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Auteur Martin KHARRAZI |
Documents disponibles écrits par cet auteur (7)



Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California / Gayle C. WINDHAM in Journal of Autism and Developmental Disorders, 46-2 (February 2016)
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Titre : Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California Type de document : Texte imprimé et/ou numérique Auteurs : Gayle C. WINDHAM, Auteur ; Kristen LYALL, Auteur ; Meredith C. ANDERSON, Auteur ; Martin KHARRAZI, Auteur Année de publication : 2016 Article en page(s) : p.478-488 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Steroid hormones Estrogen Alpha-fetoprotein hCG Prenatal screening Estriol Index. décimale : PER Périodiques Résumé : We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD (n = 2586) and of non-cases (n = 600,103). Adjusted odds ratios (AOR) were calculated by logistic regression. Lower uE3 (AOR for < 10th percentile vs. 25th–74th percentiles = 1.21, 95 % CI 1.06–1.37), and higher MSAFP (AOR = 1.21, 95 % CI 1.07–1.37 for > 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02–1.32 for < 10th percentile; AOR = 1.19, 95 % CI 1.05–1.36 for > 90th percentile). Our results further support prenatal hormone involvement in ASD risk. En ligne : http://dx.doi.org/10.1007/s10803-015-2587-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=280
in Journal of Autism and Developmental Disorders > 46-2 (February 2016) . - p.478-488[article] Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California [Texte imprimé et/ou numérique] / Gayle C. WINDHAM, Auteur ; Kristen LYALL, Auteur ; Meredith C. ANDERSON, Auteur ; Martin KHARRAZI, Auteur . - 2016 . - p.478-488.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 46-2 (February 2016) . - p.478-488
Mots-clés : Autism spectrum disorder Steroid hormones Estrogen Alpha-fetoprotein hCG Prenatal screening Estriol Index. décimale : PER Périodiques Résumé : We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD (n = 2586) and of non-cases (n = 600,103). Adjusted odds ratios (AOR) were calculated by logistic regression. Lower uE3 (AOR for < 10th percentile vs. 25th–74th percentiles = 1.21, 95 % CI 1.06–1.37), and higher MSAFP (AOR = 1.21, 95 % CI 1.07–1.37 for > 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02–1.32 for < 10th percentile; AOR = 1.19, 95 % CI 1.05–1.36 for > 90th percentile). Our results further support prenatal hormone involvement in ASD risk. En ligne : http://dx.doi.org/10.1007/s10803-015-2587-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=280 Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) study / Lisa A. CROEN in Autism Research, 1-2 (April 2008)
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Titre : Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) study Type de document : Texte imprimé et/ou numérique Auteurs : Lisa A. CROEN, Auteur ; David J. HANSEN, Auteur ; Martin KHARRAZI, Auteur ; Bruce FIREMAN, Auteur ; Cathleen K. YOSHIDA, Auteur ; Robert YOLKEN, Auteur ; Daniel BRAUNSCHWEIG, Auteur ; Paula GOINES, Auteur ; Judy VAN DE WATER, Auteur ; Judith K. GRETHER, Auteur Année de publication : 2008 Article en page(s) : p.130-137 Langues : Anglais (eng) Mots-clés : biologic-markers neurotrophin autism BDNF prenatal Index. décimale : PER Périodiques Résumé : To investigate levels of brain-derived neurotrophic factor (BDNF) in mid-pregnancy and neonatal blood specimens as early biologic markers for autism, we conducted a population-based case-control study nested within the cohort of infants born from July 2000 to September 2001 to women who participated in the prenatal screening program in Orange County, CA. Cases (n=84) were all children receiving services for autism at the Regional Center of Orange County. Two comparison groups from the same study population were included: children with mental retardation or developmental delay (n=49) receiving services at the same regional center, and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (n=159), and frequency matched to autism cases on sex, birth year, and birth month. BDNF concentrations were measured in archived mid-pregnancy and neonatal blood specimens drawn during routine prenatal and newborn screening using a highly sensitive bead-based assay (Luminex, Biosource Human BDNF Antibody Bead Kit, Invitrogen-Biosource, Carlsbad, CA). The concentration of BDNF in maternal mid-pregnancy and neonatal specimens was similar across all three study groups. These data do not support previous findings of an association between BDNF and autism and suggest that the concentration of BDNF during critical periods of early neurodevelopment is not likely to be a useful biomarker for autism susceptibility. En ligne : http://dx.doi.org/10.1002/aur.14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=930
in Autism Research > 1-2 (April 2008) . - p.130-137[article] Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) study [Texte imprimé et/ou numérique] / Lisa A. CROEN, Auteur ; David J. HANSEN, Auteur ; Martin KHARRAZI, Auteur ; Bruce FIREMAN, Auteur ; Cathleen K. YOSHIDA, Auteur ; Robert YOLKEN, Auteur ; Daniel BRAUNSCHWEIG, Auteur ; Paula GOINES, Auteur ; Judy VAN DE WATER, Auteur ; Judith K. GRETHER, Auteur . - 2008 . - p.130-137.
Langues : Anglais (eng)
in Autism Research > 1-2 (April 2008) . - p.130-137
Mots-clés : biologic-markers neurotrophin autism BDNF prenatal Index. décimale : PER Périodiques Résumé : To investigate levels of brain-derived neurotrophic factor (BDNF) in mid-pregnancy and neonatal blood specimens as early biologic markers for autism, we conducted a population-based case-control study nested within the cohort of infants born from July 2000 to September 2001 to women who participated in the prenatal screening program in Orange County, CA. Cases (n=84) were all children receiving services for autism at the Regional Center of Orange County. Two comparison groups from the same study population were included: children with mental retardation or developmental delay (n=49) receiving services at the same regional center, and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (n=159), and frequency matched to autism cases on sex, birth year, and birth month. BDNF concentrations were measured in archived mid-pregnancy and neonatal blood specimens drawn during routine prenatal and newborn screening using a highly sensitive bead-based assay (Luminex, Biosource Human BDNF Antibody Bead Kit, Invitrogen-Biosource, Carlsbad, CA). The concentration of BDNF in maternal mid-pregnancy and neonatal specimens was similar across all three study groups. These data do not support previous findings of an association between BDNF and autism and suggest that the concentration of BDNF during critical periods of early neurodevelopment is not likely to be a useful biomarker for autism susceptibility. En ligne : http://dx.doi.org/10.1002/aur.14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=930 Increased mid-gestational IFN-gamma, IL-4, and IL-5 in women giving birth to a child with autism: a case-control study / Paula GOINES in Molecular Autism, (August 2011)
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Titre : Increased mid-gestational IFN-gamma, IL-4, and IL-5 in women giving birth to a child with autism: a case-control study Type de document : Texte imprimé et/ou numérique Auteurs : Paula GOINES, Auteur ; Lisa A. CROEN, Auteur ; Daniel BRAUNSCHWEIG, Auteur ; Cathleen K. YOSHIDA, Auteur ; Judith K. GRETHER, Auteur ; David J. HANSEN, Auteur ; Martin KHARRAZI, Auteur ; Paul ASHWOOD, Auteur ; Judy VAN DE WATER, Auteur Année de publication : 2011 Article en page(s) : 41 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background
Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders.
Methods
Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis.
Results
Elevated concentrations of IFN-gamma, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism.
Conclusion
The profile of elevated serum IFN-gamma, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.En ligne : http://dx.doi.org/10.1186/2040-2392-2-13 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=141
in Molecular Autism > (August 2011) . - 41 p.[article] Increased mid-gestational IFN-gamma, IL-4, and IL-5 in women giving birth to a child with autism: a case-control study [Texte imprimé et/ou numérique] / Paula GOINES, Auteur ; Lisa A. CROEN, Auteur ; Daniel BRAUNSCHWEIG, Auteur ; Cathleen K. YOSHIDA, Auteur ; Judith K. GRETHER, Auteur ; David J. HANSEN, Auteur ; Martin KHARRAZI, Auteur ; Paul ASHWOOD, Auteur ; Judy VAN DE WATER, Auteur . - 2011 . - 41 p.
Langues : Anglais (eng)
in Molecular Autism > (August 2011) . - 41 p.
Index. décimale : PER Périodiques Résumé : Background
Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders.
Methods
Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis.
Results
Elevated concentrations of IFN-gamma, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism.
Conclusion
The profile of elevated serum IFN-gamma, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.En ligne : http://dx.doi.org/10.1186/2040-2392-2-13 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=141 Maternal Vitamin D Levels During Pregnancy in Association With Autism Spectrum Disorders (ASD) or Intellectual Disability (ID) in Offspring; Exploring Non-linear Patterns and Demographic Sub-groups / Gayle C. WINDHAM in Autism Research, 13-12 (December 2020)
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Titre : Maternal Vitamin D Levels During Pregnancy in Association With Autism Spectrum Disorders (ASD) or Intellectual Disability (ID) in Offspring; Exploring Non-linear Patterns and Demographic Sub-groups Type de document : Texte imprimé et/ou numérique Auteurs : Gayle C. WINDHAM, Auteur ; Michelle PEARL, Auteur ; Victor POON, Auteur ; Kimberly BERGER, Auteur ; Jasmine W. SORIANO, Auteur ; Darryl EYLES, Auteur ; Kristen LYALL, Auteur ; Martin KHARRAZI, Auteur ; Lisa A. CROEN, Auteur Article en page(s) : p.2216-2229 Langues : Anglais (eng) Mots-clés : 25(oh)d Asd autism hydroxy-vitamin D intellectual disability race/ethnic differences sex differences vitamin D Index. décimale : PER Périodiques Résumé : Increasing vitamin D deficiency and evidence for vitamin D's role in brain and immune function have recently led to studies of neurodevelopment; however, few are specific to autism spectrum disorder (ASD) and vitamin D in pregnancy, a likely susceptibility period. We examined this in a case-control study of 2000-2003 Southern Californian births; ASD and intellectual disability (ID) were identified through the Department of Developmental Services and controls from birth certificates (N =?534, 181, and 421, respectively, in this analysis). Total 25-Hydroxyvitamin D (25(OH)D) was measured in mid-pregnancy serum, categorized as deficient (<50?nmol/L), insufficient (50-74?nmol/L), or sufficient (?75?nmol/L, referent category), and examined continuously (per 25?nmol/L). Crude and adjusted odds ratios (AORs) and 95% confidence intervals (95% CI) were calculated. Non-linearity was examined with cubic splines. AORs (95% CI) for ASD were 0.79 (0.49-1.3) for maternal deficiency (9.5%), 0.93 (0.68-1.3) for insufficiency (25.6%), and 0.95 (0.86, 1.05) for linear continuous 25(OH)D. Results were similarly null for ASD with or without ID, and ID only. Interactions were observed; non-Hispanic whites (NHW) (AOR = 0.82, 95% CI = 0.69-0.98) and males (AOR = 0.89, 95% CI = 0.80-0.99) had protective associations for ASD with continuous 25(OH)D. A positive association with ASD was observed in females (AOR = 1.40, 95% CI = 1.06-1.85). With splines, a non-linear inverted j-shaped pattern was seen overall (P =?0.009 for non-linearity), with the peak around 100?nmol/L; a non-linear pattern was not observed among NHW, females, nor for ID. Our findings from a large study of ASD and prenatal vitamin D levels indicate that further research is needed to investigate non-linear patterns and potentially vulnerable sub-groups. LAY SUMMARY: We studied whether mothers' vitamin D levels during pregnancy were related to their children having autism (or low IQ) later. Low vitamin D levels were not related to greater risk of autism or low IQ in children overall. With higher levels of mothers' vitamin D, risk of autism went down in boys, but went up in girls. Risk of autism also went down in children of non-Hispanic white mothers with higher vitamin D levels, but we did not find a relation in other race/ethnic groups. En ligne : http://dx.doi.org/10.1002/aur.2424 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=434
in Autism Research > 13-12 (December 2020) . - p.2216-2229[article] Maternal Vitamin D Levels During Pregnancy in Association With Autism Spectrum Disorders (ASD) or Intellectual Disability (ID) in Offspring; Exploring Non-linear Patterns and Demographic Sub-groups [Texte imprimé et/ou numérique] / Gayle C. WINDHAM, Auteur ; Michelle PEARL, Auteur ; Victor POON, Auteur ; Kimberly BERGER, Auteur ; Jasmine W. SORIANO, Auteur ; Darryl EYLES, Auteur ; Kristen LYALL, Auteur ; Martin KHARRAZI, Auteur ; Lisa A. CROEN, Auteur . - p.2216-2229.
Langues : Anglais (eng)
in Autism Research > 13-12 (December 2020) . - p.2216-2229
Mots-clés : 25(oh)d Asd autism hydroxy-vitamin D intellectual disability race/ethnic differences sex differences vitamin D Index. décimale : PER Périodiques Résumé : Increasing vitamin D deficiency and evidence for vitamin D's role in brain and immune function have recently led to studies of neurodevelopment; however, few are specific to autism spectrum disorder (ASD) and vitamin D in pregnancy, a likely susceptibility period. We examined this in a case-control study of 2000-2003 Southern Californian births; ASD and intellectual disability (ID) were identified through the Department of Developmental Services and controls from birth certificates (N =?534, 181, and 421, respectively, in this analysis). Total 25-Hydroxyvitamin D (25(OH)D) was measured in mid-pregnancy serum, categorized as deficient (<50?nmol/L), insufficient (50-74?nmol/L), or sufficient (?75?nmol/L, referent category), and examined continuously (per 25?nmol/L). Crude and adjusted odds ratios (AORs) and 95% confidence intervals (95% CI) were calculated. Non-linearity was examined with cubic splines. AORs (95% CI) for ASD were 0.79 (0.49-1.3) for maternal deficiency (9.5%), 0.93 (0.68-1.3) for insufficiency (25.6%), and 0.95 (0.86, 1.05) for linear continuous 25(OH)D. Results were similarly null for ASD with or without ID, and ID only. Interactions were observed; non-Hispanic whites (NHW) (AOR = 0.82, 95% CI = 0.69-0.98) and males (AOR = 0.89, 95% CI = 0.80-0.99) had protective associations for ASD with continuous 25(OH)D. A positive association with ASD was observed in females (AOR = 1.40, 95% CI = 1.06-1.85). With splines, a non-linear inverted j-shaped pattern was seen overall (P =?0.009 for non-linearity), with the peak around 100?nmol/L; a non-linear pattern was not observed among NHW, females, nor for ID. Our findings from a large study of ASD and prenatal vitamin D levels indicate that further research is needed to investigate non-linear patterns and potentially vulnerable sub-groups. LAY SUMMARY: We studied whether mothers' vitamin D levels during pregnancy were related to their children having autism (or low IQ) later. Low vitamin D levels were not related to greater risk of autism or low IQ in children overall. With higher levels of mothers' vitamin D, risk of autism went down in boys, but went up in girls. Risk of autism also went down in children of non-Hispanic white mothers with higher vitamin D levels, but we did not find a relation in other race/ethnic groups. En ligne : http://dx.doi.org/10.1002/aur.2424 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=434 Neonatal thyroid hormone levels in association with autism spectrum disorder / Kristen LYALL in Autism Research, 10-4 (April 2017)
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Titre : Neonatal thyroid hormone levels in association with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Kristen LYALL, Auteur ; Meredith C. ANDERSON, Auteur ; Martin KHARRAZI, Auteur ; Gayle C. WINDHAM, Auteur Article en page(s) : p.585-592 Langues : Anglais (eng) Mots-clés : risk factors thyroid hormones autism spectrum disorder neonatal hormones Index. décimale : PER Périodiques Résumé : Thyroid hormones (TH) are critical in early neurodevelopment, but few studies have examined whether neonatal TH levels influence risk of autism spectrum disorder (ASD). This study linked California neonatal screening data with live birth and Department of Developmental Services records to examine newborn TH levels in relation to ASD. Thyroxine (T4) and thyroid-stimulating hormone (TSH) levels were measured in newborn bloodspots as part of routine screening, in 1996 and 2002, respectively. Mean levels of T4 and TSH were compared between ASD cases and non-cases. Four hundred forty-seven thousand, fifty-nine screened, singleton births from 1996 and 446,424 from 2002 were examined, including 4,818 ASD cases. Binomial regression, using categories of T4 and TSH percentiles was used to calculate crude and adjusted risk ratios (RR). Covariates included maternal and child factors, gestational age, and age at blood draw. No significant associations were found with TSH levels and ASD in crude or adjusted analyses. ASD cases had significantly lower mean T4 levels than non-cases, but this association was no longer significant in adjusted analyses (RR in individuals in lowest 5th percentile of T4 levels?=?1.13, 95% 0.93–1.37). However, this association appeared stronger in certain subgroup analyses, particularly among neonates with blood draw ?48 hr from birth (RR?=?1.67, 95% CI 1.08, 2.60), when TH levels become more stable. Thus, results from this large, population-based study did not suggest strong associations between neonatal TH and ASD, but certain subgroups of newborns with the lowest T4 levels may have modestly increased ASD risk. En ligne : http://dx.doi.org/10.1002/aur.1708 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307
in Autism Research > 10-4 (April 2017) . - p.585-592[article] Neonatal thyroid hormone levels in association with autism spectrum disorder [Texte imprimé et/ou numérique] / Kristen LYALL, Auteur ; Meredith C. ANDERSON, Auteur ; Martin KHARRAZI, Auteur ; Gayle C. WINDHAM, Auteur . - p.585-592.
Langues : Anglais (eng)
in Autism Research > 10-4 (April 2017) . - p.585-592
Mots-clés : risk factors thyroid hormones autism spectrum disorder neonatal hormones Index. décimale : PER Périodiques Résumé : Thyroid hormones (TH) are critical in early neurodevelopment, but few studies have examined whether neonatal TH levels influence risk of autism spectrum disorder (ASD). This study linked California neonatal screening data with live birth and Department of Developmental Services records to examine newborn TH levels in relation to ASD. Thyroxine (T4) and thyroid-stimulating hormone (TSH) levels were measured in newborn bloodspots as part of routine screening, in 1996 and 2002, respectively. Mean levels of T4 and TSH were compared between ASD cases and non-cases. Four hundred forty-seven thousand, fifty-nine screened, singleton births from 1996 and 446,424 from 2002 were examined, including 4,818 ASD cases. Binomial regression, using categories of T4 and TSH percentiles was used to calculate crude and adjusted risk ratios (RR). Covariates included maternal and child factors, gestational age, and age at blood draw. No significant associations were found with TSH levels and ASD in crude or adjusted analyses. ASD cases had significantly lower mean T4 levels than non-cases, but this association was no longer significant in adjusted analyses (RR in individuals in lowest 5th percentile of T4 levels?=?1.13, 95% 0.93–1.37). However, this association appeared stronger in certain subgroup analyses, particularly among neonates with blood draw ?48 hr from birth (RR?=?1.67, 95% CI 1.08, 2.60), when TH levels become more stable. Thus, results from this large, population-based study did not suggest strong associations between neonatal TH and ASD, but certain subgroups of newborns with the lowest T4 levels may have modestly increased ASD risk. En ligne : http://dx.doi.org/10.1002/aur.1708 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307 Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability / Jennifer L. AMES in Autism Research, 13-3 (March 2020)
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PermalinkPrenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders / Vincent M. YAU in Journal of Autism and Developmental Disorders, 45-3 (March 2015)
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