-receptor-targeted chimeric protein, on bleomycin lung injury,

    INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2005
    Michael J. Segel
    Summary The role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro-fibrotic effect for lymphocytes. The high-affinity interleukin-2 receptor (haIL-2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL-2R provides the basis for therapeutic strategies that target IL-2R-expressing cells. We hypothesized that elimination of activated lymphocytes by IL-2R-targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL-2-Bax, a novel apoptosis-inducing IL-2R-targeted chimeric protein, on bleomycin-induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice-daily intraperitoneal injections of IL-2-Bax; (ii) intratracheal bleomycin and intraperitoneal IL-2-PE664Glu, an older-generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi-quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL-2-Bax and IL-2-PE664Glu. However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL-2-Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis. [source]


    Flu: Effect of Vaccine in Elderly Care Home Residents: A Randomized Trial

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2007
    Fiona Gaughran MD
    OBJECTIVES: To determine whether assessing seroprotection after influenza vaccine and administering booster vaccination where not achieved reduces hospitalization and death. To estimate the overall seroprotection rate of influenza vaccine. DESIGN: A two-arm, partially blind, randomized, multicenter, parallel-group, controlled trial. SETTING: Twenty-six care homes in three South London boroughs in fall 2004. PARTICIPANTS: Two hundred seventy-seven elderly permanent care home residents meeting eligibility criteria. INTERVENTION: Postvaccination blood samples were randomized to booster evaluation or no booster evaluation (control). If evaluation revealed inadequate seroprotection, a booster vaccine was administered. MEASUREMENTS: Primary outcome was hospitalization to end April 2005; secondary outcomes were death, antibiotic use, and seroprotection. RESULTS: Sixty percent of the controls and 41% of the booster evaluation group responded to routine vaccination. Booster vaccination where indicated increased seroprotection rates in the booster evaluation group to 66%. Treatment groups did not differ in any outcome measures in the intention-to-treat analysis (hospitalization odds ratio=1.02, 95% confidence interval=0.55,1.87). There was a tendency towards greater differences between groups in the per-protocol analysis than in the intention-to-treat analysis, particularly regarding seroprotection rates. The same effect was observed in the a priori exploratory analysis of residents not seroprotected after routine vaccination alone. CONCLUSION: In a year without circulating influenza, there is no clinical benefit of administering a booster vaccine if routine trivalent vaccination fails to result in seroprotection. Hemagglutination titers rose in two strains postbooster vaccination but fell against the novel strain, Wyoming. The benefit of such a booster strategy when influenza is prevalent thus remains unc ertain. [source]


    Estrogen as a neuroprotective agent in rat spinal cord injury

    JOURNAL OF NEUROCHEMISTRY, Issue 2002
    N. L. Banik
    Spinal cord injury (SCI) is a neurological problem affecting approximately 11 000 Americans each year. Several treatment agents have been proposed; however, only methylprednisolone has limited efficacy. Estrogen is a multiactive neuroprotectant with antioxidant and anti-inflammatory properties and attenuates calcium (Ca2+) influx following neuronal injury. To examine the neuroprotective effects of estrogen in SCI, we induced SCI (40 g/cm injury) in rats. Treatment groups were sham (laminectomy only), SCI plus vehicle, and SCI plus estrogen. Injured rats were treated with either 4 mg/kg 17 ,-estradiol (estrogen group) or dimethylsulfoxide (vehicle group) at 15 min and 24 h following injury. All rats were killed at 48 h to analyze SCI segments for calpain content and Bax/Bcl-2 ratio by Western blotting. Tissue was also examined using calcium green-2 to measure intracellular [Ca2+], JC-1 to measure mitochondrial membrane potential, and double immunofluorescence for macrophages and calpain. Calpain content in the lesion penumbra, adjacent to the injury, was higher in vehicle than sham and this increase was attenuated in estrogen treated rats. In the lesion penumbra, the Bax/Bcl-2 ratio was increased in vehicle rats as compared to sham. This increase was attenuated in estrogen treated rats. Estrogen treated rats had less Ca2+ influx, less inflammatory cell infiltration, and increased maintenance of mitochondrial membrane potential compared to vehicle treated rats. Our preliminary data suggest that estrogen may be effective in decreasing Ca2+ influx, inflammatory cell infiltration, and Bax/Bcl-2 ratio following SCI. Acknowledgements:, Supported in part by grants from NIH-NINDS and South Carolina Electric and Gas. [source]


    Effect of obesity on outcomes after fondaparinux, enoxaparin, or heparin treatment for acute venous thromboembolism in the Matisse trials

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2007
    B. L. DAVIDSON
    Summary.,Background: Selecting initial anticoagulant dose by patient weight for acute pulmonary embolism and deep vein thrombosis has clinical credibility; however, uncertainty remains regarding how to dose obese patients with newer anticoagulants because outcome data are sparse. Objectives: To use the Matisse trials' comparison of sc fondaparinux once daily with control heparin therapies (intravenous unfractionated heparin for pulmonary embolism, sc enoxaparin 1 mg/kg b.i.d. for deep vein thrombosis) for initial treatment in order to compare primary outcomes (venous thromboembolism recurrence and major bleeding) in obese patients. Patients and methods: Primary outcomes were compared in subsets composed of patients weighing , and > 100 kg and with body mass index (BMI) < 30 and , 30 kg/m2. Medians and ranges for weight and BMI were compared for patients suffering either recurrence or major bleeding. Results: Twenty-two thousand and one patients received fondaparinux and 2217 received enoxaparin or unfractionated heparin. Four hundred and ninety-six patients (11%) weighed > 100 kg and 1216 (28%) had a BMI , 30. Treatment groups had similar characteristics. The upper limit in subject weight for recurrence was 166 kg (BMI 58), and for major bleeding 120 kg (BMI 39). The incidences of recurrence and major bleeding were similar for each patient subset of weight and BMI for both fondaparinux and heparin treatment groups. Among patients with a primary outcome, median weights and BMIs were also similar. Conclusions: The current recommended doses of fondaparinux and heparins for the treatment of venous thromboembolism appear to provide similar protection against recurrence and major bleeding to one another and to obese and non-obese patients. [source]


    Protective Effect of Total Flavones of Abelmoschus manihot L. Medic Against Poststroke Depression Injury in Mice and Its Action Mechanism

    THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2009
    Mei Liu
    Abstract Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic. We investigated the protective effect of TFA against poststroke depression (PSD) injury in mice and its action mechanism. A mouse model of PSD was induced by middle cerebral artery occlusion (MACO) 30 min/reperfusion, followed by isolation feeding and chronic unpredictable mild stress for 2 weeks. Treatment groups received TFA at three different doses (160, 80, and 40 mg/kg, p.o.) or fluoxetine (Flu, 2.5 mg/kg, p.o.) daily for 24 days. Change in behavior, brain tissue malondialdehyde (MDA) levels, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. The expression of brain-derived neurotrophic factor (BDNF) was detected by immunohistochemistry, and mRNA expression of BDNF and cAMP response element-binding protein (CREB) analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Treatment with TFA (160, 80, and 40 mg/kg) significantly ameliorated mice escape-directed behavioral impairment induced by PSD, markedly reduced MDA levels, and increased the activity of SOD, GSH-Px close to normal levels. TFA administration also attenuated PSD-induced neuronal death/losses, upregulated expression of BDNF both at mRNA and protein levels, as well as CREB mRNA levels. TFA had a protective effect against PSD injury in mice. Cardioprotection involves the inhibition of lipid peroxidation and upregulation of BDNF-CREB levels in the hippocampus, which may also be important mechanism of its antidepressants. This potential protection makes TFA a promising therapeutic agent for the PSD. Anat Rec, 292:412,422, 2009. © 2009 Wiley-Liss, Inc. [source]


    Pulsed electromagnetic fields induce peripheral nerve regeneration and endplate enzymatic changes

    BIOELECTROMAGNETICS, Issue 1 2005
    J.A. De Pedro
    Abstract An experimental study was carried out in rats with the purpose of demonstrating the capacity of pulsed electromagnetic fields (PEMFs) to stimulate regeneration of the peripheral nervous system (PNS). Wistar and Brown Norway (BN) rats were used. Direct sciatic nerve anastomoses were performed after section or allograft interposition. Treatment groups then received 4 weeks of PEMFs. Control groups received no stimulation. The evaluation of the results was carried out by quantitative morphometric analysis, demonstrating a statistically significant increase in regeneration indices (P,<,0.05) in the stimulated groups (9000,±,5000 and 4000,±,6000) compared to the non-stimulated groups (2000,±,4000 and 700,±,200). An increase of NAD specific isocitrate dehydrogenase (IDH) activity was found along with an increase in the activity of acetyl cholinesterase at the motor plate. The present study might lead to the search for new alternatives in the stimulation of axonal regenerative processes in the PNS and other possible clinical applications. Bioelectromagnetics 26:20,27, 2005. © 2004 Wiley-Liss, Inc. [source]


    Conflict resolution and moral reasoning

    CONFLICT RESOLUTION QUARTERLY, Issue 1 2003
    Warren R. Heydenberk
    The effects of conflict resolution training on students' moral reasoning were examined in this five-year study. Inspired by pilot studies that found increased attachment, cooperation, and prosocial skills in treatment classrooms, the study was conducted with elementary students (ten treatment groups and eight comparison groups) in a low-income Philadelphia school and in two schools in a suburban low-income district. Treatment group teachers were trained in integrated conflict resolution strategies, and they were provided ongoing support to ensure classroom implementation of conflict resolution skills. Treatment group students demonstrated significant improvement in moral reasoning. [source]


    Improving the Efficiency and Effectiveness of Grading Through the Use of Computer-Assisted Grading Rubrics

    DECISION SCIENCES JOURNAL OF INNOVATIVE EDUCATION, Issue 1 2008
    Linda Anglin
    ABSTRACT This study tests the use of computer-assisted grading rubrics compared to other grading methods with respect to the efficiency and effectiveness of different grading processes for subjective assignments. The test was performed on a large Introduction to Business course. The students in this course were randomly assigned to four treatment groups based on the grading method. Efficiency was measured by the professor's time to grade the assignments; effectiveness was measured by a student satisfaction survey. Results suggest that the computer-assisted grading rubrics were almost 200% faster than traditional hand grading without rubrics, more than 300% faster than hand grading with rubrics, and nearly 350% faster than typing the feedback into a Learning Content Management System. Results also seemed to indicate that the use of a computer-assisted grading rubric did not negatively affect student attitudes concerning the helpfulness of their feedback, their satisfaction with the speed with which they received their feedback, or their satisfaction with the method by which they received feedback. [source]


    Effect of storage media on human periodontal ligament cell apoptosis

    DENTAL TRAUMATOLOGY, Issue 1 2008
    Mónica M. Chamorro
    However, the mechanisms by which different storage conditions alter the functional status of PDL cells have not been determined. The purpose of the present study was to investigate, in vitro, the level of programed cell death or apoptosis in a population of PDL cells following storage under different conditions. Primary human PDL cells were plated into 24-well-culture plates and allowed to attach for 24 h. Cells were then exposed for 1 h to milk, Hank's balanced salt solution (HBSS), Soft Wear contact lens solution or Gatorade at room temperature or on ice. Culture medium was used as a negative control. Apoptosis was evaluated at 24, 48, and 72 h after treatment on quadruplicate samples by using the ST 160 ApopTag Fluorescein Direct In Situ Detection Kit. The total number of cells and the total number of apoptotic cells were counted. The results indicated that at 24 and 72 h, PDL treated with Gatorade and the contact lens solution displayed the highest percentages of apoptotic cells when compared with the other treatment groups at room temperature. Overall, cells treated on ice showed significantly lower levels of apoptosis when compared with treatments at room temperature. In conclusion, the results indicated that apoptosis plays a major role in cell death in cells treated with Gatorade and contact lens solutions in comparison to other storage solutions and that storage on ice can inhibit programed cell death. [source]


    Does defense style or psychological mindedness predict treatement response in major depression?

    DEPRESSION AND ANXIETY, Issue 7 2009
    Kim Kronström M.D.
    Abstract Background: The aim of this study was to define the impact of defense style and psychological mindedness (PM) on the prognosis of major depressive disorder (MDD) in patients treated with either fluoxetine (FLX) or short-term psychodynamic psychotherapy (STPP) in a randomized comparative study. Method: 50 patients with MDD received either STPP or FLX treatment for 16 weeks. The Hamilton Depression Rating Scale (HDRS) was the outcome measure completed at baseline and in the follow-ups at 4- and 12-months. Patients completed the Psychological Mindedness Scale (PMS) and the Defense Style Questionnaire at the baseline. Results: In the FLX group recovery measured by the decrease in the HDRS during the 4-month follow-up associated with baseline mature defense style (r=,.59, P=.015). There were no correlations between the PMS-scores and the outcome measures in either treatment groups nor defense status and the outcome in the STPP group. Conclusion: Mature defense style predicts good response to FLX therapy in major depression. This association was not found in the psychotherapy group. The results may imply that patients with immature defenses benefit relatively more from brief psychotherapy than medication. PM measured by the PMS was not useful in predicting recovery in MDD. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc. [source]


    A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder

    DEPRESSION AND ANXIETY, Issue 1 2007
    Mark H. Pollack M.D.
    Abstract To date, no large-scale, controlled trial comparing a serotonin,norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75,mg/day or 150,mg/day), or paroxetine 40,mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions,Severity (CGI-S) and ,Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder. Depression and Anxiety 24:1,14, 2007. © 2006 Wiley-Liss, Inc. [source]


    Treatment of Facial Telangiectasia With Variable-Pulse High-Fluence Pulsed-Dye Laser: Comparison of Efficacy with Fluences Immediately Above and Below the Purpura Threshold

    DERMATOLOGIC SURGERY, Issue 7 2003
    Murad Alam MD
    Background. Pulsed-dye laser treatment has been shown to be highly effective for the treatment of facial telangiectasia. Posttreatment purpura after such treatment has limited patient acceptance of the procedure. Objective. To determine whether purpura-free treatment with recently introduced variable-pulsed pulsed-dye lasers can effectively reduce facial telangiectasia. Methods. This was a prospective, randomized, controlled, nonblinded trial. Eleven patients received variable-pulse pulsed-dye laser treatment with and without induction of purpura. Telangiectasia were graded on a "telangiectasia density scale," on which a 1 signified extremely fine, sparsely distributed telangiectasia, and 5 referred to thick, ropelike telangiectasia covering the affected area. For each subject, two areas on either side of the facial midline with equivalent telangiectasia density ratings were randomized to the purpura and purpura-free treatment groups, respectively. All treatments used a 7-mm spot size and a 10-ms pulse duration. The fluence associated with the purpura threshold for each patient was determined in test areas. Purpura-free treatment entailed a fluence 1.0 J/cm2 less than the purpura threshold, and purpura-level treatment entailed a fluence 0.5 J/cm2 greater than the threshold. Results. Six weeks after a single purpura-free treatment, mean telangiectasia ratings were reduced from 2.7 to 2.4. Purpura-level treatments resulted in a decrease to 1.4 from the same baseline. Thicker, denser telangiectasia appeared to benefit more from purpura-level treatment (a mean telangiectasia density scale reduction of 1.7) than finer, sparser telangiectasia (a mean reduction of 0.8). In 81% of cases, both investigators and patients rated the side treated with purpura as undergoing a greater reduction in telangiectasia density. Conclusion. Although facial telangiectasia do improve after a single purpura-free treatment with the variable-pulse pulsed-dye laser, they improve more after purpura is induced. Purpura-free and purpura-level treatments may be close to equivalent for treating fine telangiectasia, but purpura-level treatments have a distinct advantage for treating thicker telangiectasia. Significantly, the variable-pulse pulsed-dye laser offers patients the option of effective treatment of some telangiectasia without bruising. [source]


    A randomized study of massed three-week cognitive behavioural therapy schedule for panic disorder

    ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2009
    M. K. Bohni
    Objective:, To compare the efficacy of massed vs. spaced group cognitive behavioural therapy (CBT) for patients with panic disorder with or without agoraphobia (PD). Method:, Thirty-nine PD patients were randomly assigned to massed group CBT (daily 4-h sessions in week 1, two 2-h sessions in week 2 and one 2-h session in week 3) or traditional spaced weekly group CBT (13 consecutive, weekly 2-h sessions). The content and number of hours in the two treatment schedules were identical. Outcome was assessed after treatment, and at 3, 6 and 18 months of follow-up. Results:, Both treatment groups achieved significant improvement on all measures with large pre- to post-treatment and pre-treatment to follow-up effect sizes. No between-group differences were registered. Adherence and patient satisfaction did not differ between groups. Conclusion:, The massed, 3-week group CBT schedule proved to be effective and feasible for PD patients with outcomes comparable with that of standard, spaced group CBT. [source]


    Comparing botulinum toxin A with casting for treatment of dynamic equinus in children with cerebral palsy

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2005
    Jeffrey D Ackman MD
    The purpose of this study was to compare the cumulative efficacy (three treatment sessions) of botulinum toxin A (BTX-A) alone, casting alone, and the combination of BTX-A and casting in the management of dynamic equinus in ambulatory children with spastic cerebral palsy (CP). Thirty-nine children with spastic CP (mean age 5y 10mo, range 3 to 9y) were enrolled in the study. A multicenter, randomized, double blind, placebo-controlled prospective study was used. Children were randomly assigned to one of three treatment groups: BTX-A only (B), placebo injection plus casting (C), or BTX-A plus casting (B+C). The dosage for the BTX-A injections was 4U/kg per extremity. Assessments were performed at baseline, 3,6,7.5, and 12 months with a total of three treatments administered after the evaluations at baseline, 3, and 6 months. Primary outcome measures were ankle kinematics, velocity, and stride length. Secondary outcome measures were ankle spasticity, strength, range of motion, and ankle kinetics. Group B made no significant change in any variable at any time. Groups C and B+C demonstrated significant improvements in ankle kinematics, spasticity, passive range of motion, and dorsiflexor strength. Results of this 1-year study indicate that BTX-A alone provided no improvement in the parameters measured in this study, while casting and BTX-A/casting were effective in the short- and long-term management of dynamic equinus in children with spastic CP. [source]


    Organizational effects of maternal testosterone on reproductive behavior of adult house sparrows

    DEVELOPMENTAL NEUROBIOLOGY, Issue 14 2008
    Jesko Partecke
    Abstract Despite the well-known, long-term, organizational actions of sex steroids on phenotypic differences between the sexes, studies of maternal steroids in the vertebrate egg have mainly focused on effects seen in early life. Long-term organizational effects of yolk hormones on adult behavior and the underlying mechanisms that generate them have been largely ignored. Using an experiment in which hand-reared house sparrows (Passer domesticus) from testosterone- or control-treated eggs were kept under identical conditions, we show that testosterone treatment in the egg increased the frequency of aggressive, dominance, and sexual behavior of 1-year-old, reproductively competent house sparrows. We also show that circulating plasma levels of progesterone, testosterone, 5,-dihydrotestosterone, and 17,-estradiol did not differ between treatment groups. Thus, a simple change in adult gonadal hormone secretion is not the primary physiological cause of long-term effects of maternal steroids on adult behavior. Rather, differences in adult behavior caused by exposure to yolk testosterone during embryonic development are likely generated by organizational modifications of brain function. Furthermore, our data provide evidence that hormone-mediated maternal effects are an epigenetic mechanism causing intra-sexual variation in adult behavioral phenotype. © 2008 Wiley Periodicals, Inc. Develop Neurobiol 2008 [source]


    Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus

    DIABETES OBESITY & METABOLISM, Issue 5 2009
    E. Bosi
    Aim:, To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM). Methods:, This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA1c) of 7.5,11% (N = 1179) were randomized equally to receive vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily), vildagliptin plus low-dose metformin combination therapy (50 mg + 500 mg twice daily), vildagliptin monotherapy (50 mg twice daily) or high-dose metformin monotherapy (1000 mg twice daily). The primary objective was to demonstrate that HbA1c reduction from baseline with either combination therapy is superior to both monotherapies at the week 24 endpoint. Patients who failed glycaemic-screening criteria [HbA1c >11% or fasting plasma glucose (FPG) >15 mmol/l (270 mg/dl)] could enter a 24-week, single-arm substudy. These patients (N = 94) received open-label vildagliptin plus high-dose metformin combination therapy (100 mg + 1000 mg twice daily). Results:, From comparable baseline values (8.6,8.7%), HbA1c decreased in all four treatment groups, to the greatest extent with vildagliptin plus high-dose metformin combination therapy. Mean (SE) HbA1c change from baseline was ,1.8% (0.06%), ,1.6% (0.06%), ,1.1% (0.06%) and ,1.4% (0.06%) with vildagliptin plus high-dose metformin combination therapy, vildagliptin plus low-dose metformin combination therapy, and vildagliptin and metformin monotherapies respectively. The between-group difference was superior with vildagliptin plus high-dose metformin combination therapy (p < 0.001 vs. both monotherapies) and vildagliptin plus low-dose metformin combination therapy (p < 0.001 and p = 0.004, vs. vildagliptin and metformin monotherapies, respectively). Higher baseline HbA1c values were linked to greater HbA1c reductions, with changes of ,3.2% (0.22%), ,2.7% (0.22%), ,1.5% (0.24%) and ,2.6% (0.26%) respectively, occurring in patients with baseline HbA1c,10%. Reductions in FPG were superior with vildagliptin plus high-dose metformin combination therapy [change from baseline ,2.63 (0.13) mmol/l] compared with both monotherapies [,1.26 (0.13) mmol/l and ,1.92 (0.13) mmol/l, respectively; p < 0.001]. There was no incidence of hypoglycaemia or severe hypoglycaemia with either combination therapy, and neither was associated with weight gain. All treatments were well tolerated and displayed a comparable incidence of adverse events overall. Despite superior HbA1c lowering, the vildagliptin plus low-dose metformin combination therapy group demonstrated a favourable gastrointestinal (GI) tolerability profile compared with metformin monotherapy. Conclusions:, In treatment-naive patients, combinations of vildagliptin and both high-dose and low-dose metformin provide superior efficacy to monotherapy treatments with a comparable overall tolerability profile and low risk of hypoglycaemia. The potential dose-sparing effect of adding vildagliptin to low-dose metformin in preference to the up-titration of metformin may allow patients to achieve equivalent or superior HbA1c lowering without the GI tolerability issues associated with higher doses of metformin. [source]


    Comparison of additional metformin or NPH insulin to mealtime insulin lispro therapy with mealtime human insulin therapy in secondary OAD failure

    DIABETES OBESITY & METABOLISM, Issue 6 2003
    Y. Altuntas
    Aim:, It has been found that non-fasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. The main aim of treatment of type 2 diabetic patients is to control plasma glucose and HbA1c levels. In this study, we aimed to assess the effects of three different insulin regimens (group I: lispro insulin + NPH insulin, group II: lispro insulin + metformin and group III: regular insulin + NPH insulin) on overall glycaemic control and metabolic parameters in type 2 diabetic patients with secondary oral anti-diabetic drug failure. Methods:, Sixty type 2 diabetic patients with secondary OAD failure were randomly allocated into three different treatment groups equally. There were no significant differences between groups concerning age, body mass index, diabetes duration, HbA1c and serum lipid levels at the beginning of the study. During the 6-month treatment period, blood glucose levels were determined 10 times during 24 h at pre-meal, post-prandial 1 and 2 h and at bedtime. Results:, Group I was found to be the most effective treatment regimen in controlling HbA1c levels (group I vs. group II, p = 0.013; group I vs. group III, p = 0.001; group II vs. group III, p > 0.05). When the comparison was made in each group, change in HbA1c was statistically significant for all groups (,3.18%, p = 0.001; ,2.02%, p = 0.043 and ,2.66%, p = 0.008 respectively). Group I was found to be more effective in controlling fasting and post-prandial plasma glucose levels measured at all times during the day when compared with group II and group III. In group II triglyceride levels were found to be significantly reduced, whereas other groups had no effect on lipids. No serious hypoglycaemic episodes were observed in any of the cases, whereas in group I hypoglycaemic episode rates were increased (,2 = 8.843, p = 0.012). Conclusions:, Lispro insulin plus NPH insulin regimen is more effective in controlling both pre- and post-prandial glucose levels and HbA1c when compared to regular insulin plus NPH insulin combination. Mealtime lispro insulin plus metformin combination therapy should also be seriously considered as an effective and alternative treatment regimen. It is worthy of attention that insulin lispro plus metformin lowered triglyceride levels. [source]


    Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus

    DIABETIC MEDICINE, Issue 3 2000
    B. -L.
    Summary Aims Recent studies have indicated that proinsulin C-peptide shows specific binding to cell membrane binding sites and may exert biological effects when administered to patients with Type 1 diabetes mellitus. This study was undertaken to determine if combined treatment with C-peptide and insulin might reduce the level of microalbuminuria in patients with Type 1 diabetes and incipient nephropathy. Methods Twenty-one normotensive patients with microalbuminuria were studied for 6 months in a double-blind, randomized, cross-over design. The patients received s.c. injections of either human C-peptide (600 nmol/24 h) or placebo plus their regular insulin regimen for 3 months. Results Glycaemic control improved slightly during the study and to a similar extent in both treatment groups. Blood pressure was unaltered throughout the study. During the C-peptide treatment period, urinary albumin excretion decreased progressively on average from 58 ,g/min (basal) to 34 ,g/min (3 months, P < 0.01) and it tended to increase, but not significantly so, during the placebo period. The difference between the two treatment periods was statistically significant (P < 0.01). In the 12 patients with signs of autonomic neuropathy prior to the study, respiratory heart rate variability increased by 21 ± 9% (P < 0.05) during treatment with C-peptide but was unaltered during placebo. Thermal thresholds were significantly improved during C-peptide treatment in comparison to placebo (n = 6, P < 0.05). Conclusion These results indicate that combined treatment with C-peptide and insulin for 3 months may improve renal function by diminishing urinary albumin excretion and ameliorate autonomic and sensory nerve dysfunction in patients with Type 1 diabetes mellitus. [source]


    Changes in antioxidant defense status in response to cisplatin and 5-FU in esophageal carcinoma

    DISEASES OF THE ESOPHAGUS, Issue 2 2008
    T. Kaur
    SUMMARY., The ability of reactive oxygen species to induce cellular damage and to cause cell death opens the possibility of exploiting this property in the treatment of esophageal cancer through a free radical mediated mechanism. The present study was carried out with the aim of evaluating the changes in the antioxidant defense status in esophageal cancer patients treated without and with neoadjuvant therapy (NAT). Forty surgically resected tissue specimens from tumors, tissue adjoining the tumors and paired macroscopically normal mucosa were obtained from esophageal cancer patients treated with or without chemo-radiotherapy. An evaluation of antioxidant defense system in the normal, adjoining and tumor esophageal tissues in response to NAT revealed decreased catalase activity in tumor and adjoining tissues as compared to their respective normal tissue levels. Similarly, decreased superoxide dismutase activity was observed in tumor tissue in response to NAT. In both the treatment groups (with and without NAT), no significant change was observed in the enzyme activity of glutathione reductase in the normal, adjoining and tumor tissues. Enhanced glutathione peroxidase activity was found in tumor tissue, as compared to the adjoining and paired normal tissue of patients after NAT. Estimation of reduced glutathione (GSH) levels showed a significant decline in GSH levels in esophageal tumors after NAT. Depletion of GSH, an endogenous antioxidant, would elevate drug sensitivity and might predispose neoplastic cells to apoptosis in response to NAT. The antioxidant enzymes in the esophageal carcinoma thus may play an important role in influencing the final outcome upon NAT course. [source]


    Randomized controlled trial of intrasphincteric botulinum toxin A injection versus balloon dilatation in treatment of achalasia cardia

    DISEASES OF THE ESOPHAGUS, Issue 3-4 2001
    U. C. Ghoshal
    As the few randomized controlled trials available in the literature comparing botulinum toxin (BT) injection with established endoscopic treatment of achalasia cardia, i.e. pneumatic dilatation, showed conflicting results, we conducted a prospective randomized trial. Seventeen consecutive patients with achalasia cardia diagnosed during a period between December 1997 and February 2000 were randomized into two treatment groups [pneumatic dilatation by Rigiflex dilator (n=10), BT injection by sclerotherapy needle into four quadrants of lower esophageal sphincter (LES) (n=7) 80 units in five cases, 60 units in two cases] after dysphagia grading, endoscopy, barium esophagogram, and manometry, all of which were repeated 1 week after treatment. Patients were followed up clinically for 35.2 ± 14 weeks. Chi-squares, Wilcoxon rank-sum test, Kaplan,Meier method and log-rank tests were used for statistical analysis. After 1 week, 6/7 (86%) BT-treated vs. 8/10 (80%) dilatation-treated patients improved (P=NS). There was no difference in LES pressure and maximum esophageal diameter in the barium esophagogram in the two groups before therapy. Both therapies resulted in significant reduction in LES pressure. The cumulative dysphagia-free state using the Kaplan,Meier method decreased progressively in BT-treated compared with dilatation-treated patients (P=0.027). Two patients with tortuous megaesophagus, one of whom had failed dilatation complicated by perforation previously, improved after BT. One other patient in whom pneumatic dilatation had previously failed improved in a similar manner. BT is as good as pneumatic dilatation in achieving an initial improvement in dysphagia of achalasia cardia. It is also effective in patients with tortuous megaesophagus and previous failed pneumatic dilatation. However, dysphagia often recurs during 1-year follow up. [source]


    Can music therapy engage patients in group cognitive behaviour therapy for substance abuse treatment?

    DRUG AND ALCOHOL REVIEW, Issue 2 2008
    GENEVIEVE A. DINGLE PhD
    Abstract Introduction and Aims. Despite the availability of effective treatments for substance use disorders, engaging people in treatment remains a challenge. This clinical study describes a 7-week trial of music therapy as an adjunct to group cognitive behaviour therapy with the aim of increasing patient engagement in a private hospital open group programme. Design and Methods. Patient attendance rates and perceptions of the music therapy were collected at the end of each music therapy session by means of an anonymous survey, and only data from each patient's first survey were used in the analysis. Twenty-four surveys were analysed, representing feedback from 10 men and 14 women, aged between 17 and 52 years. Results. The average attendance rate over the 7-week trial was 75%. The results indicated that enjoyment and motivation to participate during the sessions was uniformly high (mean ratings of 4.3 and 4.0 out of 5, respectively). The majority (83%) of participants reported that they would attend another music therapy session, and almost half (46%) endorsed that ,(music therapy) would help them to feel more a part of the group'. Additional analyses revealed that music therapy was able to engage patients regardless of their age group (25 years and under vs. over-25 years) or substance (alcohol only vs. other drugs). Discussion and Conclusions. Music therapy is a promising approach to improving engagement in substance abuse treatment groups. [source]


    The characteristics of heroin users entering treatment: findings from the Australian Treatment Outcome Study (ATOS)

    DRUG AND ALCOHOL REVIEW, Issue 5 2005
    JOANNE ROSS
    Abstract The current study aimed to describe the characteristics (demographics, drug use, mental and physical health) of entrants to treatment for heroin dependence in three treatment modalities; and to compare these characteristics with heroin users not in or seeking treatment. Participants were 825 current heroin users recruited from Sydney, Adelaide and Melbourne: 277 entering methadone/buprenorphine maintenance treatment (MT), 288 entering detoxification (DTX), 180 entering drug-free residential rehabilitation (RR) and 80 not in treatment (NT). Treatment entrants were generally long-term heroin users with previous treatment experience. The majority of the sample (55%) were criminally active in the month preceding interview. Injection-related health problems (74%) and a history of heroin overdose (58%) were commonly reported. There were high degrees of psychiatric co-morbidity, with 49% reporting severe psychological distress, 28% having current major depression, 37% having attempted suicide and 42% having a lifetime history of post-traumatic stress disorder. Personality disorders were also prevalent, with 72% meeting criteria for antisocial personality disorder and 47% screening positive for borderline personality disorder. Striking similarities were noted between the non-treatment and treatment groups in length of heroin use career, drug use and treatment histories. [source]


    Reducing sex under the influence of drugs or alcohol for patients in substance abuse treatment

    ADDICTION, Issue 1 2010
    Donald A. Calsyn
    ABSTRACT Aims In a previous report, the effectiveness of the Real Men Are Safe (REMAS) intervention in reducing the number of unprotected sexual occasions among male drug abuse treatment patients was demonstrated. A secondary aim of REMAS was to reduce the frequency with which men engage in sex under the influence (SUI) of drugs or alcohol. Design Men in methadone maintenance (n = 173) or out-patient psychosocial treatment (n = 104) completed assessments at baseline, 3 and 6 months post-intervention. Participants The participants were assigned randomly to attend either REMAS (five sessions containing information, motivational exercises and skills training, including one session specifically targeting reducing SUI) or human immunodeficiency virus (HIV) education (HIV-Ed; one session containing HIV prevention information). SUI during the most recent sexual event served as the primary outcome in a repeated measures logistic regression model. Findings Men assigned to the REMAS condition reporting SUI at the most recent sexual event decreased from 36.8% at baseline to 25.7% at 3 months compared to a increase from 36.9% to 38.3% in the HIV-Ed condition (tintervention = ,2.16, P = 0.032). No difference between the treatment groups was evident at 6-month follow-up. At each assessment time-point, sex with a casual partner versus a regular partner, and being in methadone maintenance versus psychosocial out-patient treatment, were associated with engaging in SUI. Conclusions Overall, a motivational and skills training HIV prevention intervention designed for men was associated with greater reduction in SUI than standard HIV education at the 3-month follow-up. [source]


    Do Proper Accommodation Assignments Make a Difference?

    EDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 3 2007
    Examining the Impact of Improved Decision Making on Scores for English Language Learners
    Does it matter if students are appropriately assigned to test accommodations? Using a randomized method, this study found that individual students assigned accommodations keyed to their particular needs were significantly more efficacious for English language learners (ELLs) and that little difference was reported between students receiving incomplete or not recommended accommodations and no accommodations whatsoever. A sample of third and fourth grade ELLs in South Carolina (N = 272) were randomly assigned to various types of test accommodations on a mathematics assessment. Results indicated that those students who received the appropriate test accommodations, as recommended by a version of a computerized accommodation taxonomy for ELLs (the selection taxonomy for English language learners accommodations; STELLA), had significantly higher test scores than ELLs who received no accommodations or those who received incomplete or not recommended accommodation packages. Additionally, students who were given no test accommodations scored no differently than those students that received accommodation packages that were incomplete or not recommended, given the students' particular needs and challenges. These findings are important in light of research and anecdotal reports that suggest a general lack of systematicity in the current system of assigning accommodations and a tendency to give all available accommodations regardless of individual child characteristics. The results also have important implications for how future accommodation research should be structured to determine the benefits of particular accommodations and accommodation packages. This study would suggest that control and treatment groups should be assembled based on specific student needs in order for direct comparisons to be made. [source]


    A double-blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow-release oral morphine versus methadone in opioid-dependent in-patients willing to undergo detoxification

    ADDICTION, Issue 9 2009
    Ekkehard Madlung-Kratzer
    ABSTRACT Aims Evaluation of the efficacy and safety of slow-release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment. Design Randomized, double-blind, double-dummy, comparative multi-centre study with parallel groups. Setting Three psychiatric hospitals in Austria specializing in in-patient detoxification. Participants Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence. Interventions Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days. Measurements Efficacy analyses were based on the number of patients per treatment group completing the study, as well as on the control of signs and symptoms of withdrawal [measured using Short Opioid Withdrawal Scale (SOWS)] and suppression of opiate craving. In addition, self-reported somatic and psychic symptoms (measured using Symptom Checklist SCL-90-R) were monitored. Findings Of the 208 patients enrolled into the study, 202 were eligible for analysis (SROM: n = 102, methadone: n = 100). Completion rates were 51% in the SROM group and 49% in the methadone group [difference between groups: 2%; 95% confidence interval (CI): ,12% to 16%]. The rate of discontinuation in the study was high mainly because of patients voluntarily withdrawing from treatment. No statistically significant differences between treatment groups were found in terms of signs and symptoms of opiate withdrawal, craving for opiates or self-reported symptoms. SROM and methadone were both well tolerated. Conclusions Detoxification from maintenance treatment with tapered dose reduction of SROM is non-inferior to methadone. [source]


    No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days,,

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2010
    Kristine L. Witt
    Abstract Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282,1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats. Environ. Mol. Mutagen. 2010. Published 2009 Wiley-Liss, Inc. [source]


    Evaluation of mutant frequencies of chemically induced tumors and normal tissues in ,/cII transgenic mice

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005
    Jon C. Mirsalis
    Abstract Genomic instability has been implicated as an important component in tumor progression. Evaluation of mutant frequencies (MFs) in tumors of transgenic mice containing nontranscribed marker genes should be useful for quantitating mutation rates in tumors as the physiologically inactive transgene provides neither a positive nor a negative selective pressure on the tumor. We have conducted long-term carcinogenicity studies in ,/cII transgenic B6C3F1 mice using a variety of genotoxic and nongenotoxic test agents and have evaluated the mutant frequencies in both tumors and normal tissues from these animals. Mice were administered diethylnitrosamine (DEN) as three intraperitoneal injections of 15 mg/kg; phenobarbital (PB) or oxazepam (OXP) provided ad libitum at 0.1% or 0.25% in the diet, respectively; DEN initiation plus PB in the diet; or urethane (UTH) provided ad libitum at 0.2% in the drinking water. Normal tissues and tumors were isolated at various times over a 2-year period and half of each tissue/tumor was evaluated histopathologically and the other half was evaluated for MF in the cII transgene. Approximately 20 mutants from each of 166 individual tissues (tumor and nontumor) were sequenced to determine whether increases in MF represented unique mutations or were due to clonal expansion. UTH produced significant increases in MF in normal liver and lung. DEN either with or without PB promotion produced significant increases in MF in liver and correction of MF for clonality produced little change in the overall MF in these groups. PB produced a twofold increase in liver MF over controls after 27 weeks of treatment, but a similar increase was not observed with longer dosing times; at later time points, the MF in the PB groups was lower than that of the control group, suggesting that PB is not producing direct DNA damage in the liver. OXP failed to produce an increase in MF over controls, even after 78 weeks of treatment. Selected cases of genomic instability were observed in tumors from all treatments except OXP, with individual liver tumors showing very high MF values even after clonal correction. One rare and interesting finding was noted in a single mouse treated with UTH, where a mammary metastasis had an MF approximately 10-fold greater than the parent tumor, with 75% of the mutations independent, providing strong evidence of genomic instability. There was no clear correlation between tumor phenotype and MF except that pulmonary adenomas generally had higher MFs than normal lung in both genotoxic and nongenotoxic treatment groups. Likewise, there was no correlation between tumor size and MF after correction for clonality. The results presented here demonstrate that individual tumors can show significant genomic instability, with very significant increases in MF that are not attributed to clonal expansion of a single mutant cell. Environ. Mol. Mutagen., 2005. © 2004 Wiley-Liss, Inc. [source]


    Adenosine A1 Antagonism Attenuates Atropine-resistant Hypoxic Bradycardia in Rats

    ACADEMIC EMERGENCY MEDICINE, Issue 9 2003
    Justin L. Kaplan MD
    Abstract Objectives: To test the following hypotheses: Hypoxia induces bradycardia and hemodynamic compromise that are resistant to atropine but responsive to selective antagonism of the adenosine A1 receptor (A1AdoR). The mechanism for such attenuation is independent of the vagus nerve. Methods: Ten minutes after sham or actual bilateral cervical vagotomy, paralyzed ventilated rats were made hypoxic (5% fractional inspired oxygen, continued until death). Five minutes after beginning hypoxia, intravenous treatment with BG-9719, a selective A1AdoR antagonist (0.1 mg/kg); atropine (0.1 mg/kg); BG-9719 vehicle; or saline was initiated. These drug doses were based on pilot studies. Of the eight treatment groups (eight possible combinations of vagotomy status and drug/vehicle treatment), n= 8 in all except nonvagotomized, vehicle-treated rats (where n= 7). Results: Heart rate and left ventricular contractility decreased rapidly with hypoxia. Atropine had minimal effects in prolonging survival (from mean ± SEM of 15.5 ± 2.1 minutes to 20.2 ± 2.5 minutes, p = 0.94) and attenuating posthypoxic decreases in heart rate (p = 0.89) and contractility (p = 0.83) compared with saline. BG-9719 prolonged survival, however, from 14.4 ± 1.9 minutes (with vehicle treatment) to 37.2 ± 6.8 minutes (p < 0.001). Survival, heart rate, and contractility were preserved with BG-9719 compared with atropine and vehicle (p < 0.05, all comparisons). Vagotomy prevented the effects of BG-9719 on survival prolongation (p = 0.003), heart rate (p = 0.01), and contractility (p < 0.001) but did not affect those outcomes in saline-treated rats. Conclusions: Survival, heart rate, and contractility were better preserved with BG-9719 than atropine. A1AdoR selective antagonism, possibly because of its multiple mechanisms for attenuating hypoxic cardiac insufficiency, resulted in better hemodynamic and clinical outcomes. That attenuation seems to have a component of vagal mediation. [source]