Carmen Rodríguez - Academia.edu (original) (raw)

Papers by Carmen Rodríguez

Research paper thumbnail of Absorption of orally supplied immunoglobulins in neonatal piglets

Livestock Science, 2010

Low birth weight piglets have a reduced viability because of a low colostrum immunoglobulin (Ig) ... more Low birth weight piglets have a reduced viability because of a low colostrum immunoglobulin (Ig) and energy intake. Additional supply of energy and Ig may improve their survival and immuno-competence. This study was conducted to determine the absorption of IgG from oral supplements containing IgG from porcine plasma and an additional energy substrate, as compared to IgG absorption from sow colostrum. Sixty newborn piglets (mean body weight (BW) 1183 g) from eight sows were removed from the dam prior to suckling and allocated to five treatments. Piglets received either 28 g of standardised sows colostrum per kg of BW (control) or one out of four products containing porcine IgG and fats, glycerine, dextrose or a combination of these as additional energy source. After 12 h of fasting in which only drinking water was supplied, plasma IgG content was determined and efficiency of IgG absorption calculated as total plasma IgG divided by ingested IgG. Treatment means of plasma IgG varied from 1.8 to 7.3 mg/mL (P b 0.001), being 6.8 mg/mL for control piglets. Relative efficiency of absorption varied from 0.05 to 0.28 (P b 0.001), being 0.20 for control piglets. These results indicate that the energy component of the supplements had a major influence on the IgG absorption. IgG absorption from products based on dextrose, medium chain and vegetable long chain triglycerides was similar or higher than IgG absorption from sow colostrum, thus allowing perspective for the development of supplements to improve viability of neonatal piglets.

Research paper thumbnail of Relevance of MIA and S100 serum tumor markers to monitor BRAF inhibitor therapy in metastatic melanoma patients

Clinica chimica acta; international journal of clinical chemistry, Jan 15, 2014

BRAF V600 mutation has been reported in more than 50% of melanoma cases and its presence predicts... more BRAF V600 mutation has been reported in more than 50% of melanoma cases and its presence predicts clinical activity of BRAF inhibitors (iBRAF). We evaluated the role of MIA, S100 and LDH to monitor iBRAF efficiency in advanced melanoma patients presenting BRAF V600 mutations. This was a prospective study of melanoma patients harboring the BRAF V600 mutation and treated with iBRAF within a clinical trial (dabrafenib) or as part of an expanded access program (vemurafenib). MIA, S100 and LDH were analyzed in serum at baseline, and every 4-6 weeks during treatment. Eighteen patients with melanoma stages IIIc-IV were enrolled with 88.8% of response rate to iBRAF. Baseline concentrations of all the tumor markers correlated with tumor burden. MIA and S100 concentrations decreased significantly one month after the beginning of treatment and, upon progression, their concentrations increased significantly above the minimum levels previously achieved. MIA levels lower than 9 μg/L one month aft...

Research paper thumbnail of Jewish ethnicity and prostate cancer mortality in two large US cohorts

Cancer causes & control : CCC, 2002

To investigate prospectively the relationship between Jewish ethnicity and prostate cancer mortal... more To investigate prospectively the relationship between Jewish ethnicity and prostate cancer mortality. Men were selected from white male participants in two large American Cancer Society cohorts: Cancer Prevention Studies I (CPS-I) (enrolled in 1959 and followed through 1972) and II (CPS-II) (enrolled in 1982 and followed through 1996). During the follow-up periods there were 1,751 prostate cancer deaths among 417,018 men in CPS-1 and 3594 deaths among 447,780 men in CPS-II. Cox proportional hazards modeling was used to compute rate ratios (RR) and to adjust for known and suspected risk factors for prostate cancer. Prostate cancer death rates were substantially lower among Jewish men than other white men in both cohorts (multivariate adjusted rate ratios (RR) = 0.54, 95% CI = 0.38-0.77 in CPS-I; RR = 0.72, 95% CI = 0.61-0.86 in CPS-II). Factors such as tobacco avoidance and measured dietary patterns did not account for this difference. Lower prostate cancer death rates were observed ...

Research paper thumbnail of Quantitative Cell-Free Circulating BRAFV600E Mutation Analysis by Use of Droplet Digital PCR in the Follow-up of Patients with Melanoma Being Treated with BRAF Inhibitors

Clinical Chemistry, 2014

Around 50% of cutaneous melanomas harbor the BRAF(V600E) mutation and can be treated with BRAF in... more Around 50% of cutaneous melanomas harbor the BRAF(V600E) mutation and can be treated with BRAF inhibitors. DNA carrying this mutation can be released into circulation as cell-free BRAF(V600E) (cfBRAF(V600E)). Droplet digital PCR (ddPCR) is an analytically sensitive technique for quantifying small concentrations of DNA. We studied the plasma concentrations of cfBRAF(V600E) by ddPCR in patients with melanoma during therapy with BRAF inhibitors. Plasma concentrations of cfBRAF(V600E) were measured in 8 controls and 20 patients with advanced melanoma having the BRAF(V600E) mutation during treatment with BRAF inhibitors at baseline, first month, best response, and progression. The BRAF(V600E) mutation was detected by ddPCR even at a fractional abundance of 0.005% in the wild-type gene. Agreement between tumor tissue BRAF(V600E) and plasma cfBRAF(V600E) was 84.3%. Baseline cfBRAF(V600E) correlated with tumor burden (r = 0.742, P < 0.001). cfBRAF(V600E) concentrations decreased significantly at the first month of therapy (basal median, 216 copies/mL; Q1-Q3, 27-647 copies/mL; first response median, 0 copies/mL; Q1-Q3, 0-49 copies/mL; P < 0.01) and at the moment of best response (median, 0 copies/mL; Q1-Q3, 0-33 copies/mL; P < 0.01). At progression, there was a significant increase in the concentration of cfBRAF(V600E) compared with best response (median, 115 copies/mL; Q1-Q3, 3-707 copies/mL; P = 0.013). Lower concentrations of basal cfBRAF(V600E) were significantly associated with longer overall survival and progression-free survival (27.7 months and 9 months, respectively) than higher basal concentrations (8.6 months and 3 months, P < 0.001 and P = 0.024, respectively). cfBRAF(V600E) quantification in plasma by ddPCR is useful as a follow-up to treatment response in patients with advanced melanoma.

Research paper thumbnail of No transmission of hepatitis E virus in pigs fed diets containing commercial spray-dried porcine plasma: a retrospective study of samples from several swine trials

Virology journal, Jan 24, 2014

BackgroundHepatitis E virus (HEV) has been reported in the human population and pigs are a recogn... more BackgroundHepatitis E virus (HEV) has been reported in the human population and pigs are a recognized reservoir for HEV and a possible source of HEV transmission to humans. Spray-dried porcine plasma (SDPP) is an ingredient commonly used in feed for pigs around the world. Even though processing conditions used to produce SDPP should be adequate to inactivate HEV, it was of interest to analyze commercial SDPP samples for presence of genome and antibodies (AB) against HEV and to retrospectively analyze serum samples collected from pigs used in past experiments that had been fed diets containing either 0% or 8% SDPP to detect potential transmission of HEV as determined by seroconversion.ResultsEighty-five commercial SDPP samples were analyzed by ELISA and 100% of them contained AB against HEV, while 22.4% (11 of 49 samples analyzed) were positive for HEV RNA.Frozen sera samples (n¿=¿140) collected from 70 pigs used in past experiments that had been fed diets containing either 0% or 8% ...

Research paper thumbnail of Cognitive age as a criterion explaining senior tourists' motivations

International Journal of Culture, Tourism and Hospitality Research, 2009

Purpose – The purpose of this paper is to gain a broader knowledge of the concept of cognitive ag... more Purpose – The purpose of this paper is to gain a broader knowledge of the concept of cognitive age and its use as a variable when segmenting the market of people aged over 55. Design/methodology/approach – A proposal for measuring this variable was developed, the dimensions used being: actions, interests, feelings, health, thinking and expectations. A personal survey of 400

Research paper thumbnail of Glucose series complexity in hypertensive patients

Journal of the American Society of Hypertension, 2014

Nonlinear methods have been applied to the analysis of biological signals. Complexity analysis of... more Nonlinear methods have been applied to the analysis of biological signals. Complexity analysis of glucose time series may be a useful tool for the study of the initial phases of glucoregulatory dysfunction. This observational, cross-sectional study was performed in patients with essential hypertension. Glucose complexity was measured with detrended fluctuation analysis (DFA), and glucose variability was measured by the mean amplitudes of glycemic excursion (MAGE). We included 91 patients with a mean age of 59 AE 10 years. We found significant correlations for the number of metabolic syndrome (MS)-defining criteria with DFA (r ¼ 0.233, P ¼ .026) and MAGE (r ¼ 0.396, P < .0001). DFA differed significantly between patients who complied with MS and those who did not (1.44 vs. 1.39, P ¼ .018). The MAGE (f ¼ 5.3, P ¼ .006), diastolic blood pressures (f ¼ 4.1, P ¼ .018), and homeostasis model assessment indices (f ¼ 4.2, P ¼ .018) differed between the DFA tertiles. Multivariate analysis revealed that the only independent determinants of the DFA values were MAGE (b coefficient ¼ 0.002, 95% confidence interval: 0.001-0.004, P ¼ .001) and abdominal circumference (b coefficient ¼ 0.002, 95% confidence interval: 0.000015-0.004, P ¼ .048). In our population, DFA was associated with MS and a number of MS criteria. Complexity analysis seemed to be capable of detecting differences in variables that are arguably related to the risk of the development of type 2 diabetes. J Am Soc Hypertens 2014;-(-):1-7.

Research paper thumbnail of Efectos a corto plazo de la contaminación atmosférica sobre la motalidad. Resultados del proyecto EMECAM en la ciudad de Barcelona, 1991-95

Revista Española de Salud Pública, 1999

Research paper thumbnail of Magnetic resonances and electric fields in the TJ-II Heliac

Plasma Physics and Controlled Fusion, 2011

TJ-II is a medium-sized Heliac-type stellarator operating at low magnetic shear. Low-order ration... more TJ-II is a medium-sized Heliac-type stellarator operating at low magnetic shear. Low-order rational values of the rotational transform ι = 1/q (magnetic resonances, for brevity) can be introduced anywhere in its plasmas causing modifications in the electric potential and, consequently, radial structures in the radial electric fields that can be used to alter transport and stability in an externally controllable way. The ability of the Heliac to perform dynamic configuration scans has been used to illustrate these aspects and find practical realizations, such as exerting control on the L-H transition.

Research paper thumbnail of Genome-wide association study of prostate cancer identifies a second risk locus at 8q24

Nature Genetics, 2007

Prostate cancer is the most common malignancy in many industrialized countries and the second cau... more Prostate cancer is the most common malignancy in many industrialized countries and the second cause of cancerrelated death in Europe and the United States. The incidence of the disease has been increasing in Arab populations. Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied. Genetic susceptibility to prostate cancer differs significantly across ethnicities. It would be of interest to identify the common alleles associated with prostate cancer risk in Arab population.

Research paper thumbnail of Multiple loci identified in a genome-wide association study of prostate cancer

Nature Genetics, 2008

We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals... more We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P o 10 À10 ). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P o 7.31 Â 10 À13 and P o 2.14 Â 10 À6 ). Loci on chromosome 10 include MSMB, which encodes b-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P o 2.5 Â 10 À5 ), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.

Research paper thumbnail of Regulation of antioxidant enzymes: a significant role for melatonin

Journal of Pineal Research, 2004

Antioxidant enzymes form the first line of defense against free radicals in organisms. Their regu... more Antioxidant enzymes form the first line of defense against free radicals in organisms. Their regulation depends mainly on the oxidant status of the cell, given that oxidants are their principal modulators. However, other factors have been reported to increase antioxidant enzyme activity and/or gene expression. During the last decade, the antioxidant melatonin has been shown to possess genomic actions, regulating the expression of several genes. Melatonin also influences both antioxidant enzyme activity and cellular mRNA levels for these enzymes. In the present report, we review the studies which document the influence of melatonin on the activity and expression of the antioxidative enzymes glutathione peroxidase, superoxide dismutases and catalase both under physiological and under conditions of elevated oxidative stress. We also analyze the possible mechanisms by which melatonin regulates these enzymes.

Research paper thumbnail of Body Mass Index and Mortality in a Prospective Cohort of US Adults

Journal of Cardiopulmonary Rehabilitation, 2000

Body-mass index (the weight in kilograms divided by the square of the height in meters) is known ... more Body-mass index (the weight in kilograms divided by the square of the height in meters) is known to be associated with overall mortality. We investigated the effects of age, race, sex, smoking status, and history of disease on the relation between body-mass index and mortality. In a prospective study of more than 1 million adults in the United States (457,785 men and 588,369 women), 201,622 deaths occurred during 14 years of follow-up. We examined the relation between body-mass index and the risk of death from all causes in four subgroups categorized according to smoking status and history of disease. In healthy people who had never smoked, we further examined whether the relation varied according to race, cause of death, or age. The relative risk was used to assess the relation between mortality and body-mass index. The association between body-mass index and the risk of death was substantially modified by smoking status and the presence of disease. In healthy people who had never smoked, the nadir of the curve for body-mass index and mortality was found at a body-mass index of 23.5 to 24.9 in men and 22.0 to 23.4 in women. Among subjects with the highest body-mass indexes, white men and women had a relative risk of death of 2.58 and 2.00, respectively, as compared with those with a body-mass index of 23.5 to 24.9. Black men and women with the highest body-mass indexes had much lower risks of death (1.35 and 1.21), which did not differ significantly from 1.00. A high body-mass index was most predictive of death from cardiovascular disease, especially in men (relative risk, 2.90; 95 percent confidence interval, 2.37 to 3.56). Heavier men and women in all age groups had an increased risk of death. The risk of death from all causes, cardiovascular disease, cancer, or other diseases increases throughout the range of moderate and severe overweight for both men and women in all age groups. The risk associated with a high body-mass index is greater for whites than for blacks.

Research paper thumbnail of HIV-2 viral tropism influences CD4+ T cell count regardless of viral load

Journal of Antimicrobial Chemotherapy, 2014

HIV-2 infection is characterized by low plasma viraemia and slower progression to AIDS in compari... more HIV-2 infection is characterized by low plasma viraemia and slower progression to AIDS in comparison with HIV-1 infection. However, antiretroviral therapy in patients with HIV-2 is less effective and often fails to provide optimal CD4 recovery. We examined viral tropism in persons with HIV-2 infection enrolled in the HIV-2 Spanish cohort. Viral tropism was estimated based on V3 sequences obtained from plasma RNA and/or proviral DNA. From a total of 279 individuals with HIV-2 infection recorded in the Spanish national register, 58 V3 sequences belonging to 42 individuals were evaluated. X4 viruses were recognized in 14 patients (33%). Patients with X4 viruses had lower median CD4+ cell counts than patients with R5 viruses [130 (17-210) versus 359 (180-470) cells/mm(3); P = 0.007]. This was true even considering only the subset of 19 patients on antiretroviral therapy [94 (16-147) versus 184 (43-368) cells/mm(3); P = 0.041]. In multivariate analysis, significant differences in CD4+ cell counts between patients with X4 and R5 viruses remained after adjusting for age, gender, antiretroviral therapy and viral load. The presence of X4-tropic viruses in HIV-2 infection is associated with low CD4+ cell counts, regardless of antiretroviral treatment. Along with CD4+ cell counts, viral tropism testing may assist decisions about when to initiate antiretroviral therapy in HIV-2-infected individuals.

Research paper thumbnail of Estrogen Replacement Therapy and Ovarian Cancer Mortality in a Large Prospective Study of US Women

JAMA, 2001

Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2... more Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established. To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use. The American Cancer Society&#39;s Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996. A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT). A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use &lt;15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use &gt;/=15 years ago, 1.31; 95% CI, 0.79-2.17). In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.

Research paper thumbnail of Obesity-Related Plasma Hemodilution and PSA Concentration Among Men With Prostate Cancer

JAMA, 2007

Recent studies have suggested that obese men have lower serum prostatespecific antigen (PSA) conc... more Recent studies have suggested that obese men have lower serum prostatespecific antigen (PSA) concentrations than nonobese men. Because men with higher body mass index (BMI) have greater circulating plasma volumes, lower PSA concentrations among obese men may be due to hemodilution.

Research paper thumbnail of Alternative statistical methods for interpreting airborne Alder (Alnus glutimosa (L.) Gaertner) pollen concentrations

International Journal of Biometeorology, 2009

This paper reports on the behaviour of Alnus glutinosa (alder) pollen grains in the atmosphere of... more This paper reports on the behaviour of Alnus glutinosa (alder) pollen grains in the atmosphere of Ponferrada (León, NW Spain) from 1995 to 2006. The study, which sought to determine the effects of various weather-related parameters on Alnus pollen counts, was performed using a volumetric method. The main pollination period for this taxon is January-February. Alder pollen is one of the eight major airborne pollen allergens found in the study area. An analysis was made of the correlation between pollen counts and major weatherrelated parameters over each period. In general, the strongest positive correlation was with temperature, particularly maximum temperature. During each period, peak pollen counts occurred when the maximum temperature fell within the range 9°C-14°C. Finally, multivariate analysis showed that the parameter exerting the greatest influence was temperature, a finding confirmed by Spearman correlation tests. Principal components analysis suggested that periods with high pollen counts were characterised by high maximum temperature, low rainfall and an absolute humidity of around 6 g m −3 . Use of this type of analysis in conjunction with other methods is essential for obtaining an accurate record of pollen-count variations over a given period.

Research paper thumbnail of Jewish ethnicity and prostate cancer mortality in two large US cohorts

Objective: To investigate prospectively the relationship between Jewish ethnicity and prostate ca... more Objective: To investigate prospectively the relationship between Jewish ethnicity and prostate cancer mortality. Methods: Men were selected from white male participants in two large American Cancer Society cohorts: Cancer Prevention Studies I (CPS-I) (enrolled in 1959 and followed through 1972) and II (CPS-II) (enrolled in 1982 and followed through 1996). During the follow-up periods there were 1751 prostate cancer deaths

Research paper thumbnail of Acceptability and use of heme-iron concentrate product added to chocolate biscuit filling as an alternative source of a highly available form of iron

CyTA - Journal of Food, 2012

Research paper thumbnail of Body Mass Index, Weight Change, and Risk of Prostate Cancer in the Cancer Prevention Study II Nutrition Cohort

Cancer Epidemiology Biomarkers & Prevention, 2007

Background: Obesity has been associated with aggressive prostate cancer. The extent of this assoc... more Background: Obesity has been associated with aggressive prostate cancer. The extent of this association, which varies by stage and grade, remains unclear. The role of recent weight change had not been previously examined. Methods: We examined body mass index (BMI) and weight change in relation to incident prostate cancer by disease stage and grade at diagnosis among 69,991 men in the Cancer Prevention Study II Nutrition Cohort. Participants provided information on height and weight in 1982, and again at enrollment in 1992. During follow-up through June 30, 2003 (excluding the first 2 years of follow-up), we documented 5,252 incident prostate cancers. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (95% CI).

Research paper thumbnail of Absorption of orally supplied immunoglobulins in neonatal piglets

Livestock Science, 2010

Low birth weight piglets have a reduced viability because of a low colostrum immunoglobulin (Ig) ... more Low birth weight piglets have a reduced viability because of a low colostrum immunoglobulin (Ig) and energy intake. Additional supply of energy and Ig may improve their survival and immuno-competence. This study was conducted to determine the absorption of IgG from oral supplements containing IgG from porcine plasma and an additional energy substrate, as compared to IgG absorption from sow colostrum. Sixty newborn piglets (mean body weight (BW) 1183 g) from eight sows were removed from the dam prior to suckling and allocated to five treatments. Piglets received either 28 g of standardised sows colostrum per kg of BW (control) or one out of four products containing porcine IgG and fats, glycerine, dextrose or a combination of these as additional energy source. After 12 h of fasting in which only drinking water was supplied, plasma IgG content was determined and efficiency of IgG absorption calculated as total plasma IgG divided by ingested IgG. Treatment means of plasma IgG varied from 1.8 to 7.3 mg/mL (P b 0.001), being 6.8 mg/mL for control piglets. Relative efficiency of absorption varied from 0.05 to 0.28 (P b 0.001), being 0.20 for control piglets. These results indicate that the energy component of the supplements had a major influence on the IgG absorption. IgG absorption from products based on dextrose, medium chain and vegetable long chain triglycerides was similar or higher than IgG absorption from sow colostrum, thus allowing perspective for the development of supplements to improve viability of neonatal piglets.

Research paper thumbnail of Relevance of MIA and S100 serum tumor markers to monitor BRAF inhibitor therapy in metastatic melanoma patients

Clinica chimica acta; international journal of clinical chemistry, Jan 15, 2014

BRAF V600 mutation has been reported in more than 50% of melanoma cases and its presence predicts... more BRAF V600 mutation has been reported in more than 50% of melanoma cases and its presence predicts clinical activity of BRAF inhibitors (iBRAF). We evaluated the role of MIA, S100 and LDH to monitor iBRAF efficiency in advanced melanoma patients presenting BRAF V600 mutations. This was a prospective study of melanoma patients harboring the BRAF V600 mutation and treated with iBRAF within a clinical trial (dabrafenib) or as part of an expanded access program (vemurafenib). MIA, S100 and LDH were analyzed in serum at baseline, and every 4-6 weeks during treatment. Eighteen patients with melanoma stages IIIc-IV were enrolled with 88.8% of response rate to iBRAF. Baseline concentrations of all the tumor markers correlated with tumor burden. MIA and S100 concentrations decreased significantly one month after the beginning of treatment and, upon progression, their concentrations increased significantly above the minimum levels previously achieved. MIA levels lower than 9 μg/L one month aft...

Research paper thumbnail of Jewish ethnicity and prostate cancer mortality in two large US cohorts

Cancer causes & control : CCC, 2002

To investigate prospectively the relationship between Jewish ethnicity and prostate cancer mortal... more To investigate prospectively the relationship between Jewish ethnicity and prostate cancer mortality. Men were selected from white male participants in two large American Cancer Society cohorts: Cancer Prevention Studies I (CPS-I) (enrolled in 1959 and followed through 1972) and II (CPS-II) (enrolled in 1982 and followed through 1996). During the follow-up periods there were 1,751 prostate cancer deaths among 417,018 men in CPS-1 and 3594 deaths among 447,780 men in CPS-II. Cox proportional hazards modeling was used to compute rate ratios (RR) and to adjust for known and suspected risk factors for prostate cancer. Prostate cancer death rates were substantially lower among Jewish men than other white men in both cohorts (multivariate adjusted rate ratios (RR) = 0.54, 95% CI = 0.38-0.77 in CPS-I; RR = 0.72, 95% CI = 0.61-0.86 in CPS-II). Factors such as tobacco avoidance and measured dietary patterns did not account for this difference. Lower prostate cancer death rates were observed ...

Research paper thumbnail of Quantitative Cell-Free Circulating BRAFV600E Mutation Analysis by Use of Droplet Digital PCR in the Follow-up of Patients with Melanoma Being Treated with BRAF Inhibitors

Clinical Chemistry, 2014

Around 50% of cutaneous melanomas harbor the BRAF(V600E) mutation and can be treated with BRAF in... more Around 50% of cutaneous melanomas harbor the BRAF(V600E) mutation and can be treated with BRAF inhibitors. DNA carrying this mutation can be released into circulation as cell-free BRAF(V600E) (cfBRAF(V600E)). Droplet digital PCR (ddPCR) is an analytically sensitive technique for quantifying small concentrations of DNA. We studied the plasma concentrations of cfBRAF(V600E) by ddPCR in patients with melanoma during therapy with BRAF inhibitors. Plasma concentrations of cfBRAF(V600E) were measured in 8 controls and 20 patients with advanced melanoma having the BRAF(V600E) mutation during treatment with BRAF inhibitors at baseline, first month, best response, and progression. The BRAF(V600E) mutation was detected by ddPCR even at a fractional abundance of 0.005% in the wild-type gene. Agreement between tumor tissue BRAF(V600E) and plasma cfBRAF(V600E) was 84.3%. Baseline cfBRAF(V600E) correlated with tumor burden (r = 0.742, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). cfBRAF(V600E) concentrations decreased significantly at the first month of therapy (basal median, 216 copies/mL; Q1-Q3, 27-647 copies/mL; first response median, 0 copies/mL; Q1-Q3, 0-49 copies/mL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and at the moment of best response (median, 0 copies/mL; Q1-Q3, 0-33 copies/mL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). At progression, there was a significant increase in the concentration of cfBRAF(V600E) compared with best response (median, 115 copies/mL; Q1-Q3, 3-707 copies/mL; P = 0.013). Lower concentrations of basal cfBRAF(V600E) were significantly associated with longer overall survival and progression-free survival (27.7 months and 9 months, respectively) than higher basal concentrations (8.6 months and 3 months, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 and P = 0.024, respectively). cfBRAF(V600E) quantification in plasma by ddPCR is useful as a follow-up to treatment response in patients with advanced melanoma.

Research paper thumbnail of No transmission of hepatitis E virus in pigs fed diets containing commercial spray-dried porcine plasma: a retrospective study of samples from several swine trials

Virology journal, Jan 24, 2014

BackgroundHepatitis E virus (HEV) has been reported in the human population and pigs are a recogn... more BackgroundHepatitis E virus (HEV) has been reported in the human population and pigs are a recognized reservoir for HEV and a possible source of HEV transmission to humans. Spray-dried porcine plasma (SDPP) is an ingredient commonly used in feed for pigs around the world. Even though processing conditions used to produce SDPP should be adequate to inactivate HEV, it was of interest to analyze commercial SDPP samples for presence of genome and antibodies (AB) against HEV and to retrospectively analyze serum samples collected from pigs used in past experiments that had been fed diets containing either 0% or 8% SDPP to detect potential transmission of HEV as determined by seroconversion.ResultsEighty-five commercial SDPP samples were analyzed by ELISA and 100% of them contained AB against HEV, while 22.4% (11 of 49 samples analyzed) were positive for HEV RNA.Frozen sera samples (n¿=¿140) collected from 70 pigs used in past experiments that had been fed diets containing either 0% or 8% ...

Research paper thumbnail of Cognitive age as a criterion explaining senior tourists' motivations

International Journal of Culture, Tourism and Hospitality Research, 2009

Purpose – The purpose of this paper is to gain a broader knowledge of the concept of cognitive ag... more Purpose – The purpose of this paper is to gain a broader knowledge of the concept of cognitive age and its use as a variable when segmenting the market of people aged over 55. Design/methodology/approach – A proposal for measuring this variable was developed, the dimensions used being: actions, interests, feelings, health, thinking and expectations. A personal survey of 400

Research paper thumbnail of Glucose series complexity in hypertensive patients

Journal of the American Society of Hypertension, 2014

Nonlinear methods have been applied to the analysis of biological signals. Complexity analysis of... more Nonlinear methods have been applied to the analysis of biological signals. Complexity analysis of glucose time series may be a useful tool for the study of the initial phases of glucoregulatory dysfunction. This observational, cross-sectional study was performed in patients with essential hypertension. Glucose complexity was measured with detrended fluctuation analysis (DFA), and glucose variability was measured by the mean amplitudes of glycemic excursion (MAGE). We included 91 patients with a mean age of 59 AE 10 years. We found significant correlations for the number of metabolic syndrome (MS)-defining criteria with DFA (r ¼ 0.233, P ¼ .026) and MAGE (r ¼ 0.396, P < .0001). DFA differed significantly between patients who complied with MS and those who did not (1.44 vs. 1.39, P ¼ .018). The MAGE (f ¼ 5.3, P ¼ .006), diastolic blood pressures (f ¼ 4.1, P ¼ .018), and homeostasis model assessment indices (f ¼ 4.2, P ¼ .018) differed between the DFA tertiles. Multivariate analysis revealed that the only independent determinants of the DFA values were MAGE (b coefficient ¼ 0.002, 95% confidence interval: 0.001-0.004, P ¼ .001) and abdominal circumference (b coefficient ¼ 0.002, 95% confidence interval: 0.000015-0.004, P ¼ .048). In our population, DFA was associated with MS and a number of MS criteria. Complexity analysis seemed to be capable of detecting differences in variables that are arguably related to the risk of the development of type 2 diabetes. J Am Soc Hypertens 2014;-(-):1-7.

Research paper thumbnail of Efectos a corto plazo de la contaminación atmosférica sobre la motalidad. Resultados del proyecto EMECAM en la ciudad de Barcelona, 1991-95

Revista Española de Salud Pública, 1999

Research paper thumbnail of Magnetic resonances and electric fields in the TJ-II Heliac

Plasma Physics and Controlled Fusion, 2011

TJ-II is a medium-sized Heliac-type stellarator operating at low magnetic shear. Low-order ration... more TJ-II is a medium-sized Heliac-type stellarator operating at low magnetic shear. Low-order rational values of the rotational transform ι = 1/q (magnetic resonances, for brevity) can be introduced anywhere in its plasmas causing modifications in the electric potential and, consequently, radial structures in the radial electric fields that can be used to alter transport and stability in an externally controllable way. The ability of the Heliac to perform dynamic configuration scans has been used to illustrate these aspects and find practical realizations, such as exerting control on the L-H transition.

Research paper thumbnail of Genome-wide association study of prostate cancer identifies a second risk locus at 8q24

Nature Genetics, 2007

Prostate cancer is the most common malignancy in many industrialized countries and the second cau... more Prostate cancer is the most common malignancy in many industrialized countries and the second cause of cancerrelated death in Europe and the United States. The incidence of the disease has been increasing in Arab populations. Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied. Genetic susceptibility to prostate cancer differs significantly across ethnicities. It would be of interest to identify the common alleles associated with prostate cancer risk in Arab population.

Research paper thumbnail of Multiple loci identified in a genome-wide association study of prostate cancer

Nature Genetics, 2008

We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals... more We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P o 10 À10 ). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P o 7.31 Â 10 À13 and P o 2.14 Â 10 À6 ). Loci on chromosome 10 include MSMB, which encodes b-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P o 2.5 Â 10 À5 ), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.

Research paper thumbnail of Regulation of antioxidant enzymes: a significant role for melatonin

Journal of Pineal Research, 2004

Antioxidant enzymes form the first line of defense against free radicals in organisms. Their regu... more Antioxidant enzymes form the first line of defense against free radicals in organisms. Their regulation depends mainly on the oxidant status of the cell, given that oxidants are their principal modulators. However, other factors have been reported to increase antioxidant enzyme activity and/or gene expression. During the last decade, the antioxidant melatonin has been shown to possess genomic actions, regulating the expression of several genes. Melatonin also influences both antioxidant enzyme activity and cellular mRNA levels for these enzymes. In the present report, we review the studies which document the influence of melatonin on the activity and expression of the antioxidative enzymes glutathione peroxidase, superoxide dismutases and catalase both under physiological and under conditions of elevated oxidative stress. We also analyze the possible mechanisms by which melatonin regulates these enzymes.

Research paper thumbnail of Body Mass Index and Mortality in a Prospective Cohort of US Adults

Journal of Cardiopulmonary Rehabilitation, 2000

Body-mass index (the weight in kilograms divided by the square of the height in meters) is known ... more Body-mass index (the weight in kilograms divided by the square of the height in meters) is known to be associated with overall mortality. We investigated the effects of age, race, sex, smoking status, and history of disease on the relation between body-mass index and mortality. In a prospective study of more than 1 million adults in the United States (457,785 men and 588,369 women), 201,622 deaths occurred during 14 years of follow-up. We examined the relation between body-mass index and the risk of death from all causes in four subgroups categorized according to smoking status and history of disease. In healthy people who had never smoked, we further examined whether the relation varied according to race, cause of death, or age. The relative risk was used to assess the relation between mortality and body-mass index. The association between body-mass index and the risk of death was substantially modified by smoking status and the presence of disease. In healthy people who had never smoked, the nadir of the curve for body-mass index and mortality was found at a body-mass index of 23.5 to 24.9 in men and 22.0 to 23.4 in women. Among subjects with the highest body-mass indexes, white men and women had a relative risk of death of 2.58 and 2.00, respectively, as compared with those with a body-mass index of 23.5 to 24.9. Black men and women with the highest body-mass indexes had much lower risks of death (1.35 and 1.21), which did not differ significantly from 1.00. A high body-mass index was most predictive of death from cardiovascular disease, especially in men (relative risk, 2.90; 95 percent confidence interval, 2.37 to 3.56). Heavier men and women in all age groups had an increased risk of death. The risk of death from all causes, cardiovascular disease, cancer, or other diseases increases throughout the range of moderate and severe overweight for both men and women in all age groups. The risk associated with a high body-mass index is greater for whites than for blacks.

Research paper thumbnail of HIV-2 viral tropism influences CD4+ T cell count regardless of viral load

Journal of Antimicrobial Chemotherapy, 2014

HIV-2 infection is characterized by low plasma viraemia and slower progression to AIDS in compari... more HIV-2 infection is characterized by low plasma viraemia and slower progression to AIDS in comparison with HIV-1 infection. However, antiretroviral therapy in patients with HIV-2 is less effective and often fails to provide optimal CD4 recovery. We examined viral tropism in persons with HIV-2 infection enrolled in the HIV-2 Spanish cohort. Viral tropism was estimated based on V3 sequences obtained from plasma RNA and/or proviral DNA. From a total of 279 individuals with HIV-2 infection recorded in the Spanish national register, 58 V3 sequences belonging to 42 individuals were evaluated. X4 viruses were recognized in 14 patients (33%). Patients with X4 viruses had lower median CD4+ cell counts than patients with R5 viruses [130 (17-210) versus 359 (180-470) cells/mm(3); P = 0.007]. This was true even considering only the subset of 19 patients on antiretroviral therapy [94 (16-147) versus 184 (43-368) cells/mm(3); P = 0.041]. In multivariate analysis, significant differences in CD4+ cell counts between patients with X4 and R5 viruses remained after adjusting for age, gender, antiretroviral therapy and viral load. The presence of X4-tropic viruses in HIV-2 infection is associated with low CD4+ cell counts, regardless of antiretroviral treatment. Along with CD4+ cell counts, viral tropism testing may assist decisions about when to initiate antiretroviral therapy in HIV-2-infected individuals.

Research paper thumbnail of Estrogen Replacement Therapy and Ovarian Cancer Mortality in a Large Prospective Study of US Women

JAMA, 2001

Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2... more Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established. To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use. The American Cancer Society&#39;s Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996. A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT). A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use &lt;15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use &gt;/=15 years ago, 1.31; 95% CI, 0.79-2.17). In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.

Research paper thumbnail of Obesity-Related Plasma Hemodilution and PSA Concentration Among Men With Prostate Cancer

JAMA, 2007

Recent studies have suggested that obese men have lower serum prostatespecific antigen (PSA) conc... more Recent studies have suggested that obese men have lower serum prostatespecific antigen (PSA) concentrations than nonobese men. Because men with higher body mass index (BMI) have greater circulating plasma volumes, lower PSA concentrations among obese men may be due to hemodilution.

Research paper thumbnail of Alternative statistical methods for interpreting airborne Alder (Alnus glutimosa (L.) Gaertner) pollen concentrations

International Journal of Biometeorology, 2009

This paper reports on the behaviour of Alnus glutinosa (alder) pollen grains in the atmosphere of... more This paper reports on the behaviour of Alnus glutinosa (alder) pollen grains in the atmosphere of Ponferrada (León, NW Spain) from 1995 to 2006. The study, which sought to determine the effects of various weather-related parameters on Alnus pollen counts, was performed using a volumetric method. The main pollination period for this taxon is January-February. Alder pollen is one of the eight major airborne pollen allergens found in the study area. An analysis was made of the correlation between pollen counts and major weatherrelated parameters over each period. In general, the strongest positive correlation was with temperature, particularly maximum temperature. During each period, peak pollen counts occurred when the maximum temperature fell within the range 9°C-14°C. Finally, multivariate analysis showed that the parameter exerting the greatest influence was temperature, a finding confirmed by Spearman correlation tests. Principal components analysis suggested that periods with high pollen counts were characterised by high maximum temperature, low rainfall and an absolute humidity of around 6 g m −3 . Use of this type of analysis in conjunction with other methods is essential for obtaining an accurate record of pollen-count variations over a given period.

Research paper thumbnail of Jewish ethnicity and prostate cancer mortality in two large US cohorts

Objective: To investigate prospectively the relationship between Jewish ethnicity and prostate ca... more Objective: To investigate prospectively the relationship between Jewish ethnicity and prostate cancer mortality. Methods: Men were selected from white male participants in two large American Cancer Society cohorts: Cancer Prevention Studies I (CPS-I) (enrolled in 1959 and followed through 1972) and II (CPS-II) (enrolled in 1982 and followed through 1996). During the follow-up periods there were 1751 prostate cancer deaths

Research paper thumbnail of Acceptability and use of heme-iron concentrate product added to chocolate biscuit filling as an alternative source of a highly available form of iron

CyTA - Journal of Food, 2012

Research paper thumbnail of Body Mass Index, Weight Change, and Risk of Prostate Cancer in the Cancer Prevention Study II Nutrition Cohort

Cancer Epidemiology Biomarkers & Prevention, 2007

Background: Obesity has been associated with aggressive prostate cancer. The extent of this assoc... more Background: Obesity has been associated with aggressive prostate cancer. The extent of this association, which varies by stage and grade, remains unclear. The role of recent weight change had not been previously examined. Methods: We examined body mass index (BMI) and weight change in relation to incident prostate cancer by disease stage and grade at diagnosis among 69,991 men in the Cancer Prevention Study II Nutrition Cohort. Participants provided information on height and weight in 1982, and again at enrollment in 1992. During follow-up through June 30, 2003 (excluding the first 2 years of follow-up), we documented 5,252 incident prostate cancers. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (95% CI).