Abstract 537: Higher Prevalence of Risk Alleles for Hyperuricemia Parallels Elevated Incidence of Gout and Growing Risk for Cardiovascular Diseases in a Hmong Population

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Youssef M Roman ◽  
Jenny D Xiong ◽  
Jeremiah S Menk ◽  
Kathleen Culhane-Pera ◽  
Robert J Straka
Keyword(s):  
Elevated Serum ◽  
Asian Population ◽  
Allele Frequencies ◽  
Fisher Exact Test ◽  
Snp Analysis ◽  
Cvd Risk ◽  
Significance Level ◽  
Exact Test ◽  
Risk Alleles ◽  
Increased Risk

Introduction: Hyperuricemia (HU) is the strongest predictor of gout and highly associated with major CVD including hypertension, HF, and CKD. The Hmong, a unique Asian population numbering > 60,000 in Minnesota, have a two-fold increased risk of gout compared to non-Hmong, rising prevalence of CVD, and may differ from other Asian populations in these regards. A genetic predisposition to elevated Serum Uric Acid (SUA) may help identify individuals at risk for gout and CVD. We quantified the Minor Allele Frequencies (MAFs) of known genetic variants (SNPs) associated with HU and compared the MAFs between our Hmong sample and both a reference (HapMap) population of Caucasian (CEU) as well as Han-Chinese (CHB). Methods: Salivary DNA from 235 self-identified Hmong was genotyped using either a Sequenom (iPLEX Gold) or TaqMan approach. MAFs for seven SNPs within candidate genes ( SLC2A9, SLC22A12, PDZK1, and ABCG2 ) identified by GWAS, were determined in our Hmong sample. Associations between HU and genotype were examined for 57/235 Hmong with known SUA levels. A Chi-Square or Fisher exact test with a Bonferroni corrected significance level (<0.007) was used to evaluate MAF differences. Mean SUA concentrations were compared by genotype using one-way ANOVA. Results: Our Hmong participant's age [mean (±SD)] was 30.2 (15.4) years, with >61% overweight or obese and a mean (±SD) SUA of 6.3 (1.7) mg/dL. Although the frequency of risk alleles in the Hmong were significantly higher compared to CEU (6/7) and CHB (3/7) populations, independent SNP by SNP analysis did not show a clear association with SUA. Risk allele frequencies were always more frequent in the Hmong versus comparator groups. Conclusion: MAFs of selected SNPs for HU are not independent of race. The higher prevalence of risk alleles for HU in the Hmong versus CEU and CHB populations may partly explain the clinically observed higher prevalence of gout and CVD risk in the Hmong. Although sample size precludes a robust assessment of an association between genotype and SUA, to our knowledge this is the first study to examine the genetic basis of HU in the Hmong.

scholarly journals The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis

2021 ◽  
Vol 11 (3) ◽  
pp. 231
Author(s):  
Faven Butler ◽  
Ali Alghubayshi ◽  
Youssef Roman
Keyword(s):  
Literature Review ◽  
Risk Allele ◽  
Statistical Significance ◽  
Elevated Serum ◽  
The United States ◽  
Allele Frequencies ◽  
Racial Groups ◽  
1000 Genomes Project ◽  
1000 Genomes ◽  
Risk Alleles

Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher’s Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising.

scholarly journals Synergistic effect of genetic polymorphisms in TLR6 and TLR10 genes on the risk of pulmonary tuberculosis in a Moldavian population

2021 ◽  
pp. 175342592110299
Author(s):  
Alexander Varzari ◽  
Igor V. Deyneko ◽  
Elena Tudor ◽  
Harald Grallert ◽  
Thomas Illig
Keyword(s):  
Pulmonary Tuberculosis ◽  
Interaction Analysis ◽  
P Value ◽  
Fisher Exact Test ◽  
Snp Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Exact Test ◽  
Pulmonary Tb ◽  
The Republic

Polymorphisms in genes that control immune function and regulation may influence susceptibility to pulmonary tuberculosis (TB). In this study, 14 polymorphisms in 12 key genes involved in the immune response ( VDR, MR1, TLR1, TLR2, TLR10, SLC11A1, IL1B, IL10, IFNG, TNF, IRAK1, and FOXP3) were tested for their association with pulmonary TB in 271 patients with TB and 251 community-matched controls from the Republic of Moldova. In addition, gene–gene interactions involved in TB susceptibility were analyzed for a total of 43 genetic loci. Single nucleotide polymorphism (SNP) analysis revealed a nominal association between TNF rs1800629 and pulmonary TB (Fisher exact test P = 0.01843). In the pairwise interaction analysis, the combination of the genotypes TLR6 rs5743810 GA and TLR10 rs11096957 GT was significantly associated with an increased genetic risk of pulmonary TB (OR = 2.48, 95% CI = 1.62–3.85; Fisher exact test P value = 1.5 × 10−5, significant after Bonferroni correction). In conclusion, the TLR6 rs5743810 and TLR10 rs11096957 two-locus interaction confers a significantly higher risk for pulmonary TB; due to its high frequency in the population, this SNP combination may serve as a novel biomarker for predicting TB susceptibility.

scholarly journals Phlebitis associated with peripheral intravenous catheters in adults admitted to hospital in the Western Brazilian Amazon

2016 ◽  
Vol 50 (2) ◽  
pp. 263-271 ◽  
Author(s):  
Sandra Maria Sampaio Enes ◽  
Simone Perufo Opitz ◽  
André Ricardo Maia da Costa de Faro ◽  
Mavilde de Luz Gonçalves Pedreira
Keyword(s):  
Intermittent Infusion ◽  
Brazilian Amazon ◽  
Fisher Exact Test ◽  
Intravenous Therapy ◽  
Chi Square ◽  
Significance Level ◽  
Exact Test ◽  
Dorsal Hand Vein ◽  
Mean Time ◽  
Intravenous Catheters

Abstract OBJECTIVE To identify the presence of phlebitis and the factors that influence the development of this complication in adult patients admitted to hospital in the western Brazilian Amazon. METHOD Exploratory study with a sample of 122 peripheral intravenous catheters inserted in 122 patients in a medical unit. Variables related to the patient and intravenous therapy were analyzed. For the analysis, we used chi-square tests of Pearson and Fisher exact test, with 5% significance level. RESULTS Complication was the main reason for catheter removal (67.2%), phlebitis was the most frequent complication (31.1%). The mean duration of intravenous therapy use was 8.81 days in continuous and intermittent infusion (61.5%), in 20G catheter (39.3%), inserted in the dorsal hand vein arc (36.9 %), with mean time of usage of 68.4 hours. The type of infusion (p=0.044) and the presence of chronic disease (p=0.005) and infection (p=0.007) affected the development of phlebitis. CONCLUSION There was a high frequency of phlebitis in the sample, being influenced by concomitant use of continuous and intermittent infusion of drugs and solutions, and more frequent in patients with chronic diseases and infection.

scholarly journals Determination of Clopidogrel Resistance by Whole Blood Platelet Aggregometry and Inhibitors of the P2Y12 Receptor

2006 ◽  
Vol 52 (3) ◽  
pp. 383-388 ◽  
Author(s):  
Boris T Ivandic ◽  
Philipp Schlick ◽  
Peter Staritz ◽  
Kerstin Kurz ◽  
Hugo A Katus ◽  
...  
Keyword(s):  
Whole Blood ◽  
Adenosine Monophosphate ◽  
Blood Platelet ◽  
P2y12 Receptor ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Clopidogrel Resistance ◽  
Impedance Aggregometry ◽  
Platelet Aggregometry ◽  
Increased Risk

Abstract Background: Inhibition of platelet aggregation by clopidogrel may be insufficient in up to 30% of users. These nonresponders carry an increased risk of cardiovascular events. We reported here a simple assay to study clopidogrel responsiveness. Methods: Electrical impedance aggregometry was performed in diluted whole blood in the presence of 5 and 20 μmol/L ADP. Some samples were incubated with 0.1 mmol/L methyl-S-adenosine monophosphate (MeSAMP), a P2Y12 receptor blocker, to maximize inhibition of aggregation before aggregometry. To validate the assay, we analyzed 6-min impedance in 21 healthy probands and 244 patients with coronary artery disease (CAD). Results: At 5 μmol/L ADP, the imprecision of the assay was 11%. Mean (SD) impedance of the healthy cohort was 12.2 (2.2) Ω. The mean − 3 SD was used to define the cutoff for clopidogrel responsiveness: responders and nonresponders exhibited a 6-min impedance ≤5 Ω and &gt;5 Ω, respectively. Samples from nonresponders were incubated with MeSAMP and analyzed again to distinguish pharmacokinetic and pharmacodynamic types of resistance. Sixteen percent of CAD patients were classified as nonresponders (38 and 2 cases of pharmacokinetic and pharmacodynamic resistance, respectively). Female sex was strongly associated with clopidogrel resistance (P = 0.0002, Fisher exact test). A higher clopidogrel loading dose (P = 0.0353, Mann–Whitney U-test) was given to responders (median, 450 mg) than nonresponders (median, 300 mg). Age and cardiovascular diagnosis showed no significant associations. Conclusions: Impedance aggregometry using 5 μmol/L ADP is a useful tool for studying clopidogrel responsiveness. MeSAMP allows characterization of responsiveness “on treatment” and may be useful for optimizing clopidogrel dosing.

Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability–positive endometrial carcinoma

2006 ◽  
Vol 16 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
B. M. Buttin ◽  
M. A. Powell ◽  
P. J. Goodfellow ◽  
S. N. Lewin ◽  
R. K. Gibb ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Microsatellite Instability ◽  
Medical Records ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Molecular Stratification ◽  
Colon Cancers ◽  
Increased Risk ◽  
Primary Colon ◽  
Endometrial Cancers

Microsatellite instability (MSI) is a feature of certain hereditary and sporadic endometrial and colon cancers. We set out to determine whether molecular stratification of endometrial cancers based on tumor MSI status could help identify patients at increased risk for abnormalities found on perioperative colon screening. From a prospectively accrued series of 413 patients, medical records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients with MSI negative (MSI−) endometrial cancers, matched by year of diagnosis. We reviewed clinicopathologic data and results of perioperative colon screening. Differences were analyzed using Fisher exact test and logistic regression analysis. There were no significant clinicopathologic differences between the two cohorts. Sixty-five percent of patients in each group underwent perioperative colon screening. However, patients with MSI+ cancers had a twofold increase in the frequency of colonic abnormalities (30% versus 14.8%, P= 0.044) over those with MSI− cancers. Furthermore, the only primary colon cancers (N= 2) were found in women with MSI+ endometrial cancers that were unmethylated at the MLH1 promoter. Our data suggest that patients with MSI+ endometrial cancers are at increased risk for abnormalities on perioperative colon screening. Those with MSI+MLH1 unmethylated cancers appear to be at highest risk.

scholarly journals Diastasis recti abdominis during pregnancy and 12 months after childbirth: prevalence, risk factors and report of lumbopelvic pain

2016 ◽  
Vol 50 (17) ◽  
pp. 1092-1096 ◽  
Author(s):  
Jorun Bakken Sperstad ◽  
Merete Kolberg Tennfjord ◽  
Gunvor Hilde ◽  
Marie Ellström-Engh ◽  
Kari Bø
Keyword(s):  
Risk Factors ◽  
Post Partum ◽  
Fisher Exact Test ◽  
Significance Level ◽  
Exact Test ◽  
Diastasis Recti ◽  
Student’S T ◽  
First Time ◽  
Diastasis Recti Abdominis ◽  
Student’S T Test

Background/aimDiastasis recti abdominis (DRA) is defined as a separation of the 2 muscle bellies of rectus abdominis. To date there is scant knowledge on prevalence, risk factors, and consequences of the condition. The present study aimed to investigate the prevalence of DRA during pregnancy and post partum, presence of possible risk factors, and the occurrence of lumbopelvic pain among women with and without DRA.MethodsThis prospective cohort study followed 300 first-time pregnant women from pregnancy till 12 months post partum. Data were collected by electronic questionnaire and clinical examinations. DRA was defined as a palpated separation of ≥2 fingerbreadths either 4.5 cm above, at or 4.5 cm below the umbilicus. Women with and without DRA were compared with independent samples Student's t-test and χ2/Fisher exact test, and OR with significance level >0.05.ResultsPrevalence of DRA was 33.1%, 60.0%, 45.4%, and 32.6% at gestation week 21, 6 weeks, 6 months and 12 months post partum, respectively. No difference in risk factors was found when comparing women with and without DRA. OR showed a greater likelihood for DRA among women reporting heavy lifting ≥20 times weekly (OR 2.18 95% CI 1.05 to 4.52). There was no difference in reported lumbopelvic pain (p=0.10) in women with and without DRA.ConclusionsPrevalence of mild DRA was high both during pregnancy and after childbirth. Women with and without DRA reported the same amount of lumbopelvic pain 12 months post partum.

scholarly journals Synergistic effect of genetic polymorphisms in TLR6 and TLR10 genes on the risk of pulmonary tuberculosis in Moldavian population

2020 ◽  
Author(s):  
Alexander M. Varzari ◽  
Igor V. Deyneko ◽  
Elena Tudor ◽  
Harald Grallert ◽  
Thomas Illig
Keyword(s):  
Pulmonary Tuberculosis ◽  
Interaction Analysis ◽  
Fisher Exact Test ◽  
Polymorphism Analysis ◽  
Bonferroni Correction ◽  
Significance Level ◽  
Exact Test ◽  
Pulmonary Tb ◽  
Efficient Recognition ◽  
Core Genes

Abstract BACKGROUND Host immunity is essential for efficient recognition and clearance of M. tuberculosis infection. Polymorphisms in genes that regulate immune response have been reported to influence the susceptibility/resistance to pulmonary tuberculosis (TB). Here we evaluated associations between 14 polymorphisms in 12 core genes involved in immune responses and pulmonary TB in Moldavian population, and investigated whether interactions between these and previously analyzed polymorphisms could exist and modulate the risk of pulmonary TB. METHODS Polymorphisms VDR rs7975232, VDR rs1544410, VDR rs2228570, MR1 rs1052632, TLR1 rs5743618, TLR2 rs111200466, TLR10 rs11096957, SLC11A1 rs2276631, IL1B rs1143643, IL10 rs1800896, IFNG rs2430561, TNF rs1800629, IRAK1 rs1059703, and FOXP3 rs2232365 were genotyped in 271 Moldavian pulmonary TB cases and 251 community-matched healthy controls. Associations were tested using Fisher test and logistic regression. Complemented with the data from our previous study (PMID: 30529560), investigation of gene-gene interactions was performed for a total of 43 loci. Significance level was adjusted by the Bonferroni correction. RESULTS Single polymorphism analysis revealed a nominal association between TNF rs1800629 and pulmonary TB (Fisher exact test p-value = 0.01843). Marginal differences between cases and controls were observed for haplotypes in the gene cluster TLR1-TLR6-TLR10 and gene TLR2. In the pairwise interaction analysis, the combination of genotypes TLR6 rs5743810 GA and TLR10 rs11096957 GT was significantly associated with an increased genetic risk of pulmonary TB (OR = 2.48, 95% CI = 1.62–3.85; Fisher exact test p-value = 1.5 × 10− 5, significant after Bonferroni correction). CONCLUSION The TLR6 rs5743810 and TLR10 rs11096957 two-locus interaction confers a significantly higher risk for pulmonary TB and has potential as a novel biomarker for predicting TB susceptibility.

scholarly journals HUBUNGAN KECEMASAN DENGAN KELANCARAN PENGELUARAN ASI PADA IBU POST PARTUM SELAMA DIRAWAT DI RUMAH SAKIT IBU DAN ANAK KASIH IBU MANADO

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Zulfikar Mardjun ◽  
Grace Korompis ◽  
Sefti Rompas
Keyword(s):  
Breast Milk ◽  
Sampling Method ◽  
Post Partum ◽  
Fisher Exact Test ◽  
Chi Square ◽  
Cross Sectional ◽  
Significance Level ◽  
Exact Test ◽  
Postpartum Mothers ◽  
The Relationship

Abstract : Smooth breastfeeding is influenced by several factors, one of which ispsychological factors, namely anxiety. In general, postpartum mothers often experiencefatigue and mood swings such as anxiety; about themselves and about their new-born baby.This anxiety can affect the smoothness of breastfeeding in post partum mothers. The purposeof this study was to determine the relationship between anxiety and smooth release of breastmilk in post partum mothers while being treated at Mother and Baby Hospital, Kasih IbuManado. The method of this research uses cross sectional research design. The sampleconsisted of 68 respondents with a non probability sampling method with a purposivesampling technique. The results using the Chi-Square did not fulfill the requirements thuscontinued with the Fisher Exact test at the significance level of 95%, obtained by the value ρ -Value 0.001 smaller than the significant value of 0.05. In conclusion, there is a relationshipbetween anxiety and the smooth releasee of breast milk in post partum mothers while beingtreated at Kasih Ibu Hospital.Keywords : Anxiety, Smooth Release of Breast MilkAbstrak : Kelancaran pengeluaran ASI dipengaruhi oleh beberapa faktor, salah satunyafaktor psikologis yaitu kecemasan. Pada umumnya ibu pasca persalinan sering mengalamikelelahan dan perubahan mood seperti kecemasan, cemas terhadap dirinya dan cemasmemikirkan bayinya. Kecemasan tersebut yang dapat mempengaruhi kelancara pengeluaranASI pada ibu post partum. Tujuan untuk mengetahui hubungan antara kecemasan dengankelancaran pengeluaran air susu ibu pada ibu post partum selama dirawat di Rumah Sakit Ibudan Anak Kasih Ibu Manado. Metode menggunakan desain penelitian cross sectional.Sampel terdiri dari 68 responden dengan metode pengambilan sampelsecara non probabilitysampling dengan teknik purposive sampling. Hasil dengan menggunakan uji Chi – Squaretetapi tidak memenuhi syarat dan dilanjutkan dengan uji Fisher Exact pada tingkatkemaknaan 95%, didapatkan nilai ρ – Value 0,001 lebih kecil dari nilai signifikan 0,05.Kesimpulan ada hubungan antara kecemasan dengan kelancaran pengeluaran air susu ibupada ibu post partum selama dirawat di Rumah Sakit Ibu dan Anak Kasih Ibu Manado.Kata Kunci : Kecemasan, Kelancaran Pengeluaran ASI

scholarly journals Migraine as a risk factor associated with hypertensive disorders of pregnancy

2014 ◽  
pp. 33-38
Author(s):  
Gabriel Braga Diégues Serva ◽  
Leonardo Santos Calvacanti Guerra ◽  
Vilneide Maria Santos Braga Diégues Serva ◽  
Waldmiro Antônio Diégues Serva ◽  
Marcela Patrícia Macêdo Belo ◽  
...  
Keyword(s):  
Fisher Exact Test ◽  
Hypertensive Disorders Of Pregnancy ◽  
Significance Level ◽  
Exact Test ◽  
Factors Associated ◽  
Follow Up Study ◽  
Hypertensive Disorders ◽  
Pregnancy And Postpartum ◽  
Hypertensive Disorders In Pregnancy

Objectives: To identify if the presence of migraine before pregnancy predisposes to hypertensive disorders of pregnancy. Methods: Observational study undertaken from a database of a follow-up study, composed of women consecutively assisted, at the first postnatal week, at IMIP. Its objective was to evaluate the course of migraine during pregnancy and postpartum in women with migraine before pregnancy. The Fisher exact test was used considering the significance level of less than 5%. Results: Of the 686 women, 38.8% were migraine sufferers before pregnancy. 14.3% referred hypertensive disorders of pregnancy. The presence of migraine before pregnancy and to have been submitted to a cesarean section (p<0.001) were factors associated with the presence of hypertensive disorders in pregnancy. Conclusion: Migraine before pregnancy is an associated factor to hypertensive disorders of pregnancy. The diagnosis of migraine should always be taken into consideration during antenatal care, for the prevention of complications.

scholarly journals Age as the Risk Factor that Affected the Increased Degree of Uterine Prolapse

2018 ◽  
Vol 1 (1) ◽  
pp. 20
Author(s):  
Shervil Kagayaita Sayko ◽  
Eighty Mardiyan Kurniawati ◽  
Pudji Lestari
Keyword(s):  
Elderly Women ◽  
Uterine Prolapse ◽  
Fisher Exact Test ◽  
Test Statistic ◽  
Cross Sectional ◽  
Significance Level ◽  
Exact Test ◽  
Significant Difference ◽  
The Relationship

Introduction: Uterine prolapse is a gynecological problem that women often experience with a prevalence of 50% and is predicted that the next 30 years will increase by 45% as life expectancy increases. Increased degrees of uterine prolapse have an impact on the deterioration of women's quality of life. The uterine prolapse is influenced by several mutually supportive factors. The purpose of this study was to analyze the relationship between these factors to the degree of uterine prolapse.Methods: This research is an observational analytic research with cross sectional approach. The number of samples were 65 patients with uterine prolapse at Policlinic Gynecology RSUD Dr. Soetomo Surabaya from 2015-2017. Sampling was done by consecutive sampling. To find out the significant level, the collected data will be tested with Fisher Exact Test statistic at significance level α = 0,05.Results: The result showed that there was significant difference between degree of uterine prolapse with age factor (p = 0,016) and obesity (p = 0,041). As for the parity factor (p = 0.508) there was no significant difference between the parity factor and the degree of uterine prolapse.Discussion: Age is a major factor affecting the degree of uterine prolapse, weakening of pelvic floor tissue and muscle in elderly women is the main cause. While on the obesity factor, there is no data to support that obesity is related to the degree of uterine prolapse because the trend indicates that the majority of patients are not obese. In contrast the parity factor, although according to the statistical test there is no difference to the degree of uterine prolapse, the trend shows that parity leads to increased incidence of uterine prolapse itself.Conclusion: Age is a factor that affects the degree of uterine prolapse.

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