Effects of Paracetamol (Acetaminophen) Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis

Several studies explored the effects of paracetamol (acetaminophen) ingestion on endurance performance, but their findings are conflicting. Therefore, this review aimed to conduct a meta-analysis examining the effects of paracetamol ingestion on endurance performance. Five databases were searched to find relevant studies. The PEDro checklist was used to assess the methodological quality of the included studies. Data reported in the included studies were pooled in a random-effects meta-analysis. A total of ten studies with good or excellent methodological quality were included in the meta-analysis (pooled n = 141). All included studies had a randomized, double-blind, crossover design. In the main meta-analysis, there was no significant difference between the effects of placebo and paracetamol on endurance performance (Cohen’s d = 0.09; 95% confidence interval (CI): −0.04, 0.22; p = 0.172). However, an ergogenic effect was found when we considered only the studies that provided paracetamol 45 to 60 min before exercise (Cohen’s d = 0.14; 95% CI: 0.07, 0.21; p < 0.001). In a subgroup analysis that focused on time-to-exhaustion tests, there was a significant ergogenic effect of paracetamol ingestion (Cohen’s d = 0.19; 95% CI: 0.06, 0.33; p = 0.006). There was no significant difference between placebo and paracetamol in a subgroup analysis that focused on time trial tests (Cohen’s d = 0.05; 95% CI: −0.12, 0.21; p = 0.561). In conclusion, paracetamol ingestion appears to enhance performance (a) in time-to-exhaustion endurance tests and (b) when consumed 45 to 60 min before exercise.

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Antipsychotics Efficacy in Treatment of Schizophrenia Negative Symptoms: Meta-analysis of Randomized Clinical Trials

European Psychiatry ◽

10.1016/s0924-9338(09)70585-1 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

J. Darbá ◽

A. Minoves ◽

E. Rojo ◽

F. Jiménez ◽

J. Rejas

Keyword(s):

Negative Symptoms ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Effect Sizes ◽

Controlled Trials ◽

Cochrane Central Register ◽

Double Blind ◽

Cohen’S D ◽

Meta Analyses ◽

Cohen's D

Purpose:To examine the efficacy of second-generation-antipsychotics (SGAs) in the treatment of negative symptoms in Schizophrenia.Methods:Two meta-analyses were carried out using placebo or haloperidol as comparators. Studies were identified by searching for randomized, double-blind, placebo and/or haloperidol -controlled trials reporting data on efficacy of SGAs. Search was extended to the following databases: Pubmed, The Cochrane Central Register of Controlled Trials, Proquest Health and Medical Complete, Science Citation Index Expanded, and Current Contents Connect. The outcome measure used was the change in negative symptoms, choosing a standardized statistic (Cohen's d) to synthesize data.Results:A total of 46 homogeneous trials (Q=45.18, df=50, p=0.667, I2=0%) were included. In the placebo-controlled meta-analysis, the effect sizes (Cohen's d) obtained for amisulpride, haloperidol, olanzapine, quetiapine, risperidone and ziprasidone were 0.52, 0.34, 0.43, 0.36, 0.40 and 0.46, respectively, favoring active treatment against placebo (p< 0.001 in all cases). Comparing SGAs against haloperidol, showed just a statistically significant trend favoring SGA's in treatment of negative symptoms (Cohen's d = 0.15, p=0.008). Comparisons by drug showed a significant low and low-to-moderate standardized mean favoring SGA: Cohen's d = 0.34, p< 0.001; Cohen's d = 0.27, p< 0.001 and Cohen's d = 0.19, p=0.030, respectively for ziprasidone, risperidone and olanzapine.Conclusion:Most antipsychotics (aminosulpride, haloperidol, olanzapine. quetiapine, risperidone, ziprasidone) are effective in treatment of negative symptoms, showing moderate effect sizes. Amisulpride and ziprasidone were slightly better than the rest of drugs when compared with placebo. Compared with haloperidol, SGA showed controversial results.

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Antipsychotics Efficacy in Treatment of Schizophrenia Negative Symptoms: Meta-analysis of Randomized Clinical Trials

European Psychiatry ◽

10.1016/s0924-9338(09)71420-8 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

J. Darbá ◽

A. Minoves ◽

E. Rojo ◽

F. Jiménez ◽

J. Rejas

Keyword(s):

Negative Symptoms ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Effect Sizes ◽

Controlled Trials ◽

Cochrane Central Register ◽

Double Blind ◽

Cohen’S D ◽

Meta Analyses ◽

Cohen's D

Purpose:To examine the efficacy of second-generation-antipsychotics (SGAs) in the treatment of negative symptoms in Schizophrenia.Methods:Two meta-analyses were carried out using placebo or haloperidol as comparators. Studies were identified by searching for randomized, double-blind, placebo and/or haloperidol -controlled trials reporting data on efficacy of SGAs. Search was extended to the following databases: Pubmed, the Cochrane Central Register of Controlled Trials, Proquest Health and Medical Complete, Science Citation Index Expanded, and Current Contents Connect. the outcome measure used was the change in negative symptoms, choosing a standardized statistic (Cohen's d) to synthesize data.Results:A total of 46 homogeneous trials (Q=45.18, df=50, p=0.667, I2=0%) were included. in the placebo-controlled meta-analysis, the effect sizes (Cohen's d) obtained for amisulpride, haloperidol, olanzapine, quetiapine, risperidone and ziprasidone were 0.52, 0.34, 0.43, 0.36, 0.40 and 0.46, respectively, favoring active treatment against placebo (p< 0.001 in all cases). Comparing SGAs against haloperidol, showed just a statistically significant trend favoring SGA's in treatment of negative symptoms (Cohen's d = 0.15, p=0.008). Comparisons by drug showed a significant low and low-to-moderate standardized mean favoring SGA: Cohen's d = 0.34, p< 0.001; Cohen's d = 0.27, p< 0.001 and Cohen's d = 0.19, p=0.030, respectively for ziprasidone, risperidone and olanzapine.Conclusion:Most antipsychotics (aminosulpride, haloperidol, olanzapine. quetiapine, risperidone, ziprasidone) are effective in treatment of negative symptoms, showing moderate effect sizes. Amisulpride and ziprasidone were slightly better than the rest of drugs when compared with placebo. Compared with haloperidol, SGA showed controversial results.

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Negative Effects of Mental Fatigue on Performance in the Yo-Yo Test, Loughborough Soccer Passing and Shooting Tests: A Meta-Analysis

Journal of Functional Morphology and Kinesiology ◽

10.3390/jfmk7010010 ◽

2022 ◽

Vol 7 (1) ◽

pp. 10

Author(s):

Jozo Grgic ◽

Ivan Mikulic ◽

Pavle Mikulic

Keyword(s):

Methodological Quality ◽

Meta Analysis ◽

Mental Fatigue ◽

Cochrane Library ◽

Bibliographic Databases ◽

Negative Effects ◽

Cohen’S D ◽

Original Time ◽

Cohen's D

We aimed to examine the effects of mental fatigue on the Yo-Yo test and Loughborough soccer passing and shooting tests performance using a meta-analysis. The search for studies was performed through eight bibliographic databases (Academic Search Elite, AUSPORT, Cochrane Library, PsycInfo, PubMed/MEDLINE, Scopus, SPORTDiscus, and Web of Science). The methodological quality of the included studies was assessed using the PEDro checklist. A random-effects meta-analysis was performed for data analysis. After reviewing 599 search results, seven studies with a total of ten groups were included in the review. All studies were classified as being of good methodological quality. Mental fatigue reduced the distance covered in the Yo-Yo test (Cohen’s d: −0.49; 95% confidence interval [CI]: −0.66, −0.32). In the Loughborough soccer passing test, mental fatigue increased the original time needed to complete the test (Cohen’s d: −0.24; 95% CI: −0.46, −0.03), increased penalty time (Cohen’s d: −0.39; 95% CI: −0.46, −0.31), and decreased performance time (Cohen’s d: −0.52; 95% CI: −0.80, −0.24). In the Loughborough soccer shooting test, mental fatigue decreased points per shot (Cohen’s d: −0.37; 95% CI: −0.70, −0.04) and shot speed (Cohen’s d: −0.35; 95% CI: −0.64, −0.06). Overall, the findings presented in this review demonstrated that mental fatigue negatively impacts endurance-based running performance as well as soccer passing and shooting skills.

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Assessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis

Journal of Psychopharmacology ◽

10.1177/02698811211044688 ◽

2021 ◽

pp. 026988112110446

Author(s):

Robert F Leger ◽

Ellen M Unterwald

Keyword(s):

Clinical Trials ◽

Depressive Disorders ◽

Meta Analysis ◽

Multiple Dosing ◽

Positive Effects ◽

Cohen’S D ◽

Significant Difference ◽

Cohen's D ◽

Serotonin 2A ◽

Positive Effect

Background: Classical psychedelics are a group of drugs which act as agonists on the serotonin-2A (5-HT2A) receptor. Evidence suggests they may have a uniquely rapid and enduring positive effect on mood. However, marked heterogeneity between methodological designs in this emerging field remains a significant concern. Aims: To determine how differences in the type of psychedelic agent used and the number of dosing sessions administered affect subjects’ depression and anxiety outcomes and adverse drug reactions (ADR). Methods: This review collected and screened 1591 records from the MEDLINE and Web of Science databases for clinical trials reporting objective data on mood for subjects with a known anxiety or depression. Results: After screening, nine clinical trials met inclusion criteria. Meta-analysis of these studies showed significant, large positive effect sizes for measures of anxiety (Cohen’s d = 1.26) and depression (Cohen’s d = 1.38) overall. These positive effects were also significant at acute (⩽1 week) and extended (>1 week) time points. No significant differences were observed between trials using different psychedelic agents (psilocybin, ayahuasca or lysergic acid diethylamide (LSD)), however, a significant difference was observed in favour of trials with multiple dosing sessions. No serious ADR were reported. Conclusion: Psilocybin, ayahuasca and LSD all appear to be effective and relatively safe agents capable of producing rapid and sustained improvements in anxiety and depression. Moreover, the findings of the present analysis suggest that they may show a greater efficacy when given to patients over multiple sessions as compared to the more common single session used in many of the existing trials.

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Ergogenic Effects of Acute Caffeine Intake on Muscular Endurance and Muscular Strength in Women: A Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18115773 ◽

2021 ◽

Vol 18 (11) ◽

pp. 5773

Author(s):

Jozo Grgic ◽

Juan Del Coso

Keyword(s):

Subgroup Analysis ◽

Muscular Strength ◽

Meta Analysis ◽

Ergogenic Effect ◽

Upper Body ◽

Caffeine Intake ◽

Muscular Endurance ◽

Lower Body ◽

Caffeine Ingestion ◽

Significant Difference

This meta-analysis aimed to explore the effects of caffeine ingestion on muscular endurance and muscular strength in women. Five databases were searched to find relevant studies. A random-effects meta-analysis of standardized mean differences (SMD) was performed for data analysis. Subgroup meta-analyses explored the effects of caffeine on upper-body and lower-body muscular endurance and muscular strength. Eight crossover placebo-controlled studies were included in the review. In the main meta-analysis that considered data from all included studies, there was a significant ergogenic effect of caffeine on muscular endurance (SMD = 0.25; p = 0.027) and muscular strength (SMD = 0.18; p < 0.001). In a subgroup analysis that considered only upper-body exercises, there was a significant ergogenic effect of caffeine on muscular endurance (SMD = 0.20; p = 0.007) and muscular strength (SMD = 0.17; p < 0.001). In a subgroup analysis that considered only lower-body exercises, there was no significant difference between caffeine and placebo for muscular endurance (SMD = 0.43; p = 0.092) or muscular strength (SMD = 0.16; p = 0.109). The main finding of this meta-analysis is that caffeine ingestion has a significant ergogenic effect on muscular endurance and muscular strength in women. The effects reported in this analysis are similar to those previously observed in men and suggest that women may use caffeine supplementation as an ergogenic aid for muscular performance. Future research is needed to explore the effects of caffeine on lower-body muscular endurance and muscular strength in this population.

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The high risk of malarial recurrence in patients with Plasmodium-mixed infection after treatment with antimalarial drugs: a systematic review and meta-analysis

Parasites & Vectors ◽

10.1186/s13071-021-04792-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Aongart Mahittikorn ◽

Frederick Ramirez Masangkay ◽

Kwuntida Uthaisar Kotepui ◽

Giovanni De Jesus Milanez ◽

Manas Kotepui

Keyword(s):

Systematic Review ◽

Mixed Infection ◽

Subgroup Analysis ◽

Initial Treatment ◽

Meta Analysis ◽

Antimalarial Drugs ◽

Secondary Outcome ◽

Significant Heterogeneity ◽

Pooled Prevalence ◽

Significant Difference

Abstract Background Malaria mixed infections are often unrecognized by microscopists in the hospitals, and a delay or failure to treat Plasmodium-mixed infection may lead to aggravated morbidity and increased mortality. The present study aimed to quantify the pooled proportion and risk of malarial recurrences after the treatment of Plasmodium-mixed infection. The results of the study may provide benefits in the management of Plasmodium-mixed infection in co-endemic regions. Methods This systematic review and meta-analysis searched the international Prospective Register of Systematic Reviews (PROSPERO; ID = CRD42020199709), MEDLINE, Web of Science, and Scopus for potentially relevant studies in any language published between January 1, 1936, and July 20, 2020, assessing drug efficacy in patients with Plasmodium-mixed infection. The primary outcome was the pooled prevalence of Plasmodium parasitemia after initiating antimalarial treatment for Plasmodium-mixed infection. The secondary outcome was the pooled risk ratio (RR) of malarial recurrence in Plasmodium-mixed infection compared with those in Plasmodium falciparum and Plasmodium vivax mono-infection. The pooled analyses were calculated by random-effects meta-analysis. After the initial treatment in different days of recurrences (≤ 28 days or > 28 days), the risk of Plasmodium parasitemia was compared in subgroup analysis. Results Out of 5217 screened studies, 11 were included in the meta-analysis, including 4390 patients from six countries. The pooled prevalence of all recurrences of Plasmodium-mixed parasitemia was 30% (95% confidence interval (CI) 16–43; I2: 99.2%; 11 studies). The RR of malarial recurrence within 28 days after the initial treatment (clinical treatment failure) of Plasmodium-mixed parasitemia compared with the treatment of P. falciparum was 1.22 (p: 0.029; 95% CI 1.02–1.47; Cochran Q: 0.93; I2: 0%; six studies), while there was no significant difference in the risk of recurrence 28 days after initial treatment compared with the treatment of P. falciparum (p: 0.696, RR: 1.14; 95% CI 0.59–2.18; Cochran Q < 0.05; I2: 98.2%; four studies). The subgroup analysis of antimalarial drugs showed that significant malarial recurrence within 28 days was observed in patients treated with artemisinin-based combination therapies (ACTs) with no significant heterogeneity (p: 0.028, RR: 1.31; 95% CI 1.03–1.66; Cochran Q: 0.834; I2: 0%). Conclusions The present findings showed a high prevalence of malarial recurrence after the initial treatment of Plasmodium-mixed infection. Moreover, significant malaria recurrence of mixed infection occurred within 28 days after treatment with ACTs. Graphic Abstract

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Diagnostic Value of Telomerase Activity in Patients With Bladder Cancer: A Meta-Analysis of Diagnostic Test

Frontiers in Oncology ◽

10.3389/fonc.2020.570127 ◽

2020 ◽

Vol 10 ◽

Author(s):

Lei Peng ◽

Jinze Li ◽

Chunyang Meng ◽

Jinming Li ◽

Dandan Tang ◽

...

Keyword(s):

Bladder Cancer ◽

Subgroup Analysis ◽

Meta Analysis ◽

Negative Likelihood Ratio ◽

High Specificity ◽

Diagnostic Value ◽

Telomerase Activity ◽

Low Grade ◽

Potential Biomarker ◽

Significant Difference

BackgroundThis study aimed to evaluate the diagnostic value of telomerase activity (TA) for bladder cancer (BC) by meta-analysis.MethodsWe conducted a systematic search of studies published on PubMed, Embase, and Web of Science up to June 1, 2019. We used Stata 15 and Review Manager 5.3 for calculations and statistical analysis.ResultsTo evaluate the diagnostic value of TA for BC, we performed a meta-analysis on 22 studies, with a total of 2,867 individuals, including sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR), and 95% confidence intervals (CIs). The pooled parameters were calculated from all studies, and we found a sensitivity of 0.79 (95% CI: 0.72–0.84), a specificity of 0.91 (95% CI: 0.87–0.94), a PLR of 8.91 (95% CI: 5.91–13.43), an NLR of 0.24 (95% CI: 0.15–0.37), a DOR of 37.90 (95% CI: 23.32–61.59), and an AUC of 0.92 (95% CI: 0.90–0.94). We also conducted a subgroup analysis based on the different stages and grades of BC. Results from the subgroup analysis showed that there was no significant difference in TA in either high and low stages of BC, but that low-grade tumors had a lower TA than high-grade tumours.ConclusionsTA can be used as a potential biomarker for the diagnosis of bladder cancer with its high specificity. Rigorous and high-quality prospective studies are required to verify our conclusion.

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1241. PfSPZ Vaccine Administered by Direct Venous Inoculation to Prevent Plasmodium falciparum Malaria is as Safe as Normal Saline – a Meta-analysis of 12 Randomized Controlled Clinical Trials

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1426 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S639-S640

Author(s):

L W Preston Church

Keyword(s):

Plasmodium Falciparum ◽

Random Effects ◽

Normal Saline ◽

Meta Analysis ◽

Laboratory Data ◽

Plasmodium Falciparum Malaria ◽

Sub Saharan Africa ◽

Sensitivity Analyses ◽

Double Blind ◽

Significant Difference

Abstract Background Sanaria’s PfSPZ Vaccine prevents Plasmodium falciparum (Pf) infection transmitted in the field and by controlled human malaria infection. Safety of PfSPZ Vaccine has been demonstrated in 12 randomized, double-blind, placebo-controlled trials (RCT) varying in regimen from 3 to 5 doses over 4 to 20 weeks and in size from 18 to 332 subjects in adults in the US and EU and 5-month to 65-year-olds in 5 countries in sub-Saharan Africa. This study was conducted to analyze solicited adverse event (AE) and laboratory data by random effects meta-analysis. Methods PfSPZ Vaccine is composed of radiation-attenuated, aseptic, purified, cryopreserved Pf sporozoites (SPZ) administered by direct venous inoculation (DVI). Normal saline (NS) is always the placebo. Data from all completed RCTs were included as either age > 18 years (n=598) or age 5 months to 17 years (n=641). Any subject receiving at least one dose was included. A random-effects model was used to study vaccine safety and I2 to evaluate heterogeneity. Analysis was performed for any systemic solicited AE and for the most frequently observed AEs and laboratory abnormalities. Sensitivity analyses were performed by removal of trials with zero events to evaluate potential bias. Results When examined individually, only 1 trial had a significant difference between PfSPZ Vaccine and NS for any AE (myalgias in adults). In the adult meta-analysis, there was no difference in the random effects risk ratios (RR) for having any vaccine-related AEs (1.40, 95% confidence interval (CI) 0.88-2.28), or for fever (0.75, 0.24-2.35), headache (1.23, 0.74-2.02), fatigue (0.72, 0.19-2.54), or myalgia (1.09, 0.26-4.68). In the pediatric meta-analysis there was no difference between the RR for PfSPZ Vaccine and NS for any AE (0.84, 0.59-1.18) or for fever (1.09, 0.44-2.69). No significant differences in the most common grade 2 or higher laboratory abnormalities – declines in hemoglobin, neutrophil or platelet count – were detected. Sensitivity analysis did not change the results. Conclusion There was no difference in risk for AEs or lab abnormalities between PfSPZ Vaccine and NS, indicating that PfSPZ Vaccine administered by DVI was extremely safe and well tolerated in 5-month- to 65-year-olds. Disclosures LW Preston Church, MD, FIDSA, Sanaria Inc. (Employee)

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Zao Ren An Shen capsule for insomnia: A double-blind, randomized, placebo-controlled trial

SLEEP ◽

10.1093/sleep/zsab266 ◽

2021 ◽

Author(s):

Yoann Birling ◽

Xiaoshu Zhu ◽

Nicole Avard ◽

Caterina Tannous ◽

Paul P Fahey ◽

...

Keyword(s):

Herbal Medicine ◽

Adverse Events ◽

Chinese Herbal Medicine ◽

Controlled Trial ◽

Double Blind ◽

Subjective Sleep ◽

Chinese Herbal ◽

Cohen’S D ◽

Cohen's D ◽

Insomnia Severity

Abstract Study Objectives The aim of this study was to test the efficacy and safety of Zao Ren An Shen (ZRAS) capsule, a Chinese herbal medicine product, for the treatment of insomnia. Methods We conducted a double-blind randomized placebo-controlled trial. After a one-week placebo run-in, a total of 85 people with insomnia were randomly allocated to receive ZRAS or placebo for four weeks. The primary outcomes were insomnia severity assessed with the Insomnia Severity Index (ISI) and the number of participants with adverse events. Secondary outcomes included objective and subjective sleep parameters, psychological status, fatigue level, quality of life, acceptability, and tolerability. Results A non-significant (p > 0.05) difference of 0.7 points in ISI in favor of ZRAS capsule was found at the end of the treatment. The number of participants with adverse events was not significantly different (p > 0.05) between the two groups. Except for subjective sleep onset latency, which had a non-significant (p > 0.05) medium effect (Cohen’s d = 0.5), the effects in secondary efficacy outcomes were all small (Cohen’s d < 0.4) and non-significant (p > 0.05). The acceptability and tolerability were high in the active group. Conclusions ZRAS capsule is safe, acceptable, and tolerable, yet not more effective than placebo in the treatment of insomnia. As previous evidence showed that Chinese herbal medicine was effective for insomnia, these results may be explained by the dose of the product, which was lower than the dose generally used in the clinic.

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Racecadotril for acute diarrhoea in children: systematic review and meta-analyses

Archives of Disease in Childhood ◽

10.1136/archdischild-2015-309676 ◽

2015 ◽

Vol 101 (3) ◽

pp. 234-240 ◽

Cited By ~ 14

Author(s):

Morris Gordon ◽

Anthony Akobeng

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Methodological Quality ◽

Data Extraction ◽

Meta Analysis ◽

Acute Diarrhoea ◽

Risk Of Bias ◽

Duration Of Symptoms ◽

Duration Of Illness ◽

Significant Difference

ObjectiveRacecadotril is an antisecretory agent that can prevent fluid/electrolyte depletion from the bowel as a result of acute diarrhoea without affecting intestinal motility. An up-to-date systematic review is indicated to summarise the evidence on racecadotril for the treatment of acute diarrhoea in children.DesignA Cochrane format systematic review of randomised controlled trials (RCTs). Data extraction and assessment of methodological quality were performed independently by two reviewers. Methodological quality was assessed using the Cochrane risk of bias tool.PatientsChildren with acute diarrhoea, as defined by the primary studies.InterventionsRCTs comparing racecadotril with placebo or other interventions.Main outcome measursDuration of illness, stool output/volume and adverse events.ResultsSeven RCTs were included, five comparing racecadotril with placebo or no intervention, one with pectin/kaolin and one with loperamide. Moderate to high risk of bias was present in all studies. There was no significant difference in efficacy or adverse events between racecadotril and loperamide. A meta-analysis of three studies with 642 participants showed significantly shorter duration of symptoms with racecadotril compared with placebo (mean difference −53.48 h, 95% CI −65.64 to −41.33). A meta-analysis of five studies with 949 participants showed no significant difference in adverse events between racecadotril and placebo (risk ratio 0.99, 95% CI 0.73 to 1.34).ConclusionsThere is some evidence that racecadotril is more effective than placebo or no intervention in reducing the duration of illness and stool output in children with acute diarrhoea. However, the overall quality of the evidence is limited due to sparse data, heterogeneity and risk of bias. Racecadotril appears to be safe and well tolerated.

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