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Sample records for normal mendelian ratio

  1. Hilar height ratio in normal Korea

    International Nuclear Information System (INIS)

    Yoo, Kyung Ho; Lee, Nam Joon; Seol, Hae Young; Chung, Kyoo Byung

    1979-01-01

    Hilar displacement is one of the significant sign of pulmonary volume change. The hilar height ratio (HHR) is a value that express the normal position of hilum in its hemithorax, and it is calculated by dividing the distance from the hilum to the lung apex by the distance from the hilum to the diaphragm. Displacement of one hilum is usually easy to detect but both are displaced in the same direction especially, recognition is more difficult. Knowledge of normal HHR allows evaluation of hilar positional change even when the relative hilar position are not altered. Normal chest PA views of 275 cases taken at Korea University Hospital during the period of April 1978 to Jun 1979 were analyzed. The right hilum is positioned in lower half of the right hemithorax, while the left hilum is situated in the upper half of left hemithorax. The difference of hilar ratio according to age group is slight, but there is significant difference between right-HHR and left-HHR. The value of right-HHR is 1.28 ± 0.14, the value of left-HHR is 0.88 ± 0.09.

  2. Colloid normalizes resuscitation ratio in pediatric burns.

    Science.gov (United States)

    Faraklas, Iris; Lam, Uyen; Cochran, Amalia; Stoddard, Gregory; Saffle, Jeffrey

    2011-01-01

    Fluid resuscitation of burned children is challenging because of their small size and intolerance to over- or underresuscitation. Our American Burn Association-verified regional burn center has used colloid "rescue" as part of our pediatric resuscitation protocol. With Institutional Review Board approval, the authors reviewed children with ≥15% TBSA burns admitted from January 1, 2004, to May 1, 2009. Resuscitation was based on the Parkland formula, which was adjusted to maintain urine output. Patients requiring progressive increases in crystalloid were placed on a colloid protocol. Results were expressed as an hourly resuscitation ratio (I/O ratio) of fluid infusion (ml/kg/%TBSA/hr) to urine output (ml/kg/hr). We reviewed 53 patients; 29 completed resuscitation using crystalloid alone (lactated Ringer's solution [LR]), and 24 received colloid supplementation albumin (ALB). Groups were comparable in age, gender, weight, and time from injury to admission. ALB patients had more inhalation injuries and larger total and full-thickness burns. LR patients maintained a median I/O of 0.17 (range, 0.08-0.31), whereas ALB patients demonstrated escalating ratios until the institution of albumin produced a precipitous return of I/O comparable with that of the LR group. Hospital stay was lower for LR patients than ALB patients (0.59 vs 1.06 days/%TBSA, P = .033). Twelve patients required extremity or torso escharotomy, but this did not differ between groups. There were no decompressive laparotomies. The median resuscitation volume for ALB group was greater than LR group (9.7 vs 6.2 ml/kg/%TBSA, P = .004). Measuring hourly I/O is a helpful means of evaluating fluid demands during burn shock resuscitation. The addition of colloid restores normal I/O in pediatric patients.

  3. Explorations in Statistics: The Analysis of Ratios and Normalized Data

    Science.gov (United States)

    Curran-Everett, Douglas

    2013-01-01

    Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This ninth installment of "Explorations in Statistics" explores the analysis of ratios and normalized--or standardized--data. As researchers, we compute a ratio--a numerator divided by a denominator--to compute a…

  4. Explorations in statistics: the analysis of ratios and normalized data.

    Science.gov (United States)

    Curran-Everett, Douglas

    2013-09-01

    Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This ninth installment of Explorations in Statistics explores the analysis of ratios and normalized-or standardized-data. As researchers, we compute a ratio-a numerator divided by a denominator-to compute a proportion for some biological response or to derive some standardized variable. In each situation, we want to control for differences in the denominator when the thing we really care about is the numerator. But there is peril lurking in a ratio: only if the relationship between numerator and denominator is a straight line through the origin will the ratio be meaningful. If not, the ratio will misrepresent the true relationship between numerator and denominator. In contrast, regression techniques-these include analysis of covariance-are versatile: they can accommodate an analysis of the relationship between numerator and denominator when a ratio is useless.

  5. The frontal ventriculocerebral ratio no normal computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jeong Yeon; Kim, Yeon Jung; Hah, Hae Koo [College of Medicine, Han Yang University, Seoul (Korea, Republic of)

    1980-12-15

    From the Hanyng University hospital's computer memory bank containing the CT scans of over 3000 patients, 400 normal patients between age of 1 to 69 years were selected at random. These scans were performed as a screening test in patient with minimal, vague neurologic manifestations such as headache, dizziness, convulsion and depression or suffering the traffic accident. Determination of ventridulocerebral ratio between the width of brain and dimension representing the distance between the outer border of the lateral ventricle was made at the two sites, using the image 4 or 5 at the demonstrating the level of Monro's formen.

  6. Magnetization transfer ratio relates to cognitive impairment in normal elderly

    Directory of Open Access Journals (Sweden)

    Stephan eSeiler

    2014-09-01

    Full Text Available Magnetization transfer imaging (MTI can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR in gray and white matter and cognitive functioning in 355 participants of the Austrian Stroke Prevention Family Study (ASPS-Fam aged 38 to 86 years. MTR maps were generated for the neocortex, deep gray matter structures, white matter hyperintensities, and normal appearing white matter. Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and normal appearing white matter correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions and cortex volume.Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia.

  7. Iso-effect tables and therapeutic ratios for epidermoid cancer and normal tissue stroma

    International Nuclear Information System (INIS)

    Cohen, L.; Creditor, M.

    1983-01-01

    Available literature on radiation injury to normal tissue stroma and ablation of epidermoid carcinoma was surveyed. Computer programs (RAD3 and RAD1) were then used to derive cell kinetic parameters and generate iso-effect tables for the relevant tissues. The two tables provide a set of limiting doses for tolerance of normal connective tissue (16% risk of injury) and for ablation of epidermoid cancer (16% risk of recurrence) covering a wide range of treatment schedules. Calculating the ratios of normal tissue tolerance to tumor control doses for each treatment scheme provides an array of therapeutic ratios, from which appropriate treatment schemes can be selected

  8. Ratio of organs to blood of mercury during its uptake by normal and acatalasemic mice

    International Nuclear Information System (INIS)

    Ogata, M.; Aikoh, H.

    1987-01-01

    The brain/blood, liver/blood, and heart/blood ratios of acatalasemic mice after intraperitoneal injection of labelled metallic mercury or after exposure to labelled metallic mercury vapor were significantly higher than those of normal mice. These ratios of normal or acatalasemic mice after injection with metallic mercury or exposure to metallic mercury vapor were significantly higher than those of normal and acatalasemic mice injected with mercuric ion. The amount of metallic mercury exhaled from acatalasemic mice injected with metallic mercury was greater than that from normal mice, indicating that the level of metallic mercury in blood of the former was higher than that of the latter. Actually, metallic mercury in the blood of acatalasemic mice injected with metallic mercury is higher than that in the blood of normal mice, suggesting that metallic mercury is easily transferred from blood to brain, liver, kidney, and heart

  9. Normal frontal lobe gray matter-white matter CT volume ratio in children

    International Nuclear Information System (INIS)

    Thompson, J.R.; Engelhart, J.; Hasso, A.N.; Hinshaw, D.B. Jr.

    1985-01-01

    We attempted to establish a computed tomographic value representing the normal volume ratio of gray matter to white matter (G/W) in children in order to have a baseline for studying various developmental disorders such as white matter hypoplasia. The records of 150 children 16 years of age or younger who had normal cranial computed tomography were reviewed. From these a group of 119 were excluded for various reasons. The remaining 3 were presumed to have normal brains. Using the region of interest function for tracing gray and white matter boundaries, superior and ventral to the foramen of Munro area, measurements were determined for consecutive adjacent frontal slices. Volumes were then calculated for both gray and white matter. A volume ratio of 2.010 (sigma=0.349), G/W, was then derived from each of 31 children. The clinical value of this ratio will be determined by future investigation. (orig.)

  10. Raised international normalized ratio: an early warning for a late cardiac tamponade?

    NARCIS (Netherlands)

    Shah, Ammad; van den Brink, Albert; de Mol, Bas

    2006-01-01

    Seven consecutive cases of late cardiac tamponade after valvular surgery are reported; all were postoperatively treated with acenocoumarol and 6 had an international normalized ratio peak greater than 6.0 within 3 days preceding tamponade. It is suggested that during this excessive anticoagulation

  11. Tolerance limits and tolerance intervals for ratios of normal random variables using a bootstrap calibration.

    Science.gov (United States)

    Flouri, Marilena; Zhai, Shuyan; Mathew, Thomas; Bebu, Ionut

    2017-05-01

    This paper addresses the problem of deriving one-sided tolerance limits and two-sided tolerance intervals for a ratio of two random variables that follow a bivariate normal distribution, or a lognormal/normal distribution. The methodology that is developed uses nonparametric tolerance limits based on a parametric bootstrap sample, coupled with a bootstrap calibration in order to improve accuracy. The methodology is also adopted for computing confidence limits for the median of the ratio random variable. Numerical results are reported to demonstrate the accuracy of the proposed approach. The methodology is illustrated using examples where ratio random variables are of interest: an example on the radioactivity count in reverse transcriptase assays and an example from the area of cost-effectiveness analysis in health economics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Women as Mendelians and Geneticists

    Science.gov (United States)

    Richmond, Marsha L.

    2015-01-01

    After the rediscovery of Mendel's laws of heredity in 1900, the biologists who began studying heredity, variation, and evolution using the new Mendelian methodology—performing controlled hybrid crosses and statistically analyzing progeny to note the factorial basis of characters—made great progress. By 1910, the validity of Mendelism was widely recognized and the field William Bateson christened `genetics' was complemented by the chromosome theory of heredity of T. H. Morgan and his group in the United States. Historians, however, have largely overlooked an important factor in the early establishment of Mendelism and genetics: the large number of women who contributed to the various research groups. This article examines the social, economic, and disciplinary context behind this new wave of women's participation in science and describes the work of women Mendelians and geneticists employed at three leading experimental research institutes, 1900-1940. It argues that the key to more women working in science was the access to higher education and the receptivity of emerging interdisciplinary fields such as genetics to utilize the expertise of women workers, which not only advanced the discipline but also provided new opportunities for women's employment in science.

  13. Estimates and Standard Errors for Ratios of Normalizing Constants from Multiple Markov Chains via Regeneration.

    Science.gov (United States)

    Doss, Hani; Tan, Aixin

    2014-09-01

    In the classical biased sampling problem, we have k densities π 1 (·), …, π k (·), each known up to a normalizing constant, i.e. for l = 1, …, k , π l (·) = ν l (·)/ m l , where ν l (·) is a known function and m l is an unknown constant. For each l , we have an iid sample from π l , · and the problem is to estimate the ratios m l /m s for all l and all s . This problem arises frequently in several situations in both frequentist and Bayesian inference. An estimate of the ratios was developed and studied by Vardi and his co-workers over two decades ago, and there has been much subsequent work on this problem from many different perspectives. In spite of this, there are no rigorous results in the literature on how to estimate the standard error of the estimate. We present a class of estimates of the ratios of normalizing constants that are appropriate for the case where the samples from the π l 's are not necessarily iid sequences, but are Markov chains. We also develop an approach based on regenerative simulation for obtaining standard errors for the estimates of ratios of normalizing constants. These standard error estimates are valid for both the iid case and the Markov chain case.

  14. Normal values of urine total protein- and albumin-to-creatinine ratios in term newborns.

    Science.gov (United States)

    El Hamel, Chahrazed; Chianea, Thierry; Thon, Séverine; Lepichoux, Anne; Yardin, Catherine; Guigonis, Vincent

    2017-01-01

    It is important to have an accurate assessment of urinary protein when glomerulopathy or kidney injury is suspected. Currently available normal values for the neonate population have limited value, in part because they are based on small populations and obsolete creatinine assays. We have performed a prospective study with the aim to update the normal upper values of the urinary total protein-to-creatinine and albumin-to-creatinine ratios in term newborns. Urine samples were collected from 277 healthy, full-term newborns within the first 48 hours (D0-1) and between 72 and 120 h of life (D3-4). Total protein, albumin, creatinine and osmolality were measured and the upper limit of normal (upper-limit) values determined. At D0-1 and D3-4, the upper-limit values for the total protein-to-creatinine ratio were 1431 and 1205 mg/g (162 and 136 g/mol) and those for the albumin-to-creatinine ratio were 746 and 301 mg/g (84 and 34 g/mol), respectively. The upper-limit values were significantly higher at D0-1 than at D3-4 only for the albumin-to-creatinine ratio. This study determined the upper limit of normal values for urinary total protein-to-creatinine and albumin-to-creatinine ratios in the largest population of newborns studied to date. These values can therefore be considered as the most clinically relevant data currently available for the detection and diagnosis of glomerular injury in daily clinical practice in this population.

  15. Bladder cancer mapping in Libya based on standardized morbidity ratio and log-normal model

    Science.gov (United States)

    Alhdiri, Maryam Ahmed; Samat, Nor Azah; Mohamed, Zulkifley

    2017-05-01

    Disease mapping contains a set of statistical techniques that detail maps of rates based on estimated mortality, morbidity, and prevalence. A traditional approach to measure the relative risk of the disease is called Standardized Morbidity Ratio (SMR). It is the ratio of an observed and expected number of accounts in an area, which has the greatest uncertainty if the disease is rare or if geographical area is small. Therefore, Bayesian models or statistical smoothing based on Log-normal model are introduced which might solve SMR problem. This study estimates the relative risk for bladder cancer incidence in Libya from 2006 to 2007 based on the SMR and log-normal model, which were fitted to data using WinBUGS software. This study starts with a brief review of these models, starting with the SMR method and followed by the log-normal model, which is then applied to bladder cancer incidence in Libya. All results are compared using maps and tables. The study concludes that the log-normal model gives better relative risk estimates compared to the classical method. The log-normal model has can overcome the SMR problem when there is no observed bladder cancer in an area.

  16. Abnormal X : autosome ratio, but normal X chromosome inactivation in human triploid cultures

    Directory of Open Access Journals (Sweden)

    Norwood Thomas H

    2006-07-01

    Full Text Available Abstract Background X chromosome inactivation (XCI is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi in normal female cells, leaving them with a single active X (Xa as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1 that normal development requires a ratio of one Xa per diploid autosomal set, and 2 that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default. Results Triploids provide a test of these ideas because the ratio of one Xa per diploid autosomal set cannot be achieved, yet this abnormal ratio should not necessarily affect the one-Xa choice mechanism for XCI. Previous studies of XCI patterns in murine triploids support the single-Xa model, but human triploids mostly have two-Xa cells, whether they are XXX or XXY. The XCI patterns we observe in fibroblast cultures from different XXX human triploids suggest that the two-Xa pattern of XCI is selected for, and may have resulted from rare segregation errors or Xi reactivation. Conclusion The initial X inactivation pattern in human triploids, therefore, is likely to resemble the pattern that predominates in murine triploids, i.e., a single Xa, with the remaining X's inactive. Furthermore, our studies of XIST RNA accumulation and promoter methylation suggest that the basic features of XCI are normal in triploids despite the abnormal X:autosome ratio.

  17. Signal-to-background-ratio preferences of normal-hearing listeners as a function of music

    Science.gov (United States)

    Barrett, Jillian G.

    2005-04-01

    The primary purpose of speech is to convey a message. Many factors affect the listener's overall reception, several of which have little to do with the linguistic content itself, but rather with the delivery (e.g., prosody, intonation patterns, pragmatics, paralinguistic cues). Music, however, may convey a message either with or without linguistic content. In instances in which music has lyrics, one cannot assume verbal content will take precedence over sonic properties. Lyric emphasis over other aspects of music cannot be assumed. Singing introduces distortion of the vowel-consonant temporal ratio of speech, emphasizing vowels and de-emphasizing consonants. The phonemic production alterations of singing make it difficult for even those with normal hearing to understand the singer. This investigation was designed to identify singer-to-background-ratio (SBR) prefer- ences for normal hearing adult listeners (as opposed to SBR levels maxi-mizing speech discrimination ability). Stimuli were derived from three different original songs, each produced in two different genres and sung by six different singers. Singer and genre were the two primary contributors to significant differences in SBR preferences, though results clearly indicate genre, style and singer interact in different combinations for each song, each singer, and for each subject in an unpredictable manner.

  18. Shear Stress-Normal Stress (Pressure) Ratio Decides Forming Callus in Patients with Diabetic Neuropathy

    Science.gov (United States)

    Noguchi, Hiroshi; Takehara, Kimie; Ohashi, Yumiko; Suzuki, Ryo; Yamauchi, Toshimasa; Kadowaki, Takashi; Sanada, Hiromi

    2016-01-01

    Aim. Callus is a risk factor, leading to severe diabetic foot ulcer; thus, prevention of callus formation is important. However, normal stress (pressure) and shear stress associated with callus have not been clarified. Additionally, as new valuables, a shear stress-normal stress (pressure) ratio (SPR) was examined. The purpose was to clarify the external force associated with callus formation in patients with diabetic neuropathy. Methods. The external force of the 1st, 2nd, and 5th metatarsal head (MTH) as callus predilection regions was measured. The SPR was calculated by dividing shear stress by normal stress (pressure), concretely, peak values (SPR-p) and time integral values (SPR-i). The optimal cut-off point was determined. Results. Callus formation region of the 1st and 2nd MTH had high SPR-i rather than noncallus formation region. The cut-off value of the 1st MTH was 0.60 and the 2nd MTH was 0.50. For the 5th MTH, variables pertaining to the external forces could not be determined to be indicators of callus formation because of low accuracy. Conclusions. The callus formation cut-off values of the 1st and 2nd MTH were clarified. In the future, it will be necessary to confirm the effect of using appropriate footwear and gait training on lowering SPR-i. PMID:28050567

  19. Shear Stress-Normal Stress (Pressure Ratio Decides Forming Callus in Patients with Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Ayumi Amemiya

    2016-01-01

    Full Text Available Aim. Callus is a risk factor, leading to severe diabetic foot ulcer; thus, prevention of callus formation is important. However, normal stress (pressure and shear stress associated with callus have not been clarified. Additionally, as new valuables, a shear stress-normal stress (pressure ratio (SPR was examined. The purpose was to clarify the external force associated with callus formation in patients with diabetic neuropathy. Methods. The external force of the 1st, 2nd, and 5th metatarsal head (MTH as callus predilection regions was measured. The SPR was calculated by dividing shear stress by normal stress (pressure, concretely, peak values (SPR-p and time integral values (SPR-i. The optimal cut-off point was determined. Results. Callus formation region of the 1st and 2nd MTH had high SPR-i rather than noncallus formation region. The cut-off value of the 1st MTH was 0.60 and the 2nd MTH was 0.50. For the 5th MTH, variables pertaining to the external forces could not be determined to be indicators of callus formation because of low accuracy. Conclusions. The callus formation cut-off values of the 1st and 2nd MTH were clarified. In the future, it will be necessary to confirm the effect of using appropriate footwear and gait training on lowering SPR-i.

  20. Classification between normal and tumor tissues based on the pair-wise gene expression ratio

    International Nuclear Information System (INIS)

    Yap, YeeLeng; Zhang, XueWu; Ling, MT; Wang, XiangHong; Wong, YC; Danchin, Antoine

    2004-01-01

    Precise classification of cancer types is critically important for early cancer diagnosis and treatment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. However, reliable cancer-related signals are generally lacking. Using recent datasets on colon and prostate cancer, a data transformation procedure from single gene expression to pair-wise gene expression ratio is proposed. Making use of the internal consistency of each expression profiling dataset this transformation improves the signal to noise ratio of the dataset and uncovers new relevant cancer-related signals (features). The efficiency in using the transformed dataset to perform normal/tumor classification was investigated using feature partitioning with informative features (gene annotation) as discriminating axes (single gene expression or pair-wise gene expression ratio). Classification results were compared to the original datasets for up to 10-feature model classifiers. 82 and 262 genes that have high correlation to tissue phenotype were selected from the colon and prostate datasets respectively. Remarkably, data transformation of the highly noisy expression data successfully led to lower the coefficient of variation (CV) for the within-class samples as well as improved the correlation with tissue phenotypes. The transformed dataset exhibited lower CV when compared to that of single gene expression. In the colon cancer set, the minimum CV decreased from 45.3% to 16.5%. In prostate cancer, comparable CV was achieved with and without transformation. This improvement in CV, coupled with the improved correlation between the pair-wise gene expression ratio and tissue phenotypes, yielded higher classification efficiency, especially with the colon dataset – from 87.1% to 93.5%. Over 90% of the top ten discriminating axes in both datasets showed significant improvement after data transformation. The high classification efficiency achieved suggested

  1. Magnetization transfer on T2-weighted image : magnetization Transfer ratios in normal brain and cerebral lesions

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Myung Kwan; Roh, Hong Gee; Suh, Chang Hae; Cho, Young Kook; Kim, Hyung Jin; Kim, Jin Hee; Kim, Sung Tae; Choi, Sung Kyu [Inha Univ. College of Medicine, Incheon (Korea, Republic of)

    1998-07-01

    To evaluate the magnetization transfer ratio(MTR) of various normal structures and pathologic lesions, as seen on magnetization transfer T2-weighted images (MT+T2WI). Materials and Methods : In ten normal volunteers, T2-weighted images without MT (MT-T2WI) and with MT(MT+T2WI) were obtained. Off-set pulses used in MT+T2WI were 400, 600, 1000, 1500, and 2000Hz. In 60 clinical cases infarction(n=10), brain tumors(n=5), traumatic hematomas(n=5), other hematomas(n=3) vascular malformation(n=2) white matter disease(n=2) normal(n=31) and others(n=2), both MT-T2WI and MT+T2WI images were obtained using an off-set pulse of 600 Hz. In all volunteers and patients, MTR in various normal brain parenchyma and abnormal areas was measured. Results : The MTRs of white and gray matter were 48% and 45% respectively at 400 Hz, 26% and 22% at 600Hz, 12% and 11% of 1000Hz, 10% and 9% 1500HZ, and 9% and 8% at 2000Hz of RF. The MTR of CSF was 43% at 400 Hz of off-resonance RF, while the contrast resolution of T2WI was poor. An off-resonance of 600Hz appeared to be the optimal frequency. In diseased areas,MTRs varied but were usually similar to or lower than those of brain parenchyma. Conclusion : The optimal off-resonance RF on MT+T2WI appears to be 600 Hz for relatively high MTR of brain parenchyma and low MTR of CSF,in which MTRs of white and gray matter were 26% and 22%, respectively, of 600Hz off-set pulse. The MTRs of cerebral lesions varied and further studies of various cerebral lesions are needed.

  2. Sharp tooth induced sublingual hematoma in a patient with elevated international normalized ratio

    Directory of Open Access Journals (Sweden)

    John Baliah

    2015-01-01

    Full Text Available Sublingual hematoma secondary to anticoagulation is a rare fatal condition. Hemorrhagic complications of warfarin are well-known. This particular case is unique because the patient was on warfarin for the past 2 years but did not develop the sublingual hematoma. However, a trauma by an attrited sharp cusp triggered the episode of the sublingual hematoma in this patient. Being a medical emergency, patient was promptly hospitalized in cardiac care unit and managed by medical team. The patient was transfused with 2 units of fresh frozen plasma and warfarin was temporarily stopped for 4 days. Alternate day regimen of warfarin was started after 4 days, and international normalized ratio dropped to 3. In dental management, enameloplasty of the mandibular first molar tooth was done to prevent trauma and ulcer development in the floor of the mouth. The hematoma resolved, and no new hematoma formation was observed for a period of 6 months.

  3. Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated Patients With Supratherapeutic International Normalized Ratios?

    Science.gov (United States)

    Shim, Choong Nam; Chung, Hyun Soo; Park, Jun Chul; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan; Kim, Ha Yan; Kim, Dong Wook; Lee, Hyuk

    2016-01-01

    The management of upper gastrointestinal bleeding (UGIB) in anticoagulated patients with supratherapeutic international normalized ratios (INRs) presents a challenge. The purpose of the study was to evaluate the safety of endoscopic therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated patients who underwent endoscopic treatment for UGIB were enrolled in the study. Patients were divided into 2 groups based on the occurrence of rebleeding within 30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from gastric cancer and bleeding at the duodenum were significantly related to rebleeding in a univariate analysis. Multivariate analysis determined that presenting symptoms other than melena (hematemesis, hematochezia, or others) (odds ratio, 3.93; 95% confidence interval, 1.44-10.76) and bleeding from gastric cancer (odds ratio, 6.10; 95% confidence interval, 1.27-29.25) were significant factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic therapy was not significantly associated with rebleeding in either univariate or multivariate analysis. Significant differences in bleeding-related mortality, additional intervention to control bleeding, length of hospital stay, and transfusion requirements were revealed between the rebleeding and no-rebleeding groups. There were no significant differences in therapeutic outcomes between patients with INR within the therapeutic range and those with supratherapeutic INR. Supratherapeutic INR at the time of endoscopic therapy did not change rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy for UGIB in anticoagulated patients, irrespective of INR at the time of endoscopic therapy.

  4. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction

    DEFF Research Database (Denmark)

    Breum, Leif; Rasmussen, Michael H; Hilsted, Jannik

    2003-01-01

    BACKGROUND: Plasma tryptophan concentrations and the ratio of tryptophan to other large neutral amino acids (plasma tryptophan ratio) are reportedly low in obese subjects. The plasma tryptophan ratio predicts brain tryptophan uptake and serotonin production. If this ratio is low in obese subjects......, serotonin function may also be low. Plasma tryptophan concentrations and ratios have been measured only at single time points in obese subjects; it is not known whether low values for these 2 variables persist throughout a 24-h period. OBJECTIVE: Our objective was to determine whether plasma tryptophan...... concentrations and ratios in obese subjects are lower than those in normal-weight subjects throughout a 24-h period and whether they increase when body weight is reduced. DESIGN: Plasma tryptophan concentrations and ratios were examined in obese subjects before and after weight loss and in nonobese control...

  5. International normalized ratio self-testing and self-management: improving patient outcomes

    Directory of Open Access Journals (Sweden)

    Pozzi M

    2016-10-01

    Full Text Available Matteo Pozzi,1 Julia Mitchell,2 Anna Maria Henaine,3 Najib Hanna,4 Ola Safi,4 Roland Henaine2 1Department of Adult Cardiac Surgery, “Louis Pradel” Cardiologic Hospital, Lyon, France; 2Department of Congenital Cardiac Surgery, “Louis Pradel” Cardiologic Hospital, Lyon, France; 3Clinical Pharmacology Unit, Lebanese University, Beirut, Lebanon; 4Pediatric Unit, “Hotel Dieu de France” Hospital, Saint Joseph University, Beirut, Lebanon Abstract: Long term oral anti-coagulation with vitamin K antagonists is a risk factor of hemorrhagic or thromebomlic complications. Periodic laboratory testing of international normalized ratio (INR and a subsequent dose adjustment are therefore mandatory. The use of home testing devices to measure INR has been suggested as a potential way to improve the comfort and compliance of the patients and their families, the frequency of monitoring and, finally, the management and safety of long-term oral anticoagulation. In pediatric patients, increased doses to obtain and maintain the therapeutic target INR, more frequent adjustments and INR testing, multiple medication, inconstant nutritional intake, difficult venepunctures, and the need to go to the laboratory for testing (interruption of school and parents’ work attendance highlight those difficulties. After reviewing the most relevant published studies of self-testing and self-management of INR for adult patients and children on oral anticoagulation, it seems that these are valuable and effective strategies of INR control. Despite an unclear relationship between INR control and clinical effects, these self-strategies provide a better control of the anticoagulant effect, improve patients and their family quality of life, and are an appealing solution in term of cost-effectiveness. Structured education and knowledge evaluation by trained health care professionals is required for children, to be able to adjust their dose treatment safely and accurately. However

  6. Signal-to-background ratio preferences of normal-hearing listeners as a function of music

    Science.gov (United States)

    Barrett, Jillian Gallant

    The purpose of this study was to identify listeners' signal-to-background-ratio (SBR) preference levels for vocal music and to investigate whether or not SBR differences existed for different music genres. The ``signal'' was the singer's voice, and the ``background'' was the accompanying music. Three songs were each produced in two different genres (total of 6 genres represented). Each song was performed by three male and three female singers. Analyses addressed influences of musical genre, singing style, and singer timbre on listener's SBR choices. Fifty-three normal-hearing California State University of Northridge students ranging in age from 20-52 years participated as subjects. Subjects adjusted the overall music loudness to a comfortable listening level, and manipulated a second gain control which affected only the singer's voice. Subjects listened to 72 stimuli and adjusted the singer's voice to the level they felt sounded appropriate in comparison to the background music. Singer and Genre were the two primary contributors to significant differences in subject's SBR preferences, although the results clearly indicate Genre, Style and Singer interact in different combinations under different conditions. SBR differences for each song, each singer, and each subject did not occur in a predictable manner, and support the hypothesis that SBR preferences are neither fixed nor dependent merely upon music application or setting. Further investigations regarding psychoacoustical bases responsible for differences in SBR preferences are warranted.

  7. Establishing an external quality assessment scheme for point-of-care international normalized ratio in Thailand.

    Science.gov (United States)

    Tientadakul, P; Chuntarut, A

    2015-08-01

    Effective warfarin therapy management has gained national interest, resulting in the increased use of point-of-care testing (POCT) for international normalized ratio (INR). External quality assessment (EQA) is recommended to ensure quality of the testing. CoaguChek XS and CoaguChek XS Plus are the only commonly available POCT INR monitors in Thailand. Therefore, Thailand NEQAS for Blood Coagulation initiated the scheme for POCT INR in 2013, including only hospitals using these devices. Questionnaires were sent to the hospitals, enquiring about their interest in EQA participation. Two surveys were distributed; each included five certified European Concerted Action on Anticoagulation (ECAA) INR plasma sets. Unsatisfactory performance was indicated by a 15% deviation from the certified mean INR value. There were 156 hospitals using the devices. Thirty-five hospitals responded to the questionnaires. Medical personnel undertaking POCT INR were limited to laboratory staff in 29 (83%) of these centers, and 31 hospitals actually participated. The medians of results from participants were the same or nearly the same as the certified mean INRs. External quality assessment for POCT INR in Thailand is feasible using the ECAA plasmas as control materials. The results therefore appear encouraging to other developing countries to establish their own EQA schemes. © 2014 John Wiley & Sons Ltd.

  8. Elevated International Normalized Ratio in a Patient Taking Warfarin and Mauby: A Case Report.

    Science.gov (United States)

    Sorbera, Maria; Joseph, Tina; DiGregorio, Robert V

    2017-10-01

    We describe a 70-year-old Haitian man who had been taking warfarin for 5 years for atrial fibrillation and pulmonary hypertension. This patient had his international normalized ratio (INR) checked in the pharmacist-run anticoagulation clinic and was followed monthly. Prior to the interaction, his INR was therapeutic for 5 months while taking warfarin 10.5 mg/d. The patient presented with an INR > 8.0. Patient held 4 days of warfarin and restarted on warfarin 8.5 mg/d. Two weeks later, his INR was 2.5. After continuing dose, patient presented 2 weeks later and INR was 4.8. Upon further questioning, the patient stated he recently began ingesting mauby. Mauby is a bitter dark liquid extracted from the bark of the mauby tree that is commonly used in the Caribbean population as a folk remedy with many health benefits. This case report illustrates that mauby may have a probable drug-herb interaction (Naranjo Algorithm Score of 6) when given with warfarin. There is a lack of published literature and unclear information on the Internet describing the interaction of mauby and warfarin. Health professionals should be cautious regarding interactions between warfarin and mauby until the interaction is fully elucidated.

  9. Effect of home testing of international normalized ratio on clinical events.

    Science.gov (United States)

    Matchar, David B; Jacobson, Alan; Dolor, Rowena; Edson, Robert; Uyeda, Lauren; Phibbs, Ciaran S; Vertrees, Julia E; Shih, Mei-Chiung; Holodniy, Mark; Lavori, Philip

    2010-10-21

    Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes. We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death). The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001). As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin

  10. International normalized ratio stabilization in newly initiated warfarin patients with nonvalvular atrial fibrillation.

    Science.gov (United States)

    Nelson, Winnie W; Desai, Sunita; Damaraju, C V; Lu, Lang; Fields, Larry E; Wildgoose, Peter; Schein, Jeff R

    2014-12-01

    Warfarin is effective for stroke prevention in patients with atrial fibrillation (AF), but international normalized ratio (INR) levels fluctuate and frequent monitoring is necessary. This study used data from a large anticoagulation management service database to analyze the relationship between INR stabilization and warfarin utilization for >1 year in patients with nonvalvular AF (NVAF). Anticoagulation records from a large US electronic database collected from 2006 to 2010 were analyzed. Patients with NVAF and ≥ 3 INR values in the dataset were identified (n = 15,276). INR stabilization was defined as the first three consecutive INR values between 2.0 and 3.0 after warfarin initiation. One quarter of patients (n = 3809) failed to reach INR stabilization. After initial stabilization, 30% of subsequent INR values were out of range. The mean (± standard deviation [SD]) follow-up time from stabilization to the end of study for these patients was 494.2 ± 418.1 days. Age ≥ 75 years (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.08-1.27), hypertension (OR = 1.19, 95% CI = 1.10-1.29), or prior stroke (OR = 1.29, 95% CI = 1.04-1.61) were positively associated with achieving stabilization; heart failure was negatively associated with stabilization (OR = 0.78, 95% CI = 0.70-0.87). Male gender (p < 0.0001) and hypertension were associated with earlier stabilization (p = 0.0013); heart failure was associated with later stabilization (p = 0.0098). Patients who achieved INR stabilization within 1 year were 10 times more likely to remain on warfarin than patients who did not achieve it. Observational data may contain incomplete records. Data on adherence, concurrent medications, vitamin K intake, genotype, reasons for discontinuation of monitoring, and patient outcomes were not available in the dataset. The study findings were generalizable only to patients with AF who were managed by anticoagulation clinics. Given the importance of stroke prevention among

  11. Monitoring of international normalized ratios: comparison of community nurses with family physicians.

    Science.gov (United States)

    Levine, Max A; Shao, Wei; Klein, Douglas

    2012-08-01

    To determine whether community-based, nurse-led monitoring of the international normalized ratio (INR) in patients requiring long-term warfarin therapy was comparable to traditional physician monitoring. A retrospective cohort analysis of patients taking long-term warfarin therapy. The study used data gathered from 3 family medicine clinics in a primary care network in Edmonton, Alta. Medical records of patients currently taking warfarin were examined. Implementation of nurse-led monitoring in a primary care network in place of standard family physician INR monitoring. The degree of INR control before and after the implementation of nurse-run INR monitoring was assessed. The average proportion of time spent outside of therapeutic INR ranges, as well as the average number of days between successive INR readings, was calculated and compared. The degree of control placed patients into either a good-control group (out of range ≤ 25% of the time) or a moderate-control group (out of range > 25% of the time) and these groups were compared. Before nurse monitoring, INR values were out of range 20.4% of the time; after nurse monitoring they were out of range 19.2% of the time (P = .115); the time between sequential INR readings also did not differ before and after implementation of nurse monitoring (23.9 vs 21.6 days, P = .789). Nurse-led monitoring of INR is as effective as traditional physician monitoring. Advantages of nurse-led monitoring might include freeing family physicians to see more patients or to spend less time at work. It might also represent potential cost savings.

  12. Normalized burn ratios link fire severity with patterns of avian occurrence

    Science.gov (United States)

    Rose, Eli T.; Simons, Theodore R.; Klein, Rob; McKerrow, Alexa

    2016-01-01

    ContextRemotely sensed differenced normalized burn ratios (DNBR) provide an index of fire severity across the footprint of a fire. We asked whether this index was useful for explaining patterns of bird occurrence within fire adapted xeric pine-oak forests of the southern Appalachian Mountains.ObjectivesWe evaluated the use of DNBR indices for linking ecosystem process with patterns of bird occurrence. We compared field-based and remotely sensed fire severity indices and used each to develop occupancy models for six bird species to identify patterns of bird occurrence following fire.MethodsWe identified and sampled 228 points within fires that recently burned within Great Smoky Mountains National Park. We performed avian point counts and field-assessed fire severity at each bird census point. We also used Landsat™ imagery acquired before and after each fire to quantify fire severity using DNBR. We used non-parametric methods to quantify agreement between fire severity indices, and evaluated single season occupancy models incorporating fire severity summarized at different spatial scales.ResultsAgreement between field-derived and remotely sensed measures of fire severity was influenced by vegetation type. Although occurrence models using field-derived indices of fire severity outperformed those using DNBR, summarizing DNBR at multiple spatial scales provided additional insights into patterns of occurrence associated with different sized patches of high severity fire.ConclusionsDNBR is useful for linking the effects of fire severity to patterns of bird occurrence, and informing how high severity fire shapes patterns of bird species occurrence on the landscape.

  13. The relation between international normalized ratio and mortality in acute pulmonary embolism: A retrospective study.

    Science.gov (United States)

    Kırış, Tuncay; Yazıcı, Selcuk; Durmuş, Gündüz; Çanga, Yiğit; Karaca, Mustafa; Nazlı, Cem; Dogan, Abdullah

    2018-01-01

    Acute pulmonary embolism (PE) is a serious clinical disease characterized by a high mortality rate. The aim of this study was to assess the prognostic value of international normalized ratio (INR) in acute PE patients not on anticoagulant therapy. The study included 244 hospitalized acute PE patients who were not receiving previous anticoagulant therapy. Based on their 30-day mortality, patients were categorized as survivors or non-survivors. INR was measured during the patients' admission, on the same day as the diagnosis of PE but before anticoagulation started. Thirty-day mortality occurred in 39 patients (16%). INR was higher in non-survivors than in survivors (1.3±0.4 vs 1.1±0.3, P=.003). In multivariate analysis, INR (HR: 3.303, 95% CI: 1.210-9.016, P=.020) was independently associated with 30-day mortality from PE. Inclusion of INR in a model with simplified pulmonary embolism severity index (sPESI) score improved the area under the receiver operating characteristics (ROC) curve from 0.736 (95% CI: 0.659-0.814) to 0.775 (95% CI: 0.701-0.849) (P=.028). Also, the addition of INR to sPESI score enhanced the net reclassification improvement (NRI=8.8%, P<.001) and integrated discrimination improvement (IDI=0.043, P=.027). Elevated INR may have prognostic value for 30-day mortality in acute PE patients not on anticoagulation. Combining INR with sPESI score improved the predictive value for all-cause mortality. However, further large-scale studies are needed to confirm it's prognostic role. © 2017 Wiley Periodicals, Inc.

  14. Patterns of international normalized ratio values among new warfarin patients with nonvalvular atrial fibrillation.

    Science.gov (United States)

    Nelson, Winnie W; Milentijevic, Dejan; Wang, Li; Baser, Onur; Damaraju, C V; Schein, Jeffrey R

    2016-12-01

    Limited information exists regarding the relationship between international normalized ratio (INR) control/stability and the discontinuation of warfarin therapy among patients with nonvalvular atrial fibrillation (NVAF). This study evaluated the association between INR stabilization and warfarin discontinuation and assessed INR patterns before and after INR stabilization among patients (≥18 years) with NVAF who newly initiated warfarin (Veterans Health Administration datasets; October 1, 2007 through September 30, 2012). Achievement of INR stabilization (≥3 consecutive in-range therapeutic INR measurements ≥7 days apart) was examined from warfarin initiation through the end of warfarin exposure. Proportion of time in therapeutic range during warfarin exposure was calculated (Rosendaal method) and categorized as at least 60% or less than 60%. Among 34 346 patients, 49.4% achieved INR stabilization (mean time to stabilization, 98 days). Approximately 40% of INR values were out-of-range, even after achieving stabilization. During 30 days following an INR 4.0 or higher, patients had more INR testing than the overall mean (2.51 vs. 1.67 tests). Warfarin discontinuation was 4.2 times more likely among patients without INR stabilization versus those with INR stabilization (P < 0.00001). Patients with poor INR control (time in therapeutic range <60%) were 1.76 times more likely to discontinue warfarin within 1 year (P < 0.0001). INR stabilization is a better predictor of warfarin discontinuation than poor INR control. Improved approaches are necessary to maintain appropriate anticoagulation levels among patients with NVAF.

  15. International normalized ratio stability in warfarin-experienced patients with nonvalvular atrial fibrillation.

    Science.gov (United States)

    Nelson, Winnie W; Desai, Sunita; Damaraju, Chandrasekharrao V; Lu, Lang; Fields, Larry E; Wildgoose, Peter; Schein, Jeffery R

    2015-06-01

    Maintaining stable levels of anticoagulation using warfarin therapy is challenging. Few studies have examined the stability of the international normalized ratio (INR) in patients with nonvalvular atrial fibrillation (NVAF) who have had ≥6 months' exposure to warfarin anticoagulation for stroke prevention. Our objective was to describe INR control in NVAF patients who had been receiving warfarin for at least 6 months. Using retrospective patient data from the CoagClinic™ database, we analyzed data from NVAF patients treated with warfarin to assess the quality of INR control and possible predictors of poor INR control. Time within, above, and below the recommended INR range (2.0-3.0) was calculated for patients who had received warfarin for ≥6 months and had three or more INR values. The analysis also assessed INR patterns and resource utilization of patients with an INR >4.0. Logistic regression models were used to determine factors associated with poor INR control. Patients (n = 9433) had an average of 1.6 measurements per 30 days. Mean follow-up time was 544 days. Approximately 39% of INR values were out of range, with 23% of INR values being 3.0. Mean percent time with INR in therapeutic range was 67%; INR 3.0 was 14%. Patients with more than one reading of INR >4.0 (~39%) required an average of one more visit and took 3 weeks to return to an in-range INR. Male sex and age >75 years were predictive of better INR control, whereas a history of heart failure or diabetes were predictive of out-of-range INR values. However, patient characteristics did not predict the likelihood of INR >4.0. Out-of-range INR values remain frequent in patients with NVAF treated with warfarin. Exposure to high INR values was common, resulting in increased resource utilization.

  16. Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an indicator of prostate cancer aggressiveness.

    Science.gov (United States)

    Lebovici, Andrei; Sfrangeu, Silviu A; Feier, Diana; Caraiani, Cosmin; Lucan, Ciprian; Suciu, Mihai; Elec, Florin; Iacob, Gheorghita; Buruian, Mircea

    2014-05-10

    We tested the feasibility of a simple method for assessment of prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between prostate cancer and healthy prostatic tissue. The requirement for institutional review board approval was waived. A set of 20 standardized core transperineal saturation biopsy specimens served as the reference standard for placement of regions of interest on ADC maps in tumorous and normal prostatic tissue of 22 men with PCa (median Gleason score: 7; range, 6-9). A total of 128 positive sectors were included for evaluation. Two diagnostic ratios were computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC central ratio (the ratio between tumor ADC and normal central zone tissue, ADC-CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason 8 and 9) was assessed using the area under the receiver operating characteristic curve (AUC). Both ADC ratios presented significantly lower values in high-risk tumors (0.48 ± 0.13 for ADC-CR and 0.40 ± 0.09 for ADC-PR) compared with low-risk tumors (0.66 ± 0.17 for ADC-CR and 0.54 ± 0.09 for ADC-PR) (p performance (ADC-CR AUC = 0.77, sensitivity = 82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%, specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%, specificity = 70.6%) for identifying high-risk lesions. The ADC ratio as an intrapatient-normalized diagnostic tool may be better in detecting high-grade lesions compared with analysis based on tumor ADCs alone, and may reduce the rate of biopsies.

  17. A review of instrumental variable estimators for Mendelian randomization.

    Science.gov (United States)

    Burgess, Stephen; Small, Dylan S; Thompson, Simon G

    2017-10-01

    Instrumental variable analysis is an approach for obtaining causal inferences on the effect of an exposure (risk factor) on an outcome from observational data. It has gained in popularity over the past decade with the use of genetic variants as instrumental variables, known as Mendelian randomization. An instrumental variable is associated with the exposure, but not associated with any confounder of the exposure-outcome association, nor is there any causal pathway from the instrumental variable to the outcome other than via the exposure. Under the assumption that a single instrumental variable or a set of instrumental variables for the exposure is available, the causal effect of the exposure on the outcome can be estimated. There are several methods available for instrumental variable estimation; we consider the ratio method, two-stage methods, likelihood-based methods, and semi-parametric methods. Techniques for obtaining statistical inferences and confidence intervals are presented. The statistical properties of estimates from these methods are compared, and practical advice is given about choosing a suitable analysis method. In particular, bias and coverage properties of estimators are considered, especially with weak instruments. Settings particularly relevant to Mendelian randomization are prioritized in the paper, notably the scenario of a continuous exposure and a continuous or binary outcome.

  18. Nilai Rerata Vascular Pedicle Width, Vascular Pedicle-Cardiac Ratio Vascular Pedicle-Thoracic Ratio Orang Dewasa Normal Indonesia Studi di RS dr. Cipto Mangunkusomo

    Directory of Open Access Journals (Sweden)

    Rommy Zunera

    2016-03-01

    Full Text Available Vascular pedicle width (VPW adalah jarak tepi luar vena kava superior ke tepi luar arteri subklavia kiri. Pemeriksaan VPW di foto toraks bersifat non-invasif, cepat dan mudah untuk memprediksi hipervolemia.Penelitian ini bertujuan untuk mengetahui rerata nilai VPW orang dewasa normal Indonesia. VPW diukurdengan dua metode: pertama pengukuran VPW tunggal yang akurasinya terbatas di foto toraks digital karenarelatif tidak dipengaruhi faktor magnifikasi. Metode kedua untuk foto toraks nondigital yaitu pengukuranrasio:vascular pedicle-cardiac ratio (VPCR dan vascular pedicle-thoracic ratio (VPTR. Pengukuran serupadilakukan terhadap  topogram CT scan toraks AP terlentang dan CT scan toraks lalu dibandingkan akurasipengukuran di topogram dengan CT scan  toraks sebagai standar baku. Sampel terdiri atas 104 foto toraksPA subyek normal dan 103 CT scan  toraks subyek terpilih. Pada pemeriksaan toraks PA didapatkan rerata VPW 48,0±5,5mm, rerata VPCR 40,3±4,6%, dan rerata VPTR 17,2±1,7%. Pada pemeriksaan topogram CTscan didapatkan rerata VPW 50,3±6,2mm, rerata VPTR 45±5,1%, dan rerata VPTR 19,8±2,5%. Rerata VPWpada CT scan toraks 50,4±6,1mm. Pengukuran di foto toraks AP 10% lebih besar dibandingkan pada fototoraks PA dan pengukuranVPW di foto toraks terbukti memiliki akurasi  tinggi. Kata kunci: fototoraks, vascular pedicle width, vascular pedicle-cardiac ratio, vascular pedicle-thoracic ratio, hipervolemia.   The Mean Value of Vascular Pedicle Width, Vascular Pedicle-Cardiac Ratio,Vascular Pedicle-Thoracic Ratio of Normal Indonesian Adult Study In dr. Cipto Mangunkusomo Hospital Abstract Vascular pedicle width (VPW is the distance, from a perpendicular line at the takeoff point of the left subclavian artery off the aorta to the point at which the superior vena cava. Measurement of VPW on chestx-ray is relatively non-invasive, fast and easy technique as  hypervolemia predictor. The purpose of thisstudy is to know the mean VPW value of normal

  19. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data.

    Science.gov (United States)

    Yavorska, Olena O; Burgess, Stephen

    2017-12-01

    MendelianRandomization is a software package for the R open-source software environment that performs Mendelian randomization analyses using summarized data. The core functionality is to implement the inverse-variance weighted, MR-Egger and weighted median methods for multiple genetic variants. Several options are available to the user, such as the use of robust regression, fixed- or random-effects models and the penalization of weights for genetic variants with heterogeneous causal estimates. Extensions to these methods, such as allowing for variants to be correlated, can be chosen if appropriate. Graphical commands allow summarized data to be displayed in an interactive graph, or the plotting of causal estimates from multiple methods, for comparison. Although the main method of data entry is directly by the user, there is also an option for allowing summarized data to be incorporated from the PhenoScanner database of genotype-phenotype associations. We hope to develop this feature in future versions of the package. The R software environment is available for download from [https://www.r-project.org/]. The MendelianRandomization package can be downloaded from the Comprehensive R Archive Network (CRAN) within R, or directly from [https://cran.r-project.org/web/packages/MendelianRandomization/]. Both R and the MendelianRandomization package are released under GNU General Public Licenses (GPL-2|GPL-3). © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

  20. Survivor bias in Mendelian randomization analysis

    DEFF Research Database (Denmark)

    Vansteelandt, Stijn; Dukes, Oliver; Martinussen, Torben

    2017-01-01

    Mendelian randomization studies employ genotypes as experimental handles to infer the effect of genetically modified exposures (e.g. vitamin D exposure) on disease outcomes (e.g. mortality). The statistical analysis of these studies makes use of the standard instrumental variables framework. Many...... of these studies focus on elderly populations, thereby ignoring the problem of left truncation, which arises due to the selection of study participants being conditional upon surviving up to the time of study onset. Such selection, in general, invalidates the assumptions on which the instrumental variables...... analysis rests. We show that Mendelian randomization studies of adult or elderly populations will therefore, in general, return biased estimates of the exposure effect when the considered genotype affects mortality; in contrast, standard tests of the causal null hypothesis that the exposure does not affect...

  1. Education and coronary heart disease: mendelian randomisation study.

    Science.gov (United States)

    Tillmann, Taavi; Vaucher, Julien; Okbay, Aysu; Pikhart, Hynek; Peasey, Anne; Kubinova, Ruzena; Pajak, Andrzej; Tamosiunas, Abdonas; Malyutina, Sofia; Hartwig, Fernando Pires; Fischer, Krista; Veronesi, Giovanni; Palmer, Tom; Bowden, Jack; Davey Smith, George; Bobak, Martin; Holmes, Michael V

    2017-08-30

    Objective  To determine whether educational attainment is a causal risk factor in the development of coronary heart disease. Design  Mendelian randomisation study, using genetic data as proxies for education to minimise confounding. Setting  The main analysis used genetic data from two large consortia (CARDIoGRAMplusC4D and SSGAC), comprising 112 studies from predominantly high income countries. Findings from mendelian randomisation analyses were then compared against results from traditional observational studies (164 170 participants). Finally, genetic data from six additional consortia were analysed to investigate whether longer education can causally alter the common cardiovascular risk factors. Participants  The main analysis was of 543 733 men and women (from CARDIoGRAMplusC4D and SSGAC), predominantly of European origin. Exposure  A one standard deviation increase in the genetic predisposition towards higher education (3.6 years of additional schooling), measured by 162 genetic variants that have been previously associated with education. Main outcome measure  Combined fatal and non-fatal coronary heart disease (63 746 events in CARDIoGRAMplusC4D). Results  Genetic predisposition towards 3.6 years of additional education was associated with a one third lower risk of coronary heart disease (odds ratio 0.67, 95% confidence interval 0.59 to 0.77; P=3×10 -8 ). This was comparable to findings from traditional observational studies (prevalence odds ratio 0.73, 0.68 to 0.78; incidence odds ratio 0.80, 0.76 to 0.83). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely, although this remains an untestable possibility. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index, and a favourable blood lipid profile. Conclusions  This mendelian randomisation study found support for the hypothesis that low education is a causal risk

  2. Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an indicator of prostate cancer aggressiveness

    International Nuclear Information System (INIS)

    Lebovici, Andrei; Sfrangeu, Silviu A; Feier, Diana; Caraiani, Cosmin; Lucan, Ciprian; Suciu, Mihai; Elec, Florin; Iacob, Gheorghita; Buruian, Mircea

    2014-01-01

    We tested the feasibility of a simple method for assessment of prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between prostate cancer and healthy prostatic tissue. The requirement for institutional review board approval was waived. A set of 20 standardized core transperineal saturation biopsy specimens served as the reference standard for placement of regions of interest on ADC maps in tumorous and normal prostatic tissue of 22 men with PCa (median Gleason score: 7; range, 6–9). A total of 128 positive sectors were included for evaluation. Two diagnostic ratios were computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC central ratio (the ratio between tumor ADC and normal central zone tissue, ADC-CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason 8 and 9) was assessed using the area under the receiver operating characteristic curve (AUC). Both ADC ratios presented significantly lower values in high-risk tumors (0.48 ± 0.13 for ADC-CR and 0.40 ± 0.09 for ADC-PR) compared with low-risk tumors (0.66 ± 0.17 for ADC-CR and 0.54 ± 0.09 for ADC-PR) (p < 0.001) and had better diagnostic performance (ADC-CR AUC = 0.77, sensitivity = 82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%, specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%, specificity = 70.6%) for identifying high-risk lesions. The ADC ratio as an intrapatient-normalized diagnostic tool may be better in detecting high-grade lesions compared with analysis based on tumor ADCs alone, and may reduce the rate of biopsies

  3. Brain perfusion ratios by 99mTc HMPAO SPECT utilizing a mean value of the visual cortex to the cerebellum ratio derived from normal subjects

    International Nuclear Information System (INIS)

    Sanchez Catasus, C.; Rodriguez, R.; Cisnero, M.; Palmero, R.; Diaz, O.; Aguila, A.

    2002-01-01

    Aim: Previous results shows that the cerebellum (CER) is the best reference to calculate relative indexes of perfusion (IP) by brain SPECT. However, it can not be used on patients with bilateral cerebellar hypoperfusion. In such cases visual cortex (VC) or an average of the whole brain activity is recommended (WB). VC and WB are less reliable than CER, making it difficult to compare SPECT scans that have been normalized with different values. Materials and Methods: To overcome this difficulty, we developed a method to calculate IP utilizing a reference value defined as (VC / ), where is the mean value of the VC/CER ratio derived from a normal database which was assumed to be constant. We called the value VC/ the 'Pseudocerebellum' (PCER). For clinical validation, we first tested statistically the VC/CER ratio on a group of 60 [ 99m Tc]-HMPAO SPECT scans of 20 normal subjects and 40 neurological patients with positive SPECT but without involvement of VC and CER. To demonstrate that IP PCER approx. IP CER , we calculated the mean value of the absolute differences CER - IP PCER vertical bar> on two groups of scans from subjects without involvement of VC and CER: 10 normal subjects (GI); and 40 patients (GII). Finally, using an indirect procedure the method was tested on a third group of SPECT scans of 30 patients with bilateral cerebellar hypoperfusion (G III). Results: The VC/CER ratio was approximately constant with gender and age at a 95% confidence level; CER - IP PCER vertical bar> was 1.22%±0.35 and 1.20%±0.42 for GI and GII, respectively. This is less than the within-subject replicability of the HMPAO SPECT studies; and thus demonstrated by an indirect approach that IP PCER is a valid procedure by which to evaluate relative perfusion on patients with bilateral cerebellar hypoperfusion and quantitatively comparable to using CER as reference region. Conclusion: The VC/CER ratio has very little inter-subject variability in individuals where these regions are not

  4. Pitfalls with the use of enhancement ratios or normalized excess mixing ratios measured in plumes to characterize pollution sources and aging

    Directory of Open Access Journals (Sweden)

    R. J. Yokelson

    2013-08-01

    Full Text Available Normalized excess mixing ratios (NEMRs, also known as enhancement ratios, are a common way to characterize plumes of pollution in atmospheric research. As single-source pollutant plumes disperse in the atmosphere, they are diluted by mixing with the adjacent background air. Changes in the composition of this background air can cause large changes to the NEMR that is subsequently measured by remote-sensing, airborne, or ground-based instruments. This scenario is common when boundary layer plumes enter the free troposphere and could also impact long-range transport or plumes near the top of the troposphere. We provide a context for these issues and an example showing that neglect of this effect could lead to serious errors in data interpretation.

  5. Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

    Science.gov (United States)

    White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

    2016-01-01

    Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for

  6. Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study.

    Science.gov (United States)

    Magnus, Maria C; Miliku, Kozeta; Bauer, Anna; Engel, Stephanie M; Felix, Janine F; Jaddoe, Vincent W V; Lawlor, Debbie A; London, Stephanie J; Magnus, Per; McGinnis, Ralph; Nystad, Wenche; Page, Christian M; Rivadeneira, Fernando; Stene, Lars C; Tapia, German; Williams, Nicholas; Bonilla, Carolina; Fraser, Abigail

    2018-06-20

    To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. One and two sample mendelian randomisation analyses. Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed. Published by the BMJ

  7. Initiation of glucose-lowering treatment decreases international normalized ratio levels among users of vitamin K antagonists

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Pottegård, Anton; Henriksen, Daniel Pilsgaard

    2016-01-01

    -lowering treatment affects international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon. PATIENTS/METHODS: We performed a self-controlled retrospective register-based study. A total of 118 patients initiating glucose-lowering treatment while being treated......-lowering treatment reduces the anticoagulant effect of VKA to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation. This article is protected by copyright. All rights reserved....

  8. Diagnosing dementia and normal aging: clinical relevance of brain ratios and cognitive performance in a Brazilian sample

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    Chaves M.L.F.

    1999-01-01

    Full Text Available The main objective of the present study was to evaluate the diagnostic value (clinical application of brain measures and cognitive function. Alzheimer and multiinfarct patients (N = 30 and normal subjects over the age of 50 (N = 40 were submitted to a medical, neurological and cognitive investigation. The cognitive tests applied were Mini-Mental, word span, digit span, logical memory, spatial recognition span, Boston naming test, praxis, and calculation tests. The brain ratios calculated were the ventricle-brain, bifrontal, bicaudate, third ventricle, and suprasellar cistern measures. These data were obtained from a brain computer tomography scan, and the cutoff values from receiver operating characteristic curves. We analyzed the diagnostic parameters provided by these ratios and compared them to those obtained by cognitive evaluation. The sensitivity and specificity of cognitive tests were higher than brain measures, although dementia patients presented higher ratios, showing poorer cognitive performances than normal individuals. Normal controls over the age of 70 presented higher measures than younger groups, but similar cognitive performance. We found diffuse losses of tissue from the central nervous system related to distribution of cerebrospinal fluid in dementia patients. The likelihood of case identification by functional impairment was higher than when changes of the structure of the central nervous system were used. Cognitive evaluation still seems to be the best method to screen individuals from the community, especially for developing countries, where the cost of brain imaging precludes its use for screening and initial assessment of dementia.

  9. The Hidden Complexity of Mendelian Traits across Natural Yeast Populations

    Directory of Open Access Journals (Sweden)

    Jing Hou

    2016-07-01

    Full Text Available Mendelian traits are considered to be at the lower end of the complexity spectrum of heritable phenotypes. However, more than a century after the rediscovery of Mendel’s law, the global landscape of monogenic variants, as well as their effects and inheritance patterns within natural populations, is still not well understood. Using the yeast Saccharomyces cerevisiae, we performed a species-wide survey of Mendelian traits across a large population of isolates. We generated offspring from 41 unique parental pairs and analyzed 1,105 cross/trait combinations. We found that 8.9% of the cases were Mendelian. Further tracing of causal variants revealed background-specific expressivity and modified inheritances, gradually transitioning from Mendelian to complex traits in 30% of the cases. In fact, when taking into account the natural population diversity, the hidden complexity of traits could be substantial, confounding phenotypic predictability even for simple Mendelian traits.

  10. Utility of Normal Tissue-to-Tumor {alpha}/{beta} Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Jin Jianyue [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Chang, Albert J. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-01-01

    Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue {alpha}/{beta} ratio divided by the tumor {alpha}/{beta} times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified.

  11. Online Mendelian Inheritance in Man (OMIM).

    Science.gov (United States)

    Hamosh, A; Scott, A F; Amberger, J; Valle, D; McKusick, V A

    2000-01-01

    Online Mendelian Inheritance In Man (OMIM) is a public database of bibliographic information about human genes and genetic disorders. Begun by Dr. Victor McKusick as the authoritative reference Mendelian Inheritance in Man, it is now distributed electronically by the National Center for Biotechnology Information (NCBI). Material in OMIM is derived from the biomedical literature and is written by Dr. McKusick and his colleagues at Johns Hopkins University and elsewhere. Each OMIM entry has a full text summary of a genetic phenotype and/or gene and has copious links to other genetic resources such as DNA and protein sequence, PubMed references, mutation databases, approved gene nomenclature, and more. In addition, NCBI's neighboring feature allows users to identify related articles from PubMed selected on the basis of key words in the OMIM entry. Through its many features, OMIM is increasingly becoming a major gateway for clinicians, students, and basic researchers to the ever-growing literature and resources of human genetics. Copyright 2000 Wiley-Liss, Inc.

  12. Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

    Directory of Open Access Journals (Sweden)

    Maria Victoria Fernández

    2017-11-01

    Full Text Available Alzheimer disease (AD, Frontotemporal lobar degeneration (FTD, Amyotrophic lateral sclerosis (ALS and Parkinson disease (PD have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

  13. Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

    Science.gov (United States)

    Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

    2017-03-01

    Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight 1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks' gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Study of the Correlations and the MAXI Hardness Ratio between the Anomalous and Normal Low States of LMC X-3

    Science.gov (United States)

    Torpin, Trevor; Boyd, Patricia T.; Smale, Alan P.

    2015-01-01

    The bright, unusual black-hole X-ray binary LMC X-3 has been monitored virtually continuously by the Japanese MAXI X-ray All-Sky Monitor aboard the International Space Station (Matsuoka, et al., PASJ, 2009) from August 2009 to the present. Comparison with RXTE PCA and ASM light curves during the ~2.33-year period of overlap demonstrate that despite slight differences in energy-band boundaries both the ASM and MAXI faithfully reproduce characteristics of the high-amplitude, nonperiodic long-term variability, on the order of 100-300 days, clearly seen in the more sensitive PCA monitoring. The mechanism for this variability at a timescale many times longer than the 1.7-day orbital period is still unknown. Models to explain the long-term variability invoke mechanisms such as changes in mass transfer rate, and/or a precessing warped accretion disk. Observations of LMC X-3 have not definitely determined whether wind accretion or Roche-love overflow is the driver of the long-term variability. Recent MAXI monitoring of LMC X-3 includes excellent coverage of a rare anomalous low state (ALS) where the X-ray source cannot be distinguished from the background, as well as several normal low states, in which the source count rate passes smoothly through a low, yet detectable value. Pointed Swift XRT and UVOT observations also sample this ALS and one normal low state well. We combine these data sets to study the correlations between the wavelength regimes observed during the ALS versus the normal low. We also examine the behavior of the X-ray hardness ratios using XRT and MAXI monitoring data during the ALS versus the normal low state.

  15. Multivariate relationships between international normalized ratio and vitamin K-dependent coagulation-derived parameters in normal healthy donors and oral anticoagulant therapy patients

    Directory of Open Access Journals (Sweden)

    Golanski Jacek

    2003-11-01

    Full Text Available Abstract Background and objectives International Normalized Ratio (INR is a world-wide routinely used factor in the monitoring of oral anticoagulation treatment (OAT. However, it was reported that other factors, e. g. factor II, may even better reflect therapeutic efficacy of OAT and, therefore, may be potentialy useful for OAT monitoring. The primary purpose of this study was to characterize the associations of INR with other vitamin K-dependent plasma proteins in a heterogenous group of individuals, including healthy donors, patients on OAT and patients not receiving OAT. The study aimed also at establishing the influence of co-morbid conditions (incl. accompanying diseases and co-medications (incl. different intensity of OAT on INR. Design and Methods Two hundred and three subjects were involved in the study. Of these, 35 were normal healthy donors (group I, 73 were patients on medication different than OAT (group II and 95 were patients on stable oral anticoagulant (acenocoumarol therapy lasting for at least half a year prior to the study. The values of INR and activated partial thromboplastin time (APTT ratio, as well as activities of FII, FVII, FX, protein C, and concentration of prothrombin F1+2 fragments and fibrinogen were obtained for all subjects. In statistical evaluation, the uni- and multivariate analyses were employed and the regression equations describing the obtained associations were estimated. Results Of the studied parameters, three (factors II, VII and X appeared as very strong modulators of INR, protein C and prothrombin fragments F1+2 had moderate influence, whereas both APTT ratio and fibrinogen had no significant impact on INR variability. Due to collinearity and low tolerance of independent variables included in the multiple regression models, we routinely employed a ridge multiple regression model which compromises the minimal number of independent variables with the maximal overall determination coefficient. The best

  16. Comprehensive genotyping in dyslipidemia: mendelian dyslipidemias caused by rare variants and Mendelian randomization studies using common variants.

    Science.gov (United States)

    Tada, Hayato; Kawashiri, Masa-Aki; Yamagishi, Masakazu

    2017-04-01

    Dyslipidemias, especially hyper-low-density lipoprotein cholesterolemia and hypertriglyceridemia, are important causal risk factors for coronary artery disease. Comprehensive genotyping using the 'next-generation sequencing' technique has facilitated the investigation of Mendelian dyslipidemias, in addition to Mendelian randomization studies using common genetic variants associated with plasma lipids and coronary artery disease. The beneficial effects of low-density lipoprotein cholesterol-lowering therapies on coronary artery disease have been verified by many randomized controlled trials over the years, and subsequent genetic studies have supported these findings. More recently, Mendelian randomization studies have preceded randomized controlled trials. When the on-target/off-target effects of rare variants and common variants exhibit the same direction, novel drugs targeting molecules identified by investigations of rare Mendelian lipid disorders could be promising. Such a strategy could aid in the search for drug discovery seeds other than those for dyslipidemias.

  17. Validation of consistency of Mendelian sampling variance.

    Science.gov (United States)

    Tyrisevä, A-M; Fikse, W F; Mäntysaari, E A; Jakobsen, J; Aamand, G P; Dürr, J; Lidauer, M H

    2018-03-01

    Experiences from international sire evaluation indicate that the multiple-trait across-country evaluation method is sensitive to changes in genetic variance over time. Top bulls from birth year classes with inflated genetic variance will benefit, hampering reliable ranking of bulls. However, none of the methods available today enable countries to validate their national evaluation models for heterogeneity of genetic variance. We describe a new validation method to fill this gap comprising the following steps: estimating within-year genetic variances using Mendelian sampling and its prediction error variance, fitting a weighted linear regression between the estimates and the years under study, identifying possible outliers, and defining a 95% empirical confidence interval for a possible trend in the estimates. We tested the specificity and sensitivity of the proposed validation method with simulated data using a real data structure. Moderate (M) and small (S) size populations were simulated under 3 scenarios: a control with homogeneous variance and 2 scenarios with yearly increases in phenotypic variance of 2 and 10%, respectively. Results showed that the new method was able to estimate genetic variance accurately enough to detect bias in genetic variance. Under the control scenario, the trend in genetic variance was practically zero in setting M. Testing cows with an average birth year class size of more than 43,000 in setting M showed that tolerance values are needed for both the trend and the outlier tests to detect only cases with a practical effect in larger data sets. Regardless of the magnitude (yearly increases in phenotypic variance of 2 or 10%) of the generated trend, it deviated statistically significantly from zero in all data replicates for both cows and bulls in setting M. In setting S with a mean of 27 bulls in a year class, the sampling error and thus the probability of a false-positive result clearly increased. Still, overall estimated genetic

  18. Influence of kidney function on risk of supratherapeutic international normalized ratio-related hemorrhage in warfarin users: a prospective cohort study

    Science.gov (United States)

    Background: Anticoagulation management is difficult in chronic kidney disease, with frequent supratherapeutic international normalized ratios (INRs >/= 4) increasing hemorrhagic risk. We evaluated whether the interaction of INR and lower estimated glomerular filtration rate (eGFR) increases hemorrha...

  19. Relation of psychological distress to the international normalized ratio in patients with venous thromboembolism with and without oral anticoagulant therapy.

    Science.gov (United States)

    Von Känel, R; Vökt, F; Biasiutti, F Demarmels; Stauber, S; Wuillemin, W A; Lukas, P S

    2012-08-01

    Psychological distress might affect the international normalized ratio (INR), but effects might vary depending on oral anticoagulant (OAC) therapy. To investigate the association of psychological distress with INR and clotting factors of the extrinsic pathway in patients with and without OAC therapy. We studied 190 patients with a previous venous thromboembolism (VTE); 148 had discontinued OAC therapy and 42 had ongoing OAC therapy. To assess psychological distress, all patients completed validated questionnaires to measure symptoms of depression, anxiety, worrying, anger and hostility. INR, fibrinogen, factor (F)II:C, FV:C, FVII:C and FX:C were measured as part of outpatient thrombophilia work-up. In VTE patients without OAC therapy, the odds of a reduced INR (therapy, INR was unrelated to a negative affect; however, lower FVII:C related to anxiety and worrying as well as lower FX:C related to anger and hostility were observed in patients with OAC therapy compared with those without OAC therapy. Psychological distress was associated with a reduced INR in VTE patients without OAC therapy. The direction of the association between psychological distress and activity in some clotting factors of the extrinsic coagulation pathway might differ depending on whether VTE patients are under OAC therapy or not. © 2012 International Society on Thrombosis and Haemostasis.

  20. International normalized ratio self-management lowers the risk of thromboembolic events after prosthetic heart valve replacement.

    Science.gov (United States)

    Eitz, Thomas; Schenk, Soren; Fritzsche, Dirk; Bairaktaris, Andreas; Wagner, Otto; Koertke, Heinrich; Koerfer, Reiner

    2008-03-01

    Although prosthetic valves are durable and easy to implant, the need for lifetime warfarin-based anticoagulation restricts their exclusive usage. We investigated if anticoagulation self-management improves outcome in a single-center series. Between 1994 and 1998, 765 patients with prosthetic valve replacements were prospectively enrolled and randomized to receive conventional anticoagulation management by their primary physician (group 1, n = 295) or to pursue anticoagulation self-management (group 2, n = 470). A study head office was implemented to coordinate and monitor anticoagulation protocols, international normalized ratios (INR), and adverse events. Patients were instructed on how to obtain and test their own blood samples and to adjust warfarin dosages according to the measured INR (target range, 2.5 to 4). Mean INR values were slightly yet significantly smaller in group 1 than in group 2 (2.8 +/- 0.7 vs 3.0 +/- .6, p events were similar in both groups. Time-related multivariate analysis identified INR self-management and higher INR as independent predictors for better outcome. Anticoagulation self-management can improve INR profiles up to 2 years after prosthetic valve replacement and reduce adverse events. Current indications of prosthetic rather than biologic valve implantations may be extended if the benefit of INR self-management is shown by future studies with longer follow-up.

  1. Comparison of International Normalized Ratio Measurement between CoaguChek XS Plus and STA-R Coagulation Analyzers

    Directory of Open Access Journals (Sweden)

    Mina Hur

    2013-01-01

    Full Text Available Background. Point-of-care testing (POCT coagulometers are increasingly being used in the hospital setting. We investigated whether the prothrombin time international normalized ratio (INR results by CoaguChek XS Plus (Roche Diagnostics GmbH, Mannheim, Germany can be used reliably without being confirmed with the INR results by STA-R system (Diagnostica Stago S.A.S, Asnières sur Seine, France. Methods. A total of 118 INR measurements by CoaguChek XS Plus and STA-R were compared using Passing/Bablok regression analysis and Bland-Altman plot. Agreement of the INR measurements was further assessed in relation to dosing decision. Results. The correlation of INR measurements between CoaguChek XS Plus and STA-R was excellent (correlation coefficient = 0.964. The mean difference tended to increase as INR results increased and was 0.25 INR in the therapeutic range (2.0-3.0 INR. The overall agreement was fair to good (kappa = 0.679, and 21/118 (17.8% INR measurements showed a difference in dosing decision. Conclusion. The positive bias of CoaguChek XS Plus may be obvious even in the therapeutic INR range, and dosing decision based on the CoaguChek XS Plus INR results would be different from that based on the STA-R results. The INR measurements by POCT coagulometers still need to be confirmed with the laboratory INR measurements.

  2. Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR)

    Energy Technology Data Exchange (ETDEWEB)

    Pourgholi, Leyla [Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, P.O. Box 7616911319, Kerman (Iran, Islamic Republic of); Goodarzynejad, Hamidreza [Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Mandegary, Ali [Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, P.O. Box 7616911319, Kerman (Iran, Islamic Republic of); Gastroenterology and Hepatology Research Center, Afzalipour' s Hospital, Imam Highway, P.O. Box 7616913911, Kerman (Iran, Islamic Republic of); Ziaee, Shayan [Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Talasaz, Azita Hajhosseini [Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences (Iran, Islamic Republic of); Jalali, Arash [Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Boroumand, Mohammadali, E-mail: maboroumand@yahoo.com [Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of)

    2016-10-15

    Background: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. Methods: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0–3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P = 0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P = 0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. Conclusion: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations. - Highlights: • NQO1 C609T variant is associated with warfarin induced bleeding at therapeutic INR. • Haplotypes of CYP2C9 (1*2 or 1*3) are also associated with bleeding events. • VKORC1, Factor VII, and EPHX1 genotypes were not associated with bleeding risk.

  3. Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR)

    International Nuclear Information System (INIS)

    Pourgholi, Leyla; Goodarzynejad, Hamidreza; Mandegary, Ali; Ziaee, Shayan; Talasaz, Azita Hajhosseini; Jalali, Arash; Boroumand, Mohammadali

    2016-01-01

    Background: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. Methods: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0–3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P = 0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P = 0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. Conclusion: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations. - Highlights: • NQO1 C609T variant is associated with warfarin induced bleeding at therapeutic INR. • Haplotypes of CYP2C9 (1*2 or 1*3) are also associated with bleeding events. • VKORC1, Factor VII, and EPHX1 genotypes were not associated with bleeding risk.

  4. Telemedicine-guided, very low-dose international normalized ratio self-control in patients with mechanical heart valve implants.

    Science.gov (United States)

    Koertke, Heinrich; Zittermann, Armin; Wagner, Otto; Secer, Songuel; Sciangula, Alfonso; Saggau, Werner; Sack, Falk-Udo; Ennker, Jürgen; Cremer, Jochen; Musumeci, Francesco; Gummert, Jan F

    2015-06-01

    To study in patients performing international normalized ratio (INR) self-control the efficacy and safety of an INR target range of 1.6-2.1 for aortic valve replacement (AVR) and 2.0-2.5 for mitral valve replacement (MVR) or double valve replacement (DVR). In total, 1304 patients undergoing AVR, 189 undergoing MVR and 78 undergoing DVR were randomly assigned to low-dose INR self-control (LOW group) (INR target range, AVR: 1.8-2.8; MVR/DVR: 2.5-3.5) or very low-dose INR self-control once a week (VLO group) and twice a week (VLT group) (INR target range, AVR: 1.6-2.1; MVR/DVR: 2.0-2.5), with electronically guided transfer of INR values. We compared grade III complications (major bleeding and thrombotic events; primary end-points) and overall mortality (secondary end-point) across the three treatment groups. Two-year freedom from bleedings in the LOW, VLO, and VLT groups was 96.3, 98.6, and 99.1%, respectively (P = 0.008). The corresponding values for thrombotic events were 99.0, 99.8, and 98.9%, respectively (P = 0.258). The risk-adjusted composite of grade III complications was in the per-protocol population (reference: LOW-dose group) as follows: hazard ratio = 0.307 (95% CI: 0.102-0.926; P = 0.036) for the VLO group and = 0.241 (95% CI: 0.070-0.836; P = 0.025) for the VLT group. The corresponding values of 2-year mortality were = 1.685 (95% CI: 0.473-5.996; P = 0.421) for the VLO group and = 4.70 (95% CI: 1.62-13.60; P = 0.004) for the VLT group. Telemedicine-guided very low-dose INR self-control is comparable with low-dose INR in thrombotic risk, and is superior in bleeding risk. Weekly testing is sufficient. Given the small number of MVR and DVR patients, results are only valid for AVR patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  5. Contribution of rivaroxaban to the international normalized ratio when switching to warfarin for anticoagulation as determined by simulation studies.

    Science.gov (United States)

    Siegmund, Hans-Ulrich; Burghaus, Rolf; Kubitza, Dagmar; Coboeken, Katrin

    2015-06-01

    This study evaluated the influence of rivaroxaban 20 mg once daily on international normalized ratio (INR) during the co-administration period when switching from rivaroxaban to warfarin. We developed a calibrated coagulation model that was qualified with phase I clinical data. Prothrombin time and INR values were simulated by use of phospholipid concentrations that matched Neoplastin Plus® and Innovin® reagents. To simulate the combined effects of rivaroxaban and warfarin on INR during switching, warfarin initiation was simulated by adjusting the magnitude of the warfarin effect to reach the desired target INRs over the course of 21 days. The warfarin effect values (obtained every 6 h) and the desired rivaroxaban plasma concentrations were used. Nomograms were generated from rivaroxaban induced increases in INR. The simulation had good prediction quality. Rivaroxaban induced increases in the total INR from the warfarin attributed INR were seen, which increased with rivaroxaban plasma concentration. When the warfarin only INR was 2.0-3.0, the INR contribution of rivaroxaban with Neoplastin Plus® was 0.5-1.2, decreasing to 0.3-0.6 with Innovin® at median trough rivaroxaban plasma concentrations (38 μg l(-1) ). The data indicate that measuring warfarin induced changes in INR are best performed at trough rivaroxaban concentrations (24 h after rivaroxaban dosing) during the co-administration period when switching from rivaroxaban to warfarin. Furthermore, Innovin® is preferable to Neoplastin Plus® because of its substantially lower sensitivity to rivaroxaban, thereby reducing the influence of rivaroxaban on the measured INR. © 2014 The British Pharmacological Society.

  6. Safety and Outcomes of Transradial Access in Patients with International Normalized Ratio 1.5 or above.

    Science.gov (United States)

    Titano, Joseph J; Biederman, Derek M; Zech, John; Korff, Ricki; Ranade, Mona; Patel, Rahul; Kim, Edward; Nowakowski, Francis; Lookstein, Robert; Fischman, Aaron M

    2018-03-01

    To examine the safety and outcomes for patients undergoing transradial noncoronary interventions with international normalized ratio (INR) ≥1.5. A retrospective review of 2,271 transradial access (TRA) cases performed from July 2012 to July 2016 was conducted. Criteria for inclusion were moderate bleeding risk cases with preprocedure INR ≥1.5. Within the study period, there were 176 moderate bleeding risk procedures (transarterial chemoembolization: 70/176 [39.8%]; Barbeau B: 121/176 [68.8%]; 5-F sheath: 157/176 [89.2%]) performed on 122 patients (age 61.6 ± 12.1 years, 68.9% male, body mass index 28.0 kg/m 2 ) with INR ≥1.5. Technical success was achieved in 98.9% of cases. Grade 1/2 hematomas developed in 10 cases (5.7%). Age ≥65 years (P = .042) and female sex (P = .046) were predictive of access site bleeding complications. Fresh frozen plasma (FFP) transfusion was administered in 11.4% of cases (n = 20). Baseline INR and creatinine were significantly different between transfused and nontransfused cases (P values .006 and .028, respectively). Minor access site bleeding occurred in 3/20 cases (15%) receiving prior FFP transfusion and 7/156 nontransfused cases (4.5%), with no significant difference between these 2 groups (P = .072). TRA in patients with elevated INR appears to be safe in our experience. Age ≥65 years and female sex were associated with increased incidence of access site bleeding. Although INR correction was not standardized in this cohort, preprocedure FFP transfusion did not decrease bleeding complications. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  7. Moderate alcohol use and cardiovascular disease from Mendelian randomization.

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    Shiu Lun Au Yeung

    Full Text Available BACKGROUND: Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD and cardiovascular disease (CVD. However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use. METHODS: We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2 genotypes (AA/GA/GG as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day with CVD risk factors (blood pressure, lipids and glucose and morbidity (self-reported IHD and CVD among men in the Guangzhou Biobank Cohort Study. RESULTS: ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6. Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI 0.02 to 0.08 and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07 but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74, LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08, log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08 or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03, self-reported CVD (odds ratio (OR 0.98, 95% CI 0.76 to 1.27 or self-reported IHD (OR 1.10, 95% CI 0.83 to 1.45. CONCLUSION: Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose.

  8. Childhood adiposity and risk of type 1 diabetes: A Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    J C Censin

    2017-08-01

    Full Text Available The incidence of type 1 diabetes (T1D is increasing globally. One hypothesis is that increasing childhood obesity rates may explain part of this increase, but, as T1D is rare, intervention studies are challenging to perform. The aim of this study was to assess this hypothesis with a Mendelian randomization approach that uses genetic variants as instrumental variables to test for causal associations.We created a genetic instrument of 23 single nucleotide polymorphisms (SNPs associated with childhood adiposity in children aged 2-10 years. Summary-level association results for these 23 SNPs with childhood-onset (<17 years T1D were extracted from a meta-analysis of genome-wide association study with 5,913 T1D cases and 8,828 reference samples. Using inverse-variance weighted Mendelian randomization analysis, we found support for an effect of childhood adiposity on T1D risk (odds ratio 1.32, 95% CI 1.06-1.64 per standard deviation score in body mass index [SDS-BMI]. A sensitivity analysis provided evidence of horizontal pleiotropy bias (p = 0.04 diluting the estimates towards the null. We therefore applied Egger regression and multivariable Mendelian randomization methods to control for this type of bias and found evidence in support of a role of childhood adiposity in T1D (odds ratio in Egger regression, 2.76, 95% CI 1.40-5.44. Limitations of our study include that underlying genes and their mechanisms for most of the genetic variants included in the score are not known. Mendelian randomization requires large sample sizes, and power was limited to provide precise estimates. This research has been conducted using data from the Early Growth Genetics (EGG Consortium, the Genetic Investigation of Anthropometric Traits (GIANT Consortium, the Tobacco and Genetics (TAG Consortium, and the Social Science Genetic Association Consortium (SSGAC, as well as meta-analysis results from a T1D genome-wide association study.This study provides genetic support for a

  9. CARDIOTHORACIC RATIO AND VERTEBRAL HEART SCALE IN CLINICALLY NORMAL BLACK-RUMPED AGOUTIS (DASYPROCTA PRYMNOLOPHA, WAGLER 1831).

    Science.gov (United States)

    de Moura, Charlys Rhands Coelho; das Neves Diniz, Anaemilia; da Silva Moura, Laecio; das Chagas Araújo Sousa, Francisco; Baltazar, Pollyana Irene; Freire, Larisse Danielle; Guerra, Porfírio Candanedo; de Sousa, João Macedo; Giglio, Robson Fortes; Pessoa, Gerson Tavares; de Sá, Renan Paraguassu; Alves, Flávio Ribeiro

    2015-06-01

    Wild rodents, such as the lowland paca (Cuniculus paca), capybara (Hydrochoerus hydrochaeris), rock cavy (Kerodon rupestris), guinea pig (Cavia aperea), and black-rumped agouti (Dasyprocta prymnolopha) are intensely hunted throughout Amazonia and at the semiarid regions of northeastern Brazil. To contribute to the preservation of these species, more information about their anatomy, physiology and pathophysiology is needed. The aim of this study was to standardize the vertebral heart scale (VHS) and cardiothoracic ratio (CTR) in clinically normal black-rumped agouti, as well as to compare the results of these two methods, which are commonly used to evaluate the cardiac silhouette in domestic animals. Twelve healthy black-rumped agoutis, divided into two groups (six males and six females), obtained from the Nucleus for Wild Animal Studies and Conservation at the Federal University of Piauí, were radiographed in right and left lateral and dorsoventral projections. The values of the VHS were 8.00±0.31v (the number of thoracic vertebral length spanned by each dimension, starting at T4) for males and 8.11±0.41v for females, and there was no statistical difference between the decubitus (right and left) or between males and females (P>0.05). The CTR mean values obtained were 0.51±0.03 for males, and 0.52±0.02 for females, and there was no statistical difference between the genders (P>0.05). However, there was positive correlation between VHS and CTR (r=0.77 right decubitus and r=0.82 left decubitus). The thoracic and heart diameter had mean values of 6.72±0.61 and 3.48±0.30 cm (males), and for the females, it was 6.61±0.51 and 3.5±0.30 cm, respectively, and there was statistical difference between the genders. The results demonstrated high correlation between the VHS and CTR producing similar results, indicating similar clinical precision for assessing the size of the cardiac silhouette in the black-rumped agoutis.

  10. Biodistribution, pharmacokinetics and uptake ratio of 131I-4-Iodo-phenylacetic acid in normal and tumour implied animals

    International Nuclear Information System (INIS)

    Szuecs, Z.; Sello, T.; Sathekge, M.

    2012-01-01

    per gram of tissue (%ID/g) is given in Table 1 for nine animals as three were considered outliers predominantly due to a high percentage of activity remaining in the tail after injection. The tumour to background ratio was calculated by comparing the muscle on the left flank as opposed to the right flank where the tumour was induced. The labeling via isotopic exchange did yield a low specific activity of the tracer which meant that a substantial amount of 4-iodo-phenylacetic acid was injected. This would amount to 30 μg per rat or 75 μg/kg or 1.1 μg/ml blood (mass of rats 400g and assuming 7% of body weight is blood). The LD50 value for phenyl acetic acid is 1600 mg/kg for intraperitoneal injection in rats which is orders of magnitude higher than the amount injected and therefore one can assume the 0,075 mg/kg injected 4-iodo-phenyl-acetic acid would not adversely interfere with the biological processes in the rat. The amount of phenyl-acetic acid in normal tissue is 16.8 μg/ml which is also a two orders of magnitude higher than the amount of 4-iodophenyl-acetic acid injected. This implies that the biodistribution of the tracer was not influenced by its metabolic product due to equilibrium with phenyl-acetic acid already present in the body. 131 I-4-iodo-phenyl-acetic acid was successfully prepared and the biodistribution in rats recorded. As expected no target organ was found after 5 h (although at the early stages a high cardiac blood pool uptake was recorded) with fast excretion from all organs via the kidney into the urine. In xenograft mice study a 4% tumour uptake and a tumour to background ratio of 2 was recorded after 5 h although high activity levels in the blood still remained at this time point.

  11. Relationship between iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid washout ratio and oxygen consumption in normal and ischemic myocardium

    International Nuclear Information System (INIS)

    Saito, Kimimasa; Okamoto, Ryuji; Saito, Yasuhiro

    1997-01-01

    The relationship between oxygen consumption and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid ( 123 I-BMIPP) washout at rest and after exercise was investigated in normal and ischemic myocardium. Sixteen healthy volunteers and 14 patients with ischemic heart disease were examined. After injection of 111 MBq of 123 I-BMIPP, serial single photon emission computed tomography imaging was performed to evaluate washout ratio after 30 min and 1 hour of rest and after exercise. In the volunteers, the mean washout ratio was 3.3±3.5% after 1 hour of rest and increased during exercise. The exercise washout ratio showed a better correlation with net pressure rate product (net PRP: cumulative values of PRP during exercise) than with the peak PRP. The exercise washout ratio showed a strong correlation with the net PRP in the range from 180 to 300x10 3 mmHg·beat/min and a plateau of 10-15%. In the nine ischemic patients with net PRP≥300x10 3 mmHg·beat/min, the exercise washout ratio values were significantly elevated in normal segments relative to ischemic segments (10.1±1.9% vs 4.7±2.9%, p 3 mmHg·beat/min, washout ratio at rest and after exercise did not differ significantly between normal and ischemic segments. 123 I-BMIPP washout ratio increased with increased oxygen consumption during exercise in normal myocardium but not in ischemic myocardium. The patient must exercise before fatty acid metabolism can be compared between normal and ischemic myocardium. (author)

  12. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

    Science.gov (United States)

    Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey

    2013-09-26

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. High-resolution computed tomography evaluation of the bronchial lumen to vertebral body diameter and pulmonary artery to vertebral body diameter ratios in anesthetized ventilated normal cats.

    Science.gov (United States)

    Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Tillson, D Michael; Garbarino, Rachel; Barney, Sharron

    2017-10-01

    Objectives Bronchial lumen to pulmonary artery diameter (BA) ratio has been utilized to investigate pulmonary pathology on high-resolution CT images. Diseases affecting both the bronchi and pulmonary arteries render the BA ratio less useful. The purpose of the study was to establish bronchial lumen diameter to vertebral body diameter (BV) and pulmonary artery diameter to vertebral body diameter (AV) ratios in normal cats. Methods Using high-resolution CT images, 16 sets of measurements (sixth thoracic vertebral body [mid-body], each lobar bronchi and companion pulmonary artery diameter) were acquired from young adult female cats and 41 sets from pubertal female cats. Results Young adult and pubertal cat BV ratios were not statistically different from each other in any lung lobe. Significant differences between individual lung lobe BV ratios were noted on combined age group analysis. Caudal lung lobe AV ratios were significantly different between young adult and pubertal cats. All other lung lobe AV ratios were not significantly different. Caudal lung lobe AV ratios were significantly different from all other lung lobes but not from each other in both the young adult and pubertal cats. Conclusions and relevance BV ratio reference intervals determined for individual lung lobes could be applied to both young adult and pubertal cats. Separate AV ratios for individual lung lobes would be required for young adult and pubertal cats. These ratios should allow more accurate evaluation of cats with concurrent bronchial and pulmonary arterial disease.

  14. Comparison of hematocrit/hemoglobin ratios in subjects with alpha-thalassemia, with subjects having chronic kidney disease and normal subjects.

    Science.gov (United States)

    Insiripong, Somchai; Supattarobol, Tanarat; Jetsrisuparb, Arunee

    2013-07-04

    The ratio of hematocrit (Hct) to hemoglobin (Hb) in the people with normal red blood cell (RBC) morphology is generally three to one. We studied Hct/Hb ratios among patients with alpha-thalassemias (Hb H, H-CS, AEBart, AEBart-CS, EFBart and EFBart-CS diseases) diagnosed by high performance liquid chromatography, and compared them with normal subjects and with patients having anemia due to chronic kidney disease (CKD). The Hct and Hb levels were derived by automated analyzer. The means +/- SD of the Hct/Hb ratios were 3.5 +/- 0.2 (range 3.3 - 4.1), 3.0 +/- 0.1 (range 2.9 - 3.2) and 3.0 +/- 0.1 (range 2.8 - 3.2) in the alpha-thalassemia, normal and CKD groups, respectively. The mean Hct/Hb ratio in subjects with alpha-thalassemia was higher than the mean in normal subjects and in those with CKD. The Hct/Hb ratios for each genotype of the alpha-thalassemia were not different from each other. The underlying mechanisms for the higher Hct/Hb ratio among those with alpha-thalassemia are theorized to be less density and/or more hydration of a-thalassemia RBCs, more entrapment of plasma in the spun RBC, the high percent of nucleated RBC and WBC interference. A ratio of 3.5 +/- 0.2 may be helpful in cases of moderate anemia when typing only shows Hb A and E, to consider investigation for alpha-thalassemia, or in cases of alpha-thalassemia with acute blood loss, if the Hct is less than 35%, in the decision to transfuse.

  15. Extracting real-crack properties from non-linear elastic behaviour of rocks: abundance of cracks with dominating normal compliance and rocks with negative Poisson ratios

    Directory of Open Access Journals (Sweden)

    V. Y. Zaitsev

    2017-09-01

    Full Text Available Results of examination of experimental data on non-linear elasticity of rocks using experimentally determined pressure dependences of P- and S-wave velocities from various literature sources are presented. Overall, over 90 rock samples are considered. Interpretation of the data is performed using an effective-medium description in which cracks are considered as compliant defects with explicitly introduced shear and normal compliances without specifying a particular crack model with an a priori given ratio of the compliances. Comparison with the experimental data indicated abundance (∼ 80 % of cracks with the normal-to-shear compliance ratios that significantly exceed the values typical of conventionally used crack models (such as penny-shaped cuts or thin ellipsoidal cracks. Correspondingly, rocks with such cracks demonstrate a strongly decreased Poisson ratio including a significant (∼ 45 % portion of rocks exhibiting negative Poisson ratios at lower pressures, for which the concentration of not yet closed cracks is maximal. The obtained results indicate the necessity for further development of crack models to account for the revealed numerous examples of cracks with strong domination of normal compliance. Discovering such a significant number of naturally auxetic rocks is in contrast to the conventional viewpoint that occurrence of a negative Poisson ratio is an exotic fact that is mostly discussed for artificial structures.

  16. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Søren D Østergaard

    2015-06-01

    Full Text Available Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR.We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49, fasting glucose (NSNPs = 36, insulin resistance (NSNPs = 10, body mass index (BMI, NSNPs = 32, total cholesterol (NSNPs = 73, HDL-cholesterol (NSNPs = 71, LDL-cholesterol (NSNPs = 57, triglycerides (NSNPs = 39, systolic blood pressure (SBP, NSNPs = 24, smoking initiation (NSNPs = 1, smoking quantity (NSNPs = 3, university completion (NSNPs = 2, and years of education (NSNPs = 1. We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3. Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8. Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3, although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28. We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1. Potential limitations of this study

  17. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Science.gov (United States)

    Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

    2015-06-01

    Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this

  18. Noncentral Chi-Square versus Normal Distributions in Describing the Likelihood Ratio Statistic: The Univariate Case and Its Multivariate Implication

    Science.gov (United States)

    Yuan, Ke-Hai

    2008-01-01

    In the literature of mean and covariance structure analysis, noncentral chi-square distribution is commonly used to describe the behavior of the likelihood ratio (LR) statistic under alternative hypothesis. Due to the inaccessibility of the rather technical literature for the distribution of the LR statistic, it is widely believed that the…

  19. Correlation of morphological variants of the soft palate and Need's ratio in normal individuals: A digital cephalometric study

    International Nuclear Information System (INIS)

    Verma, Pradhuman; Verma, Kanika Gupta; Sachdeva, Suresh K; Juneja, Suruchi; Kumaraswam; Kikkeri Lakshminarayana; Basavaraju, Suman

    2014-01-01

    The present study was aimed to investigate the variation of soft palate morphology in different age and gender groups. The correlations of radiographic velar length (VL), velar width (VW), pharyngeal depth (PD), and Need's ratio with soft palate variants were also studied in the North Indian subpopulation. The study sample consisted of 300 subjects aged between 15 and 45 (mean: 31.32) years. The velar morphology on lateral cephalograms was examined and grouped into six types. The results obtained were subjected to a statistical analysis to find the correlation between variants of the soft palate with gender and different age groups. The most frequent type of soft palate was leaf shaped (48.7%), and the least common was crook shaped (3.0%) among both the genders and various age groups, showing a significant correlation. The mean VL, VW, and PD values were significantly higher in males and significantly correlated with the types of soft palate. A significant correlation was observed between the mean VL, VW, PD, and Need's ratio with various age groups, showing an inconsistent pattern with an increase in age. The types of soft palate, gender, and Need's ratio were also significantly correlated, with an overall higher mean value of the Need's ratio among female subjects and the S-shaped soft palate. The knowledge of a varied spectrum of velar morphology and the variants of the soft palate help in a better understanding of the velopharyngeal closure and craniofacial anomalies.

  20. The relationship of normal body temperature, end-expired breath temperature, and BAC/BrAC ratio in 98 physically fit human test subjects.

    Science.gov (United States)

    Cowan, J Mack; Burris, James M; Hughes, James R; Cunningham, Margaret P

    2010-06-01

    The relationship between normal body temperature, end-expired breath temperature, and blood alcohol concentration (BAC)/breath alcohol concentration (BrAC) ratio was studied in 98 subjects (84 men, 14 women). Subjects consumed alcohol sufficient to produce a BrAC of at least 0.06 g/210 L 45-75 min after drinking. Breath samples were analyzed using an Intoxilyzer 8000 specially equipped to measure breath temperature. Venous blood samples and body temperatures were then taken. The mean body temperature of the men (36.6 degrees C) was lower than the women (37.0 degrees C); however, their mean breath temperatures were virtually identical (men: 34.5 degrees C; women: 34.6 degrees C). The BAC exceeded the BrAC for every subject. BAC/BrAC ratios were calculated from the BAC and BrAC analytical results. There was no difference in the BAC/BrAC ratios for men (1:2379) and women (1:2385). The correlation between BAC and BrAC was high (r = 0.938, p body temperature and end-expired breath temperature, body temperature and BAC/BrAC ratio, and breath temperature and BAC/BrAC ratio were much lower. Neither normal body temperature nor end-expired breath temperature was strongly associated with BAC/BrAC ratio.

  1. Mendelian and non-mendelian mutations affecting surface antigen expression in Paramecium tetraurelia

    International Nuclear Information System (INIS)

    Epstein, L.M.; Forney, J.D.

    1984-01-01

    A screening procedure was devised for the isolation of X-ray-induced mutations affecting the expression of the A immobilization antigen (i-antigen) in Paramecium tetraurelia. Two of the mutations isolated by this procedure proved to be in modifier genes. The two genes are unlinked to each other and unlinked to the structural A i-antigen gene. These are the first modifier genes identified in a Paramecium sp. that affect surface antigen expression. Another mutation was found to be a deletion of sequences just downstream from the A i-antigen gene. In cells carrying this mutation, the A i-antigen gene lies in close proximity to the end of a macronuclear chromosome. The expression of the A i-antigen is not affected in these cells, demonstrating that downstream sequences are not important for the regulation and expression of the A i-antigen gene. A stable cell line was also recovered which shows non-Mendelian inheritance of a macronuclear deletion of the A i-antigen gene. This mutant does not contain the gene in its macronucleus, but contains a complete copy of the gene in its micronucleus. In the cytoplasm of wild-type animals, the micronuclear gene is included in the developing macronucleus; in the cytoplasm of the mutant, the incorporation of the A i-antigen gene into the macronucleus is inhibited. This is the first evidence that a mechanism is available in ciliates to control the expression of a gene by regulating its incorporation into developing macronuclei

  2. The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study-Brief Report.

    Science.gov (United States)

    Gill, Dipender; Del Greco M, Fabiola; Walker, Ann P; Srai, Surjit K S; Laffan, Michael A; Minelli, Cosetta

    2017-09-01

    Iron status is a modifiable trait that has been implicated in cardiovascular disease. This study uses the Mendelian randomization technique to investigate whether there is any causal effect of iron status on risk of coronary artery disease (CAD). A 2-sample Mendelian randomization approach is used to estimate the effect of iron status on CAD risk. Three loci (rs1800562 and rs1799945 in the HFE gene and rs855791 in TMPRSS6 ) that are each associated with serum iron, transferrin saturation, ferritin, and transferrin in a pattern suggestive of an association with systemic iron status are used as instruments. SNP (single-nucleotide polymorphism)-iron status association estimates are based on a genome-wide association study meta-analysis of 48 972 individuals. SNP-CAD estimates are derived by combining the results of a genome-wide association study meta-analysis of 60 801 CAD cases and 123 504 controls with those of a meta-analysis of 63 746 CAD cases and 130 681 controls obtained from Metabochip and genome-wide association studies. Combined Mendelian randomization estimates are obtained for each marker by pooling results across the 3 instruments. We find evidence of a protective effect of higher iron status on CAD risk (iron odds ratio, 0.94 per SD unit increase; 95% confidence interval, 0.88-1.00; P =0.039; transferrin saturation odds ratio, 0.95 per SD unit increase; 95% confidence interval, 0.91-0.99; P =0.027; log-transformed ferritin odds ratio, 0.85 per SD unit increase; 95% confidence interval, 0.73-0.98; P =0.024; and transferrin odds ratio, 1.08 per SD unit increase; 95% confidence interval, 1.01-1.16; P =0.034). This Mendelian randomization study supports the hypothesis that higher iron status reduces CAD risk. These findings may highlight a therapeutic target. © 2017 American Heart Association, Inc.

  3. Mendelian randomisation analysis provides no evidence for a relationship between adult height and testicular cancer risk.

    Science.gov (United States)

    Levy, M; Hall, D; Sud, A; Law, P; Litchfield, K; Dudakia, D; Haugen, T B; Karlsson, R; Reid, A; Huddart, R A; Grotmol, T; Wiklund, F; Houlston, R S; Turnbull, C

    2017-09-01

    Observational studies have suggested anthropometric traits, particularly increased height are associated with an elevated risk of testicular cancer (testicular germ cell tumour). However, there is an inconsistency between study findings, suggesting the possibility of the influence of confounding factors. To examine the association between anthropometric traits and testicular germ cell tumour using an unbiased approach, we performed a Mendelian randomisation study. We used genotype data from genome wide association studies of testicular germ cell tumour totalling 5518 cases and 19,055 controls. Externally weighted polygenic risk scores were created and used to evaluate associations with testicular germ cell tumour risk per one standard deviation (s.d) increase in genetically-defined adult height, adult BMI, adult waist hip ratio adjusted for BMI (WHRadjBMI), adult hip circumference adjusted for BMI (HIPadjBMI), adult waist circumference adjusted for BMI (WCadjBMI), birth weight (BW) and childhood obesity. Mendelian randomisation analysis did not demonstrate an association between any anthropometric trait and testicular germ cell tumour risk. In particular, despite good power, there was no global evidence for association between height and testicular germ cell tumour. However, three SNPs for adult height individually showed association with testicular germ cell tumour (rs4624820: OR = 1.47, 95% CI: 1.41-1.55, p = 2.7 × 10 -57 ; rs12228415: OR = 1.17, 95% CI: 1.11-1.22, p = 3.1 × 10 -10 ; rs7568069: OR = 1.13, 95% CI: 1.07-1.18, p = 1.1 × 10 -6 ). This Mendelian randomisation analysis, based on the largest testicular germ cell tumour genome wide association dataset to date, does not support a causal etiological association between anthropometric traits and testicular germ cell tumour aetiology. Our findings are more compatible with confounding by shared environmental factors, possibly related to prenatal growth with exposure to these risk factors

  4. Importance of Android/Gynoid Fat Ratio in Predicting Metabolic and Cardiovascular Disease Risk in Normal Weight as well as Overweight and Obese Children

    Science.gov (United States)

    Regier, Michael

    2014-01-01

    Numerous studies have shown that android or truncal obesity is associated with a risk for metabolic and cardiovascular disease, yet there is evidence that gynoid fat distribution may be protective. However, these studies have focused on adults and obese children. The purpose of our study was to determine if the android/gynoid fat ratio is positively correlated with insulin resistance, HOMA2-IR, and dislipidemia in a child sample of varying body sizes. In 7–13-year-old children with BMI percentiles ranging from 0.1 to 99.6, the android/gynoid ratio was closely associated with insulin resistance and combined LDL + VLDL-cholesterol. When separated by sex, it became clear that these relationships were stronger in boys than in girls. Subjects were stratified into BMI percentile based tertiles. For boys, the android/gynoid ratio was significantly related to insulin resistance regardless of BMI tertile with and LDL + VLDL in tertiles 1 and 3. For girls, only LDL + VLDL showed any significance with android/gynoid ratio and only in tertile 2. We conclude that the android/gynoid fat ratio is closely associated with insulin resistance and LDL + VLDL-, “bad,” cholesterol in normal weight boys and may provide a measurement of metabolic and cardiovascular disease risk in that population. PMID:25302115

  5. Importance of android/gynoid fat ratio in predicting metabolic and cardiovascular disease risk in normal weight as well as overweight and obese children.

    Science.gov (United States)

    Samsell, Lennie; Regier, Michael; Walton, Cheryl; Cottrell, Lesley

    2014-01-01

    Numerous studies have shown that android or truncal obesity is associated with a risk for metabolic and cardiovascular disease, yet there is evidence that gynoid fat distribution may be protective. However, these studies have focused on adults and obese children. The purpose of our study was to determine if the android/gynoid fat ratio is positively correlated with insulin resistance, HOMA2-IR, and dislipidemia in a child sample of varying body sizes. In 7-13-year-old children with BMI percentiles ranging from 0.1 to 99.6, the android/gynoid ratio was closely associated with insulin resistance and combined LDL + VLDL-cholesterol. When separated by sex, it became clear that these relationships were stronger in boys than in girls. Subjects were stratified into BMI percentile based tertiles. For boys, the android/gynoid ratio was significantly related to insulin resistance regardless of BMI tertile with and LDL + VLDL in tertiles 1 and 3. For girls, only LDL + VLDL showed any significance with android/gynoid ratio and only in tertile 2. We conclude that the android/gynoid fat ratio is closely associated with insulin resistance and LDL + VLDL-, "bad," cholesterol in normal weight boys and may provide a measurement of metabolic and cardiovascular disease risk in that population.

  6. Does higher education protect against obesity? Evidence using Mendelian randomization.

    Science.gov (United States)

    Böckerman, Petri; Viinikainen, Jutta; Pulkki-Råback, Laura; Hakulinen, Christian; Pitkänen, Niina; Lehtimäki, Terho; Pehkonen, Jaakko; Raitakari, Olli T

    2017-08-01

    The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization. Participants (N=2011) were from the on-going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m 2 ) measurements in 2007 and 2011 and genetic information were linked to comprehensive register-based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization and used a genetic score as an instrument for education. The genetic score was based on 74 genetic variants that genome-wide association studies (GWASs) have found to be associated with the years of education. Because the genotypes are randomly assigned at conception, the instrument causes exogenous variation in the years of education and thus enables identification of causal effects. The years of education in 2007 were associated with lower BMI in 2007/2011 (regression coefficient (b)=-0.22; 95% Confidence Intervals [CI]=-0.29, -0.14) according to the linear regression results. The results based on Mendelian randomization suggests that there may be a negative causal effect of education on BMI (b=-0.84; 95% CI=-1.77, 0.09). The findings indicate that education could be a protective factor against obesity in advanced countries. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Optic Disc Change during Childhood Myopic Shift: Comparison between Eyes with an Enlarged Cup-To-Disc Ratio and Childhood Glaucoma Compared to Normal Myopic Eyes.

    Directory of Open Access Journals (Sweden)

    Hae-Young Lopilly Park

    Full Text Available Progressive disc tilting and the development or enlargement of peripapillary atrophy (PPA are observed during a myopic shift in children. This could be related to the changes around the optic nerve head during eyeball elongation. If the biomechanical properties at or around the optic nerve head are changed after exposure to elevated intraocular pressure (IOP in glaucoma eyes, different response of the disc tilting and PPA changes could take place during eyeball elongation by myopic shift. On the basis of this background, the aim of this study was to compare the morphological changes in the optic disc induced by a myopic shift during childhood between normal control eyes, eyes from disc suspects with an enlarged cup-to-disc ratio (CDR, and eyes with childhood glaucoma.Total of 82 eyes from 82 subjects younger than 14 years of age were included in the study. Serial disc photographs were classified into one of two groups: eyes with an optic nerve head (ONH or peripapillary atrophy (PPA change or without an ONH/PPA change. Using ImageJ software, the outlines of the optic disc and PPA were plotted, and the vertical disc diameter (VDD, horizontal disc diameter (HDD, and maximum PPA width (PPW were measured. The changes in the ratios of these parameters and the relationships between the degree of myopic shift or the ONH/PPA change were analyzed.Twenty-five eyes with normal optic disc appearance, 36 eyes with enlarged cup-to-disc ratio, and 21 eyes of glaucoma patients were analyzed. The initial intraocular pressure (IOP at diagnosis was significantly different among the groups (P<0.001. The degree of myopic shift during follow-up period was not significantly different among the groups (P=0.612. However, the changes in the HDD/VDD and PPW/VDD ratios were significantly greater in the disc suspect group and significantly smaller in the glaucoma group. Among the 42 eyes with an ONH/PPA change, 16 (38.1% were from the normal control group, 24 (57.1% were

  8. Autonomic Neuropathy—a Prospective Cohort Study of Symptoms and E/I Ratio in Normal Glucose Tolerance, Impaired Glucose Tolerance, and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Malin Zimmerman

    2018-03-01

    Full Text Available BackgroundAutonomic neuropathy in diabetes, in addition to causing a range of symptoms originating from the autonomic nervous system, may increase cardiovascular morbidity. Our aim was to study the progression of autonomic neuropathy, based on symptom score and evaluation of an autonomic test, in persons with normal and impaired glucose tolerance and in patients with type 2 diabetes (T2D.MethodsParticipants were recruited in 2003/2004 with a follow-up in 2014. The participants’ glucose tolerance was categorized using oral glucose tolerance tests. Symptoms were evaluated using an autonomic symptom score (ASS, ECG was used to test cardiac autonomic function based on the expiration/inspiration ratio (E/I ratio, and blood samples were taken on both occasions.ResultsASSs were higher at follow-up in the T2D patients than in the normal glucose tolerance group (mean 1.21 ± 1.30 vs. 0.79 ± 0.7; p < 0.05. E/I ratio did not deteriorate more than could be expected as an aging effect in well-controlled T2D. No relationship was found between E/I ratio and HbA1c or ASS.ConclusionThe presence of autonomic symptoms increased over time in T2D patients, but the symptoms did not correlate with the E/I ratio in this metabolically well-controlled cohort. ASSs can be a useful clinical tool when assessing the progression of autonomic dysfunction in patients with abnormal glucose metabolism.

  9. Common variants in mendelian kidney disease genes and their association with renal function

    NARCIS (Netherlands)

    A. Parsa (Afshin); C. Fuchsberger (Christian); A. Köttgen (Anna); C.M. O'Seaghdha (Conall); C. Pattaro (Cristian); M. de Andrade (Mariza); D.I. Chasman (Daniel); A. Teumer (Alexander); K. Endlich (Karlhans); M. Olden (Matthias); M-H. Chen (Ming-Huei); A. Tin (Adrienne); Y-J. Kim (Yong-Jin); D. Taliun (Daniel); M. Li (Man); M.F. Feitosa (Mary Furlan); M. Gorski (Mathias); Q. Yang (Qiong); C. Hundertmark (Claudia); M.C. Foster (Michael); N. Glazer (Nicole); A.J. Isaacs (Aaron); M. Rao (Madhumathi); G.D. Smith; J.R. O´Connell; M.V. Struchalin (Maksim); T. Tanaka (Toshiko); G. Li (Guo); S.J. Hwang; E.J. Atkinson (Elizabeth); K. Lohman (Kurt); M. Cornelis (Marilyn); A. Johansson (Åsa); A. Tönjes (Anke); A. Dehghan (Abbas); V. Couraki (Vincent); E.G. Holliday (Elizabeth); R. Sorice; Z. Kutalik (Zoltán); T. Lehtimäki (Terho); T. Esko (Tõnu); H. Deshmukh (Harshal); S. Ulivi (Shelia); A.Y. Chu (Audrey); D. Murgia (Daniela); S. Trompet (Stella); M. Imboden (Medea); B. Kollerits (Barbara); G. Pistis (Giorgio); T.B. Harris (Tamara); L.J. Launer (Lenore); T. Aspelund (Thor); G. Eiriksdottir (Gudny); B.D. Mitchell (Braxton); E.A. Boerwinkle (Eric); H. Schmidt (Helena); E. Hofer (Edith); F.B. Hu (Frank); A. Demirkan (Ayşe); B.A. Oostra (Ben); S.T. Turner (Stephen); J. Ding (Jingzhong); J.S. Andrews (Jeanette); B.I. Freedman (Barry); F. Giulianini (Franco); W. Koenig (Wolfgang); T. Illig (Thomas); A. Döring (Angela); H.E. Wichmann (Heinz Erich); L. Zgaga (Lina); T. Zemunik (Tatijana); M. Boban (Mladen); C. Minelli (Cosetta); H.E. Wheeler (Heather); W. Igl (Wilmar); G. Zaboli (Ghazal); S.H. Wild (Sarah); A.F. Wright (Alan); H. Campbell (Harry); D. Ellinghaus (David); U. Nöthlings (Ute); G. Jacobs (Gunnar); R. Biffar (Reiner); F.D.J. Ernst (Florian); G. Homuth (Georg); H.K. Kroemer (Heyo); M. Nauck (Matthias); S. Stracke (Sylvia); U. Vol̈ker (Uwe); H. Völzke (Henry); P. Kovacs (Peter); M. Stumvoll (Michael); R. Mägi (Reedik); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); Y.S. Aulchenko (Yurii); O. Polasek (Ozren); N. Hastie (Nick); V. Vitart (Veronique); C. Helmer (Catherine); J.J. Wang (Jie Jin); B. Stengel (Bernd); D. Ruggiero; S.M. Bergmann (Sven); M. Kähönen (Mika); J. Viikari (Jorma); T. Nikopensius (Tiit); M.A. Province (Mike); H.M. Colhoun (H.); A.S.F. Doney (Alex); A. Robino (Antonietta); B.K. Krämer (Bernhard); L. Portas (Laura); I. Ford (Ian); B.M. Buckley (Brendan M.); M. Adam (Martin); G.-A. Thun (Gian-Andri); B. Paulweber (Bernhard); M. Haun (Margot); C. Sala (Cinzia); P. Mitchell (Paul); M. Ciullo; P. Vollenweider (Peter); O. Raitakari (Olli); A. Metspalu (Andres); C.N.A. Palmer (Colin); P. Gasparini (Paolo); M. Pirastu (Mario); J.W. Jukema (Jan Wouter); N.M. Probst-Hensch (Nicole M.); F. Kronenberg (Florian); D. Toniolo (Daniela); V. Gudnason (Vilmundur); A.R. Shuldiner (Alan); J. Coresh (Josef); R. Schmidt (Reinhold); L. Ferrucci (Luigi); C.M. van Duijn (Cornelia); I.B. Borecki (Ingrid); S.L.R. Kardia (Sharon); Y. Liu (YongMei); G.C. Curhan (Gary); I. Rudan (Igor); U. Gyllensten (Ulf); J.F. Wilson (James); A. Franke (Andre); P.P. Pramstaller (Peter Paul); R. Rettig (Rainer); I. Prokopenko (Inga); J.C.M. Witteman (Jacqueline); C. Hayward (Caroline); P.M. Ridker (Paul); M. Bochud (Murielle); I.M. Heid (Iris); D.S. Siscovick (David); C.S. Fox (Caroline); W.H.L. Kao (Wen); C.A. Böger (Carsten)

    2013-01-01

    textabstractMany common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with

  10. The patients' perspective of international normalized ratio self-testing, remote communication of test results and confidence to move to self-management.

    Science.gov (United States)

    Grogan, Anne; Coughlan, Michael; Prizeman, Geraldine; O'Connell, Niamh; O'Mahony, Nora; Quinn, Katherine; McKee, Gabrielle

    2017-12-01

    To elicit the perceptions of patients, who self-tested their international normalized ratio and communicated their results via a text or phone messaging system, to determine their satisfaction with the education and support that they received and to establish their confidence to move to self-management. Self-testing of international normalized ratio has been shown to be reliable and is fast becoming common practice. As innovations are introduced to point of care testing, more research is needed to elicit patients' perceptions of the self-testing process. This three site study used a cross-sectional prospective descriptive survey. Three hundred and thirty patients who were prescribed warfarin and using international normalized ratio self-testing were invited to take part in the study. The anonymous survey examined patient profile, patients' usage, issues, perceptions, confidence and satisfaction with using the self-testing system and their preparedness for self-management of warfarin dosage. The response rate was 57% (n = 178). Patients' confidence in self-testing was high (90%). Patients expressed a high level of satisfaction with the support received, but expressed the need for more information on support groups, side effects of warfarin, dietary information and how to dispose of needles. When asked if they felt confident to adjust their own warfarin levels 73% agreed. Chi-squared tests for independence revealed that none of the patient profile factors examined influenced this confidence. The patients cited the greatest advantages of the service were reduced burden, more autonomy, convenience and ease of use. The main disadvantages cited were cost and communication issues. Patients were satisfied with self-testing. The majority felt they were ready to move to self-management. The introduction of innovations to remote point of care testing, such as warfarin self-testing, needs to have support at least equal to that provided in a hospital setting. © 2017 John

  11. Tritium distribution ratios between the 30 % tributyl phosphate(TBP)-normal dodecane(nDD) organic phase and uranyl nitrate-nitric acid aqueous phase

    International Nuclear Information System (INIS)

    Fujine, Sachio; Uchiyama, Gunzou; Sugikawa, Susumu; Maeda, Mitsuru; Tsujino, Takeshi.

    1989-10-01

    Tritium distribution ratios between the organic and aqueous phases were measured for the system of 30 % tributyl phosphate(TBP)-normal dodecane(nDD)/uranyl nitrate-nitric acid water. It was confirmed that tritium is extracted by TBP into the organic phase in both chemical forms of tritiated water (HTO) and tritiated nitric acid (TNO 3 ). The value of tritium distribution ratio ranged from 0.002 to 0.005 for the conditions of 0-6 mol/L nitric acid, 0.5-800 mCi/L tritium in aqueous phase, and 0-125 g-U/L uranium in organic phase. Isotopic distribution coefficient of tritium between the organic and aqueous phases was observed to be about 0.95. (author)

  12. Fish to meat intake ratio and cooking oils are associated with hepatitis C virus carriers with persistently normal alanine aminotransferase levels.

    Science.gov (United States)

    Otsuka, Momoka; Uchida, Yuki; Kawaguchi, Takumi; Taniguchi, Eitaro; Kawaguchi, Atsushi; Kitani, Shingo; Itou, Minoru; Oriishi, Tetsuharu; Kakuma, Tatsuyuki; Tanaka, Suiko; Yagi, Minoru; Sata, Michio

    2012-10-01

      Dietary habits are involved in the development of chronic inflammation; however, the impact of dietary profiles of hepatitis C virus carriers with persistently normal alanine transaminase levels (HCV-PNALT) remains unclear. The decision-tree algorithm is a data-mining statistical technique, which uncovers meaningful profiles of factors from a data collection. We aimed to investigate dietary profiles associated with HCV-PNALT using a decision-tree algorithm.   Twenty-seven HCV-PNALT and 41 patients with chronic hepatitis C were enrolled in this study. Dietary habit was assessed using a validated semiquantitative food frequency questionnaire. A decision-tree algorithm was created by dietary variables, and was evaluated by area under the receiver operating characteristic curve analysis (AUROC).   In multivariate analysis, fish to meat ratio, dairy product and cooking oils were identified as independent variables associated with HCV-PNALT. The decision-tree algorithm was created with two variables: a fish to meat ratio and cooking oils/ideal bodyweight. When subjects showed a fish to meat ratio of 1.24 or more, 68.8% of the subjects were HCV-PNALT. On the other hand, 11.5% of the subjects were HCV-PNALT when subjects showed a fish to meat ratio of less than 1.24 and cooking oil/ideal bodyweight of less than 0.23 g/kg. The difference in the proportion of HCV-PNALT between these groups are significant (odds ratio 16.87, 95% CI 3.40-83.67, P = 0.0005). Fivefold cross-validation of the decision-tree algorithm showed an AUROC of 0.6947 (95% CI 0.5656-0.8238, P = 0.0067).   The decision-tree algorithm disclosed that fish to meat ratio and cooking oil/ideal bodyweight were associated with HCV-PNALT. © 2012 The Japan Society of Hepatology.

  13. Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.

    Science.gov (United States)

    Borges, Maria Carolina; Barros, Aluísio J D; Ferreira, Diana L Santos; Casas, Juan Pablo; Horta, Bernardo Lessa; Kivimaki, Mika; Kumari, Meena; Menon, Usha; Gaunt, Tom R; Ben-Shlomo, Yoav; Freitas, Deise F; Oliveira, Isabel O; Gentry-Maharaj, Aleksandra; Fourkala, Evangelia; Lawlor, Debbie A; Hingorani, Aroon D

    2017-12-01

    Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis -acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population. Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant. © 2017 The Authors.

  14. Bilirubin and Stroke Risk Using a Mendelian Randomization Design.

    Science.gov (United States)

    Lee, Sun Ju; Jee, Yon Ho; Jung, Keum Ji; Hong, Seri; Shin, Eun Soon; Jee, Sun Ha

    2017-05-01

    Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. The 14 single-nucleotide polymorphisms (SNPs) (bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPs selected from the top SNPs. Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPs (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke. © 2017 American Heart Association, Inc.

  15. Distribution pattern of urine albumin creatinine ratio and the prevalence of high-normal levels in untreated asymptomatic non-diabetic hypertensive patients.

    Science.gov (United States)

    Ohmaru, Natsuki; Nakatsu, Takaaki; Izumi, Reishi; Mashima, Keiichi; Toki, Misako; Kobayashi, Asako; Ogawa, Hiroko; Hirohata, Satoshi; Ikeda, Satoru; Kusachi, Shozo

    2011-01-01

    Even high-normal albuminuria is reportedly associated with cardiovascular events. We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels. The UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR ≥30 and creatinine and a UCAR ≥300 µg/mg·creatinine, respectively. The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 µg/mg·creatinine, respectively. When a high-normal UACR was set at >20 to creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Microalbuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR. The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

  16. Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase.

    Directory of Open Access Journals (Sweden)

    Young-Il Kim

    Full Text Available The role of serum alpha-fetoprotein (AFP levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment.A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4-8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence.The etiology of HCC was related to chronic hepatitis B virus (HBV infection in 562 patients (77.8%, chronic hepatitis C virus (HCV infection in 74 (10.2%, and non-viral cause in 86 (11.9%. There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001 and non-viral causes (p<0.05, and limited only to patients who had normal alanine aminotransferase (ALT levels.Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT.

  17. Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase

    Science.gov (United States)

    Park, Joong-Won

    2016-01-01

    Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT. PMID:27304617

  18. Effect of second to first normal stress difference ratio at the die exit on neck-in phenomenon in polymeric flat film production

    Science.gov (United States)

    Barborik, Tomas; Zatloukal, Martin

    2017-05-01

    In this study, viscoelastic modeling of the extrusion film casting process, based on the lD membrane model and modified Leonov constitutive equation, was conducted and the effect of the viscoelastic stress state at the die exit (captured here via second to first normal stress difference ratio) on the unwanted neck-in phenomenon has been analyzed for wide range of Deborah numbers and materials having different level of uniaxial and planar extensional strain hardening. Relevant experimental data for LDPE and theoretical predictions based on multimode eXtended Pom-Pom model acquired from the open literature were used for the validation purposes. It was found that firstly, the predicting capabilities of both constitutive equations for given material and processing conditions are comparable even if the single mode modified Leonov model was used and secondly, the agreement between theoretical and experimental data on neck-in is fairly good. Results of the theoretical study revealed that the viscoelastic stress state at the die exit (i.e. -N2/N1 ratio) increases the level of neck-in if uniaxial extensional strain hardening, planar to uniaxial extensional viscosity ratio and Deborah number increases. It has also been revealed that there exists threshold value for Deborah number and extensional strain hardening below which the neck-in becomes independent on the die exit stress state.

  19. Sex ratio at birth: scenario from normal- and high-level natural radiation areas of Kerala coast in south-west India

    International Nuclear Information System (INIS)

    Koya, P.K.M.; Jaikrishan, G.; Sudheer, K.R.; Madhusoodhanan, M.; Jagadeesan, C.K.; Das, Birajalaxmi; Andrews, V.J.

    2015-01-01

    Newborns were monitored for congenital malformations in four government hospitals located in high-level (ambient dose >1.5 mGy/year) and normal-level (≤1.5 mGy/year) natural radiation areas of Kerala, India, from August 1995 to December 2012. Sex ratio at birth (SRB) among live singleton newborns and among previous children, if any, of their mothers without history of any abortion, stillbirth or twins is reported here. In the absence of environmental stress or selective abortion of females, global average of SRB is about 1050 males to 1000 females. A total of 151,478 singleton, 1031 twins, 12 triplets and 1 quadruplet deliveries were monitored during the study period. Sex ratio among live singleton newborns was 1046 males (95 % CI 1036-1057) for 1000 females (77,153 males:73,730 females) and was comparable to the global average. It was similar in high-level and normal-level radiation areas of Kerala with SRB of 1050 and 1041, respectively. It was consistently more than 1000 and had no association with background radiation levels, maternal and paternal age at birth, parental age difference, gravida status, ethnicity, consanguinity or year of birth. Analysis of SRB of the children of 139,556 women whose reproductive histories were available suggested that couples having male child were likely to opt for more children and this, together with enhanced rate of males at all birth order, was skewing the overall SRB in favour of male children. Though preference for male child was apparent, extreme steps of sex-selective abortion or infanticide were not prevalent. (orig.)

  20. Sex ratio at birth: scenario from normal- and high-level natural radiation areas of Kerala coast in south-west India

    Energy Technology Data Exchange (ETDEWEB)

    Koya, P.K.M.; Jaikrishan, G.; Sudheer, K.R. [Bhabha Atomic Research Centre, Low Level Radiation Research Laboratory, Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Kollam (India); Madhusoodhanan, M. [Victoria Hospital, Department of Paediatrics, Kollam (India); Jagadeesan, C.K. [Directorate of Health Services, Thiruvananthapuram (India); Das, Birajalaxmi [Bhabha Atomic Research Centre, Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Mumbai (India); Andrews, V.J.

    2015-11-15

    Newborns were monitored for congenital malformations in four government hospitals located in high-level (ambient dose >1.5 mGy/year) and normal-level (≤1.5 mGy/year) natural radiation areas of Kerala, India, from August 1995 to December 2012. Sex ratio at birth (SRB) among live singleton newborns and among previous children, if any, of their mothers without history of any abortion, stillbirth or twins is reported here. In the absence of environmental stress or selective abortion of females, global average of SRB is about 1050 males to 1000 females. A total of 151,478 singleton, 1031 twins, 12 triplets and 1 quadruplet deliveries were monitored during the study period. Sex ratio among live singleton newborns was 1046 males (95 % CI 1036-1057) for 1000 females (77,153 males:73,730 females) and was comparable to the global average. It was similar in high-level and normal-level radiation areas of Kerala with SRB of 1050 and 1041, respectively. It was consistently more than 1000 and had no association with background radiation levels, maternal and paternal age at birth, parental age difference, gravida status, ethnicity, consanguinity or year of birth. Analysis of SRB of the children of 139,556 women whose reproductive histories were available suggested that couples having male child were likely to opt for more children and this, together with enhanced rate of males at all birth order, was skewing the overall SRB in favour of male children. Though preference for male child was apparent, extreme steps of sex-selective abortion or infanticide were not prevalent. (orig.)

  1. Rate of transformation and normal range about cardiac size and cardiothoracic ratio according to patient position and age at chest radiography of Korean adult man

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Young Cheol [Dept. of Radiology, Samsung Medical Center, Seoul (Korea, Republic of); Lim, Cheong Hwan; Jung, Hong Ryang [Dept. of Radiological Science, Hanseo University, Seosan (Korea, Republic of); Kim, Yun Min [Dept. of Radiotechnology, Wonkwang Health Science University, Iksan (Korea, Republic of); Hong, Dong Hee [Dept. of Radiological Science, Far East University, Eumseong (Korea, Republic of)

    2017-06-15

    Purpose of this study is present the normal range of cardiac size and cardiothoracic ratio according to patient position(chest PA and AP) and age of Korean adult male on digital chest X - ray, And to propose a mutually compatible conversion rate. 1,024 males were eligible for this study, among 1,300 normal chest patients who underwent chest PA and low-dose CT examinations on the same day at the 'S' Hospital Health Examination Center in Seoul From January to December 2014. CS and CTR were measured by Danzer (1919). The mean difference between CS and CTR was statistically significant (p<0.01) in Chest PA (CS 135.48 mm, CTR 43.99%) and Chest AP image (CS 155.96 mm, CTR 51.75%). There was no statistically significant difference between left and right heart in chest PA and AP images(p>0.05). CS showed statistically significant difference between Chest PA (p>0. 05) and Chest AP (p<0.05). The thorax size and CTR were statistically significant (p<0.01) in both age and chest PA and AP. Result of this study, On Chest AP image CS was magnified 15%, CTR was magnified 17% compare with Chest PA image. CS and CTR were about 10% difference by changing posture at all ages.

  2. Potential for waist-to-height ratio to detect overfat adolescents from a Pacific Island, even those within the normal BMI range.

    Science.gov (United States)

    Frayon, Stéphane; Cavaloc, Yolande; Wattelez, Guillaume; Cherrier, Sophie; Lerrant, Yannick; Ashwell, Margaret; Galy, Olivier

    2017-12-15

    Waist-to-height ratio (WHtR) is a simple anthropometric proxy for central body fat; it is easy to use from a health education perspective. A WHtR value >0.5 has been proposed as a first level indicator of health risk. The first aim of this study was to compare WHtR with values based on body mass index (BMI) in their prediction of the percentage of body fat (%BF) in a multi-ethnic population of adolescents from New-Caledonia (age 11-16year). Secondly, to see whether WHtR >0.5 could be used to detect overfat subjects whose BMI was in the normal range. Body fat percentage (%BF, based on skinfold measurements), BMI and WHtR were calculated for New Caledonian adolescents from different ethnic backgrounds. The relationship between %BF, BMI and WHtR was determined using quadratic models and from linear regression equations. The sensitivity and specificity of WHtR for detecting overfat adolescents (%BF >25% in boys and >30% in girls) were assessed and compared with those from the BMI-based classification. WHtR showed better correlation with %BF than BMI-based measurements. WHtR >0.5 was also more accurate than BMI in detecting overfat adolescents. Moreover, using this boundary value, 8% of adolescents in the normal BMI range were shown to be over-fat. WHtR is a good anthropometric proxy to detect overfat adolescents. Detecting overfat adolescents within the normal BMI range is particularly important for preventing non communicable diseases. We therefore recommend using WHtR for health education programs in the Pacific area and more generally. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  3. Calibration and validation of the relative differenced Normalized Burn Ratio (RdNBR) to three measures of fire severity in the Sierra Nevada and Klamath Mountains, California, USA

    Science.gov (United States)

    Miller, J.D.; Knapp, E.E.; Key, C.H.; Skinner, C.N.; Isbell, C.J.; Creasy, R.M.; Sherlock, J.W.

    2009-01-01

    Multispectral satellite data have become a common tool used in the mapping of wildland fire effects. Fire severity, defined as the degree to which a site has been altered, is often the variable mapped. The Normalized Burn Ratio (NBR) used in an absolute difference change detection protocol (dNBR), has become the remote sensing method of choice for US Federal land management agencies to map fire severity due to wildland fire. However, absolute differenced vegetation indices are correlated to the pre-fire chlorophyll content of the vegetation occurring within the fire perimeter. Normalizing dNBR to produce a relativized dNBR (RdNBR) removes the biasing effect of the pre-fire condition. Employing RdNBR hypothetically allows creating categorical classifications using the same thresholds for fires occurring in similar vegetation types without acquiring additional calibration field data on each fire. In this paper we tested this hypothesis by developing thresholds on random training datasets, and then comparing accuracies for (1) fires that occurred within the same geographic region as the training dataset and in similar vegetation, and (2) fires from a different geographic region that is climatically and floristically similar to the training dataset region but supports more complex vegetation structure. We additionally compared map accuracies for three measures of fire severity: the composite burn index (CBI), percent change in tree canopy cover, and percent change in tree basal area. User's and producer's accuracies were highest for the most severe categories, ranging from 70.7% to 89.1%. Accuracies of the moderate fire severity category for measures describing effects only to trees (percent change in canopy cover and basal area) indicated that the classifications were generally not much better than random. Accuracies of the moderate category for the CBI classifications were somewhat better, averaging in the 50%-60% range. These results underscore the difficulty in

  4. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

    Science.gov (United States)

    Ploner, Alexander; Fischer, Krista; Horikoshi, Momoko; Sarin, Antti-Pekka; Thorleifsson, Gudmar; Ladenvall, Claes; Kals, Mart; Kuningas, Maris; Draisma, Harmen H. M.; Ried, Janina S.; van Zuydam, Natalie R.; Huikari, Ville; Mangino, Massimo; Sonestedt, Emily; Benyamin, Beben; Nelson, Christopher P.; Rivera, Natalia V.; Kristiansson, Kati; Shen, Huei-yi; Havulinna, Aki S.; Dehghan, Abbas; Donnelly, Louise A.; Kaakinen, Marika; Nuotio, Marja-Liisa; Robertson, Neil; de Bruijn, Renée F. A. G.; Ikram, M. Arfan; Amin, Najaf; Balmforth, Anthony J.; Braund, Peter S.; Doney, Alexander S. F.; Döring, Angela; Elliott, Paul; Esko, Tõnu; Franco, Oscar H.; Gretarsdottir, Solveig; Hartikainen, Anna-Liisa; Heikkilä, Kauko; Herzig, Karl-Heinz; Holm, Hilma; Hottenga, Jouke Jan; Hyppönen, Elina; Illig, Thomas; Isaacs, Aaron; Isomaa, Bo; Karssen, Lennart C.; Kettunen, Johannes; Koenig, Wolfgang; Kuulasmaa, Kari; Laatikainen, Tiina; Laitinen, Jaana; Lindgren, Cecilia; Lyssenko, Valeriya; Läärä, Esa; Rayner, Nigel W.; Männistö, Satu; Pouta, Anneli; Rathmann, Wolfgang; Rivadeneira, Fernando; Ruokonen, Aimo; Savolainen, Markku J.; Sijbrands, Eric J. G.; Small, Kerrin S.; Smit, Jan H.; Steinthorsdottir, Valgerdur; Syvänen, Ann-Christine; Taanila, Anja; Tobin, Martin D.; Uitterlinden, Andre G.; Willems, Sara M.; Willemsen, Gonneke; Witteman, Jacqueline; Perola, Markus; Evans, Alun; Ferrières, Jean; Virtamo, Jarmo; Kee, Frank; Tregouet, David-Alexandre; Arveiler, Dominique; Amouyel, Philippe; Ferrario, Marco M.; Brambilla, Paolo; Hall, Alistair S.; Heath, Andrew C.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant W.; Whitfield, John B.; Jula, Antti; Knekt, Paul; Oostra, Ben; van Duijn, Cornelia M.; Penninx, Brenda W. J. H.; Davey Smith, George; Kaprio, Jaakko; Samani, Nilesh J.; Gieger, Christian; Peters, Annette; Wichmann, H.-Erich; Boomsma, Dorret I.; de Geus, Eco J. C.; Tuomi, TiinaMaija; Power, Chris; Hammond, Christopher J.; Spector, Tim D.; Lind, Lars; Orho-Melander, Marju; Palmer, Colin Neil Alexander; Morris, Andrew D.; Groop, Leif; Järvelin, Marjo-Riitta; Salomaa, Veikko; Vartiainen, Erkki; Hofman, Albert; Ripatti, Samuli; Metspalu, Andres; Thorsteinsdottir, Unnur; Stefansson, Kari; Pedersen, Nancy L.; McCarthy, Mark I.; Ingelsson, Erik; Prokopenko, Inga

    2013-01-01

    Background The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI–trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03–1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1–1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational

  5. The role of adiposity in cardiometabolic traits: a Mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Tove Fall

    Full Text Available The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV for body mass index (BMI in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i rs9939609 and BMI (n  =  198,502, (ii rs9939609 and 24 traits, and (iii BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39 and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p < 0.05. For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p < 0.05. The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p  =  0

  6. A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    DEFF Research Database (Denmark)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.

    2013-01-01

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to c...... of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases....

  7. Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study.

    Science.gov (United States)

    Thomsen, Mette; Varbo, Anette; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2014-05-01

    Increased nonfasting plasma triglycerides marking increased amounts of cholesterol in remnant lipoproteins are important risk factors for cardiovascular disease, but whether lifelong reduced concentrations of triglycerides on a genetic basis ultimately lead to reduced all-cause mortality is unknown. We tested this hypothesis. Using individuals from the Copenhagen City Heart Study in a mendelian randomization design, we first tested whether low concentrations of nonfasting triglycerides were associated with reduced all-cause mortality in observational analyses (n = 13 957); second, whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). During a median 24 and 17 years of 100% complete follow-up, 9991 and 4005 individuals died in observational and genetic analyses, respectively. In observational analyses compared to individuals with nonfasting plasma triglycerides of 266-442 mg/dL (3.00-4.99 mmol/L), multivariably adjusted hazard ratios for all-cause mortality were 0.89 (95% CI 0.78-1.02) for 177-265 mg/dL (2.00-2.99 mmol/L), 0.74 (0.65-0.84) for 89-176 mg/dL (1.00-1.99 mmol/L), and 0.59 (0.51-0.68) for individuals with nonfasting triglycerides triglycerides was 0.50 (0.30-0.82), with a corresponding observational hazard ratio of 0.87 (0.85-0.89). Also, the odds ratio for a genetically derived 50% lower concentration in nonfasting triglycerides was 0.43 (0.23-0.80), with a corresponding observational hazard ratio of 0.73 (0.70-0.77). Genetically reduced concentrations of nonfasting plasma triglycerides are associated with reduced all-cause mortality, likely through reduced amounts of cholesterol in remnant lipoproteins.

  8. Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study

    Science.gov (United States)

    Granell, Raquel; Henderson, A. John; Evans, David M.; Smith, George Davey; Ness, Andrew R.; Lewis, Sarah; Palmer, Tom M.; Sterne, Jonathan A. C.

    2014-01-01

    Background Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach. Methods and Findings We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-valuesBMI on asthma was 1.55 (95% CI 1.16–2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19–3.03) than for atopic asthma (1.37, 95% CI 0.89–2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11–1.79) per 0.5 kg and 2.25 (95% CI 1.23–4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects. Conclusions Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century. Please see later in the article for the Editors' Summary PMID:24983943

  9. Testing concordance of instrumental variable effects in generalized linear models with application to Mendelian randomization

    Science.gov (United States)

    Dai, James Y.; Chan, Kwun Chuen Gary; Hsu, Li

    2014-01-01

    Instrumental variable regression is one way to overcome unmeasured confounding and estimate causal effect in observational studies. Built on structural mean models, there has been considerale work recently developed for consistent estimation of causal relative risk and causal odds ratio. Such models can sometimes suffer from identification issues for weak instruments. This hampered the applicability of Mendelian randomization analysis in genetic epidemiology. When there are multiple genetic variants available as instrumental variables, and causal effect is defined in a generalized linear model in the presence of unmeasured confounders, we propose to test concordance between instrumental variable effects on the intermediate exposure and instrumental variable effects on the disease outcome, as a means to test the causal effect. We show that a class of generalized least squares estimators provide valid and consistent tests of causality. For causal effect of a continuous exposure on a dichotomous outcome in logistic models, the proposed estimators are shown to be asymptotically conservative. When the disease outcome is rare, such estimators are consistent due to the log-linear approximation of the logistic function. Optimality of such estimators relative to the well-known two-stage least squares estimator and the double-logistic structural mean model is further discussed. PMID:24863158

  10. Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

    LENUS (Irish Health Repository)

    Trompet, Stella

    2009-12-01

    Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.

  11. Genetic diagnosis of Mendelian disorders via RNA sequencing.

    Science.gov (United States)

    Kremer, Laura S; Bader, Daniel M; Mertes, Christian; Kopajtich, Robert; Pichler, Garwin; Iuso, Arcangela; Haack, Tobias B; Graf, Elisabeth; Schwarzmayr, Thomas; Terrile, Caterina; Koňaříková, Eliška; Repp, Birgit; Kastenmüller, Gabi; Adamski, Jerzy; Lichtner, Peter; Leonhardt, Christoph; Funalot, Benoit; Donati, Alice; Tiranti, Valeria; Lombes, Anne; Jardel, Claude; Gläser, Dieter; Taylor, Robert W; Ghezzi, Daniele; Mayr, Johannes A; Rötig, Agnes; Freisinger, Peter; Distelmaier, Felix; Strom, Tim M; Meitinger, Thomas; Gagneur, Julien; Prokisch, Holger

    2017-06-12

    Across a variety of Mendelian disorders, ∼50-75% of patients do not receive a genetic diagnosis by exome sequencing indicating disease-causing variants in non-coding regions. Although genome sequencing in principle reveals all genetic variants, their sizeable number and poorer annotation make prioritization challenging. Here, we demonstrate the power of transcriptome sequencing to molecularly diagnose 10% (5 of 48) of mitochondriopathy patients and identify candidate genes for the remainder. We find a median of one aberrantly expressed gene, five aberrant splicing events and six mono-allelically expressed rare variants in patient-derived fibroblasts and establish disease-causing roles for each kind. Private exons often arise from cryptic splice sites providing an important clue for variant prioritization. One such event is found in the complex I assembly factor TIMMDC1 establishing a novel disease-associated gene. In conclusion, our study expands the diagnostic tools for detecting non-exonic variants and provides examples of intronic loss-of-function variants with pathological relevance.

  12. The international normalized ratio (INR as seen in a population of patients with atrial fibrillation and cerebral infarction undergoing long-term treatment with vitamin K antagonists

    Directory of Open Access Journals (Sweden)

    Szczepańska-Szerej Anna

    2015-12-01

    Full Text Available It is estimated that nearly 20% of all cerebral infarctions in the total population are the result of a complication of atrial fibrillation (AF. While oral anticoagulation with vitamin K antagonists (AVKs substantially reduces this risk, this requires regular monitoring of the international normalized ratio (INR in order to achieve therapeutic levels (2,0-3,0. The aim of this study was to evaluate a group at high risk of cerebral infarction, among patients with AF undergoing long-term treatment with VKAs, taking into account the significance of therapeutic INR values. The analysed group consisted of 90 acute ischaemic stroke patients with paroxysmal or chronic “non-valvular” AF, receiving treatment with VKAs. As a result of the study, therapeutic INR values (≥ 2 were seen in thirty-five of these individuals (38,8%, while 55 (61,2% showed non-therapeutic INR values. Moreover, there were no differences in demographics, vascular risk factors, biochemical and morphological blood parameters, mean CHA2DS2-VASc score and TOAST classification between either of the two groups. Furthermore, no additional factor that would increase their risk of cerebral infarction during the adequate treatment with VKAs was found. However, patients with non-therapeutic INR values had a statistically significantly higher frequency of concomitant moderate pathology of the bicuspid valve, p<0.05. Hence, a lack of proper control of INR can proved to be particularly dangerous for this subgroup of patients. Hence, this is a group with an elevated risk of cerebral infarction and therefore requires special oversight of VKA treatment or NOA treatment.

  13. Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

    Science.gov (United States)

    Rodriguez-Flores, Juan L.; Fakhro, Khalid; Hackett, Neil R.; Salit, Jacqueline; Fuller, Jennifer; Agosto-Perez, Francisco; Gharbiah, Maey; Malek, Joel A.; Zirie, Mahmoud; Jayyousi, Amin; Badii, Ramin; Al-Marri, Ajayeb Al-Nabet; Chouchane, Lotfi; Stadler, Dora J.; Hunter-Zinck, Haley; Mezey, Jason G.; Crystal, Ronald G.

    2013-01-01

    Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared to 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Pre-marital genetic screening in Qatar tests for only 4 out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance. PMID:24123366

  14. Out-of-range international normalized ratio values and healthcare cost among new warfarin patients with non-valvular atrial fibrillation.

    Science.gov (United States)

    Nelson, Winnie W; Wang, Li; Baser, Onur; Damaraju, C V; Schein, Jeffrey R

    2015-05-01

    Patients with out-of-range international normalized ratio (INR) values 3.0 have been associated with increased risk of thromboembolic and bleeding events. INR monitoring is costly, because of associated physician and nurse time, laboratory resource use, and dose adjustments. This study assessed the healthcare cost burden associated with out-of-range INR among warfarin initiator patients diagnosed with non-valvular atrial fibrillation (NVAF) in the US Veterans Health Administration (VHA) population. Adult NVAF patients (≥18 years) initiating warfarin were selected from the VHA dataset for the study period October 1, 2007-September 30, 2012. Only valid INR measurements (0.5 ≤ INR ≤ 20) were examined for the follow-up period, from the index date (warfarin initiation date) until the end of warfarin exposure or death. All-cause healthcare costs within 30 days were measured starting from the second month (31 days post-index date) to the end of the study period. Costs for inpatient stays, emergency room, outpatient facility, physician office visits, and other services were computed separately. Multiple regression was performed using the generalized linear model for overall cost analysis. In total, 29,463 patients were included in the study sample. Mean costs for out-of-range INR ranged from $3419 to $5126. Inpatient, outpatient, outpatient pharmacy, and total costs were significantly higher after patients experienced out-of-range results (INR  3), compared with in-range INR (2 ≤ INR ≤ 3). When exposed to out-of-range INR, patients also incurred higher mean total costs within 2-6 months ($3840-$5820) than after the first 6 months ($2789-$3503) of warfarin therapy. In the VHA population, INR measures outside of the 2-3 range were associated with significantly higher healthcare costs. Increased costs were especially apparent when INR values were below 2, although INR measures above 3 were also associated with higher costs relative to in

  15. Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk

    DEFF Research Database (Denmark)

    Thrift, Aaron P.; Gong, Jian; Peters, Ulrike

    2015-01-01

    Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate...... the causal association between BMI and colorectal cancer. Methods: We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study–identified variants associated......, rather than overall obesity, is a more important risk factor for men requires further investigation. Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer....

  16. Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: The CARTA consortium

    NARCIS (Netherlands)

    A.E. Taylor (Amy E.); M.E. Fluharty (Meg E.); J.H. Bjørngaard (Johan H.); M.E. Gabrielsen (Maiken Elvestad); F. Skorpen (Frank); R.E. Marioni (Riccardo); A. Campbell (Archie); J. Engmann (Jorgen); S.S. Mirza (Saira); A. Loukola (Anu); T. Laatikainen (Tiina); T. Partonen (Timo); M. Kaakinen (Marika); F. Ducci (Francesca); A. Cavadino (Alana); L.L.N. Husemoen (Lise Lotte); T.S. Ahluwalia (Tarunveer Singh); R.K. Jacobsen (Rikke Kart); T. Skaaby (Tea); J.F. Ebstrup (Jeanette Frost); E.L. Mortensen (Erik); C.C. Minica (Camelia C.); J.M. Vink (Jacqueline); G.A.H.M. Willemsen (Gonneke); P. Marques-Vidal (Pedro); C.E. Dale (Caroline E.); A. Amuzu (Antoinette); L.T. Lennon (Lucy T.); J. Lahti (Jari); A. Palotie (Aarno); K. Räikkönen (Katri); A. Wong (Andrew); L. Paternoster (Lavinia); A.P.-Y. Wong (Angelita Pui-Yee); L.J. Horwood (L. John); M. Murphy (Michael); E.C. Johnstone (Elaine C.); M.A. Kennedy (Martin A.); Z. Pausova (Zdenka); T. Paus (Tomáš); Y. Ben-Shlomo; C. Nohr (Christian); D. Kuh (Diana); M. Kivimaki (Mika); J.G. Eriksson (Johan G.); R. Morris (Richard); J.P. Casas (Juan); M. Preisig (Martin); D.I. Boomsma (Dorret); A. Linneberg (Allan); C. Power (Christopher); E. Hypponen (Elina); J. Veijola (Juha); M.-R. Jarvelin (Marjo-Riitta); T. Korhonen (Tellervo); H.W. Tiemeier (Henning); M. Kumari (Meena); D.J. Porteous (David J.); C. Hayward (Caroline); P.R. Romundstad (Pa˚l R.); G.D. Smith; M.R. Munafò (Marcus)

    2014-01-01

    textabstractObjectives: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and

  17. Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction.

    Science.gov (United States)

    Pierce, Brandon L; Tong, Lin; Argos, Maria; Gao, Jianjun; Farzana, Jasmine; Roy, Shantanu; Paul-Brutus, Rachelle; Rahaman, Ronald; Rakibuz-Zaman, Muhammad; Parvez, Faruque; Ahmed, Alauddin; Quasem, Iftekhar; Hore, Samar K; Alam, Shafiul; Islam, Tariqul; Harjes, Judith; Sarwar, Golam; Slavkovich, Vesna; Gamble, Mary V; Chen, Yu; Yunus, Mohammad; Rahman, Mahfuzar; Baron, John A; Graziano, Joseph H; Ahsan, Habibul

    2013-12-01

    Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal. Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls. Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62). We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.

  18. Causal Association of Overall Obesity and Abdominal Obesity with Type 2 Diabetes: A Mendelian Randomization Analysis.

    Science.gov (United States)

    Wang, Tao; Zhang, Rong; Ma, Xiaojing; Wang, Shiyun; He, Zhen; Huang, Yeping; Xu, Bo; Li, Yangyang; Zhang, Hong; Jiang, Feng; Bao, Yuqian; Hu, Cheng; Jia, Weiping

    2018-05-01

    This study aimed to compare the causal effect of overall obesity and abdominal obesity on type 2 diabetes among Chinese Han individuals. The causal relationship of BMI and waist-to-hip ratio (WHR) with the risk of glucose deterioration and glycemic traits was compared using two different genetic instruments based on 30 BMI loci and 6 WHR loci with Mendelian randomization (MR) in three prospective cohorts (n = 6,476). Each 1-SD genetically instrumented higher WHR was associated with a 65.7% higher risk of glucose deterioration (95% CI = 1.069-2.569, P = 0.024), whereas no significant association of BMI with glucose deterioration was observed. Furthermore, a causal relationship was found only between BMI and homeostatic model assessment β-cell function (HOMA-B) (β = 0.143, P = 0.001), and there was a nominal association with Stumvoll second-phase insulin secretion traits (β = 0.074, P = 0.022). The significance level did not persist in sensitivity analyses, except in the causal estimate of WHR on the Gutt index in MR-Egger (β = -0.379, P = 0.022) and the causal estimate of BMI on homeostatic model assessment β-cell function in weighted median MR (β = 0.128, P = 0.017). The data from this study support the potential causal relationship between abdominal obesity and hyperglycemia, which may be driven by aggravated insulin resistance, in contrast with the potential causal relationship between overall obesity and insulin secretion. © 2018 The Obesity Society.

  19. Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis

    Science.gov (United States)

    Tomioka, Yukiko; Kinoshita, Makoto; Umehara, Hidehiro; Watanabe, Shin-ya; Nakataki, Masahito; Iwayama, Yoshimi; Toyota, Tomoko; Ikeda, Masashi; Yamamori, Hidenaga; Shimodera, Shinji; Tajima, Atsushi; Hashimoto, Ryota; Iwata, Nakao; Yoshikawa, Takeo; Ohmori, Tetsuro

    2018-01-01

    Background Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway. Methods We first conducted a case–control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population (n = 10 689). Finally, we assessed the effect of serum pyridoxal levels on schizophrenia risk using a Mendelian randomization (MR) approach. Results Serum pyridoxal levels were significantly lower in patients with schizophrenia than in controls, not only in our cohort, but also in the pooled data set of the meta-analysis of association studies (standardized mean difference −0.48, 95% confidence interval [CI] −0.57 to −0.39, p = 9.8 × 10−24). We failed to find a significant association between rs4654748 and schizophrenia. Furthermore, an MR analysis failed to find a causal relationship between pyridoxal levels and schizophrenia risk (odds ratio 0.99, 95% CI 0.65–1.51, p = 0.96). Limitations Food consumption and medications may have affected serum pyridoxal levels in our cross-sectional study. Sample size, number of instrumental variables and substantial heterogeneity among patients with schizophrenia are limitations of an MR analysis. Conclusion We found decreased serum pyridoxal levels in patients with schizophrenia in this observational study. However, we failed to obtain data supporting a causal relationship between pyridoxal levels and schizophrenia risk using the MR approach. PMID:29688875

  20. Normal Female Germ Cell Differentiation Requires the Female X Chromosome to Autosome Ratio and Expression of Sex-Lethal in DROSOPHILA MELANOGASTER

    OpenAIRE

    Schüpbach, Trudi

    1985-01-01

    In somatic cells of Drosophila, the ratio of X chromosomes to autosomes (X:A ratio) determines sex and dosage compensation. The present paper addresses the question of whether germ cells also use the X:A ratio for sex determination and dosage compensation. Triploid female embryos were generated which, through the loss of an unstable ring-X chromosome, contained some germ cells of 2X;3A constitution in their ovaries. Such germ cells were shown to differentiate along one of two alternative pat...

  1. Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion

    DEFF Research Database (Denmark)

    Huang, Lam Opal; Infante-RIvard, Claire; Labbe, Aurélie

    2016-01-01

    Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium...

  2. C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Jacobsen, Benedikte; Füchtbauer, Annette

    2016-01-01

    of C4.4A in normal physiology and cancer progression. The unchallenged C4.4A-deficient mice were viable, fertile, born in a normal Mendelian distribution and, surprisingly, displayed normal development of squamous epithelia. The C4.4A-deficient mice were, nonetheless, significantly lighter than...

  3. Molecular-Based Mechanisms of Mendelian Forms of Salt-Dependent Hypertension Questioning the Prevailing Theory

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Dominiczak, A. F.; DiCarlo, S. E.; Pravenec, Michal; Morris Jr., R. C.

    2015-01-01

    Roč. 65, č. 5 (2015), s. 932-941 ISSN 0194-911X R&D Projects: GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : Mendelian * salt sensitive hypertension * vasodysfunction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.350, year: 2015

  4. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study

    Science.gov (United States)

    This study examined whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. A Mendelian randomization study was employed, using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental var...

  5. A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes

    NARCIS (Netherlands)

    Sluijs, Ivonne; Holmes, Michael V.; van der Schouw, Yvonne T.; Beulens, Joline W J; Asselbergs, Folkert W.; Huerta, José María; Palmer, Tom M.; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Boeing, Heiner; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Franks, Paul W.; Gavrila, Diana; Kaaks, Rudolf; Khaw, Kay T ee; Kühn, Tilman; Molina-Montes, Esther; Mortensen, Lotte M axild; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sala, Núria; Schmidt, Julie A.; Scott, Robert A.; Sieri, Sabina; Slimani, Nadia; Spijkerman, Annemieke M W; Tjonneland, Anne; Travis, Ruth C.; Tumino, Rosario; van der A, Daphne L.; Sharp, Stephen J.; Forouhi, Nita G.; Langenberg, Claudia; Riboli, Elio; Wareham, Nicholas J.

    2015-01-01

    We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition

  6. Association between alcohol and cardiovascular disease : Mendelian randomisation analysis based on individual participant data

    NARCIS (Netherlands)

    Holmes, Michael V.; Dale, Caroline E.; Zuccolo, Luisa; Silverwood, Richard J.; Guo, Yiran; Ye, Zheng; Prieto-Merino, David; Dehghan, Abbas; Trompet, Stella; Wong, Andrew; Cavadino, Alana; Drogan, Dagmar; Padmanabhan, Sandosh; Li, Shanshan; Yesupriya, Ajay; Leusink, Maarten|info:eu-repo/dai/nl/357581164; Sundstrom, Johan; Hubacek, Jaroslav A.; Pikhart, Hynek; Swerdlow, Daniel I.; Panayiotou, Andrie G.; Borinskaya, Svetlana A.; Finan, Chris; Shah, Sonia; Kuchenbaecker, Karoline B.; Shah, Tina; Engmann, Jorgen; Folkersen, Lasse; Eriksson, Per; Ricceri, Fulvio; Melander, Olle; Sacerdote, Carlotta; Gamble, Dale M.; Rayaprolu, Sruti; Ross, Owen A.; McLachlan, Stela; Vikhireva, Olga; Sluijs, Ivonne; Scott, Robert A.; Adamkova, Vera; Flicker, Leon; Van Bockxmeer, Frank M.; Power, Christine; Marques-Vidal, Pedro; Meade, Tom; Marmot, Michael G.; Ferro, Jose M.; Paulos-Pinheiro, Sofia; Humphries, Steve E.; Talmud, Philippa J.; Leach, Irene Mateo; Verweij, Niek; Linneberg, Allan; Skaaby, Tea; Doevendans, Pieter A.; Cramer, Maarten J.; Van Der Harst, Pim; Klungel, Olaf H.|info:eu-repo/dai/nl/181447649; Dowling, Nicole F.; Dominiczak, Anna F.; Kumari, Meena; Nicolaides, Andrew N.; Weikert, Cornelia; Boeing, Heiner; Ebrahim, Shah; Gaunt, Tom R.; Price, Jackie F.; Lannfelt, Lars; Peasey, Anne; Kubinova, Ruzena; Pajak, Andrzej; Malyutina, Sofia; Voevoda, Mikhail I.; Tamosiunas, Abdonas; Maitland-van Der Zee, Anke H.|info:eu-repo/dai/nl/255164688; Norman, Paul E.; Hankey, Graeme J.; Bergmann, Manuela M.; Hofman, Albert; Franco, Oscar H.; Cooper, Jackie; Palmen, Jutta; Spiering, Wilko; De Jong, Pim A.; Kuh, Diana; Hardy, Rebecca; Uitterlinden, Andre G.; Ikram, M. Arfan; Ford, Ian; Hyppönen, Elina; Almeida, Osvaldo P.; Wareham, Nicholas J.; Khaw, Kay Tee; Hamsten, Anders; Husemoen, Lise Lotte N; Tjønneland, Anne; Tolstrup, Janne S.; Rimm, Eric; Beulens, Joline W J; Verschuren, W. M Monique; Onland-Moret, N. Charlotte; Hofker, Marten H.; Wannamethee, S. Goya; Whincup, Peter H.; Morris, Richard; Vicente, Astrid M.; Watkins, Hugh; Farrall, Martin; Jukema, J. Wouter; Meschia, James; Cupples, L. Adrienne; Sharp, Stephen J.; Fornage, Myriam; Kooperberg, Charles; LaCroix, Andrea Z.; Dai, James Y.; Lanktree, Matthew B.; Siscovick, David S.; Jorgenson, Eric; Spring, Bonnie; Coresh, Josef; Li, Yun R.; Buxbaum, Sarah G.; Schreiner, Pamela J.; Ellison, R. Curtis; Tsai, Michael Y.; Patel, Sanjay R.; Redline, Susan; Johnson, Andrew D.; Hoogeveen, Ron C.; Hakonarson, Hakon; Rotter, Jerome I.; Boerwinkle, Eric; De Bakker, Paul I W; Kivimaki, Mika; Asselbergs, Folkert W.; Sattar, Naveed; Lawlor, Debbie A.; Whittaker, John; Smith, George Davey; Mukamal, Kenneth; Psaty, Bruce M.; Wilson, James G.; Lange, Leslie A.; Hamidovic, Ajna; Nordestgaard, Børge G.; Bobak, Martin; Leon, David A.; Langenberg, Claudia; Palmer, Tom M.; Reiner, Alex P.; Keating, Brendan J.; Dudbridge, Frank; Casas, Juan P.

    2014-01-01

    Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design: Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants: 261 991 individuals of European

  7. Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study.

    LENUS (Irish Health Repository)

    Hung, Chi-Fa

    2014-07-01

    Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue.

  8. Adult height, coronary heart disease and stroke : A multi-locus Mendelian randomization meta-analysis

    NARCIS (Netherlands)

    Nüesch, Eveline; Dale, Caroline; Palmer, Tom M.; White, Jon; Keating, Brendan J.; van Iperen, Erik P A; Goel, Anuj; Padmanabhan, Sandosh; Asselbergs, F. W.; Verschuren, W. M.; Wijmenga, C.; Van der Schouw, Y. T.; Onland-Moret, N. C.; Lange, Leslie A.; Hovingh, G. K.; Sivapalaratnam, Suthesh; Morris, Richard W.; Whincup, Peter H.; Wannamethe, Goya S.; Gaunt, Tom R.; Ebrahim, Shah; Steel, Laura; Nair, Nikhil; Reiner, Alexander P.; Kooperberg, Charles; Wilson, James F.; Bolton, Jennifer L.; McLachlan, Stela; Price, Jacqueline F.; Strachan, Mark W J; Robertson, Christine M.; Kleber, Marcus E.; Delgado, Graciela; März, Winfried; Melander, Olle; Dominiczak, Anna F.; Farrall, Martin; Watkins, Hugh; Leusink, Maarten; Maitland-van der Zee, Anke H.; de Groot, Mark C H; Dudbridge, Frank; Hingorani, Aroon; Ben-Shlomo, Yoav; Lawlor, Debbie A.; Amuzu, A.; Caufield, M.; Cavadino, A.; Cooper, J.; Davies, T. L.; Day, I. N.; Drenos, F.; Engmann, J.; Finan, C.; Giambartolomei, C.; Hardy, R.; Humphries, S. E.; Hypponen, E.; Kivimaki, M.; Kuh, D.; Kumari, M.; Ong, K.; Plagnol, V.; Power, C.; Richards, M.; Shah, S.; Shah, T.; Sofat, R.; Talmud, P. J.; Wareham, N.; Warren, H.; Whittaker, J. C.; Wong, A.; Zabaneh, D.; Smith, George Davey; Wells, Jonathan C.; Leon, David A.; Holmes, Michael V.; Casas, Juan P.

    2016-01-01

    Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We developed an allele score based on 69 single nucleotide

  9. Common variants in Mendelian kidney disease genes and their association with renal function.

    Science.gov (United States)

    Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

    2013-12-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

  10. Identification of Mendelian inconsistencies between SNP and pedigree Information of Sibs

    NARCIS (Netherlands)

    Calus, M.P.L.; Mulder, H.A.; Bastiaansen, J.W.M.

    2011-01-01

    Background Using SNP genotypes to apply genomic selection in breeding programs is becoming common practice. Tools to edit and check the quality of genotype data are required. Checking for Mendelian inconsistencies makes it possible to identify animals for which pedigree information and genotype

  11. Identification of Mendelian inconsistencies between SNP and pedigree information of sibs

    Directory of Open Access Journals (Sweden)

    Calus Mario PL

    2011-10-01

    Full Text Available Abstract Background Using SNP genotypes to apply genomic selection in breeding programs is becoming common practice. Tools to edit and check the quality of genotype data are required. Checking for Mendelian inconsistencies makes it possible to identify animals for which pedigree information and genotype information are not in agreement. Methods Straightforward tests to detect Mendelian inconsistencies exist that count the number of opposing homozygous marker (e.g. SNP genotypes between parent and offspring (PAR-OFF. Here, we develop two tests to identify Mendelian inconsistencies between sibs. The first test counts SNP with opposing homozygous genotypes between sib pairs (SIBCOUNT. The second test compares pedigree and SNP-based relationships (SIBREL. All tests iteratively remove animals based on decreasing numbers of inconsistent parents and offspring or sibs. The PAR-OFF test, followed by either SIB test, was applied to a dataset comprising 2,078 genotyped cows and 211 genotyped sires. Theoretical expectations for distributions of test statistics of all three tests were calculated and compared to empirically derived values. Type I and II error rates were calculated after applying the tests to the edited data, while Mendelian inconsistencies were introduced by permuting pedigree against genotype data for various proportions of animals. Results Both SIB tests identified animal pairs for which pedigree and genomic relationships could be considered as inconsistent by visual inspection of a scatter plot of pairwise pedigree and SNP-based relationships. After removal of 235 animals with the PAR-OFF test, SIBCOUNT (SIBREL identified 18 (22 additional inconsistent animals. Seventeen animals were identified by both methods. The numbers of incorrectly deleted animals (Type I error, were equally low for both methods, while the numbers of incorrectly non-deleted animals (Type II error, were considerably higher for SIBREL compared to SIBCOUNT. Conclusions

  12. Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer's disease and Parkinson's disease: Mendelian randomisation study.

    Science.gov (United States)

    Benn, Marianne; Nordestgaard, Børge G; Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne

    2017-04-24

    Objective  To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis( PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase ( HMGCR ), respectively) is associated with a high risk of Alzheimer's disease, vascular dementia, any dementia, and Parkinson's disease in the general population. Design  Mendelian randomisation study. Setting  Copenhagen General Population Study and Copenhagen City Heart Study. Participants  111 194 individuals from the Danish general population. Main outcome measures  Risk of Alzheimer's disease, vascular dementia, all dementia, and Parkinson's disease. Results  In observational analyses, the multifactorially adjusted hazard ratio for Parkinson's disease in participants with an LDL cholesterol level LDL cholesterol level. In genetic, causal analyses adjusted for age, sex, and year of birth, the risk ratios for a lifelong 1 mmol/L lower LDL cholesterol level were 0.57 (0.27 to 1.17) for Alzheimer's disease, 0.81 (0.34 to 1.89) for vascular dementia, 0.66 (0.34 to 1.26) for any dementia, and 1.02 (0.26 to 4.00) for Parkinson's disease. Summary level data from the International Genomics of Alzheimer's Project using Egger Mendelian randomisation analysis gave a risk ratio for Alzheimer's disease of 0.24 (0.02 to 2.79) for 26 PCSK9 and HMGCR variants, and of 0.64 (0.52 to 0.79) for 380 variants of LDL cholesterol level lowering. Conclusion  Low LDL cholesterol levels due to PCSK9 and HMGCR variants had no causal effect on high risk of Alzheimer's disease, vascular dementia, any dementia, or Parkinson's disease; however, low LDL cholesterol levels may have a causal effect in reducing the risk of Alzheimer's disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

    Science.gov (United States)

    Khankari, Nikhil K.; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei

    2016-01-01

    Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the

  14. Ca/P concentration ratio at different sites of normal and osteoporotic rabbit bones evaluated by Auger and energy dispersive X-ray spectroscopy

    OpenAIRE

    Kourkoumelis, Nikolaos; Balatsoukas, Ioannis; Tzaphlidou, Margaret

    2011-01-01

    Osteoporosis is a systemic skeletal disorder associated with reduced bone mineral density and the consequent high risk of bone fractures. Current practice relates osteoporosis largely with absolute mass loss. The assessment of variations in chemical composition in terms of the main elements comprising the bone mineral and its effect on the bone’s quality is usually neglected. In this study, we evaluate the ratio of the main elements of bone mineral, calcium (Ca), and phosphorus (P), as a suit...

  15. Correlation of morphological variants of the soft palate and Need's ratio in normal individuals: A digital cephalometric study

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Pradhuman; Verma, Kanika Gupta; Sachdeva, Suresh K; Juneja, Suruchi [Surendera Dental College and Research Institute, Sriganganagar (India); Kumaraswam; Kikkeri Lakshminarayana [Dept. of Oral Pathology and Microbiology, Farooqia Dental College, Mysore (India); Basavaraju, Suman [Dept. of Periodontics, J.S.S Dental College, Mysore (India)

    2014-09-15

    The present study was aimed to investigate the variation of soft palate morphology in different age and gender groups. The correlations of radiographic velar length (VL), velar width (VW), pharyngeal depth (PD), and Need's ratio with soft palate variants were also studied in the North Indian subpopulation. The study sample consisted of 300 subjects aged between 15 and 45 (mean: 31.32) years. The velar morphology on lateral cephalograms was examined and grouped into six types. The results obtained were subjected to a statistical analysis to find the correlation between variants of the soft palate with gender and different age groups. The most frequent type of soft palate was leaf shaped (48.7%), and the least common was crook shaped (3.0%) among both the genders and various age groups, showing a significant correlation. The mean VL, VW, and PD values were significantly higher in males and significantly correlated with the types of soft palate. A significant correlation was observed between the mean VL, VW, PD, and Need's ratio with various age groups, showing an inconsistent pattern with an increase in age. The types of soft palate, gender, and Need's ratio were also significantly correlated, with an overall higher mean value of the Need's ratio among female subjects and the S-shaped soft palate. The knowledge of a varied spectrum of velar morphology and the variants of the soft palate help in a better understanding of the velopharyngeal closure and craniofacial anomalies.

  16. Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study.

    Science.gov (United States)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne

    2015-04-01

    Increased alcohol consumption has been associated with depression and alcoholism, but whether these associations are causal remains unclear. We tested whether alcohol consumption is causally associated with depression and alcoholism. We included 78,154 men and women aged 20-100 years randomly selected in 1991-2010 from the general population of Copenhagen, Denmark, and genotyped 68,486 participants for two genetic variants in two alcohol dehydrogenase (ADH) genes, ADH-1B (rs1229984) and ADH-1C (rs698). We performed observational and causal analyses using a Mendelian randomization design with antidepressant medication use and hospitalization/death, with depression and alcoholism as outcomes. In prospective analyses, the multifactorially adjusted hazard ratio for participants reporting >6 drinks/day vs participants reporting 0.1-1 drinks/day was 1.28 (95% confidence interval, 1.00-1.65) for prescription antidepressant use, with a corresponding hazard ratio of 0.80 (0.45-1.45) for hospitalization/death with depression and of 11.7 (8.77-15.6) for hospitalization/death with alcoholism. For hospitalization/death with alcoholism, instrumental variable analysis yielded a causal odds ratio of 28.6 (95 % confidence interval 6.47-126) for an increase of 1 drink/day estimated from the combined genotype combination, whereas the corresponding multifactorially adjusted observational odds ratio was 1.28 (1.25-1.31). Corresponding odds ratios were 1.11 (0.67-1.83) causal and 1.04 (1.03-1.06) observational for prescription antidepressant use, and 4.52 (0.99-20.5) causal and 0.98 (0.94-1.03) observational for hospitalization/death with depression. These data indicate that the association between increased alcohol consumption and alcoholism is causal, without similar strong evidence for depression. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  17. Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies

    Science.gov (United States)

    Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upst...

  18. Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Robert Carreras-Torres

    Full Text Available Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR, or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR [95% confidence interval (CI] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00] for each standard deviation (SD increase in BMI [4.6 kg/m2], but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08] (Pheterogeneity = 4.3x10-3. Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3, providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl, while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l. Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results.Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.

  19. Inflammation, insulin resistance, and diabetes--Mendelian randomization using CRP haplotypes points upstream.

    Directory of Open Access Journals (Sweden)

    Eric J Brunner

    2008-08-01

    Full Text Available Raised C-reactive protein (CRP is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study. Homeostasis model assessment-insulin resistance (HOMA-IR and hemoglobin A1c (HbA1c were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52-0.92. The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11. Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88. Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls using three SNPs in tight linkage disequilibrium with our

  20. CD4+, CD8+, CD3+ cell counts and CD4+/CD8+ ratio among patients with mycobacterial diseases (leprosy, tuberculosis), HIV infections, and normal healthy adults: a comparative analysis of studies in different regions of India.

    Science.gov (United States)

    Hussain, Tahziba; Kulshreshtha, K K; Yadav, V S; Katoch, Kiran

    2015-01-01

    In this study, we estimated the CD4+, CD8+, CD3+ cell counts and the CD4/CD8 ratio among normal healthy controls (adults and children), leprosy patients (without any complications and during reactional states), TB patients (with and without HIV), and HIV-positive patients (early infection and full-blown AIDS) and correlated the changes with disease progression. In our study, it was observed that among adults, CD4+ cell counts ranged from 518-1098, CD8+ from 312-952, whereas CD4/CD8 ratio from 0.75-2.30. Among children, both CD4+ and CD8+ cells were more and the CD4/CD8 ratio varied from 0.91-3.17. With regard to leprosy patients, we observed that CD4+ and CD8+ cell counts were lower among PB (pauci-bacillary) and MB (multi-bacillary) patients. CD4/CD8 ratio was 0.99 ± 0.28 among PB patients while the ratio was lower, 0.78 ± 0.20, among MB patients. CD4+ cell counts were raised during RR (reversal reactions) and ENL (erythema nodosum leprosum) among the PB and MB patients whereas the CD8+ cell counts were lower among PB and MB patients. CD4/CD8 ratio doubled during reactional episodes of RR and ENL. Among the HIV-negative tuberculosis (TB) patients, both the CD4+ and CD8+ cell counts were found to be less and the CD4/CD8 ratio varied between 0.53-1.75. Among the HIV-positive TB patients and HIV-positive patients, both the CD4+ and CD8+ cells were very less and ratio drops significantly. In the initial stages of infection, as CD4+ counts drop, an increase in the CD8+ cell counts was observed and the ratio declines. In full-blown cases, CD4+ cell counts were very low, 3-4 to 54 cells, CD8+ cells from 12-211 and the ratio drops too low. This study is the first of its kind in this region of the country and assumes importance since no other study has reported the values of CD4+ and CD8+ T-lymphocyte counts among patients with mycobacterial diseases (leprosy and TB), HIV infections along with normal healthy individuals of the region, and correlation with clinical

  1. Impact of co-morbidities and patient characteristics on international normalized ratio control over time in patients with nonvalvular atrial fibrillation.

    Science.gov (United States)

    Nelson, Winnie W; Choi, Jiyoon C; Vanderpoel, Julie; Damaraju, Chandrasekharra V; Wildgoose, Peter; Fields, Larry E; Schein, Jeffrey R

    2013-08-15

    This study determined the association between co-morbidities, including heart failure (HF) and time in therapeutic range (TTR), in patients with nonvalvular atrial fibrillation. Longitudinal patient-level anticoagulation management records collected from 2006 to 2010 were analyzed. Adult patients with nonvalvular atrial fibrillation who used warfarin for a 12-month period with no gap of >60 days between visits were identified. TTR <55% was defined as "lower" TTR. CHADS₂ score of ≥2 was defined as "higher" CHADS₂. Logistic regression analyses were conducted to determine the association between co-morbidities and TTR. A total of 23,425 patients met the study criteria. The mean age ± SD was 74.8 ± 9.7 years, with 84.8% aged ≥65 years. The most common co-morbidities were hypertension (41.7%), diabetes (24.1%), HF (11.7%), and previous stroke (11.1%). The mean TTR ± SD was 67.3 ± 14.4%, with 18.6% of patients in the lower TTR range. In multivariate analyses using age, gender, hypertension, diabetes, stroke, and region as covariates, HF (adjusted odds ratio [OR] 1.41, 95% confidence interval [CI] 1.28 to 1.56; p <0.001), diabetes (OR 1.28, 95% CI 1.19 to 1.38; p <0.001), and previous stroke (OR 1.15, 95% CI 1.04 to 1.27; p <0.001) were associated with lower TTR. In a second set of multivariate analyses using gender and region as covariates, a higher CHADS₂ score was associated with lower TTR (OR 1.11, 95% CI 1.04 to 1.18; p <0.001). In conclusion, HF was associated with the greatest likelihood of a lower TTR, followed by diabetes, then stroke. Anticoagulation control may be more challenging for patients with these conditions. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Habitual coffee consumption and risk of type 2 diabetes, ischemic heart disease, depression and Alzheimer's disease: a Mendelian randomization study.

    Science.gov (United States)

    Kwok, Man Ki; Leung, Gabriel M; Schooling, C Mary

    2016-11-15

    Observationally, coffee is inversely associated with type 2 diabetes mellitus (T2DM), depression and Alzheimer's disease, but not ischemic heart disease (IHD). Coffee features as possibly protective in the 2015 Dietary Guidelines for Americans. Short-term trials suggest coffee has neutral effect on most glycemic traits, but raises lipids and adiponectin. To clarify we compared T2DM, depression, Alzheimer's disease, and IHD and its risk factors by genetically predicted coffee consumption using two-sample Mendelian randomization applied to large extensively genotyped case-control and cross-sectional studies. Childhood cognition was used as a negative control outcome. Genetically predicted coffee consumption was not associated with T2DM (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.76 to 1.36), depression (0.89, 95% CI 0.66 to 1.21), Alzheimer's disease (1.17, 95% CI 0.96 to 1.43), IHD (0.96, 95% CI 0.80 to 1.14), lipids, glycemic traits, adiposity or adiponectin. Coffee was unrelated to childhood cognition. Consistent with observational studies, coffee was unrelated to IHD, and, as expected, childhood cognition. However, contrary to observational findings, coffee may not have beneficial effects on T2DM, depression or Alzheimer's disease. These findings clarify the role of coffee with relevance to dietary guidelines and suggest interventions to prevent these complex chronic diseases should be sought elsewhere.

  3. Utility of waist-to-height ratio in assessing the status of central obesity and related cardiometabolic risk profile among normal weight and overweight/obese children: The Bogalusa Heart Study

    Directory of Open Access Journals (Sweden)

    Xu Jihua

    2010-10-01

    Full Text Available Abstract Background Body Mass Index (BMI is widely used to assess the impact of obesity on cardiometabolic risk in children but it does not always relate to central obesity and varies with growth and maturation. Waist-to-Height Ratio (WHtR is a relatively constant anthropometric index of abdominal obesity across different age, sex or racial groups. However, information is scant on the utility of WHtR in assessing the status of abdominal obesity and related cardiometabolic risk profile among normal weight and overweight/obese children, categorized according to the accepted BMI threshold values. Methods Cross-sectional cardiometabolic risk factor variables on 3091 black and white children (56% white, 50% male, 4-18 years of age were used. Based on the age-, race- and sex-specific percentiles of BMI, the children were classified as normal weight (5th - 85th percentiles and overweight/obese (≥ 85th percentile. The risk profiles of each group based on the WHtR ( Results 9.2% of the children in the normal weight group were centrally obese (WHtR ≥0.5 and 19.8% among the overweight/obese were not (WHtR Conclusion WHtR not only detects central obesity and related adverse cardiometabolic risk among normal weight children, but also identifies those without such conditions among the overweight/obese children, which has implications for pediatric primary care practice.

  4. Stearoyl-CoA desaturase indexes and n-6/n-3 fatty acids ratio as biomarkers of cardiometabolic risk factors in normal-weight rabbits fed high fat diets.

    Science.gov (United States)

    Alarcón, Gabriela; Roco, Julieta; Medina, Analia; Van Nieuwenhove, Carina; Medina, Mirta; Jerez, Susana

    2016-01-20

    Biomarkers for cardiometabolic risk (CMR) factors would be important tools to maximize the effectiveness of dietary interventions to prevent cardiovascular diseases. Thus, the aim of this work was to analyze stearoyl-CoA desaturase (SCD) indexes and n-6/n-3 fatty acids (FA) ratio as biomarkers of CMR induced by feeding rabbits on high fat diets (HFDs). Rabbits were fed either regular diet or 18 % fat in regular diet (HFD) or 1 % cholesterol diet (HD) or diet containing 1 % cholesterol and 18 % fat (HFD-HD) during 6 weeks. Body weights (BW), blood pressure, visceral abdominal fat (VAF) and glucose tolerance test were determined. Total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (TG), fasting glucose (FG), and FA levels from plasma were measured. SCD indexes were calculated as product/precursor ratios of individual FA. BW was similar in all diet groups. HD increased TC, LDL-C, HDL-C, and TG. HFD increased TG, VAF and FG, and decreased HDL-C. The addition of HFD to HD joined to dyslipidemia increased VAF and FG. SCD indexes were increased and n-6/n-3 was unchanged in HD. SCD indexes were reduced and n-6/n-3 FA ratio was increased in HFD and HFD-HD. CMR factors were correlated positively with n-6/n-3 FA ratio. Although VAF had a stronger correlation with n-6/n-3 FA ratio than with SCD indexes, VAF was associated independently to both markers. HFD simulating lipid composition of the average Western-style diet induced experimental rabbit models of normal-weight metabolic syndrome (MS). SCD indexes and n-6/n-3 were modified according to the type of dietary fat. Considering that VAF and CMR factors appear to be stronger associated to n-6/n-3 FA ratio than to SCD indexes, n-6/n-3 FA ratio may be a better biomarker of MS and CMR in normal-weight subjects than SCD indexes.

  5. C reactive protein and chronic obstructive pulmonary disease: a Mendelian randomisation approach

    DEFF Research Database (Denmark)

    Dahl, Morten; Vestbo, Jørgen; Zacho, Jeppe

    2011-01-01

    Background It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design. Methods The authors measured high......-sensitivity CRP in plasma, genotyped for four single nucleotide polymorphisms in the CRP gene, and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32¿652 individuals from the Copenhagen General Population Study. Results Elevated...... plasma CRP >3 mg/l compared with Study and the Copenhagen General Population Study, respectively. Genotype combinations...

  6. Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium

    NARCIS (Netherlands)

    Morris, R.W.; Taylor, A.E.; Fluharty, M.E.; Bjorngaard, J.H.; Asvold, B.O.; Elvestad Gabrielsen, M.; Campbell, A.; Marioni, R.; Kumari, M.; Korhonen, T.; Männistö, S.; Marques-Vidal, P.; Kaakinen, M.; Cavadino, A.; Postmus, I.; Husemoen, L.L.N.; Skaaby, T.; Ahluwalia, T.S.; Treur, J.L.; Willemsen, G.; Dale, C.; Wannamethee, S.G.; Lahti, J.; Palotie, A.; Räikkönen, K.; McConnachie, A.; Padmanabhan, S.; Wong, A.; Dalgard, C.; Paternoster, L.; Ben-Shlomo, Y.; Tyrrell, J.; Horwood, J.; Fergusson, D.M.; Kennedy, M.A.; Nohr, E.A.; Christiansen, L.; Kyvik, K.O.; Kuh, D; Watt, G.; Eriksson, J.G.; Whincup, P.H.; Vink, J.M.; Boomsma, D.I.; Davey Smith, G.; Lawlor, D.; Linneberg, A.; Ford, I.; Jukema, J.W.; Power, C.; Hyppönen, E.; Jarvelin, M.R.; Preisig, M.; Borodulin, K.; Kaprio, J.; Kivimaki, M.; Smith, B.H.; Hayward, C.; Romundstad, P.R.; Sørensen, T.I.A.; Munafò, M.; Sattar, N.

    2015-01-01

    Objectives: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730

  7. Heavier smoking may lead to a relative increase in waist circumference: Evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium

    NARCIS (Netherlands)

    Morris, R.W.; Taylor, A.E.; Fluharty, M.E.; Björngaard, J.H.; Asvold, B.A.; Elvestad Gabrielsen, M.; Campbell, A.; Marioni, R.E.; Kumari, M.; Korhonen, T.; Mannisto, S.; Marques-Vidal, P.; Kaakinen, M.; Cavadino, A.; Postmus, I.; Husemoen, L.L.N.; Skaaby, T.; Ahluwalia, T.V.S.; Treur, J.L.; Willemsen, G.; Dale, C.E.; Wannamethee, S.G.; Lahti, J.; Palotie, A.; Raikkonen, K.; McConnachie, A.; Padmanabhan, S.; Wong, A.; Dalgard, C.; Paternoster, L.; Ben-Shlomo, Y.; Tyrrell, J.; Horwood, J.; Fergusson, D.M.; Kennedy, M.A.; Nohr, E.A.; Christiansen, L.; Kyvik, K.O.; Kuh, D.; Watt, G.; Eriksson, J.G.; Whincup, P.H.; Vink, J.M.; Boomsma, D.I.; Davey Smith, G.; Lawlor, D.A.; Linneberg, A.; Ford, I.; Jukema, J.W.; Power, C.; Hypponen, E.; Jarvelin, M.R.; Preisig, M.; Borodulin, K.; Kaprio, J.; Kivimaki, M.; Smith, B.H.; Hayward, C.; Romundstad, P.R.; Sorensen, T.I.A.; Munafò, M.R.; Sattar, N.

    2015-01-01

    OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730

  8. Analysis of case-parent trios for imprinting effect using a loglinear model with adjustment for sex-of-parent-specific transmission ratio distortion

    DEFF Research Database (Denmark)

    Huang, Lam Opal; Infante-Rivard, Claire; Labbe, Aurélie

    2017-01-01

    Transmission ratio distortion (TRD) is a phenomenon where parental transmission of disease allele to the child does not follow the Mendelian inheritance ratio. TRD occurs in a sex-of-parent-specific or non-sex-of-parent-specific manner. An offset computed from the transmission probability of the ...

  9. Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study

    Science.gov (United States)

    Abbasi, Ali; Deetman, Petronella E.; Corpeleijn, Eva; Gansevoort, Ron T.; Gans, Rijk O.B.; Hillege, Hans L.; van der Harst, Pim; Stolk, Ronald P.; Navis, Gerjan; Alizadeh, Behrooz Z.; Bakker, Stephan J.L.

    2014-01-01

    Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6%). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. T2D developed in a total of 210 (6.2%) participants during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; Pbilirubin levels, we observed a 25% (OR 0.75 [95%CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95%CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant. PMID:25368098

  10. Vitamin D and C-Reactive Protein: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Marte C Liefaard

    Full Text Available Vitamin D deficiency is widely prevalent and has been associated with many diseases. It has been suggested that vitamin D has effects on the immune system and inhibits inflammation. The aim of our study was to investigate whether vitamin D has an inhibitory effect on systemic inflammation by assessing the association between serum levels of vitamin D and C-reactive protein. We studied the association between serum 25-hydroxyvitamin D and C-reactive protein through linear regression in 9,649 participants of the Rotterdam Study, an observational, prospective population-based cohort study. We used genetic variants related to vitamin D and CRP to compute a genetic risk score and perform bi-directional Mendelian randomization analysis. In linear regression adjusted for age, sex, cohort and other confounders, natural log-transformed CRP decreased with 0.06 (95% CI: -0.08, -0.03 unit per standard deviation increase in 25-hydroxyvitamin D. Bi-directional Mendelian randomization analyses showed no association between the vitamin D genetic risk score and lnCRP (Beta per SD = -0.018; p = 0.082 or the CRP genetic risk score and 25-hydroxyvitamin D (Beta per SD = 0.001; p = 0.998. In conclusion, higher levels of Vitamin D are associated with lower levels of C-reactive protein. In this study we did not find evidence for this to be the result of a causal relationship.

  11. The Number of Candidate Variants in Exome Sequencing for Mendelian Disease under No Genetic Heterogeneity

    Directory of Open Access Journals (Sweden)

    Jo Nishino

    2013-01-01

    Full Text Available There has been recent success in identifying disease-causing variants in Mendelian disorders by exome sequencing followed by simple filtering techniques. Studies generally assume complete or high penetrance. However, there are likely many failed and unpublished studies due in part to incomplete penetrance or phenocopy. In this study, the expected number of candidate single-nucleotide variants (SNVs in exome data for autosomal dominant or recessive Mendelian disorders was investigated under the assumption of “no genetic heterogeneity.” All variants were assumed to be under the “null model,” and sample allele frequencies were modeled using a standard population genetics theory. To investigate the properties of pedigree data, full-sibs were considered in addition to unrelated individuals. In both cases, particularly regarding full-sibs, the number of SNVs remained very high without controls. The high efficacy of controls was also confirmed. When controls were used with a relatively large total sample size (e.g., N=20, 50, filtering incorporating of incomplete penetrance and phenocopy efficiently reduced the number of candidate SNVs. This suggests that filtering is useful when an assumption of no “genetic heterogeneity” is appropriate and could provide general guidelines for sample size determination.

  12. Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.

    Science.gov (United States)

    Goldberg, Y P; Pimstone, S N; Namdari, R; Price, N; Cohen, C; Sherrington, R P; Hayden, M R

    2012-10-01

    We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Nav1.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Nav1.7. In a small pilot study, we showed that XEN402 blocks Nav1.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery. © 2012 John Wiley & Sons A/S.

  13. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.

    Science.gov (United States)

    Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A

    2005-01-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

  14. Childhood BMI and Adult Type 2 Diabetes, Coronary Artery Diseases, Chronic Kidney Disease, and Cardiometabolic Traits: A Mendelian Randomization Analysis.

    Science.gov (United States)

    Geng, Tingting; Smith, Caren E; Li, Changwei; Huang, Tao

    2018-05-01

    To test the causal effect of childhood BMI on adult cardiometabolic diseases using a Mendelian randomization analysis. We used 15 single nucleotide polymorphisms as instrumental variables for childhood BMI to test the causal effect of childhood BMI on cardiometabolic diseases using summary-level data from consortia. We found that a 1-SD increase in childhood BMI (kg/m 2 ) was associated with an 83% increase in risk of type 2 diabetes (odds ratio [OR] 1.83 [95% CI 1.46, 2.30]; P = 2.5 × 10 -7 ) and a 28% increase in risk of coronary artery disease (CAD) (OR 1.28 [95% CI 1.17, 1.39]; P = 2.1 × 10 -8 ) at the Bonferroni-adjusted level of significance ( P BMI was associated with a 0.587-SD increase in adulthood BMI (kg/m 2 ), a 0.062-SD increase in hip circumference (cm), a 0.602-SD increase in waist circumference (cm), a 0.111 pmol/L increase in log fasting insulin, a 0.068 increase in log-transformed HOMA of ß-cell function (%), a 0.126 increase in log-transformed HOMA of insulin resistance (%), and a 0.109-SD increase in triglyceride (mg/dL) but a 0.138-SD decrease in HDL (mg/dL) in adults at the Bonferroni-adjusted level of significance ( P BMI was associated with increased risk of type 2 diabetes and CAD in adult life. These results provide evidence supportive of a causal association between childhood BMI and these outcomes. © 2018 by the American Diabetes Association.

  15. The Mendelian inheritance of rare flesh and shell colour variants in the black-lipped pearl oyster (Pinctada margaritifera).

    Science.gov (United States)

    Ky, Chin-Long; Nakasai, Seiji; Pommier, Steve; Sham Koua, Manaarii; Devaux, Dominique

    2016-10-01

    Pinctada margaritifera is French Polynesia's most economically important aquaculture species. This pearl oyster has the specific ability to produce cultured pearls with a very wide range of colours, depending on the colour phenotypes of donor oysters used. Its aquaculture is still based on natural spat collection from wild stocks. We investigated three rare colour variants of P. margaritifera - orange flesh, and red and white shell colour phenotypes - in comparison with the wild-type black flesh and shell commonly found in this species. The study aimed to assess the geographic distribution and genetic basis of these colour variants. Colour frequencies were evaluated during transfer and graft processes of pearl oyster seed captured at collector stations. Among the collection locations studied, Mangareva Island showed the highest rate of the orange flesh phenotype, whereas Takaroa and Takume atolls had relatively high rates of red and white shell phenotypes respectively. Broodstocks were made of these rare colour variants, and crosses were performed to produce first- and second-generation progenies to investigate segregation. The results were consistent with Mendelian ratios and suggest a distinct model with no co-dominance: (i) a two-allele model for flesh trait, whereby the orange allele is recessive to the black fleshed type, and (ii) a three-allele model for shell trait, whereby the black wild-type allele is dominant to the red coloration, which is dominant to the white shell. Furthermore, the proposed model provides the basis for producing selected donor pearl oyster lines through hatchery propagation. © 2016 Stichting International Foundation for Animal Genetics.

  16. GALC deletions increase the risk of primary open-angle glaucoma: the role of Mendelian variants in complex disease.

    Directory of Open Access Journals (Sweden)

    Yutao Liu

    Full Text Available DNA copy number variants (CNVs have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC. This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1. (p = 0.017, fisher's exact test. It was validated with array comparative genomic hybridization (arrayCGH and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio = 3.5, 95% CI -1.1-12.0. Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6-16.4. Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.

  17. Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study.

    Science.gov (United States)

    Legason, Ismail D; Pfeiffer, Ruth M; Udquim, Krizia-Ivana; Bergen, Andrew W; Gouveia, Mateus H; Kirimunda, Samuel; Otim, Isaac; Karlins, Eric; Kerchan, Patrick; Nabalende, Hadijah; Bayanjargal, Ariunaa; Emmanuel, Benjamin; Kagwa, Paul; Talisuna, Ambrose O; Bhatia, Kishor; Yeager, Meredith; Biggar, Robert J; Ayers, Leona W; Reynolds, Steven J; Goedert, James J; Ogwang, Martin D; Fraumeni, Joseph F; Prokunina-Olsson, Ludmila; Mbulaiteye, Sam M

    2017-11-01

    Plasmodium falciparum (Pf) malaria infection is suspected to cause endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse relationship between sickle cell trait (SCT) and eBL, which supports that between malaria and eBL, has been reported before, but in small studies with low power. We investigated this hypothesis in children in a population-based study in northern Uganda using Mendelian Randomization. Malaria-related polymorphisms (SCT, IL10, IL1A, CD36, SEMA3C, and IFNAR1) were genotyped in 202 eBL cases and 624 controls enrolled during 2010-2015. We modeled associations between genotypes and eBL or malaria using logistic regression. SCT was associated with decreased risk of eBL (adjusted odds ratio [OR] 0·37, 95% CI 0·21-0·66; p=0·0003). Decreased risk of eBL was associated with IL10 rs1800896-CT (OR 0·73, 95% CI 0·50-1·07) and -CC genotypes (OR 0·53, 95% CI 0·29-0·95, p trend =0·019); IL1A rs2856838-AG (OR 0·56, 95% CI 0·39-0·81) and -AA genotype (OR 0·50, 95% CI 0·28-1·01, p trend =0·0016); and SEMA3C rs4461841-CT or -CC genotypes (OR 0·57, 95% CI 0·35-0·93, p=0·0193). SCT and IL10 rs1800896, IL1A rs2856838, but not SEMA3C rs4461841, polymorphisms were associated with decreased risk of malaria in the controls. Our results support a causal effect of malaria infection on eBL. Published by Elsevier B.V.

  18. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Petroula Proitsi

    2014-09-01

    Full Text Available Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD and test the hypothesis that genetically raised lipid levels increase the risk of LOAD.We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578. We constructed weighted genotype risk scores (GRSs for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013. Both full GRSs using all SNPs associated with each trait at p<5×10-8 and trait specific scores using SNPs associated exclusively with each trait at p<5 × 10-8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]=1.005, 95% CI 0.82-1.24, p = 0.962 per 1 unit increase in HDL-c; OR=0.901, 95% CI 0.65-1.25, p=0.530 per 1 unit increase in LDL-c; OR=1.104, 95% CI 0.89-1.37, p=0.362 per 1 unit increase in triglycerides; and OR=0.954, 95% CI 0.76-1.21, p=0.688 per 1 unit increase in total cholesterol. Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance.Genetic predisposition to increased blood cholesterol and

  19. The causal effect of vitamin D binding protein (DBP levels on calcemic and cardiometabolic diseases: a Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Aaron Leong

    2014-10-01

    Full Text Available Observational studies have shown that vitamin D binding protein (DBP levels, a key determinant of 25-hydroxy-vitamin D (25OHD levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease.We measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos. Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age- and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n = 2,254. DBP had a strong observational and causal association with 25OHD levels (p = 3.2 × 10(-19. While DBP levels were observationally associated with calcium and body mass index (BMI, these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI -0.01, 0.01]; p = 1.00; n = 46,186; fasting insulin (0.01 pmol/l [95% CI -0.00, 0.01,]; p = 0.22; n = 46,186; BMI (0.00 kg/m(2 [95% CI -0.01, 0.01]; p = 0.80; n = 127,587; bone mineral density (0.01 g/cm(2 [95% CI -0.01, 0.03]; p = 0.36; n = 32,961; mean arterial pressure (-0.06 mm Hg [95% CI -0.19, 0.07]; p = 0.36; n = 28,775; ischemic stroke (odds ratio [OR]  = 1.00 [95% CI 0.97, 1.04]; p = 0.92; n

  20. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

    NARCIS (Netherlands)

    Haycock, P.C.; Burgess, S.; Nounu, A.; Zheng, J.; Okoli, G.N.; Bowden, J.; Wade, K.H.; Timpson, N.J.; Evans, D.M.; Willeit, P.; Aviv, A.; Gaunt, T.R.; Hemani, G.; Mangino, M.; Ellis, H.P.; Kurian, K.M.; Pooley, K.A.; Eeles, R.A.; Lee, J.E.; Fang, S.; Chen, W.V.; Law, M.H.; Bowdler, L.M.; Iles, M.M.; Yang, Q.; Worrall, B.B.; Markus, H.S.; Hung, R.J.; Amos, C.I.; Spurdle, A.B.; Thompson, D.J.; O'Mara, T.A.; Wolpin, B.; Amundadottir, L.; Stolzenberg-Solomon, R.; Trichopoulou, A.; Onland-Moret, N.C.; Lund, E.; Duell, E.J.; Canzian, F.; Severi, G.; Overvad, K.; Gunter, M.J.; Tumino, R.; Svenson, U.; Rij, A. van; Baas, A.F.; Bown, M.J.; Samani, N.J.; t'Hof, F.N.G. van; Tromp, G.; Jones, G.T.; Kuivaniemi, H.; Elmore, J.R.; Johansson, M.; McKay, J.; Scelo, G.; Carreras-Torres, R.; Gaborieau, V.; Brennan, P.; Bracci, P.M.; Neale, R.E.; Olson, S.H.; Gallinger, S.; Li, D.; Petersen, G.M.; Risch, H.A.; Klein, A.P.; Han, J.; Abnet, C.C.; Freedman, N.D.; Taylor, P.R.; Maris, J.M.; Aben, K.K.H.; Kiemeney, L.A.; Vermeulen, S.H.; Wiencke, J.K.; Walsh, K.M.; Wrensch, M.; Rice, T.; Turnbull, C.; Litchfield, K.; Paternoster, L.; Standl, M.; Abecasis, G.R.; SanGiovanni, J.P.; Li, Y.; Mijatovic, V.; Sapkota, Y.; Low, S.K.; Zondervan, K.T.; Montgomery, G.W.; Nyholt, D.R.; Heel, D.A. van; Hunt, K.; Arking, D.E.; Ashar, F.N.; Sotoodehnia, N.; Woo, D.; et al.,

    2017-01-01

    Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study,

  1. Statistical guidance for experimental design and data analysis of mutation detection in rare monogenic mendelian diseases by exome sequencing.

    Directory of Open Access Journals (Sweden)

    Degui Zhi

    Full Text Available Recently, whole-genome sequencing, especially exome sequencing, has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. However, it is unclear whether this approach can be generalized and effectively applied to other Mendelian diseases with high locus heterogeneity. Moreover, the current exome sequencing approach has limitations such as false positive and false negative rates of mutation detection due to sequencing errors and other artifacts, but the impact of these limitations on experimental design has not been systematically analyzed. To address these questions, we present a statistical modeling framework to calculate the power, the probability of identifying truly disease-causing genes, under various inheritance models and experimental conditions, providing guidance for both proper experimental design and data analysis. Based on our model, we found that the exome sequencing approach is well-powered for mutation detection in recessive, but not dominant, Mendelian diseases with high locus heterogeneity. A disease gene responsible for as low as 5% of the disease population can be readily identified by sequencing just 200 unrelated patients. Based on these results, for identifying rare Mendelian disease genes, we propose that a viable approach is to combine, sequence, and analyze patients with the same disease together, leveraging the statistical framework presented in this work.

  2. Mendelian Genetics as a Platform for Teaching about Nature of Science and Scientific Inquiry: The Value of Textbooks

    Science.gov (United States)

    Campanile, Megan F.; Lederman, Norman G.; Kampourakis, Kostas

    2015-01-01

    The purpose of this study was to analyze seven widely used high school biology textbooks in order to assess the nature of science knowledge (NOS) and scientific inquiry (SI) aspects they, explicitly or implicitly, conveyed in the Mendelian genetics sections. Textbook excerpts that directly and/or fully matched our statements about NOS and SI were…

  3. Genetic Determinism in the Genetics Curriculum: An Exploratory Study of the Effects of Mendelian and Weldonian Emphases

    Science.gov (United States)

    Jamieson, Annie; Radick, Gregory

    2017-01-01

    Twenty-first-century biology rejects genetic determinism, yet an exaggerated view of the power of genes in the making of bodies and minds remains a problem. What accounts for such tenacity? This article reports an exploratory study suggesting that the common reliance on Mendelian examples and concepts at the start of teaching in basic genetics is…

  4. Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour

    DEFF Research Database (Denmark)

    Schou, M; Brünner, N; Spang-Thomsen, M

    2006-01-01

    Most nude mice do not allow the formation of metastases after heterotransplantation of human malignant tumours. Here we describe a substrain of BALB/c nude mice (BALB/c/AnNCr) that reproducibly allows some human cancers to metastasize. By Mendelian analysis of hybrids between this substrain and C57...

  5. Rules for resolving Mendelian inconsistencies in nuclear pedigrees typed for two-allele markers.

    Directory of Open Access Journals (Sweden)

    Sajjad Ahmad Khan

    Full Text Available Gene-mapping studies, regularly, rely on examination for Mendelian transmission of marker alleles in a pedigree as a way of screening for genotyping errors and mutations. For analysis of family data sets, it is, usually, necessary to resolve or remove the genotyping errors prior to consideration. At the Center of Inherited Disease Research (CIDR, to deal with their large-scale data flow, they formalized their data cleaning approach in a set of rules based on PedCheck output. We scrutinize via carefully designed simulations that how well CIDR's data cleaning rules work in practice. We found that genotype errors in siblings are detected more often than in parents for less polymorphic SNPs and vice versa for more polymorphic SNPs. Through computer simulations, we conclude that some of the CIDR's rules work poorly in some circumstances, and we suggest a set of modified data cleaning rules that may work better than CIDR's rules.

  6. Mendel Lives: The Survival of Mendelian Genetics in the Lysenkoist Classroom, 1937-1964

    Science.gov (United States)

    Peacock, Margaret

    2015-01-01

    The demise of Soviet genetics in the 1930s, 40s, and 50s has stood for many as a prime example of the damage that social and political dogmatism can do when allowed to meddle in the workings of science. In particular, the story of Trofim Lysenko's rise to preeminence and the fall of Mendelian genetics in the Soviet Union has become a lasting testament to the dangers of state power and a seemingly blatant manifestation of totalitarianism in practice. In recent years, historians have begun to complicate this story. The purpose of this article is to examine the extent to which this conventional account of state power in Soviet biology, symbolized by the disappearance of Mendel, still holds true. Using middle school textbooks, encyclopedias, and pedagogical journals that were published between 1934 and 1964 this article argues that despite its efforts, the state apparatus was functionally incapable of eradicating genetics from its schools.

  7. Golden Ratio

    Indian Academy of Sciences (India)

    Our attraction to another body increases if the body is symmetricaland in proportion. If a face or a structure is in proportion,we are more likely to notice it and find it beautiful.The universal ratio of beauty is the 'Golden Ratio', found inmany structures. This ratio comes from Fibonacci numbers.In this article, we explore this ...

  8. Golden Ratio

    Indian Academy of Sciences (India)

    Keywords. Fibonacci numbers, golden ratio, Sanskrit prosody, solar panel. Abstract. Our attraction to another body increases if the body is symmetricaland in proportion. If a face or a structure is in proportion,we are more likely to notice it and find it beautiful.The universal ratio of beauty is the 'Golden Ratio', found inmany ...

  9. Golden Ratio

    Indian Academy of Sciences (India)

    Our attraction to another body increases if the body is sym- metrical and in proportion. If a face or a structure is in pro- portion, we are more likely to notice it and find it beautiful. The universal ratio of beauty is the 'Golden Ratio', found in many structures. This ratio comes from Fibonacci numbers. In this article, we explore this ...

  10. Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors.

    Science.gov (United States)

    Burgess, Stephen; Scott, Robert A; Timpson, Nicholas J; Davey Smith, George; Thompson, Simon G

    2015-07-01

    Finding individual-level data for adequately-powered Mendelian randomization analyses may be problematic. As publicly-available summarized data on genetic associations with disease outcomes from large consortia are becoming more abundant, use of published data is an attractive analysis strategy for obtaining precise estimates of the causal effects of risk factors on outcomes. We detail the necessary steps for conducting Mendelian randomization investigations using published data, and present novel statistical methods for combining data on the associations of multiple (correlated or uncorrelated) genetic variants with the risk factor and outcome into a single causal effect estimate. A two-sample analysis strategy may be employed, in which evidence on the gene-risk factor and gene-outcome associations are taken from different data sources. These approaches allow the efficient identification of risk factors that are suitable targets for clinical intervention from published data, although the ability to assess the assumptions necessary for causal inference is diminished. Methods and guidance are illustrated using the example of the causal effect of serum calcium levels on fasting glucose concentrations. The estimated causal effect of a 1 standard deviation (0.13 mmol/L) increase in calcium levels on fasting glucose (mM) using a single lead variant from the CASR gene region is 0.044 (95 % credible interval -0.002, 0.100). In contrast, using our method to account for the correlation between variants, the corresponding estimate using 17 genetic variants is 0.022 (95 % credible interval 0.009, 0.035), a more clearly positive causal effect.

  11. Circulating interleukin-10 levels and human papilloma virus and Epstein-Barr virus-associated cancers: evidence from a Mendelian randomization meta-analysis based on 11,170 subjects.

    Science.gov (United States)

    Qu, Kai; Pang, Qing; Lin, Ting; Zhang, Li; Gu, Mingliang; Niu, Wenquan; Liu, Chang; Zhang, Ming

    2016-01-01

    Recent studies have showed interleukin 10 (IL-10) is a critical cytokine that determines antiviral immune response and is related to virus-associated cancers. However, whether genetically elevated circulating IL-10 levels are associated with the risk of human papilloma virus and Epstein-Barr virus-associated cancers (HEACs) is still unclear. Mendelian randomization method was implemented to meta-analyze available observational studies by employing IL-10 three variants (-592C>A, -819C>T, and -1082A>G) as instruments. A total of 24 articles encompassing 11,170 subjects were ultimately eligible for the meta-analysis. Overall, there was a significant association between IL-10 promoter variant -1082A>G and HEACs under allelic and dominant models (both PG was significant for nasopharyngeal cancer under allelic, homozygous genotypic and dominant models (all P<0.001). Moreover by ethnicity, carriers of -1082G allele had a 74% increased risk for nasopharyngeal cancer in Asians under dominant model (odds ratio [OR] =1.737; 95% confidence interval [CI]: 1.280-2.358; P<0.001). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 levels was 1.14 (95% CI: 1.01-16.99) in HEACs. Our findings provided strong evidence for a critical role of genetically elevated circulating IL-10 levels in the development of HEACs, especially in Asian population and for nasopharyngeal cancer.

  12. Sex ratios

    OpenAIRE

    West, Stuart A; Reece, S E; Sheldon, Ben C

    2002-01-01

    Sex ratio theory attempts to explain variation at all levels (species, population, individual, brood) in the proportion of offspring that are male (the sex ratio). In many cases this work has been extremely successful, providing qualitative and even quantitative explanations of sex ratio variation. However, this is not always the situation, and one of the greatest remaining problems is explaining broad taxonomic patterns. Specifically, why do different organisms show so ...

  13. Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization

    Science.gov (United States)

    Controversy persists on the association between dairy products, especially milk, and cardiovascular diseases (CVD). Genetic proxies may improve dairy intake estimations, and clarify diet- disease relationships through Mendelian randomization. We meta- analytically (n

  14. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer : Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

    NARCIS (Netherlands)

    Khankari, Nikhil K.; Shu, Xiao Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Eeles, Rosalind A.; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei; Blalock, Kendra; Campbell, Peter T.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Figueiredo, Jane; James Gauderman, W.; Gong, Jian; Green, Roger C.; Harju, John F.; Harrison, Tabitha A.; Jacobs, Eric J.; Jenkins, Mark A.; Jiao, Shuo; Li, Li; Lin, Yi; Manion, Frank J.; Moreno, Victor; Mukherjee, Bhramar; Raskin, Leon; Schumacher, Fredrick R.; Seminara, Daniela; Severi, Gianluca; Stenzel, Stephanie L.; Thomas, Duncan C.; Hopper, John L.; Southey, Melissa C.; Makalic, Enes; Schmidt, Daniel F.; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos Santos Silva, Isabel; Ahsan, Habib; Whittemore, Alice; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B.; Uitterlinden, Andre G.; Hofman, Albert; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Crisponi, Laura; Hall, Per; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Easton, Douglas F.; Turnbull, Clare; Rahman, Nazneen; Eeles, Rosalind; Kote-Jarai, Zsofia; Muir, Kenneth; Giles, Graham; Neal, David; Donovan, Jenny L.; Hamdy, Freddie C.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher; Schumacher, Fred; Travis, Ruth; Riboli, Elio; Hunter, David; Gapstur, Susan; Berndt, Sonja; Chanock, Stephen; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; McKay, James D.; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil; Teresa Landi, Maria; Heinrich, Joachim; Wu, Xifeng; Ye, Yuanqing; Christiani, David C.

    2016-01-01

    Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using

  15. Contributions of procoagulants and anticoagulants to the international normalized ratio and thrombin generation assay in patients treated with warfarin: potential role of protein Z as a powerful determinant of coagulation assays.

    Science.gov (United States)

    Choi, Qute; Kim, Ji-Eun; Hyun, Jungwon; Han, Kyou-Sup; Kim, Hyun Kyung

    2013-07-01

    The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them. The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured. The INR was significantly and inversely correlated with ETP. The therapeutic range of ETP comparable to an INR range of 2.0-3.0 was 290.1-494.6. ETP showed comparable performance to the INR as a warfarin-monitoring parameter with respect to clinical complication rate. The median levels of FII, FVII, FIX, and FX and proteins C and Z tended to decrease gradually with increasing anticoagulation intensity according to the INR or ETP. Of note, protein Z levels decreased dramatically with increasing anticoagulation status. INRs were significantly determined by FII, FVII, and protein Z. ETP was significantly dependent on FVII, and proteins C and Z concentration. Protein Z significantly reduced the total amount of thrombin generation and prolonged PT value in vitro. The INR and ETP exhibit similar efficacy for warfarin monitoring according to the clinical complication rate. Protein Z is considered to be a significant determinant of INR and ETP in patients on warfarin therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Theory‐based pharmacokinetics and pharmacodynamics of S‐ and R‐warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients

    Science.gov (United States)

    Xue, Ling; Holford, Nick; Ding, Xiao‐liang; Shen, Zhen‐ya; Huang, Chen‐rong; Zhang, Hua; Zhang, Jing‐jing; Guo, Zhe‐ning; Xie, Cheng; Zhou, Ling; Chen, Zhi‐yao; Liu, Lin‐sheng

    2016-01-01

    Aims The aims of this study are to apply a theory‐based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S‐ and R‐warfarin. Methods Clinical data were obtained from 264 patients. Total concentrations for S‐ and R‐warfarin were measured by ultra‐high performance liquid tandem mass spectrometry. Genotypes were measured using pyrosequencing. A sequential population PK parameter with data method was used to describe the international normalized ratio (INR) time course. Data were analyzed with NONMEM. Model evaluation was based on parameter plausibility and prediction‐corrected visual predictive checks. Results Warfarin PK was described using a one‐compartment model. CYP2C9 *1/*3 genotype had reduced clearance for S‐warfarin, but increased clearance for R‐warfarin. The in vitro parameters for the relationship between prothrombin complex activity (PCA) and INR were markedly different (A = 0.560, B = 0.386) from the theory‐based values (A = 1, B = 0). There was a small difference between healthy subjects and patients. A sigmoid Emax PD model inhibiting PCA synthesis as a function of S‐warfarin concentration predicted INR. Small R‐warfarin effects was described by competitive antagonism of S‐warfarin inhibition. Patients with VKORC1 AA and CYP4F2 CC or CT genotypes had lower C50 for S‐warfarin. Conclusion A theory‐based PKPD model describes warfarin concentrations and clinical response. Expected PK and PD genotype effects were confirmed. The role of predicted fat free mass with theory‐based allometric scaling of PK parameters was identified. R‐warfarin had a minor effect compared with S‐warfarin on PCA synthesis. INR is predictable from 1/PCA in vivo. PMID:27763679

  17. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.

    Directory of Open Access Journals (Sweden)

    Karani S Vimaleswaran

    Full Text Available Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI and 25-hydroxyvitamin D [25(OHD] using genetic markers as instrumental variables (IVs in bi-directional Mendelian randomization (MR analysis.We used information from 21 adult cohorts (up to 42,024 participants with 12 BMI-related SNPs (combined in an allelic score to produce an instrument for BMI and four SNPs associated with 25(OHD (combined in two allelic scores, separately for genes encoding its synthesis or metabolism as an instrument for vitamin D. Regression estimates for the IVs (allele scores were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT consortium (n = 123,864. Each 1 kg/m(2 higher BMI was associated with 1.15% lower 25(OHD (p = 6.52×10⁻²⁷. The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶² and 25(OHD (-0.06% [95% CI -0.10 to -0.02], p = 0.004 in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OHD (p≤8.07×10⁻⁵⁷ for both scores but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08 in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OHD concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005. No association was seen for genetically instrumented 25(OHD with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores.On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OHD, while any effects of lower 25(OHD increasing BMI are likely to be small. Population level interventions to

  18. Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study.

    Directory of Open Access Journals (Sweden)

    Alastair J Noyce

    2017-06-01

    Full Text Available Both positive and negative associations between higher body mass index (BMI and Parkinson disease (PD have been reported in observational studies, but it has been difficult to establish causality because of the possibility of residual confounding or reverse causation. To our knowledge, Mendelian randomisation (MR-the use of genetic instrumental variables (IVs to explore causal effects-has not previously been used to test the effect of BMI on PD.Two-sample MR was undertaken using genome-wide association (GWA study data. The associations between the genetic instruments and BMI were obtained from the GIANT consortium and consisted of the per-allele difference in mean BMI for 77 independent variants that reached genome-wide significance. The per-allele difference in log-odds of PD for each of these variants was estimated from a recent meta-analysis, which included 13,708 cases of PD and 95,282 controls. The inverse-variance weighted method was used to estimate a pooled odds ratio (OR for the effect of a 5-kg/m2 higher BMI on PD. Evidence of directional pleiotropy averaged across all variants was sought using MR-Egger regression. Frailty simulations were used to assess whether causal associations were affected by mortality selection. A combined genetic IV expected to confer a lifetime exposure of 5-kg/m2 higher BMI was associated with a lower risk of PD (OR 0.82, 95% CI 0.69-0.98. MR-Egger regression gave similar results, suggesting that directional pleiotropy was unlikely to be biasing the result (intercept 0.002; p = 0.654. However, the apparent protective influence of higher BMI could be at least partially induced by survival bias in the PD GWA study, as demonstrated by frailty simulations. Other important limitations of this application of MR include the inability to analyse non-linear associations, to undertake subgroup analyses, and to gain mechanistic insights.In this large study using two-sample MR, we found that variants known to influence

  19. Genetic Determinism in the Genetics Curriculum. An Exploratory Study of the Effects of Mendelian and Weldonian Emphases

    Science.gov (United States)

    Jamieson, Annie; Radick, Gregory

    2017-12-01

    Twenty-first-century biology rejects genetic determinism, yet an exaggerated view of the power of genes in the making of bodies and minds remains a problem. What accounts for such tenacity? This article reports an exploratory study suggesting that the common reliance on Mendelian examples and concepts at the start of teaching in basic genetics is an eliminable source of support for determinism. Undergraduate students who attended a standard `Mendelian approach' university course in introductory genetics on average showed no change in their determinist views about genes. By contrast, students who attended an alternative course which, inspired by the work of a critic of early Mendelism, W. F. R. Weldon (1860-1906), replaced an emphasis on Mendel's peas with an emphasis on developmental contexts and their role in bringing about phenotypic variability, were less determinist about genes by the end of teaching. Improvements in both the new Weldonian curriculum and the study design are in view for the future.

  20. The Application of Restriction Landmark Genome Scanning Method for Surveillance of Non-Mendelian Inheritance in F1 Hybrids

    Directory of Open Access Journals (Sweden)

    Tomoko Takamiya

    2009-01-01

    Full Text Available We analyzed inheritance of DNA methylation in reciprocal F1 hybrids (subsp. japonica cv. Nipponbare × subsp. indica cv. Kasalath of rice (Oryza sativa L. using restriction landmark genome scanning (RLGS, and detected differing RLGS spots between the parents and reciprocal F1 hybrids. MspI/HpaII restriction sites in the DNA from these different spots were suspected to be heterozygously methylated in the Nipponbare parent. These spots segregated in F1 plants, but did not segregate in selfed progeny of Nipponbare, showing non-Mendelian inheritance of the methylation status. As a result of RT-PCR and sequencing, a specific allele of the gene nearest to the methylated sites was expressed in reciprocal F1 plants, showing evidence of biased allelic expression. These results show the applicability of RLGS for scanning of non-Mendelian inheritance of DNA methylation and biased allelic expression.

  1. Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

    OpenAIRE

    Liu, Junxi; Au Yeung, Shiu Lun; Lin, Shi Lin; Leung, Gabriel M.; Schooling, C. Mary

    2016-01-01

    We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT ...

  2. Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study

    OpenAIRE

    Ismail D. Legason; Ruth M. Pfeiffer; Krizia-Ivana Udquim; Andrew W. Bergen; Mateus H. Gouveia; Samuel Kirimunda; Isaac Otim; Eric Karlins; Patrick Kerchan; Hadijah Nabalende; Ariunaa Bayanjargal; Benjamin Emmanuel; Paul Kagwa; Ambrose O. Talisuna; Kishor Bhatia

    2017-01-01

    Background: Plasmodium falciparum (Pf) malaria infection is suspected to cause endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse relationship between sickle cell trait (SCT) and eBL, which supports that between malaria and eBL, has been reported before, but in small studies with low power. We investigated this hypothesis in children in a population-based study in northern Uganda using Mendelian Randomization. Methods: Malaria-related polymorphisms (SCT, IL10, I...

  3. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

    OpenAIRE

    Iglesias, Adriana I; Mishra, Aniket; Vitart, Veronique; Bykhovskaya, Yelena; Höhn, René; Springelkamp, Henriët; Cuellar-Partida, Gabriel; Gharahkhani, Puya; Bailey, Jessica N Cooke; Willoughby, Colin E; Li, Xiaohui; Yazar, Seyhan; Nag, Abhishek; Khawaja, Anthony P.; Polasek, Ozren

    2018-01-01

    Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. Pathway analyses uncover new, as well as supported the role of connective tissue-related, pathways. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan,...

  4. Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank.

    Science.gov (United States)

    Tyrrell, Jessica; Jones, Samuel E; Beaumont, Robin; Astley, Christina M; Lovell, Rebecca; Yaghootkar, Hanieh; Tuke, Marcus; Ruth, Katherine S; Freathy, Rachel M; Hirschhorn, Joel N; Wood, Andrew R; Murray, Anna; Weedon, Michael N; Frayling, Timothy M

    2016-03-08

    To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status. Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors. UK Biobank. 119,669 men and women of British ancestry, aged between 37 and 73 years. Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index. In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6 × 10(-3)) lower annual household income in men and a £1890 (£1680 to £2100; P=6 × 10(-15)) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6 × 10(-7)), and a £1130 (£680 to £1580) higher annual household income (P=4 × 10(-8)). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m(2)) caused a £2940 (£1680 to £4200; P=1 × 10(-5)) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only. These data support evidence that height and BMI play an important partial role in determining several aspects of a person

  5. Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank

    Science.gov (United States)

    Tyrrell, Jessica; Jones, Samuel E; Beaumont, Robin; Astley, Christina M; Lovell, Rebecca; Yaghootkar, Hanieh; Tuke, Marcus; Ruth, Katherine S; Freathy, Rachel M; Hirschhorn, Joel N; Wood, Andrew R; Murray, Anna; Weedon, Michael N

    2016-01-01

    Objective To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status. Design Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors. Setting UK Biobank. Participants 119 669 men and women of British ancestry, aged between 37 and 73 years. Main outcome measures Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index. Results In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6×10−3) lower annual household income in men and a £1890 (£1680 to £2100; P=6×10−15) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6×10−7), and a £1130 (£680 to £1580) higher annual household income (P=4×10−8). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m2) caused a £2940 (£1680 to £4200; P=1×10−5) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only. Conclusions These data support evidence that height and BMI play an

  6. DETECTION OF MENDELIAN AND GENOTYPE FREQUENCY OF GROWTH HORMONE GENE IN ONGOLE CROSSBRED CATTLE MATED BY THE ARTIFICIAL INSEMINATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    U. Paputungan

    2012-06-01

    Full Text Available The objectives of this study were to detect the Mendelian mode inheritance of growth hormone (GH and to establish genotype frequency of GH gene in Ongole-crossbred cattle mated by the artificial insemination (AI technique. Total of 76 blood samples were collected from Ongole-crossbred cows and bulls (G0, and their progenies (G1 at the Tumaratas AI service center in North Sulawesi province, Indonesia. All blood samples were screened for the presence of GH locus using a PCR-RFLP method involving restricted enzyme Msp1 on 1.2 % of agarose gel. Data were analyzed using statistical program function in Excel XP. The results showed that GH locus using alleles of Msp1+ and Msp1- enzyme restriction in Ongole-crossbred cows and bulls was inherited to their Ongole-crossbred progenies following the Mendelian mode inheritance. This Mendelian inheritance generated by AI technique was not under genetic equilibrium for the Msp1 genotype frequencies in groups of G0 and G1. The breeding program using genotypes of bulls and cows (G0 for generating the genotype of GH Msp1 enzyme restriction by AI technique should be maintained to increase these various allele dispersion rates for breeding under genetic equilibrium of the Ongole-crossbred cattle population.

  7. Habitual coffee consumption and risk of type 2 diabetes, ischemic heart disease, depression and Alzheimer’s disease: a Mendelian randomization study

    Science.gov (United States)

    Kwok, Man Ki; Leung, Gabriel M.; Schooling, C. Mary

    2016-01-01

    Observationally, coffee is inversely associated with type 2 diabetes mellitus (T2DM), depression and Alzheimer’s disease, but not ischemic heart disease (IHD). Coffee features as possibly protective in the 2015 Dietary Guidelines for Americans. Short-term trials suggest coffee has neutral effect on most glycemic traits, but raises lipids and adiponectin. To clarify we compared T2DM, depression, Alzheimer’s disease, and IHD and its risk factors by genetically predicted coffee consumption using two-sample Mendelian randomization applied to large extensively genotyped case-control and cross-sectional studies. Childhood cognition was used as a negative control outcome. Genetically predicted coffee consumption was not associated with T2DM (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.76 to 1.36), depression (0.89, 95% CI 0.66 to 1.21), Alzheimer’s disease (1.17, 95% CI 0.96 to 1.43), IHD (0.96, 95% CI 0.80 to 1.14), lipids, glycemic traits, adiposity or adiponectin. Coffee was unrelated to childhood cognition. Consistent with observational studies, coffee was unrelated to IHD, and, as expected, childhood cognition. However, contrary to observational findings, coffee may not have beneficial effects on T2DM, depression or Alzheimer’s disease. These findings clarify the role of coffee with relevance to dietary guidelines and suggest interventions to prevent these complex chronic diseases should be sought elsewhere. PMID:27845333

  8. Resistance to a bacterial parasite in the crustacean Daphnia magna shows Mendelian segregation with dominance.

    Science.gov (United States)

    Luijckx, P; Fienberg, H; Duneau, D; Ebert, D

    2012-05-01

    The influence of host and parasite genetic background on infection outcome is a topic of great interest because of its pertinence to theoretical issues in evolutionary biology. In the present study, we use a classical genetics approach to examine the mode of inheritance of infection outcome in the crustacean Daphnia magna when exposed to the bacterial parasite Pasteuria ramosa. In contrast to previous studies in this system, we use a clone of P. ramosa, not field isolates, which allows for a more definitive interpretation of results. We test parental, F1, F2, backcross and selfed parental clones (total 284 genotypes) for susceptibility against a clone of P. ramosa using two different methods, infection trials and the recently developed attachment test. We find that D. magna clones reliably exhibit either complete resistance or complete susceptibility to P. ramosa clone C1 and that resistance is dominant, and inherited in a pattern consistent with Mendelian segregation of a single-locus with two alleles. The finding of a single host locus controlling susceptibility to P. ramosa suggests that the previously observed genotype-genotype interactions in this system have a simple genetic basis. This has important implications for the outcome of host-parasite co-evolution. Our results add to the growing body of evidence that resistance to parasites in invertebrates is mostly coded by one or few loci with dominance.

  9. Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies1

    Science.gov (United States)

    Bowden, Jack; Relton, Caroline; Davey Smith, George

    2016-01-01

    Mendelian randomization (MR) is an increasingly important tool for appraising causality in observational epidemiology. The technique exploits the principle that genotypes are not generally susceptible to reverse causation bias and confounding, reflecting their fixed nature and Mendel’s first and second laws of inheritance. The approach is, however, subject to important limitations and assumptions that, if unaddressed or compounded by poor study design, can lead to erroneous conclusions. Nevertheless, the advent of 2-sample approaches (in which exposure and outcome are measured in separate samples) and the increasing availability of open-access data from large consortia of genome-wide association studies and population biobanks mean that the approach is likely to become routine practice in evidence synthesis and causal inference research. In this article we provide an overview of the design, analysis, and interpretation of MR studies, with a special emphasis on assumptions and limitations. We also consider different analytic strategies for strengthening causal inference. Although impossible to prove causality with any single approach, MR is a highly cost-effective strategy for prioritizing intervention targets for disease prevention and for strengthening the evidence base for public health policy. PMID:26961927

  10. Darbishire expands his vision of heredity from Mendelian genetics to inherited memory.

    Science.gov (United States)

    Wood, Roger J

    2015-10-01

    The British biologist A.D. Darbishire (1879-1915) responded to the rediscovery in 1900 of Mendel's theory of heredity by testing it experimentally, first in Oxford, then in Manchester and London. He summarised his conclusions in a textbook 'Breeding and the Mendelian Discovery' (1911), in which he questioned whether Mendelism alone could explain all aspects of practical breeding experience. Already he had begun to think about an alternative theory to give greater emphasis to the widely held conviction among breeders regarding the inheritance of characteristics acquired during an individual's life. Redefining heredity in terms of a germ-plasm based biological memory, he used vocabulary drawn partly from sources outside conventional science, including the metaphysical/vitalistic writings of Samuel Butler and Henri Bergson. An evolving hereditary memory fitted well with the conception of breeding as a creative art aimed at greater economic efficiency. For evolution beyond human control he proposed a self-modifying process, claiming it to surpass in efficiency the chancy mechanism of natural selection proposed by Darwin. From his writings, including early chapters of an unfinished book entitled 'An Introduction to a Biology', we consider how he reached these concepts and how they relate to later advances in understanding the genome and the genetic programme. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Genetic association of telomere length with hepatocellular carcinoma risk: A Mendelian randomization analysis.

    Science.gov (United States)

    Cheng, Yue; Yu, Chengxiao; Huang, Mingtao; Du, Fangzhi; Song, Ci; Ma, Zijian; Zhai, Xiangjun; Yang, Yuan; Liu, Jibin; Bei, Jin-Xin; Jia, Weihua; Jin, Guangfu; Li, Shengping; Zhou, Weiping; Liu, Jianjun; Dai, Juncheng; Hu, Zhibin

    2017-10-01

    Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk. Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls). Genetic risk score, as proxy for actual measured telomere length, derived from nine telomere length-associated genetic variants was used to evaluate the effect of telomere length on HCC risk. We observed a significant risk signal between genetically increased telomere length and HBV-related HCC risk (OR=2.09, 95% CI 1.32-3.31, P=0.002). Furthermore, a U-shaped curve was fitted by the restricted cubic spline curve, which indicated that either short or long telomere length would increase HCC risk (P=0.0022 for non-linearity test). Subgroup analysis did not reveal significant heterogeneity between different age, gender, smoking status and drinking status groups. Our results indicated that a genetic background that favors longer or shorter telomere length may increase HBV-related HCC risk-a U-shaped association. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Investigating the causal effect of vitamin D on serum adiponectin using a mendelian randomization approach

    DEFF Research Database (Denmark)

    Husemoen, L. L. N.; Skaaby, T.; Martinussen, Torben

    2014-01-01

    Background/Objectives: The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach. Subjects/Methods: Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two...... doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, Pvitamin D-binding protein gene and the filaggrin gene as instrumental variables, the causal effect in % was estimated to 61.46, 95% CI: 17.51, 120.28, P=0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10...... effect estimate in % per doubling of 25(OH)D was 37.13, 95% CI:-3.67, 95.20, P=0.080). Conclusions: The results indicate a possible causal association between serum 25(OH)D and total adiponectin. However, the association was not replicated for HMW adiponectin. Thus, further studies are needed to confirm...

  13. Correcting the Standard Errors of 2-Stage Residual Inclusion Estimators for Mendelian Randomization Studies.

    Science.gov (United States)

    Palmer, Tom M; Holmes, Michael V; Keating, Brendan J; Sheehan, Nuala A

    2017-11-01

    Mendelian randomization studies use genotypes as instrumental variables to test for and estimate the causal effects of modifiable risk factors on outcomes. Two-stage residual inclusion (TSRI) estimators have been used when researchers are willing to make parametric assumptions. However, researchers are currently reporting uncorrected or heteroscedasticity-robust standard errors for these estimates. We compared several different forms of the standard error for linear and logistic TSRI estimates in simulations and in real-data examples. Among others, we consider standard errors modified from the approach of Newey (1987), Terza (2016), and bootstrapping. In our simulations Newey, Terza, bootstrap, and corrected 2-stage least squares (in the linear case) standard errors gave the best results in terms of coverage and type I error. In the real-data examples, the Newey standard errors were 0.5% and 2% larger than the unadjusted standard errors for the linear and logistic TSRI estimators, respectively. We show that TSRI estimators with modified standard errors have correct type I error under the null. Researchers should report TSRI estimates with modified standard errors instead of reporting unadjusted or heteroscedasticity-robust standard errors. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

  14. Mendelian breeding units versus standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

    Directory of Open Access Journals (Sweden)

    Daria Sanna

    2011-01-01

    Full Text Available We report a sampling strategy based on Mendelian Breeding Units (MBUs, representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits.

  15. Age at Menarche and Time Spent in Education: A Mendelian Randomization Study.

    Science.gov (United States)

    Gill, D; Del Greco M, F; Rawson, T M; Sivakumaran, P; Brown, A; Sheehan, N A; Minelli, C

    2017-09-01

    Menarche signifies the primary event in female puberty and is associated with changes in self-identity. It is not clear whether earlier puberty causes girls to spend less time in education. Observational studies on this topic are likely to be affected by confounding environmental factors. The Mendelian randomization (MR) approach addresses these issues by using genetic variants (such as single nucleotide polymorphisms, SNPs) as proxies for the risk factor of interest. We use this technique to explore whether there is a causal effect of age at menarche on time spent in education. Instruments and SNP-age at menarche estimates are identified from a Genome Wide Association Study (GWAS) meta-analysis of 182,416 women of European descent. The effects of instruments on time spent in education are estimated using a GWAS meta-analysis of 118,443 women performed by the Social Science Genetic Association Consortium (SSGAC). In our main analysis, we demonstrate a small but statistically significant causal effect of age at menarche on time spent in education: a 1 year increase in age at menarche is associated with 0.14 years (53 days) increase in time spent in education (95% CI 0.10-0.21 years, p = 3.5 × 10 -8 ). The causal effect is confirmed in sensitivity analyses. In identifying this positive causal effect of age at menarche on time spent in education, we offer further insight into the social effects of puberty in girls.

  16. Clarifying Normalization

    Science.gov (United States)

    Carpenter, Donald A.

    2008-01-01

    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  17. Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study

    Science.gov (United States)

    Zhang, Hui; Liu, Jing; Dong, Zheng; Ding, Yue; Qian, Qiaoxia; Zhou, Jingru; Ma, Yanyun; Mei, Zhendong; Chen, Xiangxiang; Li, Yuan; Yuan, Ziyu; Zhang, Juan; Yang, Yajun; Chen, Xingdong; Jin, Li; Zou, Hejian; Wang, Xiaofeng; Wang, Jiucun

    2017-01-01

    Aim A Mendelian randomization study (MRS) can be linked to a “natural” randomized controlled trial in order to avoid potential bias of observational epidemiology. We aimed to study the possible association between serum urate (SU) and total bilirubin (TBIL) using MRS. Materials and Methods An observational epidemiological study using ordinary least squares (OLS) regression and MRS using two-stage least square (TLS) regression was conducted to assess the effect of SU on TBIL. The comparison between the OLS regression and the TLS regression was analyzed by the Durbin-Hausman test. If the p value is significant, it suggests that the OLS regression cannot evaluate the relationship between exposure and outcome, and the TLS regression is precise; while if the p value is not significant, there would be no significant difference between the two regressions. Results A total of 3,753 subjects were analyzed. In OLS regression, there was no significant association between SU and TBIL in all subjects and subgroup analysis (all p > 0.05). However, MRS revealed a negative correlation between SU and TBIL after adjustment for confounders (beta = –0.021, p = 0.010). Further analysis was conducted in different SU subgroups, and results show that elevated SU was associated with a significant reduction in TBIL after adjustment for hyperuricemic subjects (beta = –0.053, p = 0.027). In addition, the results using the Durbin-Hausman test further confirmed a negative effect of SU on TBIL (p = 0.002 and 0.010, respectively). Conclusions This research shows for the first time that elevated SU was a potential causal factor in the reduction of TBIL and it provides strong evidence to resolve the controversial association between SU and TBIL. PMID:29262606

  18. Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis.

    Science.gov (United States)

    May-Wilson, Sebastian; Sud, Amit; Law, Philip J; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Eriksson, Johan G; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Farrington, Susan M; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Timothy S; Fisher, David; Kerr, Rachel; Kerr, David; Passarelli, Michael N; Figueiredo, Jane C; Buchanan, Daniel D; Win, Aung K; Hopper, John L; Jenkins, Mark A; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steven; Conti, David; Schumacher, Fred; Casey, Graham; Aaltonen, Lauri A; Cheadle, Jeremy P; Tomlinson, Ian P; Dunlop, Malcolm G; Houlston, Richard S

    2017-10-01

    While dietary fat has been established as a risk factor for colorectal cancer (CRC), associations between fatty acids (FAs) and CRC have been inconsistent. Using Mendelian randomisation (MR), we sought to evaluate associations between polyunsaturated (PUFA), monounsaturated (MUFA) and saturated FAs (SFAs) and CRC risk. We analysed genotype data on 9254 CRC cases and 18,386 controls of European ancestry. Externally weighted polygenic risk scores were generated and used to evaluate associations with CRC per one standard deviation increase in genetically defined plasma FA levels. Risk reduction was observed for oleic and palmitoleic MUFAs (OR OA  = 0.77, 95% CI: 0.65-0.92, P = 3.9 × 10 -3 ; OR POA  = 0.36, 95% CI: 0.15-0.84, P = 0.018). PUFAs linoleic and arachidonic acid had negative and positive associations with CRC respectively (OR LA  = 0.95, 95% CI: 0.93-0.98, P = 3.7 × 10 -4 ; OR AA  = 1.05, 95% CI: 1.02-1.07, P = 1.7 × 10 -4 ). The SFA stearic acid was associated with increased CRC risk (OR SA  = 1.17, 95% CI: 1.01-1.35, P = 0.041). Results from our analysis are broadly consistent with a pro-inflammatory FA profile having a detrimental effect in terms of CRC risk. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Serum iron levels and the risk of Parkinson disease: a Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Irene Pichler

    Full Text Available Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD, epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p = 0.001 per 10 µg/dl increase in serum iron.Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.

  20. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption.

    Science.gov (United States)

    Hartwig, Fernando Pires; Davey Smith, George; Bowden, Jack

    2017-12-01

    Mendelian randomization (MR) is being increasingly used to strengthen causal inference in observational studies. Availability of summary data of genetic associations for a variety of phenotypes from large genome-wide association studies (GWAS) allows straightforward application of MR using summary data methods, typically in a two-sample design. In addition to the conventional inverse variance weighting (IVW) method, recently developed summary data MR methods, such as the MR-Egger and weighted median approaches, allow a relaxation of the instrumental variable assumptions. Here, a new method - the mode-based estimate (MBE) - is proposed to obtain a single causal effect estimate from multiple genetic instruments. The MBE is consistent when the largest number of similar (identical in infinite samples) individual-instrument causal effect estimates comes from valid instruments, even if the majority of instruments are invalid. We evaluate the performance of the method in simulations designed to mimic the two-sample summary data setting, and demonstrate its use by investigating the causal effect of plasma lipid fractions and urate levels on coronary heart disease risk. The MBE presented less bias and lower type-I error rates than other methods under the null in many situations. Its power to detect a causal effect was smaller compared with the IVW and weighted median methods, but was larger than that of MR-Egger regression, with sample size requirements typically smaller than those available from GWAS consortia. The MBE relaxes the instrumental variable assumptions, and should be used in combination with other approaches in sensitivity analyses. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association

  1. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.

    2003-01-01

    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for

  2. Evaluation of diffuse diseases of the upper abdominal organs by MRI. Determination of a normal range in signal intensity ratio of each organ to the renal medulla in T1- and T2-weighted images and evaluation of diffuse diseases of an organ by using it

    International Nuclear Information System (INIS)

    Mitsuhashi, Hiroshi

    1995-01-01

    Diffuse diseases of the upper abdominal organs, including the liver, spleen, pancreas, and vertebral marrow, were evaluated by using signal intensity ratio of each organ to the renal medulla in T1- and T2-weighted images. Conventional T1- and T2-weighted images were obtained in 1.5 T MR system in 203 persons, including 122 controls and 81 patients with a diffuse disease in the upper abdominal organ. In controls, though there was neither sexual nor age difference in signal intensity ratios of the liver and pancreas, those of the spleen and vertebral marrow showed sexual and age difference, respectively. A normal range of signal intensity ratio of each organ in each image was determined in each decade of each sex by using controls. The signal intensity ratio of the liver was significantly low in T1- and T2-weighted images in patients with abundant iron deposit and within normal limits in patients with liver cirrhosis or scant iron deposit. The signal intensity ratio of the liver was significantly high only in a T2-weighted image in patients with fatty deposit in the liver, which was suspected to be due to inflammatory change in the liver with fatty deposit. The signal intensity ratios of the spleen, pancreas, and vertebral marrow were significantly low only in a T2-weighted image in patients with iron metabolic disturbance. The signal intensity ratio of the pancreas was significantly high in 40% of patients with acute and/or chronic pancreatitis, which was more sensitive in detection of pancreatitis than data in other studies. it can be concluded that the signal intensity ratio of each organ to the renal medulla in T1- and T2-weighted images is useful for detection of diffuse diseases of the upper abdominal organs by using the normal range in each decade of each sex. (S.Y.)

  3. The causal effect of red blood cell folate on genome-wide methylation in cord blood: a Mendelian randomization approach.

    Science.gov (United States)

    Binder, Alexandra M; Michels, Karin B

    2013-12-04

    Investigation of the biological mechanism by which folate acts to affect fetal development can inform appraisal of expected benefits and risk management. This research is ethically imperative given the ubiquity of folic acid fortified products in the US. Considering that folate is an essential component in the one-carbon metabolism pathway that provides methyl groups for DNA methylation, epigenetic modifications provide a putative molecular mechanism mediating the effect of folic acid supplementation on neonatal and pediatric outcomes. In this study we use a Mendelian Randomization Unnecessary approach to assess the effect of red blood cell (RBC) folate on genome-wide DNA methylation in cord blood. Site-specific CpG methylation within the proximal promoter regions of approximately 14,500 genes was analyzed using the Illumina Infinium Human Methylation27 Bead Chip for 50 infants from the Epigenetic Birth Cohort at Brigham and Women's Hospital in Boston. Using methylenetetrahydrofolate reductase genotype as the instrument, the Mendelian Randomization approach identified 7 CpG loci with a significant (mostly positive) association between RBC folate and methylation level. Among the genes in closest proximity to this significant subset of CpG loci, several enriched biologic processes were involved in nucleic acid transport and metabolic processing. Compared to the standard ordinary least squares regression method, our estimates were demonstrated to be more robust to unmeasured confounding. To the authors' knowledge, this is the largest genome-wide analysis of the effects of folate on methylation pattern, and the first to employ Mendelian Randomization to assess the effects of an exposure on epigenetic modifications. These results can help guide future analyses of the causal effects of periconceptional folate levels on candidate pathways.

  4. Evaluation of genetic markers as instruments for Mendelian randomization studies on vitamin D.

    Directory of Open Access Journals (Sweden)

    Diane J Berry

    Full Text Available Mendelian randomization (MR studies use genetic variants mimicking the influence of a modifiable exposure to assess and quantify a causal association with an outcome, with an aim to avoid problems with confounding and reverse causality affecting other types of observational studies.We evaluated genetic markers that index differences in 25-hydroxyvitamin D (25(OHD as instruments for MR studies on vitamin D.We used data from up-to 6,877 participants in the 1958 British birth cohort with information on genetic markers and 25(OHD. As potential instruments, we selected 20 single nucleotide polymorphisms (SNP which are located in the vitamin D metabolism pathway or affect skin pigmentation/tanning, including 4 SNPs from genome-wide association (GWA meta-analyses on 25(OHD. We analyzed SNP associations with 25(OHD and evaluated the use of allele scores dividing genes to those affecting 25(OHD synthesis (DHCR7, CYP2R1 and metabolism (GC, CYP24A1, CYP27B1. In addition to the GWA SNPs, only two SNPs (CYP27B1, OCA2 showed evidence for association with 25(OHD, with the OCA2 association abolished after lifestyle adjustment. Per allele differences varied between -0.02 and -0.08 nmol/L (P≤0.02 for all, with a 6.1 nmol/L and a 10.2 nmol/L difference in 25(OHD between individuals with highest compared lowest number of risk alleles in synthesis and metabolism allele scores, respectively. Individual SNPs but not allele scores showed associations with lifestyle factors. An exception was geographical region which was associated with synthesis score. Illustrative power calculations (80% power, 5% alpha suggest that approximately 80,000 participants are required to establish a causal effect of vitamin D on blood pressure using the synthesis allele score.Combining SNPs into allele scores provides a more powerful instrument for MR analysis than a single SNP in isolation. Population stratification and the potential for pleiotropic effects need to be considered in MR

  5. Assessing causality in the association between child adiposity and physical activity levels: a Mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Rebecca C Richmond

    2014-03-01

    Full Text Available Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose-response association with body mass index (BMI has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects.The Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity. In observational analysis, a 3.3 kg/m² (one standard deviation higher BMI was associated with 22.3 (95% CI, 17.0, 27.6 movement counts/min less total physical activity (p = 1.6×10⁻¹⁶, 2.6 (2.1, 3.1 min/d less moderate-to-vigorous-intensity activity (p = 3.7×10⁻²⁹, and 3.5 (1.5, 5.5 min/d more sedentary time (p = 5.0×10⁻⁴. In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9 movement counts/min less total physical activity (p = 0.04 (∼5.3% of the mean counts/minute, 2.8 (0.1, 5.5 min/d less moderate-to-vigorous-intensity activity (p = 0.04, and 13.2 (1.3, 25.2 min/d more sedentary time (p = 0.03. There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI.Our results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to

  6. Short Communication Mendelian inheritance, linkage, and genotypic disequilibrium in microsatellite loci of Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae-Caesalpinioideae).

    Science.gov (United States)

    Moraes, M A; Kubota, T Y K; Silva, E C B; Silva, A M; Cambuim, J; Moraes, M L T; Furlani Junior, E; Sebbenn, A M

    2016-07-29

    Hymenaea stigonocarpa is a deciduous and monoecious Neotropical tree species pollinated by bats. Due to overexploitation and habitat destruction, the population size has drastically diminished in nature. No previous study has investigated Mendelian inheritance, linkage, and genotypic disequilibrium in the available microsatellite markers in this species. So, our aim was to estimate these parameters using six microsatellite loci in a sample of 470 adults and 219 juveniles from two populations of H. stigonocarpa. In addition, 30 seeds per tree from 35 seed-trees were collected. Each seed was kept record of the seed-trees and fruit origin. Based on the six microsatellite loci, we found that only 10.6% of the cases showed significant deviations from Mendelian segregation and 15.3% showed linkage. We detected no evidence of genotypic disequilibrium between the loci in the adult trees or juveniles. Thus, our results suggest that these loci can be used with great accuracy in future genetic analyses of H. stigonocarpa populations.

  7. Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes

    NARCIS (Netherlands)

    H. Yaghootkar (Hanieh); C. Lamina (Claudia); R.A. Scott (Robert); Z. Dastani (Zari); M.-F. Hivert (Marie-France); L.L. Warren (Liling); A. Stancáková (Alena); S.G. Buxbaum (Sarah); L.-P. Lyytikäinen (Leo-Pekka); P. Henneman (Peter); Y. Wu (Ying); C.Y.Y. Cheung (Chloe); J.S. Pankow (James); A.U. Jackson (Anne); S. Gustafsson (Stefan); J.H. Zhao (Jing Hua); C. Ballantyne (Christie); W. Xie (Weijia); R.N. Bergman (Richard); M. Boehnke (Michael); F. El Bouazzaoui (Fatiha); F.S. Collins (Francis); S.H. Dunn (Sandra); J. Dupuis (Josée); N.G. Forouhi (Nita); C.J. Gillson (Christopher); A.T. Hattersley (Andrew); J. Hong (Jaeyoung); M. Kähönen (Mika); J. Kuusisto (Johanna); L. Kedenko (Lyudmyla); F. Kronenberg (Florian); A. Doria (Andrea); T.L. Assimes (Themistocles); E. Ferrannini (Ele); T. Hansen (Torben); K. Hao (Ke); H. Häring (Hans); J.W. Knowles (Joshua); C.M. Lindgren (Cecilia); J.J. Nolan (John); J. Paananen (Jussi); O. Pedersen (Oluf); T. Quertermous (Thomas); U. Smith (Ulf); T. Lehtimäki (Terho); C.-T. Liu (Ching-Ti); R.J.F. Loos (Ruth); M.I. McCarthy (Mark); A.D. Morris (Andrew); R.S. Vasan (Ramachandran Srini); T.D. Spector (Timothy); T.M. Teslovich (Tanya); J. Tuomilehto (Jaakko); J.A.P. Willems van Dijk (Ko); J. Viikari (Jorma); N. Zhu (Na); C. Langenberg (Claudia); E. Ingelsson (Erik); R.K. Semple (Robert); A. Sinaiko (Alan); C.N.A. Palmer (Colin); M. Walker (Mark); K.S.L. Lam (Karen); B. Paulweber (Bernhard); K.L. Mohlke (Karen); C.M. van Duijn (Cornelia); O. Raitakari (Olli); A. Bidulescu (Aurelian); N.J. Wareham (Nick); M. Laakso (Markku); D. Waterworth (Dawn); D.A. Lawlor (Debbie); J.B. Meigs (James); J.B. Richards (Brent); T.M. Frayling (Timothy)

    2013-01-01

    textabstractAdiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used

  8. Mendelian Randomisation Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

    DEFF Research Database (Denmark)

    Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A

    2013-01-01

    Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes but its causal role remains controversial. We used a Mendelian randomisation approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic varian...

  9. Malware Normalization

    OpenAIRE

    Christodorescu, Mihai; Kinder, Johannes; Jha, Somesh; Katzenbeisser, Stefan; Veith, Helmut

    2005-01-01

    Malware is code designed for a malicious purpose, such as obtaining root privilege on a host. A malware detector identifies malware and thus prevents it from adversely affecting a host. In order to evade detection by malware detectors, malware writers use various obfuscation techniques to transform their malware. There is strong evidence that commercial malware detectors are susceptible to these evasion tactics. In this paper, we describe the design and implementation of a malware normalizer ...

  10. Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis

    Science.gov (United States)

    Zhang, Ge; Bacelis, Jonas; Lengyel, Candice; Teramo, Kari; Hallman, Mikko; Helgeland, Øyvind; Johansson, Stefan; Myhre, Ronny; Sengpiel, Verena; Njølstad, Pål Rasmus; Jacobsson, Bo; Muglia, Louis

    2015-01-01

    Background Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. Methods and Findings We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10−9), birth weight (p = 2.19 × 10−15), and gestational age (p = 1.51 × 10−7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal

  11. Normal accidents

    International Nuclear Information System (INIS)

    Perrow, C.

    1989-01-01

    The author has chosen numerous concrete examples to illustrate the hazardousness inherent in high-risk technologies. Starting with the TMI reactor accident in 1979, he shows that it is not only the nuclear energy sector that bears the risk of 'normal accidents', but also quite a number of other technologies and industrial sectors, or research fields. The author refers to the petrochemical industry, shipping, air traffic, large dams, mining activities, and genetic engineering, showing that due to the complexity of the systems and their manifold, rapidly interacting processes, accidents happen that cannot be thoroughly calculated, and hence are unavoidable. (orig./HP) [de

  12. Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis

    DEFF Research Database (Denmark)

    Taylor, Amy E; Martin, Richard M; Geybels, Milan S

    2017-01-01

    Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee...... consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium. Associations between genetic...... variants and prostate cancer case status, stage and grade were assessed by logistic regression and with all-cause and prostate cancer-specific mortality using Cox proportional hazards regression. There was no clear evidence that a genetic risk score combining rs4410790 and rs2472297 was associated...

  13. Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: a two-sample bidirectional Mendelian randomization study.

    Science.gov (United States)

    Verweij, Karin J H; Treur, Jorien L; Vink, Jacqueline M

    2018-07-01

    Epidemiological studies consistently show co-occurrence of use of different addictive substances. Whether these associations are causal or due to overlapping underlying influences remains an important question in addiction research. Methodological advances have made it possible to use published genetic associations to infer causal relationships between phenotypes. In this exploratory study, we used Mendelian randomization (MR) to examine the causality of well-established associations between nicotine, alcohol, caffeine and cannabis use. Two-sample MR was employed to estimate bidirectional causal effects between four addictive substances: nicotine (smoking initiation and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units per week) and cannabis (initiation). Based on existing genome-wide association results we selected genetic variants associated with the exposure measure as an instrument to estimate causal effects. Where possible we applied sensitivity analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy. Most MR tests did not reveal causal associations. There was some weak evidence for a causal positive effect of genetically instrumented alcohol use on smoking initiation and of cigarettes per day on caffeine use, but these were not supported by the sensitivity analyses. There was also some suggestive evidence for a positive effect of alcohol use on caffeine use (only with MR-Egger) and smoking initiation on cannabis initiation (only with weighted median). None of the suggestive causal associations survived corrections for multiple testing. Two-sample Mendelian randomization analyses found little evidence for causal relationships between nicotine, alcohol, caffeine and cannabis use. © 2018 Society for the Study of Addiction.

  14. Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.

    Science.gov (United States)

    Dale, Caroline E; Fatemifar, Ghazaleh; Palmer, Tom M; White, Jon; Prieto-Merino, David; Zabaneh, Delilah; Engmann, Jorgen E L; Shah, Tina; Wong, Andrew; Warren, Helen R; McLachlan, Stela; Trompet, Stella; Moldovan, Max; Morris, Richard W; Sofat, Reecha; Kumari, Meena; Hyppönen, Elina; Jefferis, Barbara J; Gaunt, Tom R; Ben-Shlomo, Yoav; Zhou, Ang; Gentry-Maharaj, Aleksandra; Ryan, Andy; Mutsert, Renée de; Noordam, Raymond; Caulfield, Mark J; Jukema, J Wouter; Worrall, Bradford B; Munroe, Patricia B; Menon, Usha; Power, Chris; Kuh, Diana; Lawlor, Debbie A; Humphries, Steve E; Mook-Kanamori, Dennis O; Sattar, Naveed; Kivimaki, Mika; Price, Jacqueline F; Davey Smith, George; Dudbridge, Frank; Hingorani, Aroon D; Holmes, Michael V; Casas, Juan P

    2017-06-13

    The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m 2 ; OR for CHD, 1.36; 95% CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%-77% per 1 SD). Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus

  15. Reconstructing Normality

    DEFF Research Database (Denmark)

    Gildberg, Frederik Alkier; Bradley, Stephen K.; Fristed, Peter Billeskov

    2012-01-01

    Forensic psychiatry is an area of priority for the Danish Government. As the field expands, this calls for increased knowledge about mental health nursing practice, as this is part of the forensic psychiatry treatment offered. However, only sparse research exists in this area. The aim of this study...... was to investigate the characteristics of forensic mental health nursing staff interaction with forensic mental health inpatients and to explore how staff give meaning to these interactions. The project included 32 forensic mental health staff members, with over 307 hours of participant observations, 48 informal....... The intention is to establish a trusting relationship to form behaviour and perceptual-corrective care, which is characterized by staff's endeavours to change, halt, or support the patient's behaviour or perception in relation to staff's perception of normality. The intention is to support and teach the patient...

  16. Pursuing Normality

    DEFF Research Database (Denmark)

    Madsen, Louise Sofia; Handberg, Charlotte

    2018-01-01

    implying an influence on whether to participate in cancer survivorship care programs. Because of "pursuing normality," 8 of 9 participants opted out of cancer survivorship care programming due to prospects of "being cured" and perceptions of cancer survivorship care as "a continuation of the disease......BACKGROUND: The present study explored the reflections on cancer survivorship care of lymphoma survivors in active treatment. Lymphoma survivors have survivorship care needs, yet their participation in cancer survivorship care programs is still reported as low. OBJECTIVE: The aim of this study...... was to understand the reflections on cancer survivorship care of lymphoma survivors to aid the future planning of cancer survivorship care and overcome barriers to participation. METHODS: Data were generated in a hematological ward during 4 months of ethnographic fieldwork, including participant observation and 46...

  17. Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

    Science.gov (United States)

    Schrader, Kasmintan A; Cheng, Donavan T; Joseph, Vijai; Prasad, Meera; Walsh, Michael; Zehir, Ahmet; Ni, Ai; Thomas, Tinu; Benayed, Ryma; Ashraf, Asad; Lincoln, Annie; Arcila, Maria; Stadler, Zsofia; Solit, David; Hyman, David M; Hyman, David; Zhang, Liying; Klimstra, David; Ladanyi, Marc; Offit, Kenneth; Berger, Michael; Robson, Mark

    2016-01-01

    Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. To estimate the burden of germline variants identified through routine clinical tumor sequencing. Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99

  18. Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279 013 individuals.

    Science.gov (United States)

    Lauridsen, Bo Kobberø; Stender, Stefan; Kristensen, Thomas Skårup; Kofoed, Klaus Fuglsang; Køber, Lars; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2018-02-01

    In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. In a cohort study of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2.41 (1.28-4.51)(P-trend = 0.004). The corresponding OR for IHD in individuals with vs. without NAFLD was 1.65 (1.34-2.04)(P = 3×10-6). PNPLA3 I148M was associated with a stepwise increase in liver fat content of up to 28% in MM vs. II-homozygotes (P-trend = 0.0001) and with ORs of 2.03 (1.52-2.70) for NAFLD (P = 3×10-7), 3.28 (2.37-4.54) for cirrhosis (P = 4×10-12), and 0.95 (0.86-1.04) for IHD (P = 0.46). In agreement, in meta-analysis (N = 279 013/IHD = 71 698), the OR for IHD was 0.98 (0.96-1.00) per M-allele vs. I-allele. The OR for IHD per M-allele higher genetically determined liver fat content was 0.98 (0.94-1.03) vs. an observational estimate of 1.05 (1.02-1.09)(P for comparison = 0.02). Despite confirming the known observational association of liver fat content and NAFLD with IHD, lifelong, genetically high liver fat content was not causally associated with risk of IHD. These results suggest that the observational association is due to confounding or reverse causation. Published on behalf of the European Society of Cardiology. All rights reserved.

  19. Using genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium

    Science.gov (United States)

    Shungin, Dmitry; Cornelis, Marilyn C; Divaris, Kimon; Holtfreter, Birte; Shaffer, John R; Yu, Yau-Hua; Barros, Silvana P; Beck, James D; Biffar, Reiner; Boerwinkle, Eric A; Crout, Richard J.; Ganna, Andrea; Hallmans, Goran; Hindy, George; Hu, Frank B; Kraft, Peter; McNeil, Daniel W; Melander, Olle; Moss, Kevin L; North, Kari E; Orho-Melander, Marju; Pedersen, Nancy L; Ridker, Paul M; Rimm, Eric B; Rose, Lynda M; Rukh, Gull; Teumer, Alexander; Weyant, Robert J; Chasman, Daniel I; Joshipura, Kaumudi; Kocher, Thomas; Magnusson, Patrik KE; Marazita, Mary L; Nilsson, Peter; Offenbacher, Steve; Davey Smith, George; Lundberg, Pernilla; Palmer, Tom M; Timpson, Nicholas J; Johansson, Ingegerd; Franks, Paul W

    2015-01-01

    Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI:1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide

  20. Instrumental variable estimation of the causal effect of plasma 25-hydroxy-vitamin D on colorectal cancer risk: a mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Evropi Theodoratou

    Full Text Available Vitamin D deficiency has been associated with several common diseases, including cancer and is being investigated as a possible risk factor for these conditions. We reported the striking prevalence of vitamin D deficiency in Scotland. Previous epidemiological studies have reported an association between low dietary vitamin D and colorectal cancer (CRC. Using a case-control study design, we tested the association between plasma 25-hydroxy-vitamin D (25-OHD and CRC (2,001 cases, 2,237 controls. To determine whether plasma 25-OHD levels are causally linked to CRC risk, we applied the control function instrumental variable (IV method of the mendelian randomization (MR approach using four single nucleotide polymorphisms (rs2282679, rs12785878, rs10741657, rs6013897 previously shown to be associated with plasma 25-OHD. Low plasma 25-OHD levels were associated with CRC risk in the crude model (odds ratio (OR: 0.76, 95% Confidence Interval (CI: 0.71, 0.81, p: 1.4×10(-14 and after adjusting for age, sex and other confounding factors. Using an allele score that combined all four SNPs as the IV, the estimated causal effect was OR 1.16 (95% CI 0.60, 2.23, whilst it was 0.94 (95% CI 0.46, 1.91 and 0.93 (0.53, 1.63 when using an upstream (rs12785878, rs10741657 and a downstream allele score (rs2282679, rs6013897, respectively. 25-OHD levels were inversely associated with CRC risk, in agreement with recent meta-analyses. The fact that this finding was not replicated when the MR approach was employed might be due to weak instruments, giving low power to demonstrate an effect (<0.35. The prevalence and degree of vitamin D deficiency amongst individuals living in northerly latitudes is of considerable importance because of its relationship to disease. To elucidate the effect of vitamin D on CRC cancer risk, additional large studies of vitamin D and CRC risk are required and/or the application of alternative methods that are less sensitive to weak instrument

  1. Novel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels.

    Science.gov (United States)

    Holmes, Michael V; Exeter, Holly J; Folkersen, Lasse; Nelson, Christopher P; Guardiola, Montse; Cooper, Jackie A; Sofat, Reecha; Boekholdt, S Matthijs; Khaw, Kay-Tee; Li, Ka-Wah; Smith, Andrew J P; Van't Hooft, Ferdinand; Eriksson, Per; Franco-Cereceda, Anders; Asselbergs, Folkert W; Boer, Jolanda M A; Onland-Moret, N Charlotte; Hofker, Marten; Erdmann, Jeanette; Kivimaki, Mika; Kumari, Meena; Reiner, Alex P; Keating, Brendan J; Humphries, Steve E; Hingorani, Aroon D; Mallat, Ziad; Samani, Nilesh J; Talmud, Philippa J

    2014-04-01

    Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis. Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5 mRNA expression levels as a proxy for sPLA2-V levels. We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case-control studies with 27 230 events and 70 500 controls. rs525380C>A showed the strongest association with PLA2G5 mRNA expression (P=5.1×10(-6)). There was no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals [-0.9%, 1.6%]; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals [0.99, 1.04]; P=0.20). This novel approach for single-nucleotide polymorphism selection for this modified Mendelian randomization analysis showed no association between rs525380 (the lead single-nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels) and CHD events. The evidence does not support a causal role for sPLA2-V in CHD.

  2. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Matthew J Spindler

    Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  3. Semiparametric methods for estimation of a nonlinear exposure‐outcome relationship using instrumental variables with application to Mendelian randomization

    Science.gov (United States)

    Staley, James R.

    2017-01-01

    ABSTRACT Mendelian randomization, the use of genetic variants as instrumental variables (IV), can test for and estimate the causal effect of an exposure on an outcome. Most IV methods assume that the function relating the exposure to the expected value of the outcome (the exposure‐outcome relationship) is linear. However, in practice, this assumption may not hold. Indeed, often the primary question of interest is to assess the shape of this relationship. We present two novel IV methods for investigating the shape of the exposure‐outcome relationship: a fractional polynomial method and a piecewise linear method. We divide the population into strata using the exposure distribution, and estimate a causal effect, referred to as a localized average causal effect (LACE), in each stratum of population. The fractional polynomial method performs metaregression on these LACE estimates. The piecewise linear method estimates a continuous piecewise linear function, the gradient of which is the LACE estimate in each stratum. Both methods were demonstrated in a simulation study to estimate the true exposure‐outcome relationship well, particularly when the relationship was a fractional polynomial (for the fractional polynomial method) or was piecewise linear (for the piecewise linear method). The methods were used to investigate the shape of relationship of body mass index with systolic blood pressure and diastolic blood pressure. PMID:28317167

  4. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders.

    Science.gov (United States)

    Amberger, Joanna S; Bocchini, Carol A; Schiettecatte, François; Scott, Alan F; Hamosh, Ada

    2015-01-01

    Online Mendelian Inheritance in Man, OMIM(®), is a comprehensive, authoritative and timely research resource of curated descriptions of human genes and phenotypes and the relationships between them. The new official website for OMIM, OMIM.org (http://omim.org), was launched in January 2011. OMIM is based on the published peer-reviewed biomedical literature and is used by overlapping and diverse communities of clinicians, molecular biologists and genome scientists, as well as by students and teachers of these disciplines. Genes and phenotypes are described in separate entries and are given unique, stable six-digit identifiers (MIM numbers). OMIM entries have a structured free-text format that provides the flexibility necessary to describe the complex and nuanced relationships between genes and genetic phenotypes in an efficient manner. OMIM also has a derivative table of genes and genetic phenotypes, the Morbid Map. OMIM.org has enhanced search capabilities such as genome coordinate searching and thesaurus-enhanced search term options. Phenotypic series have been created to facilitate viewing genetic heterogeneity of phenotypes. Clinical synopsis features are enhanced with UMLS, Human Phenotype Ontology and Elements of Morphology terms and image links. All OMIM data are available for FTP download and through an API. MIMmatch is a novel outreach feature to disseminate updates and encourage collaboration. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

    Science.gov (United States)

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  6. Does high tobacco consumption cause psychological distress? A mendelian randomization study

    DEFF Research Database (Denmark)

    Skov-Ettrup, Lise S.; Nordestgaard, Børge G.; Petersen, Christina B.

    2017-01-01

    variable for tobacco consumption. Three dimensions of psychological distress were studied: Stress, fatigue, and hopelessness. Analyses with the CHRNA3 genotype were stratified by smoking status. Results: Self-reported amount of smoking was associated with all three dimensions of psychological distress....... For instance among participants smoking 30 cigarettes/day or more, the odds ratio (OR) for stress was 1.67 (95% confidence interval [CI] 1.47-1.89) compared to never-smokers. Corresponding ORs for fatigue and hopelessness were 2.18 (95% CI 1.92-2.47) and 3.08 (95% CI 2.62-3.62). Among current smokers...

  7. CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer

    Science.gov (United States)

    Thompson, Deborah J; O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Michailidou, Kyriaki; Tyrer, Jonathan P; Maranian, Mel J; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Zhao, Hui; Depreeuw, Jeroen; Schrauwen, Stefanie; Amant, Frederic; Goode, Ellen L; Fridley, Brooke L; Dowdy, Sean C; Winham, Stacey J; Salvesen, Helga B; Trovik, Jone; Njolstad, Tormund S; Werner, Henrica M J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Carvajal-Carmona, Luis; Tham, Emma; Liu, Tao; Mints, Miriam; Scott, Rodney J; McEvoy, Mark; Attia, John; Holliday, Elizabeth G; Montgomery, Grant W; Martin, Nicholas G; Nyholt, Dale R; Henders, Anjali K; Hopper, John L; Traficante, Nadia; Ruebner, Matthias; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Lambrechts, Diether; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Bolla, Manjeet K; Wang, Qin; Bojesen, Stig E; Shah, Mitul; Luben, Robert; Khaw, Kay-Tee; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Dowsett, Mitch; Easton, Douglas F; Spurdle, Amanda B

    2016-01-01

    Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10−11). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10−8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11–1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03–1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction. PMID:26574572

  8. Smoking is associated with, but does not cause, depressed mood in pregnancy--a mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Sarah J Lewis

    Full Text Available Smokers have a higher prevalence of major depressive episodes and depressive symptoms than the general population, but whether this association is causal, or is due to confounding or reverse causation is uncertain because of the problems inherent in some epidemiological studies. Mendelian randomization, in which a genetic variant is used as a surrogate for measuring exposure, is an approach which may be used to better understand this association. We investigated the rs1051730 single nucleotide polymorphism in the nicotine acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4, associated with smoking phenotypes, to determine whether women who continued to smoke were also more likely to report a low mood during pregnancy. We found among women who smoked pre-pregnancy, those with the 1051730 T allele smoked more and were less likely to quit smoking during pregnancy, but were also less likely to report high levels of depressed mood at 18 weeks of pregnancy (per allele OR = 0.84, 95%CI 0.72 to 0.99, p = 0.034. The association between genotype and depressed mood was limited to women who were smokers prior to pregnancy, with weak evidence of an interaction between smoking status and genotype (p = 0.07. Our results do not support a causal role of smoking on depressed mood, but are consistent with a self-medication hypothesis, whereby smoking is used to alleviate symptoms of depression. A replication study using multiple genetic variants which influence smoking via different pathways is required to confirm these findings and provide evidence that the genetic variant is reflecting the effect of quitting smoking on depressed mood, and is not directly affecting mood.

  9. Mendelian randomization analysis of a time-varying exposure for binary disease outcomes using functional data analysis methods.

    Science.gov (United States)

    Cao, Ying; Rajan, Suja S; Wei, Peng

    2016-12-01

    A Mendelian randomization (MR) analysis is performed to analyze the causal effect of an exposure variable on a disease outcome in observational studies, by using genetic variants that affect the disease outcome only through the exposure variable. This method has recently gained popularity among epidemiologists given the success of genetic association studies. Many exposure variables of interest in epidemiological studies are time varying, for example, body mass index (BMI). Although longitudinal data have been collected in many cohort studies, current MR studies only use one measurement of a time-varying exposure variable, which cannot adequately capture the long-term time-varying information. We propose using the functional principal component analysis method to recover the underlying individual trajectory of the time-varying exposure from the sparsely and irregularly observed longitudinal data, and then conduct MR analysis using the recovered curves. We further propose two MR analysis methods. The first assumes a cumulative effect of the time-varying exposure variable on the disease risk, while the second assumes a time-varying genetic effect and employs functional regression models. We focus on statistical testing for a causal effect. Our simulation studies mimicking the real data show that the proposed functional data analysis based methods incorporating longitudinal data have substantial power gains compared to standard MR analysis using only one measurement. We used the Framingham Heart Study data to demonstrate the promising performance of the new methods as well as inconsistent results produced by the standard MR analysis that relies on a single measurement of the exposure at some arbitrary time point. © 2016 WILEY PERIODICALS, INC.

  10. The Laplace Likelihood Ratio Test for Heteroscedasticity

    Directory of Open Access Journals (Sweden)

    J. Martin van Zyl

    2011-01-01

    Full Text Available It is shown that the likelihood ratio test for heteroscedasticity, assuming the Laplace distribution, gives good results for Gaussian and fat-tailed data. The likelihood ratio test, assuming normality, is very sensitive to any deviation from normality, especially when the observations are from a distribution with fat tails. Such a likelihood test can also be used as a robust test for a constant variance in residuals or a time series if the data is partitioned into groups.

  11. Causal relationship between adiponectin and metabolic traits: a Mendelian randomization study in a multiethnic population.

    Directory of Open Access Journals (Sweden)

    Andrew Mente

    Full Text Available Adiponectin, a secretagogue exclusively produced by adipocytes, has been associated with metabolic features, but its role in the development of the metabolic syndrome remains unclear.We investigated the association between serum adiponectin level and metabolic traits, using both observational and genetic epidemiologic approaches in a multiethnic population assembled in Canada.Clinical data and serum adiponectin level were collected in 1,157 participants of the SHARE/SHARE-AP studies. Participants were genotyped for the functional rs266729 and rs1260326 SNPs in ADIPOQ and GCKR genes.Adiponectin level was positively associated with HDL cholesterol and negatively associated with body mass index, waist-to-hip ratio, triglycerides, fasting glucose, fasting insulin, systolic and diastolic pressure (all P<0.002. The rs266729 minor G allele was associated with lower adiponectin and higher HOMA-IR (P = 0.004 and 0.003, respectively. The association between rs266729 SNP and HOMA-IR was no longer significant after adjustment for adiponectin concentration (P = 0.10. The rs266729 SNP was associated with HOMA-IR to an extent that exceeded its effect on adiponectin level (0.15 SD 95% C.I. [0.06, 0.24], P<0.001. There was no significant interaction between rs266729 SNP and ethnicity on adiponectin or HOMA-IR. In contrast, the SNP rs1260326 in GCKR was associated with HOMA-IR (P<0.001, but not with adiponectin level (P = 0.67.The association of the functional promoter polymorphism rs266729 with lower serum adiponectin and increased insulin resistance in diverse ethnic groups may suggest a causal relationship between adiponectin level and insulin resistance.

  12. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  13. Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent.

    Directory of Open Access Journals (Sweden)

    Yan Guo

    2016-08-01

    Full Text Available Observational epidemiological studies have shown that high body mass index (BMI is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors.We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC (cases  =  46,325, controls  =  42,482. We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively.In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR]  =  0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 × 10-10. The associations were similar for both premenopausal (OR   =   0.44, 95% CI:0.31-0.62, p  =  9.91 × 10-8 and postmenopausal breast cancer (OR  =  0.57, 95% CI: 0.46-0.71, p  =  1.88 × 10-8. This association was replicated in the data from the DRIVE consortium (OR  =  0.72, 95% CI: 0.60-0.84, p   =   1.64 × 10-7. Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs in association with breast cancer risk at p < 0.05; for 16 of them, the

  14. Normalization: A Preprocessing Stage

    OpenAIRE

    Patro, S. Gopal Krishna; Sahu, Kishore Kumar

    2015-01-01

    As we know that the normalization is a pre-processing stage of any type problem statement. Especially normalization takes important role in the field of soft computing, cloud computing etc. for manipulation of data like scale down or scale up the range of data before it becomes used for further stage. There are so many normalization techniques are there namely Min-Max normalization, Z-score normalization and Decimal scaling normalization. So by referring these normalization techniques we are ...

  15. Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

    Directory of Open Access Journals (Sweden)

    Roman Pfister

    2011-10-01

    Full Text Available Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP levels in blood and risk of type 2 diabetes (T2D, but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36% decreased risk of incident T2D per one standard deviation (SD higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97 was similar to that expected (0.96, 0.93-0.98 based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90 and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29 per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies

  16. Financial Key Ratios

    OpenAIRE

    Tănase Alin-Eliodor

    2014-01-01

    This article focuses on computing techniques starting from trial balance data regarding financial key ratios. There are presented activity, liquidity, solvency and profitability financial key ratios. It is presented a computing methodology in three steps based on a trial balance.

  17. VVER-1000 dominance ratio

    International Nuclear Information System (INIS)

    Gorodkov, S.

    2009-01-01

    Dominance ratio, or more precisely, its closeness to unity, is important characteristic of large reactor. It allows evaluate beforehand the number of source iterations required in deterministic calculations of power spatial distribution. Or the minimal number of histories to be modeled for achievement of statistical error level desired in large core Monte Carlo calculations. In this work relatively simple approach for dominance ratio evaluation is proposed. It essentially uses core symmetry. Dependence of dominance ratio on neutron flux spatial distribution is demonstrated. (author)

  18. WWER-1000 dominance ratio

    International Nuclear Information System (INIS)

    Gorodkov, S.S.

    2009-01-01

    Dominance ratio, or more precisely, its closeness to unity, is important characteristic of large reactor. It allows evaluate beforehand the number of source iterations required in deterministic calculations of power spatial distribution. Or the minimal number of histories to be modeled for achievement of statistical error level desired in large core Monte Carlo calculations. In this work relatively simple approach for dominance ratio evaluation is proposed. It essentially uses core symmetry. Dependence of dominance ratio on neutron flux spatial distribution is demonstrated. (Authors)

  19. Sharpening Sharpe Ratios

    OpenAIRE

    William N. Goetzmann; Jonathan E. Ingersoll Jr.; Matthew I. Spiegel; Ivo Welch

    2002-01-01

    It is now well known that the Sharpe ratio and other related reward-to-risk measures may be manipulated with option-like strategies. In this paper we derive the general conditions for achieving the maximum expected Sharpe ratio. We derive static rules for achieving the maximum Sharpe ratio with two or more options, as well as a continuum of derivative contracts. The optimal strategy has a truncated right tail and a fat left tail. We also derive dynamic rules for increasing the Sharpe ratio. O...

  20. Detecting isotopic ratio outliers

    International Nuclear Information System (INIS)

    Bayne, C.K.; Smith, D.H.

    1985-01-01

    An alternative method is proposed for improving isotopic ratio estimates. This method mathematically models pulse-count data and uses iterative reweighted Poisson regression to estimate model parameters to calculate the isotopic ratios. This computer-oriented approach provides theoretically better methods than conventional techniques to establish error limits and to identify outliers. 6 refs., 3 figs., 3 tabs

  1. Detecting isotopic ratio outliers

    Science.gov (United States)

    Bayne, C. K.; Smith, D. H.

    An alternative method is proposed for improving isotopic ratio estimates. This method mathematically models pulse-count data and uses iterative reweighted Poisson regression to estimate model parameters to calculate the isotopic ratios. This computer-oriented approach provides theoretically better methods than conventional techniques to establish error limits and to identify outliers.

  2. Detecting isotopic ratio outliers

    International Nuclear Information System (INIS)

    Bayne, C.K.; Smith, D.H.

    1986-01-01

    An alternative method is proposed for improving isotopic ratio estimates. This method mathematically models pulse-count data and uses iterative reweighted Poisson regression to estimate model parameters to calculate the isotopic ratios. This computer-oriented approach provides theoretically better methods than conventional techniques to establish error limits and to identify outliers

  3. Normalized modes at selected points without normalization

    Science.gov (United States)

    Kausel, Eduardo

    2018-04-01

    As every textbook on linear algebra demonstrates, the eigenvectors for the general eigenvalue problem | K - λM | = 0 involving two real, symmetric, positive definite matrices K , M satisfy some well-defined orthogonality conditions. Equally well-known is the fact that those eigenvectors can be normalized so that their modal mass μ =ϕT Mϕ is unity: it suffices to divide each unscaled mode by the square root of the modal mass. Thus, the normalization is the result of an explicit calculation applied to the modes after they were obtained by some means. However, we show herein that the normalized modes are not merely convenient forms of scaling, but that they are actually intrinsic properties of the pair of matrices K , M, that is, the matrices already "know" about normalization even before the modes have been obtained. This means that we can obtain individual components of the normalized modes directly from the eigenvalue problem, and without needing to obtain either all of the modes or for that matter, any one complete mode. These results are achieved by means of the residue theorem of operational calculus, a finding that is rather remarkable inasmuch as the residues themselves do not make use of any orthogonality conditions or normalization in the first place. It appears that this obscure property connecting the general eigenvalue problem of modal analysis with the residue theorem of operational calculus may have been overlooked up until now, but which has in turn interesting theoretical implications.Á

  4. The Battle Between the Biometricians and the Mendelians: How Sir Francis Galton's Work Caused his Disciples to Reach Conflicting Conclusions About the Hereditary Mechanism

    Science.gov (United States)

    Gillham, Nicholas W.

    2015-01-01

    Francis Galton, Charles Darwin's cousin, had wide and varied interests. They ranged from exploration and travel writing to fingerprinting and the weather. After reading Darwin's On the Origin of Species, Galton reached the conclusion that it should be possible to improve the human stock through selective breeding, as was the case for domestic animals and cultivated plants. Much of the latter half of Galton's career was devoted to trying to devise methods to distinguish men of good stock and then to show that these qualities were inherited. But along the way he invented two important statistical methods: regression and correlation. He also discovered regression to the mean. This led Galton to believe that evolution could not proceed by the small steps envisioned by Darwin, but must proceed by discontinuous changes. Galton's book Natural Inheritance (1889) served as the inspiration for Karl Pearson, W.F.R. Weldon and William Bateson. Pearson and Weldon were interested in continuously varying characters and the application of statistical techniques to their study. Bateson was fascinated by discontinuities and the role they might play in evolution. Galton proposed his Law of Ancestral Heredity in the last decade of the nineteenth century. At first this seemed to work well as an explanation for continuously varying traits of the type that interested Pearson and Weldon. In contrast, Bateson had published a book on discontinuously varying traits so he was in a position to understand and embrace Mendel's principles of inheritance when they were rediscovered in 1900. The subsequent battle between Weldon and Pearson, the biometricians, and Bateson, the Mendelian, went on acrimoniously for several years at the beginning of the twentieth century before Mendelian theory finally won out.

  5. Sex Dimorphism of the Heart Diameters and Cardiothoracic Ratios ...

    African Journals Online (AJOL)

    Objective: To determine gender associated differences in the cardiothoracic ratio (CTR) and heart diameters in a normal Nigerian population. Subject and Method: The normal heart diameters and cardiothoracic ratios were measured from posteroanterior (PA) chest radiographs of healthy 510 male and 508 female ...

  6. Normal foot and ankle

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    The foot may be thought of as a bag of bones tied tightly together and functioning as a unit. The bones re expected to maintain their alignment without causing symptomatology to the patient. The author discusses a normal radiograph. The bones must have normal shape and normal alignment. The density of the soft tissues should be normal and there should be no fractures, tumors, or foreign bodies

  7. Difference and ratio plots

    DEFF Research Database (Denmark)

    Svendsen, Anders Jørgen; Holmskov, U; Bro, Peter

    1995-01-01

    and systemic lupus erythematosus from another previously published study (Macanovic, M. and Lachmann, P.J. (1979) Clin. Exp. Immunol. 38, 274) are also represented using ratio plots. Our observations indicate that analysis by regression analysis may often be misleading....... hitherto unnoted differences between controls and patients with either rheumatoid arthritis or systemic lupus erythematosus. For this we use simple, but unconventional, graphic representations of the data, based on difference plots and ratio plots. Differences between patients with Burkitt's lymphoma...

  8. Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Bram P Prins

    2016-06-01

    Full Text Available C-reactive protein (CRP is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal.We performed Mendelian randomization (MR analyses using two genetic risk scores (GRSs as instrumental variables (IVs. The first GRS consisted of four single nucleotide polymorphisms (SNPs in the CRP gene (GRSCRP, and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest genome-wide association study (GWAS to date (GRSGWAS. To optimize power, we used summary statistics from GWAS consortia and tested the association of these two GRSs with 32 complex somatic and psychiatric outcomes, with up to 123,865 participants per outcome from populations of European ancestry. We performed heterogeneity tests to disentangle the pleiotropic effect of IVs. A Bonferroni-corrected significance level of less than 0.0016 was considered statistically significant. An observed p-value equal to or less than 0.05 was considered nominally significant evidence for a potential causal association, yet to be confirmed. The strengths (F-statistics of the IVs were 31.92-3,761.29 and 82.32-9,403.21 for GRSCRP and GRSGWAS, respectively. CRP GRSGWAS showed a statistically significant protective relationship of a 10% genetically elevated CRP level with the risk of schizophrenia (odds ratio [OR] 0.86 [95% CI 0.79-0.94]; p < 0.001. We validated this finding with individual-level genotype data from the schizophrenia GWAS (OR 0.96 [95% CI 0.94-0.98]; p < 1.72 × 10-6. Further, we found that a standardized CRP polygenic risk score (CRPPRS at p-value thresholds of 1 × 10-4, 0.001, 0.01, 0.05, and 0.1 using individual-level data also showed a protective effect (OR < 1.00 against schizophrenia; the first CRPPRS (built of SNPs with p < 1 × 10-4 showed a statistically significant (p < 2.45 × 10-4 protective effect with an OR of 0.97 (95% CI 0.95-0.99. The CRP GRSGWAS showed that a

  9. The rectilinear Steiner ratio

    Directory of Open Access Journals (Sweden)

    PO de Wet

    2005-06-01

    Full Text Available The rectilinear Steiner ratio was shown to be 3/2 by Hwang [Hwang FK, 1976, On Steiner minimal trees with rectilinear distance, SIAM Journal on Applied Mathematics, 30, pp. 104– 114.]. We use continuity and introduce restricted point sets to obtain an alternative, short and self-contained proof of this result.

  10. [Quantification of acetabular coverage in normal adult].

    Science.gov (United States)

    Lin, R M; Yang, C Y; Yu, C Y; Yang, C R; Chang, G L; Chou, Y L

    1991-03-01

    Quantification of acetabular coverage is important and can be expressed by superimposition of cartilage tracings on the maximum cross-sectional area of the femoral head. A practical Autolisp program on PC AutoCAD has been developed by us to quantify the acetabular coverage through numerical expression of the images of computed tomography. Thirty adults (60 hips) with normal center-edge angle and acetabular index in plain X ray were randomly selected for serial drops. These slices were prepared with a fixed coordination and in continuous sections of 5 mm in thickness. The contours of the cartilage of each section were digitized into a PC computer and processed by AutoCAD programs to quantify and characterize the acetabular coverage of normal and dysplastic adult hips. We found that a total coverage ratio of greater than 80%, an anterior coverage ratio of greater than 75% and a posterior coverage ratio of greater than 80% can be categorized in a normal group. Polar edge distance is a good indicator for the evaluation of preoperative and postoperative coverage conditions. For standardization and evaluation of acetabular coverage, the most suitable parameters are the total coverage ratio, anterior coverage ratio, posterior coverage ratio and polar edge distance. However, medial coverage and lateral coverage ratios are indispensable in cases of dysplastic hip because variations between them are so great that acetabuloplasty may be impossible. This program can also be used to classify precisely the type of dysplastic hip.

  11. Baby Poop: What's Normal?

    Science.gov (United States)

    ... I'm breast-feeding my newborn and her bowel movements are yellow and mushy. Is this normal for baby poop? Answers from Jay L. Hoecker, M.D. Yellow, mushy bowel movements are perfectly normal for breast-fed babies. Still, ...

  12. Transformer ratio enhancement experiment

    International Nuclear Information System (INIS)

    Gai, W.; Power, J. G.; Kanareykin, A.; Neasheva, E.; Altmark, A.

    2004-01-01

    Recently, a multibunch scheme for efficient acceleration based on dielectric wakefield accelerator technology was outlined in J.G. Power, W. Gai, A. Kanareykin, X. Sun. PAC 2001 Proceedings, pp. 114-116, 2002. In this paper we present an experimental program for the design, development and demonstration of an Enhanced Transformer Ratio Dielectric Wakefield Accelerator (ETR-DWA). The principal goal is to increase the transformer ratio R, the parameter that characterizes the energy transfer efficiency from the accelerating structure to the accelerated electron beam. We present here an experimental design of a 13.625 GHz dielectric loaded accelerating structure, a laser multisplitter producing a ramped bunch train, and simulations of the bunch train parameters required. Experimental results of the accelerating structure bench testing and ramped pulsed train generation with the laser multisplitter are shown as well. Using beam dynamic simulations, we also obtain the focusing FODO lattice parameters

  13. Intake to Production Ratio

    DEFF Research Database (Denmark)

    Nazaroff, William; Weschler, Charles J.; Little, John C.

    2012-01-01

    BACKGROUND: Limited data are available to assess human exposure to thousands of chemicals currently in commerce. Information that relates human intake of a chemical to its production and use can help inform understanding of mechanisms and pathways that control exposure and support efforts...... to protect public health.OBJECTIVES: We introduce the intake-to-production ratio (IPR) as an economy-wide quantitative indicator of the extent to which chemical production results in human exposure.METHODS: The IPR was evaluated as the ratio of two terms: aggregate rate of chemical uptake in a human......(n-butyl) phthalate, 1,040 ppm for para-dichlorobenzene, 6,800 ppm for di(isobutyl) phthalate, 7,700 ppm for diethyl phthalate, and 8,000-24,000 ppm (range) for triclosan.CONCLUSION: The IPR is well suited as an aggregate metric of exposure intensity for characterizing population-level exposure to synthesized...

  14. Visual Memories Bypass Normalization.

    Science.gov (United States)

    Bloem, Ilona M; Watanabe, Yurika L; Kibbe, Melissa M; Ling, Sam

    2018-05-01

    How distinct are visual memory representations from visual perception? Although evidence suggests that briefly remembered stimuli are represented within early visual cortices, the degree to which these memory traces resemble true visual representations remains something of a mystery. Here, we tested whether both visual memory and perception succumb to a seemingly ubiquitous neural computation: normalization. Observers were asked to remember the contrast of visual stimuli, which were pitted against each other to promote normalization either in perception or in visual memory. Our results revealed robust normalization between visual representations in perception, yet no signature of normalization occurring between working memory stores-neither between representations in memory nor between memory representations and visual inputs. These results provide unique insight into the nature of visual memory representations, illustrating that visual memory representations follow a different set of computational rules, bypassing normalization, a canonical visual computation.

  15. Sampling from the normal and exponential distributions

    International Nuclear Information System (INIS)

    Chaplin, K.R.; Wills, C.A.

    1982-01-01

    Methods for generating random numbers from the normal and exponential distributions are described. These involve dividing each function into subregions, and for each of these developing a method of sampling usually based on an acceptance rejection technique. When sampling from the normal or exponential distribution, each subregion provides the required random value with probability equal to the ratio of its area to the total area. Procedures written in FORTRAN for the CYBER 175/CDC 6600 system are provided to implement the two algorithms

  16. Making nuclear 'normal'

    International Nuclear Information System (INIS)

    Haehlen, Peter; Elmiger, Bruno

    2000-01-01

    The mechanics of the Swiss NPPs' 'come and see' programme 1995-1999 were illustrated in our contributions to all PIME workshops since 1996. Now, after four annual 'waves', all the country has been covered by the NPPs' invitation to dialogue. This makes PIME 2000 the right time to shed some light on one particular objective of this initiative: making nuclear 'normal'. The principal aim of the 'come and see' programme, namely to give the Swiss NPPs 'a voice of their own' by the end of the nuclear moratorium 1990-2000, has clearly been attained and was commented on during earlier PIMEs. It is, however, equally important that Swiss nuclear energy not only made progress in terms of public 'presence', but also in terms of being perceived as a normal part of industry, as a normal branch of the economy. The message that Swiss nuclear energy is nothing but a normal business involving normal people, was stressed by several components of the multi-prong campaign: - The speakers in the TV ads were real - 'normal' - visitors' guides and not actors; - The testimonials in the print ads were all real NPP visitors - 'normal' people - and not models; - The mailings inviting a very large number of associations to 'come and see' activated a typical channel of 'normal' Swiss social life; - Spending money on ads (a new activity for Swiss NPPs) appears to have resulted in being perceived by the media as a normal branch of the economy. Today we feel that the 'normality' message has well been received by the media. In the controversy dealing with antinuclear arguments brought forward by environmental organisations journalists nowadays as a rule give nuclear energy a voice - a normal right to be heard. As in a 'normal' controversy, the media again actively ask themselves questions about specific antinuclear claims, much more than before 1990 when the moratorium started. The result is that in many cases such arguments are discarded by journalists, because they are, e.g., found to be

  17. The Reference Return Ratio

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Faber Frandsen, Tove

    2008-01-01

    The paper introduces a new journal impact measure called The Reference Return Ratio (3R). Unlike the traditional Journal Impact Factor (JIF), which is based on calculations of publications and citations, the new measure is based on calculations of bibliographic investments (references) and returns...... (citations). A comparative study of the two measures shows a strong relationship between the 3R and the JIF. Yet, the 3R appears to correct for citation habits, citation dynamics, and composition of document types - problems that typically are raised against the JIF. In addition, contrary to traditional...

  18. Potential support ratios

    DEFF Research Database (Denmark)

    Kjærgaard, Søren; Canudas-Romo, Vladimir

    2017-01-01

    The ‘prospective potential support ratio’ has been proposed by researchers as a measure that accurately quantifies the burden of ageing, by identifying the fraction of a population that has passed a certain measure of longevity, for example, 17 years of life expectancy. Nevertheless......, the prospective potential support ratio usually focuses on the current mortality schedule, or period life expectancy. Instead, in this paper we look at the actual mortality experienced by cohorts in a population, using cohort life tables. We analyse differences between the two perspectives using mortality models...

  19. Normal Pressure Hydrocephalus

    Science.gov (United States)

    ... improves the chance of a good recovery. Without treatment, symptoms may worsen and cause death. What research is being done? The NINDS conducts and supports research on neurological disorders, including normal pressure hydrocephalus. Research on disorders such ...

  20. Normality in Analytical Psychology

    Science.gov (United States)

    Myers, Steve

    2013-01-01

    Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity. PMID:25379262

  1. Normal pressure hydrocephalus

    Science.gov (United States)

    Hydrocephalus - occult; Hydrocephalus - idiopathic; Hydrocephalus - adult; Hydrocephalus - communicating; Dementia - hydrocephalus; NPH ... Ferri FF. Normal pressure hydrocephalus. In: Ferri FF, ed. ... Elsevier; 2016:chap 648. Rosenberg GA. Brain edema and disorders ...

  2. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  3. Normal growth and development

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002456.htm Normal growth and development To use the sharing features on this page, please enable JavaScript. A child's growth and development can be divided into four periods: ...

  4. Tau hadronic branching ratios

    CERN Document Server

    Buskulic, Damir; De Bonis, I; Décamp, D; Ghez, P; Goy, C; Lees, J P; Lucotte, A; Minard, M N; Odier, P; Pietrzyk, B; Ariztizabal, F; Chmeissani, M; Crespo, J M; Efthymiopoulos, I; Fernández, E; Fernández-Bosman, M; Gaitan, V; Martínez, M; Orteu, S; Pacheco, A; Padilla, C; Palla, Fabrizio; Pascual, A; Perlas, J A; Sánchez, F; Teubert, F; Colaleo, A; Creanza, D; De Palma, M; Farilla, A; Gelao, G; Girone, M; Iaselli, Giuseppe; Maggi, G; Maggi, M; Marinelli, N; Natali, S; Nuzzo, S; Ranieri, A; Raso, G; Romano, F; Ruggieri, F; Selvaggi, G; Silvestris, L; Tempesta, P; Zito, G; Huang, X; Lin, J; Ouyang, Q; Wang, T; Xie, Y; Xu, R; Xue, S; Zhang, J; Zhang, L; Zhao, W; Bonvicini, G; Cattaneo, M; Comas, P; Coyle, P; Drevermann, H; Engelhardt, A; Forty, Roger W; Frank, M; Hagelberg, R; Harvey, J; Jacobsen, R; Janot, P; Jost, B; Kneringer, E; Knobloch, J; Lehraus, Ivan; Markou, C; Martin, E B; Mato, P; Minten, Adolf G; Miquel, R; Oest, T; Palazzi, P; Pater, J R; Pusztaszeri, J F; Ranjard, F; Rensing, P E; Rolandi, Luigi; Schlatter, W D; Schmelling, M; Schneider, O; Tejessy, W; Tomalin, I R; Venturi, A; Wachsmuth, H W; Wiedenmann, W; Wildish, T; Witzeling, W; Wotschack, J; Ajaltouni, Ziad J; Bardadin-Otwinowska, Maria; Barrès, A; Boyer, C; Falvard, A; Gay, P; Guicheney, C; Henrard, P; Jousset, J; Michel, B; Monteil, S; Pallin, D; Perret, P; Podlyski, F; Proriol, J; Rossignol, J M; Saadi, F; Fearnley, Tom; Hansen, J B; Hansen, J D; Hansen, J R; Hansen, P H; Nilsson, B S; Kyriakis, A; Simopoulou, Errietta; Siotis, I; Vayaki, Anna; Zachariadou, K; Blondel, A; Bonneaud, G R; Brient, J C; Bourdon, P; Passalacqua, L; Rougé, A; Rumpf, M; Tanaka, R; Valassi, Andrea; Verderi, M; Videau, H L; Candlin, D J; Parsons, M I; Focardi, E; Parrini, G; Corden, M; Delfino, M C; Georgiopoulos, C H; Jaffe, D E; Antonelli, A; Bencivenni, G; Bologna, G; Bossi, F; Campana, P; Capon, G; Chiarella, V; Felici, G; Laurelli, P; Mannocchi, G; Murtas, F; Murtas, G P; Pepé-Altarelli, M; Dorris, S J; Halley, A W; ten Have, I; Knowles, I G; Lynch, J G; Morton, W T; O'Shea, V; Raine, C; Reeves, P; Scarr, J M; Smith, K; Smith, M G; Thompson, A S; Thomson, F; Thorn, S; Turnbull, R M; Becker, U; Braun, O; Geweniger, C; Graefe, G; Hanke, P; Hepp, V; Kluge, E E; Putzer, A; Rensch, B; Schmidt, M; Sommer, J; Stenzel, H; Tittel, K; Werner, S; Wunsch, M; Beuselinck, R; Binnie, David M; Cameron, W; Colling, D J; Dornan, Peter J; Konstantinidis, N P; Moneta, L; Moutoussi, A; Nash, J; San Martin, G; Sedgbeer, J K; Stacey, A M; Dissertori, G; Girtler, P; Kuhn, D; Rudolph, G; Bowdery, C K; Brodbeck, T J; Colrain, P; Crawford, G; Finch, A J; Foster, F; Hughes, G; Sloan, Terence; Whelan, E P; Williams, M I; Galla, A; Greene, A M; Kleinknecht, K; Quast, G; Raab, J; Renk, B; Sander, H G; Wanke, R; Van Gemmeren, P; Zeitnitz, C; Aubert, Jean-Jacques; Bencheikh, A M; Benchouk, C; Bonissent, A; Bujosa, G; Calvet, D; Carr, J; Diaconu, C A; Etienne, F; Thulasidas, M; Nicod, D; Payre, P; Rousseau, D; Talby, M; Abt, I; Assmann, R W; Bauer, C; Blum, Walter; Brown, D; Dietl, H; Dydak, Friedrich; Ganis, G; Gotzhein, C; Jakobs, K; Kroha, H; Lütjens, G; Lutz, Gerhard; Männer, W; Moser, H G; Richter, R H; Rosado-Schlosser, A; Schael, S; Settles, Ronald; Seywerd, H C J; Saint-Denis, R; Wolf, G; Alemany, R; Boucrot, J; Callot, O; Cordier, A; Courault, F; Davier, M; Duflot, L; Grivaz, J F; Heusse, P; Jacquet, M; Kim, D W; Le Diberder, F R; Lefrançois, J; Lutz, A M; Musolino, G; Nikolic, I A; Park, H J; Park, I C; Schune, M H; Simion, S; Veillet, J J; Videau, I; Abbaneo, D; Azzurri, P; Bagliesi, G; Batignani, G; Bettarini, S; Bozzi, C; Calderini, G; Carpinelli, M; Ciocci, M A; Ciulli, V; Dell'Orso, R; Fantechi, R; Ferrante, I; Foà, L; Forti, F; Giassi, A; Giorgi, M A; Gregorio, A; Ligabue, F; Lusiani, A; Marrocchesi, P S; Messineo, A; Rizzo, G; Sanguinetti, G; Sciabà, A; Spagnolo, P; Steinberger, Jack; Tenchini, Roberto; Tonelli, G; Triggiani, G; Vannini, C; Verdini, P G; Walsh, J; Betteridge, A P; Blair, G A; Bryant, L M; Cerutti, F; Gao, Y; Green, M G; Johnson, D L; Medcalf, T; Mir, L M; Perrodo, P; Strong, J A; Bertin, V; Botterill, David R; Clifft, R W; Edgecock, T R; Haywood, S; Edwards, M; Maley, P; Norton, P R; Thompson, J C; Bloch-Devaux, B; Colas, P; Emery, S; Kozanecki, Witold; Lançon, E; Lemaire, M C; Locci, E; Marx, B; Pérez, P; Rander, J; Renardy, J F; Roussarie, A; Schuller, J P; Schwindling, J; Trabelsi, A; Vallage, B; Johnson, R P; Kim, H Y; Litke, A M; McNeil, M A; Taylor, G; Beddall, A; Booth, C N; Boswell, R; Cartwright, S L; Combley, F; Dawson, I; Köksal, A; Letho, M; Newton, W M; Rankin, C; Thompson, L F; Böhrer, A; Brandt, S; Cowan, G D; Feigl, E; Grupen, Claus; Lutters, G; Minguet-Rodríguez, J A; Rivera, F; Saraiva, P; Smolik, L; Stephan, F; Apollonio, M; Bosisio, L; Della Marina, R; Giannini, G; Gobbo, B; Ragusa, F; Rothberg, J E; Wasserbaech, S R; Armstrong, S R; Bellantoni, L; Elmer, P; Feng, Z; Ferguson, D P S; Gao, Y S; González, S; Grahl, J; Harton, J L; Hayes, O J; Hu, H; McNamara, P A; Nachtman, J M; Orejudos, W; Pan, Y B; Saadi, Y; Schmitt, M; Scott, I J; Sharma, V; Turk, J; Walsh, A M; Wu Sau Lan; Wu, X; Yamartino, J M; Zheng, M; Zobernig, G

    1996-01-01

    From 64492 selected \\tau-pair events, produced at the Z^0 resonance, the measurement of the tau decays into hadrons from a global analysis using 1991, 1992 and 1993 ALEPH data is presented. Special emphasis is given to the reconstruction of photons and \\pi^0's, and the removal of fake photons. A detailed study of the systematics entering the \\pi^0 reconstruction is also given. A complete and consistent set of tau hadronic branching ratios is presented for 18 exclusive modes. Most measurements are more precise than the present world average. The new level of precision reached allows a stringent test of \\tau-\\mu universality in hadronic decays, g_\\tau/g_\\mu \\ = \\ 1.0013 \\ \\pm \\ 0.0095, and the first measurement of the vector and axial-vector contributions to the non-strange hadronic \\tau decay width: R_{\\tau ,V} \\ = \\ 1.788 \\ \\pm \\ 0.025 and R_{\\tau ,A} \\ = \\ 1.694 \\ \\pm \\ 0.027. The ratio (R_{\\tau ,V} - R_{\\tau ,A}) / (R_{\\tau ,V} + R_{\\tau ,A}), equal to (2.7 \\pm 1.3) \\ \\%, is a measure of the importance of Q...

  5. Assessing the Causality Factors in the Association between (Abdominal Obesity and Physical Activity among the Newfoundland Population–-A Mendelian Randomization Analysis

    Directory of Open Access Journals (Sweden)

    Frank Barning

    2016-01-01

    Full Text Available A total of 1,263 adults from Newfoundland and Labrador were studied in the research. Body mass index (BMI and percent trunk fat (PTF were analyzed as biomarkers for obesity. The Mendelian randomization (MR approach with two single-nucleotide polymorphisms in the fat-mass and obesity (FTO gene as instruments was employed to assess the causal effect. In both genders, increasing physical activity significantly reduced BMI and PTF when adjusted for age and the FTO gene. The effect of physical activity was stronger on PTF than BMI. Direct observational analyses showed significant increase in BMI/PTF when physical activity decreased. A similar association in MR analyses was not significant. The association between physical activity and BMI/PTF could be due to reversed causality or common confounding factors. Our study provides insights into the causal contributions of obesity to physical activity in adults. Health intervention strategies to increase physical activity among adults should include some other plans such as improving diet for reducing obesity.

  6. CGMIM: Automated text-mining of Online Mendelian Inheritance in Man (OMIM to identify genetically-associated cancers and candidate genes

    Directory of Open Access Journals (Sweden)

    Jones Steven

    2005-03-01

    Full Text Available Abstract Background Online Mendelian Inheritance in Man (OMIM is a computerized database of information about genes and heritable traits in human populations, based on information reported in the scientific literature. Our objective was to establish an automated text-mining system for OMIM that will identify genetically-related cancers and cancer-related genes. We developed the computer program CGMIM to search for entries in OMIM that are related to one or more cancer types. We performed manual searches of OMIM to verify the program results. Results In the OMIM database on September 30, 2004, CGMIM identified 1943 genes related to cancer. BRCA2 (OMIM *164757, BRAF (OMIM *164757 and CDKN2A (OMIM *600160 were each related to 14 types of cancer. There were 45 genes related to cancer of the esophagus, 121 genes related to cancer of the stomach, and 21 genes related to both. Analysis of CGMIM results indicate that fewer than three gene entries in OMIM should mention both, and the more than seven-fold discrepancy suggests cancers of the esophagus and stomach are more genetically related than current literature suggests. Conclusion CGMIM identifies genetically-related cancers and cancer-related genes. In several ways, cancers with shared genetic etiology are anticipated to lead to further etiologic hypotheses and advances regarding environmental agents. CGMIM results are posted monthly and the source code can be obtained free of charge from the BC Cancer Research Centre website http://www.bccrc.ca/ccr/CGMIM.

  7. Pst I restriction fragment length polymorphism of human placental alkaline phosphatase gene: Mendelian in segregation and localization of mutation site in the gene

    International Nuclear Information System (INIS)

    Tsavaler, L.; Penhallow, R.C.; Sussman, H.H.

    1988-01-01

    The pattern of inheritance of a Pst I restriction fragment length polymorphism (RFLP) of the human placental alkaline phosphatase gene was studied in nine nuclear families by Southern blot hybridization analysis of genomic DNA. The dimorphic RFLP is defined by the presence of allelic fragments 1.0 kilobase and 0.8 kilobase long. The results of this study show that the two alleles of the Pst I RFLP of the placental alkaline phosphatase gene segregate as codominant traits according to Mendelian expectations. For a polymorphism to be useful as a genetic marker the probability that an offspring is informative (PIC) must be at least 0.15. The allelic frequency of the 1.0-kilobase allele is 0.21, which correlates to a probability that an offspring is informative of 0.275 and is indicative of a useful polymorphism. By using probes derived from different regions of the placental alkaline phosphatase cDNA, the mutated Pst I site causing the RFLP was located in the penultimate intron 2497 base pairs downstream from the transcriptional initiation site

  8. Comparing computing formulas for estimating concentration ratios

    International Nuclear Information System (INIS)

    Gilbert, R.O.; Simpson, J.C.

    1984-03-01

    This paper provides guidance on the choice of computing formulas (estimators) for estimating concentration ratios and other ratio-type measures of radionuclides and other environmental contaminant transfers between ecosystem components. Mathematical expressions for the expected value of three commonly used estimators (arithmetic mean of ratios, geometric mean of ratios, and the ratio of means) are obtained when the multivariate lognormal distribution is assumed. These expressions are used to explain why these estimators will not in general give the same estimate of the average concentration ratio. They illustrate that the magnitude of the discrepancies depends on the magnitude of measurement biases, and on the variances and correlations associated with spatial heterogeneity and measurement errors. This paper also reports on a computer simulation study that compares the accuracy of eight computing formulas for estimating a ratio relationship that is constant over time and/or space. Statistical models appropriate for both controlled spiking experiments and observational field studies for either normal or lognormal distributions are considered. 24 references, 15 figures, 7 tables

  9. Peak power ratio generator

    Science.gov (United States)

    Moyer, R.D.

    A peak power ratio generator is described for measuring, in combination with a conventional power meter, the peak power level of extremely narrow pulses in the gigahertz radio frequency bands. The present invention in a preferred embodiment utilizes a tunnel diode and a back diode combination in a detector circuit as the only high speed elements. The high speed tunnel diode provides a bistable signal and serves as a memory device of the input pulses for the remaining, slower components. A hybrid digital and analog loop maintains the peak power level of a reference channel at a known amount. Thus, by measuring the average power levels of the reference signal and the source signal, the peak power level of the source signal can be determined.

  10. Smooth quantile normalization.

    Science.gov (United States)

    Hicks, Stephanie C; Okrah, Kwame; Paulson, Joseph N; Quackenbush, John; Irizarry, Rafael A; Bravo, Héctor Corrada

    2018-04-01

    Between-sample normalization is a critical step in genomic data analysis to remove systematic bias and unwanted technical variation in high-throughput data. Global normalization methods are based on the assumption that observed variability in global properties is due to technical reasons and are unrelated to the biology of interest. For example, some methods correct for differences in sequencing read counts by scaling features to have similar median values across samples, but these fail to reduce other forms of unwanted technical variation. Methods such as quantile normalization transform the statistical distributions across samples to be the same and assume global differences in the distribution are induced by only technical variation. However, it remains unclear how to proceed with normalization if these assumptions are violated, for example, if there are global differences in the statistical distributions between biological conditions or groups, and external information, such as negative or control features, is not available. Here, we introduce a generalization of quantile normalization, referred to as smooth quantile normalization (qsmooth), which is based on the assumption that the statistical distribution of each sample should be the same (or have the same distributional shape) within biological groups or conditions, but allowing that they may differ between groups. We illustrate the advantages of our method on several high-throughput datasets with global differences in distributions corresponding to different biological conditions. We also perform a Monte Carlo simulation study to illustrate the bias-variance tradeoff and root mean squared error of qsmooth compared to other global normalization methods. A software implementation is available from https://github.com/stephaniehicks/qsmooth.

  11. A non-Mendelian MAPK-generated hereditary unit controlled by a second MAPK pathway in Podospora anserina.

    Science.gov (United States)

    Lalucque, Hervé; Malagnac, Fabienne; Brun, Sylvain; Kicka, Sébastien; Silar, Philippe

    2012-06-01

    The Podospora anserina PaMpk1 MAP kinase (MAPK) signaling pathway can generate a cytoplasmic and infectious element resembling prions. When present in the cells, this C element causes the crippled growth (CG) cell degeneration. CG results from the inappropriate autocatalytic activation of the PaMpk1 MAPK pathway during growth, whereas this cascade normally signals stationary phase. Little is known about the control of such prion-like hereditary units involved in regulatory inheritance. Here, we show that another MAPK pathway, PaMpk2, is crucial at every stage of the fungus life cycle, in particular those controlled by PaMpk1 during stationary phase, which includes the generation of C. Inactivation of the third P. anserina MAPK pathway, PaMpk3, has no effect on the development of the fungus. Mutants of MAPK, MAPK kinase, and MAPK kinase kinase of the PaMpk2 pathway are unable to present CG. This inability likely relies upon an incorrect activation of PaMpk1, although this MAPK is normally phosphorylated in the mutants. In PaMpk2 null mutants, hyphae are abnormal and PaMpk1 is mislocalized. Correspondingly, stationary phase differentiations controlled by PaMpk1 are defective in the mutants of the PaMpk2 cascade. Constitutive activation of the PaMpk2 pathway mimics in many ways its inactivation, including an effect on PaMpk1 localization. Analysis of double and triple mutants inactivated for two or all three MAPK genes undercover new growth and differentiation phenotypes, suggesting overlapping roles. Our data underscore the complex regulation of a prion-like element in a model organism.

  12. Monitoring the normal body

    DEFF Research Database (Denmark)

    Nissen, Nina Konstantin; Holm, Lotte; Baarts, Charlotte

    2015-01-01

    of practices for monitoring their bodies based on different kinds of calculations of weight and body size, observations of body shape, and measurements of bodily firmness. Biometric measurements are familiar to them as are health authorities' recommendations. Despite not belonging to an extreme BMI category...... provides us with knowledge about how to prevent future overweight or obesity. This paper investigates body size ideals and monitoring practices among normal-weight and moderately overweight people. Methods : The study is based on in-depth interviews combined with observations. 24 participants were...... recruited by strategic sampling based on self-reported BMI 18.5-29.9 kg/m2 and socio-demographic factors. Inductive analysis was conducted. Results : Normal-weight and moderately overweight people have clear ideals for their body size. Despite being normal weight or close to this, they construct a variety...

  13. The Liquidity Coverage Ratio: the need for further complementary ratios?

    OpenAIRE

    Ojo, Marianne

    2013-01-01

    This paper considers components of the Liquidity Coverage Ratio – as well as certain prevailing gaps which may necessitate the introduction of a complementary liquidity ratio. The definitions and objectives accorded to the Liquidity Coverage Ratio (LCR) and Net Stable Funding Ratio (NSFR) highlight the focus which is accorded to time horizons for funding bank operations. A ratio which would focus on the rate of liquidity transformations and which could also serve as a complementary metric gi...

  14. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas

    2012-01-01

    , S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels...... was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies......Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants...

  15. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process......This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...

  16. Normalization of satellite imagery

    Science.gov (United States)

    Kim, Hongsuk H.; Elman, Gregory C.

    1990-01-01

    Sets of Thematic Mapper (TM) imagery taken over the Washington, DC metropolitan area during the months of November, March and May were converted into a form of ground reflectance imagery. This conversion was accomplished by adjusting the incident sunlight and view angles and by applying a pixel-by-pixel correction for atmospheric effects. Seasonal color changes of the area can be better observed when such normalization is applied to space imagery taken in time series. In normalized imagery, the grey scale depicts variations in surface reflectance and tonal signature of multi-band color imagery can be directly interpreted for quantitative information of the target.

  17. The normal holonomy group

    International Nuclear Information System (INIS)

    Olmos, C.

    1990-05-01

    The restricted holonomy group of a Riemannian manifold is a compact Lie group and its representation on the tangent space is a product of irreducible representations and a trivial one. Each one of the non-trivial factors is either an orthogonal representation of a connected compact Lie group which acts transitively on the unit sphere or it is the isotropy representation of a single Riemannian symmetric space of rank ≥ 2. We prove that, all these properties are also true for the representation on the normal space of the restricted normal holonomy group of any submanifold of a space of constant curvature. 4 refs

  18. Normality in Analytical Psychology

    Directory of Open Access Journals (Sweden)

    Steve Myers

    2013-11-01

    Full Text Available Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity.

  19. Medically-enhanced normality

    DEFF Research Database (Denmark)

    Møldrup, Claus; Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

    2003-01-01

    Objective: To consider public perspectives on the use of medicines for non-medical purposes, a usage called medically-enhanced normality (MEN). Method: Examples from the literature were combined with empirical data derived from two Danish research projects: a Delphi internet study and a Telebus...

  20. The Normal Fetal Pancreas.

    Science.gov (United States)

    Kivilevitch, Zvi; Achiron, Reuven; Perlman, Sharon; Gilboa, Yinon

    2017-10-01

    The aim of the study was to assess the sonographic feasibility of measuring the fetal pancreas and its normal development throughout pregnancy. We conducted a cross-sectional prospective study between 19 and 36 weeks' gestation. The study included singleton pregnancies with normal pregnancy follow-up. The pancreas circumference was measured. The first 90 cases were tested to assess feasibility. Two hundred ninety-seven fetuses of nondiabetic mothers were recruited during a 3-year period. The overall satisfactory visualization rate was 61.6%. The intraobserver and interobserver variability had high interclass correlation coefficients of of 0.964 and 0.967, respectively. A cubic polynomial regression described best the correlation of pancreas circumference with gestational age (r = 0.744; P pancreas circumference percentiles for each week of gestation were calculated. During the study period, we detected 2 cases with overgrowth syndrome and 1 case with an annular pancreas. In this study, we assessed the feasibility of sonography for measuring the fetal pancreas and established a normal reference range for the fetal pancreas circumference throughout pregnancy. This database can be helpful when investigating fetomaternal disorders that can involve its normal development. © 2017 by the American Institute of Ultrasound in Medicine.

  1. Energy Profit Ratio Compared

    International Nuclear Information System (INIS)

    Amano, Osamu

    2007-01-01

    We need more oil energy to take out oil under the ground. Limit resources make us consider other candidates of energy source instead of oil. Electricity shall be the main role more and more like electric vehicles and air conditioners so we should consider electricity generation ways. When we consider what kind of electric power generation is the best or suitable, we should not only power generation plant but whole process from mining to power generation. It is good way to use EPR, Energy Profit Ratio, to analysis which type is more efficient and which part is to do research and development when you see the input breakdown analysis. Electricity by the light water nuclear power plant, the hydrogen power plant and the geothermal power plant are better candidates from EPR analysis. Forecasting the world primly energy supply in 2050, it is said that the demand will be double of the demand in 2000 and the supply will not be able to satisfy the demand in 2050. We should save 30% of the demand and increase nuclear power plants 3.5 times more and recyclable energy like hydropower plants 3 times more. When the nuclear power plants are 3.5 times more then uranium peak will come and we will need breed uranium. I will analysis the EPR of FBR. Conclusion: A) the EPR of NPS in Japan is 17.4 and it is the best of all. B) Many countries will introduce new nuclear power plants rapidly may be 3.5 times in 2050. C) Uranium peak will happen around 2050. (author)

  2. Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

    Science.gov (United States)

    Joehanes, Roby; Liu, Chunyu; Aslibekyan, Stella; Demerath, Ellen W.; Guan, Weihua; Zhi, Degui; Willinger, Christine; Courchesne, Paul; Multhaup, Michael; Irvin, Marguerite R.; Schadt, Eric E.; Bressler, Jan; North, Kari; Sundström, Johan; Gustafsson, Stefan; Shah, Sonia; McRae, Allan F.; Harris, Sarah E.; Gibson, Jude; Redmond, Paul; Corley, Janie; Starr, John M.; Visscher, Peter M.; Wray, Naomi R.; Krauss, Ronald M.; Feinberg, Andrew; Fornage, Myriam; Pankow, James S.; Lind, Lars; Fox, Caroline; Ingelsson, Erik; Arnett, Donna K.; Boerwinkle, Eric; Liang, Liming; Levy, Daniel; Deary, Ian J.

    2017-01-01

    Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases. PMID:28095459

  3. Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach.

    Directory of Open Access Journals (Sweden)

    Michael M Mendelson

    2017-01-01

    Full Text Available The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.We conducted an association study of body mass index (BMI and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1], demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83 of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination.We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.

  4. Elevated sacroilac joint uptake ratios in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    De Smet, A.A.; Mahmood, T.; Robinson, R.G.; Lindsley, H.B.

    1984-01-01

    Sacroiliac joint radiographs and radionuclide sacroiliac joint uptake ratios were obtained on 14 patients with active systemic lupus erythematosus. Elevated joint ratios were found unilaterally in two patients and bilaterally in seven patients when their lupus was active. In patients whose disease became quiescent, the uptake ratios returned to normal. Two patients had persistently elevated ratios with continued clinical and laboratory evidence of active lupus. Mild sacroiliac joint sclerosis and erosions were detected on pelvic radiographs in these same two patients. Elevated quantitative sacroiliac joint uptake ratios may occur as a manifestation of active systemic lupus erythematosus

  5. The effect of hematocrit and hemoglobin on the risk of ischemic heart disease: A Mendelian randomization study.

    Science.gov (United States)

    Zhong, Y; Lin, S L; Schooling, C M

    2016-10-01

    Hematocrit and hemoglobin affect viscosity, and have been considered as risk factors for ischemic heart disease (IHD), although observations are inconsistent; randomized controlled trials targeting hematocrit or hemoglobin have not been definitive. To clarify their role, the risk of IHD was assessed according to genetically determined hematocrit and hemoglobin. We applied single nucleotide polymorphisms (SNPs) strongly determining hematocrit and hemoglobin, from a genome wide association study, to a large case (64,746) control (130,681) study of coronary artery disease, CARDIoGRAMplusC4D, to obtain unconfounded estimates using instrumental variable analysis by combining the Wald estimators for each SNP taking into account any correlation between SNPs using weighted generalized linear regression. Hematocrit was positively associated with IHD, odds ratio (OR) 1.07 per %, 95% confidence interval (CI) 1.03 to 1.11, before and after excluding SNPs from gene regions directly functionally relevant to IHD. However, hematocrit was not associated with IHD (OR 0.99, 0.94 to 1.04) after also excluding SNPs associated with lipids at genome wide significance. Hemoglobin was not associated with IHD (OR 1.06 per g/dL, 0.97 to 1.15) which was similar (OR 1.02, 0.94 to 1.11) after excluding SNPs from gene regions directly functionally relevant to IHD. Hemoglobin was negatively associated with IHD after also excluding SNPs associated with lipids at genome wide significance (OR 0.86, 0.78 to 0.94). In conclusion, hematocrit shares genetic determinants with IHD, but whether the genes contribute to IHD via hematocrit or other mechanisms is not entirely clear. Higher Hemoglobin is unlikely to cause IHD. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Idiopathic Normal Pressure Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Basant R. Nassar BS

    2016-04-01

    Full Text Available Idiopathic normal pressure hydrocephalus (iNPH is a potentially reversible neurodegenerative disease commonly characterized by a triad of dementia, gait, and urinary disturbance. Advancements in diagnosis and treatment have aided in properly identifying and improving symptoms in patients. However, a large proportion of iNPH patients remain either undiagnosed or misdiagnosed. Using PubMed search engine of keywords “normal pressure hydrocephalus,” “diagnosis,” “shunt treatment,” “biomarkers,” “gait disturbances,” “cognitive function,” “neuropsychology,” “imaging,” and “pathogenesis,” articles were obtained for this review. The majority of the articles were retrieved from the past 10 years. The purpose of this review article is to aid general practitioners in further understanding current findings on the pathogenesis, diagnosis, and treatment of iNPH.

  7. Normal Weight Dyslipidemia

    DEFF Research Database (Denmark)

    Ipsen, David Hojland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-01-01

    Objective: The liver coordinates lipid metabolism and may play a vital role in the development of dyslipidemia, even in the absence of obesity. Normal weight dyslipidemia (NWD) and patients with nonalcoholic fatty liver disease (NAFLD) who do not have obesity constitute a unique subset...... of individuals characterized by dyslipidemia and metabolic deterioration. This review examined the available literature on the role of the liver in dyslipidemia and the metabolic characteristics of patients with NAFLD who do not have obesity. Methods: PubMed was searched using the following keywords: nonobese......, dyslipidemia, NAFLD, NWD, liver, and metabolically obese/unhealthy normal weight. Additionally, article bibliographies were screened, and relevant citations were retrieved. Studies were excluded if they had not measured relevant biomarkers of dyslipidemia. Results: NWD and NAFLD without obesity share a similar...

  8. Ethics and "normal birth".

    Science.gov (United States)

    Lyerly, Anne Drapkin

    2012-12-01

    The concept of "normal birth" has been promoted as ideal by several international organizations, although debate about its meaning is ongoing. In this article, I examine the concept of normalcy to explore its ethical implications and raise a trio of concerns. First, in its emphasis on nonuse of technology as a goal, the concept of normalcy may marginalize women for whom medical intervention is necessary or beneficial. Second, in its emphasis on birth as a socially meaningful event, the mantra of normalcy may unintentionally avert attention to meaning in medically complicated births. Third, the emphasis on birth as a normal and healthy event may be a contributor to the long-standing tolerance for the dearth of evidence guiding the treatment of illness during pregnancy and the failure to responsibly and productively engage pregnant women in health research. Given these concerns, it is worth debating not just what "normal birth" means, but whether the term as an ideal earns its keep. © 2012, Copyright the Authors Journal compilation © 2012, Wiley Periodicals, Inc.

  9. The nucleoside diphosphate kinase gene Nme3 acts as quantitative trait locus promoting non-Mendelian inheritance.

    Directory of Open Access Journals (Sweden)

    Hermann Bauer

    Full Text Available The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (> 95% from heterozygous (t/+ males to their offspring. This phenotype is termed transmission ratio distortion (TRD and is caused by the interaction of the t-complex responder (Tcr with several quantitative trait loci (QTL, the t-complex distorters (Tcd1 to Tcd4, all located within the t-haplotype region. Current data suggest that the distorters collectively impair motility of all sperm derived from t/+ males; t-sperm is rescued by the responder, whereas (+-sperm remains partially dysfunctional. Recently we have identified two distorters as regulators of RHO small G proteins. Here we show that the nucleoside diphosphate kinase gene Nme3 acts as a QTL on TRD. Reduction of the Nme3 dosage by gene targeting of the wild-type allele enhanced the transmission rate of the t-haplotype and phenocopied distorter function. Genetic and biochemical analysis showed that the t-allele of Nme3 harbors a mutation (P89S that compromises enzymatic activity of the protein and genetically acts as a hypomorph. Transgenic overexpression of the Nme3 t-allele reduced t-haplotype transmission, proving it to be a distorter. We propose that the NME3 protein interacts with RHO signaling cascades to impair sperm motility through hyperactivation of SMOK, the wild-type form of the responder. This deleterious effect of the distorters is counter-balanced by the responder, SMOK(Tcr, a dominant-negative protein kinase exclusively expressed in t-sperm, thus permitting selfish behaviour and preferential transmission of the t-haplotype. In addition, the previously reported association of NME family members with RHO signaling in somatic cell motility and metastasis, in conjunction with our data involving RHO signaling in sperm motility, suggests a functional conservation between mechanisms for motility control in somatic cells and

  10. Golden ratio beauty as scientific function

    Directory of Open Access Journals (Sweden)

    Scott A. Olsen

    2018-01-01

    Full Text Available Normally when one is considering the golden ratio in the history of ideas, one is often looking at it as an aesthetic principle – usually associated with Greek art, sculpture and mathematics. However, in recent years the prevalence of the golden ratio within a broad range of scientific disciplines has brought its role in the perfection of science to the forefront. I would like to collapse these two areas by proposing a somewhat novel way of looking at the aesthetics of the golden ratio: its pervasive expression in scientific form and function is the basis of the aesthetics in the world. Therefore, science contains the same mathematical beauty as found in artistic expression. The golden ratio guides the Chaos Border of Kolmogorov, Arnold, and Moser (KAM theorem and it can be found hidden in all elementary particles, and even in the proportions of dark matter and energy relative to visible matter and energy. It is evident in the structure and growth functions of plants and animals and it can be found in the physiological functions of humans. It now appears that without the golden ratio, we would not have the form or function of the proton, cell, athlete, horse, species, planet, solar system or galaxy.

  11. Sex ratios at birth after induced abortion.

    Science.gov (United States)

    Urquia, Marcelo L; Moineddin, Rahim; Jha, Prabhat; O'Campo, Patricia J; McKenzie, Kwame; Glazier, Richard H; Henry, David A; Ray, Joel G

    2016-06-14

    Skewed male:female ratios at birth have been observed among certain immigrant groups. Data on abortion practices that might help to explain these findings are lacking. We examined 1 220 933 births to women with up to 3 consecutive singleton live births between 1993 and 2012 in Ontario. Records of live births, and induced and spontaneous abortions were linked to Canadian immigration records. We determined associations of male:female infant ratios with maternal birthplace, sex of the previous living sibling(s) and prior spontaneous or induced abortions. Male:female infant ratios did not appreciably depart from the normal range among Canadian-born women and most women born outside of Canada, irrespective of the sex of previous children or the characteristics of prior abortions. However, among infants of women who immigrated from India and had previously given birth to 2 girls, the overall male:female ratio was 1.96 (95% confidence interval [CI] 1.75-2.21) for the third live birth. The male:female infant ratio after 2 girls was 1.77 (95% CI 1.26-2.47) times higher if the current birth was preceded by 1 induced abortion, 2.38 (95% CI 1.44-3.94) times higher if preceded by 2 or more induced abortions and 3.88 (95% CI 2.02-7.50) times higher if the induced abortion was performed at 15 weeks or more gestation relative to no preceding abortion. Spontaneous abortions were not associated with male-biased sex ratios in subsequent births. High male:female ratios observed among infants born to women who immigrated from India are associated with induced abortions, especially in the second trimester of pregnancy. © 2016 Canadian Medical Association or its licensors.

  12. The J/$\\psi$ normal nuclear absorption

    CERN Document Server

    Alessandro, B; Arnaldi, R; Atayan, M; Beolè, S; Boldea, V; Bordalo, P; Borges, G; Castanier, C; Castor, J; Chaurand, B; Cheynis, B; Chiavassa, E; Cicalò, C; Comets, M P; Constantinescu, S; Cortese, P; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Fargeix, J; Force, P; Gallio, M; Gerschel, C; Giubellino, P; Golubeva, M B; Grigorian, A A; Grigorian, S; Guber, F F; Guichard, A; kanyan, H; ldzik, M; Jouan, D; Karavicheva, T L; Kluberg, L; Kurepin, A B; Le Bornec, Y; Lourenço, C; Cormick, M M; Marzari-Chiesa, A; Masera, M; Masoni, A; Monteno, M; Musso, A; Petiau, P; Piccotti, A; Pizzi, J R; Prino, F; Puddu, G; Quintans, C; Ramello, L; Ramos, S; Riccati, L; Santos, H; Saturnini, P; Scomparin, E; Serci, S; Shahoyan, R; Sigaudo, M F; Sitta, M; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, E; Villatte, L; Willis, N; Wu T

    2005-01-01

    We present a new determination of the ratio of cross-sections (J/psi) /DY as expected for nucleus-nucleus reactions if J/psi would only be normally absorbed by nuclear matter. This anticipated behaviour is based on proton-nucleus data exclusively, and compared, as a function of centrality, with updated S-U results from experiment NA38 and with the most recent Pb-Pb results from experiment NA50.

  13. Normalization of oxygen and hydrogen isotope data

    Science.gov (United States)

    Coplen, T.B.

    1988-01-01

    To resolve confusion due to expression of isotopic data from different laboratories on non-corresponding scales, oxygen isotope analyses of all substances can be expressed relative to VSMOW or VPDB (Vienna Peedee belemnite) on scales normalized such that the ??18O of SLAP is -55.5% relative to VSMOW. H3+ contribution in hydrogen isotope ratio analysis can be easily determined using two gaseous reference samples that differ greatly in deuterium content. ?? 1988.

  14. Lactose Intolerance (LCT-13910C>T) Genotype Is Associated with Plasma 25-Hydroxyvitamin D Concentrations in Caucasians: A Mendelian Randomization Study.

    Science.gov (United States)

    Alharbi, Ohood; El-Sohemy, Ahmed

    2017-06-01

    Background: The LCT -13910C>T gene variant is associated with lactose intolerance (LI) in different ethnic groups. Individuals with LI often limit or avoid dairy consumption, a major dietary source of vitamin D in North America, which may lead to inadequate vitamin D intake. Objective: The objective was to determine the prevalence of genotypes predictive of LI in different ethnic groups living in Canada and to determine whether the LCT genotype is associated with plasma 25(OH)D concentrations. Methods: Blood samples were drawn from a total of 1495 men and women aged 20-29 y from the Toronto Nutrigenomics and Health Study for genotyping and plasma 25(OH)D analysis. Intakes of dairy were assessed by using a 196-item food frequency questionnaire. The prevalence of LCT -13910C>T genotypes was compared by using χ 2 analysis. Using a Mendelian randomization approach, we examined the association between LCT genotypes and 25(OH)D concentrations. Results: Approximately 32% of Caucasians, 99% of East Asians, 74% of South Asians, and 59% of those with other or mixed ethnicities had the CC genotype associated with LI. Compared with those with the TT genotype, those with the CC genotype had a lower mean ± SE total dairy intake (2.15 ± 0.09 compared with 2.67 ± 0.12 servings/d, P = 0.003), a lower skim-milk intake (0.20 ± 0.03 compared with 0.46 ± 0.06 servings/d, P = 0.0004), and a lower plasma 25(OH)D concentration (63 ± 1.9 compared with 75.8 ± 2.4 nmol/L, P < 0.0001). The CT and CC genotypes were associated with a 50% and a 2-fold increased risk, respectively, of a suboptimal plasma 25(OH)D concentration (<75 nmol/L). Conclusions: In Caucasians, the CC genotype that predicts LI is associated with a lower plasma 25(OH)D concentration, which is attributable at least in part to a lower intake of dairy, particularly skim milk. Increased risk of suboptimal concentrations of vitamin D was also observed among those with the CT genotype, suggesting an intermediate effect of

  15. Exploring the relationship between maternal iron status and offspring’s blood pressure and adiposity: a Mendelian randomization study

    Directory of Open Access Journals (Sweden)

    Alwan NA

    2012-08-01

    was no difference between the OLS and the IV models coefficients for any of the outcomes considered.Conclusion: We found no association between maternal iron status and adult offspring’s BP and adiposity using both multivariable OLS and IV modeling. To our knowledge, this is the first study examining this relationship. Further exploration in larger studies that have genetic variation assessed in both mother and offspring should be considered.Keywords: iron, pregnancy, developmental origins, Mendelian randomization

  16. Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic.

    Science.gov (United States)

    Bowden, Jack; Del Greco M, Fabiola; Minelli, Cosetta; Davey Smith, George; Sheehan, Nuala A; Thompson, John R

    2016-12-01

    : MR-Egger regression has recently been proposed as a method for Mendelian randomization (MR) analyses incorporating summary data estimates of causal effect from multiple individual variants, which is robust to invalid instruments. It can be used to test for directional pleiotropy and provides an estimate of the causal effect adjusted for its presence. MR-Egger regression provides a useful additional sensitivity analysis to the standard inverse variance weighted (IVW) approach that assumes all variants are valid instruments. Both methods use weights that consider the single nucleotide polymorphism (SNP)-exposure associations to be known, rather than estimated. We call this the `NO Measurement Error' (NOME) assumption. Causal effect estimates from the IVW approach exhibit weak instrument bias whenever the genetic variants utilized violate the NOME assumption, which can be reliably measured using the F-statistic. The effect of NOME violation on MR-Egger regression has yet to be studied. An adaptation of the I2 statistic from the field of meta-analysis is proposed to quantify the strength of NOME violation for MR-Egger. It lies between 0 and 1, and indicates the expected relative bias (or dilution) of the MR-Egger causal estimate in the two-sample MR context. We call it IGX2 . The method of simulation extrapolation is also explored to counteract the dilution. Their joint utility is evaluated using simulated data and applied to a real MR example. In simulated two-sample MR analyses we show that, when a causal effect exists, the MR-Egger estimate of causal effect is biased towards the null when NOME is violated, and the stronger the violation (as indicated by lower values of IGX2 ), the stronger the dilution. When additionally all genetic variants are valid instruments, the type I error rate of the MR-Egger test for pleiotropy is inflated and the causal effect underestimated. Simulation extrapolation is shown to substantially mitigate these adverse effects. We

  17. Fast fission ratio and relative conversion ratio measurements in gadolinium poisoned water moderated UO2 lattices

    International Nuclear Information System (INIS)

    Murphy, M.F.

    1984-01-01

    A programme of criticality experiments has been carried out for BNFL by the Battelle reactor facility at Pacific Northwest Laboratories in Washington State, USA. A series of water moderated lattices of 4.3% enriched, 12.7 mm diameter, UO 2 fuel rods was studied, the fuel pitch was varied and the effects of gadolinium poison were measured. This report deals with the measurement of Fast Fission Ratios and Relative Conversion Ratios at the centre of five of the critical lattices. The Fast Fission Ratio (FFR) is defined here as the ratio of the fission rate per atom of U238, to the fission rate per atom of U235. The Relative Conversion Ratio (RCR) is defined as the ratio of the capture rate per ,atom of U238, to the fission rate per atom of U235, in the reactor fuel, relative to the corresponding ratio in a well thermalised neutron spectrum. A major aspect of these measurements was that the packs of foils were prepared at AEEW Winfrith, despatched to the USA for irradiation and returned to Winfrith for counting. This resulted in a considerable logistics problem but by good planning and the co-operation and diligence of all concerned this problem was overcome. However, the long distance involved inevitably meant that samples were not available for measurement until about 28 hours after the irradiation. It was therefore necessary to modify the techniques that are normally used in the Reactor Physics Division Counting Laboratory, where samples are normally available about two hours after shut-down. The techniques used and the results obtained are given below

  18. The transverse Poisson's ratio of composites.

    Science.gov (United States)

    Foye, R. L.

    1972-01-01

    An expression is developed that makes possible the prediction of Poisson's ratio for unidirectional composites with reference to any pair of orthogonal axes that are normal to the direction of the reinforcing fibers. This prediction appears to be a reasonable one in that it follows the trends of the finite element analysis and the bounding estimates, and has the correct limiting value for zero fiber content. It can only be expected to apply to composites containing stiff, circular, isotropic fibers bonded to a soft matrix material.

  19. Reference Priors For Non-Normal Two-Sample Problems

    NARCIS (Netherlands)

    Fernández, C.; Steel, M.F.J.

    1997-01-01

    The reference prior algorithm (Berger and Bernardo, 1992) is applied to locationscale models with any regular sampling density. A number of two-sample problems is analyzed in this general context, extending the dierence, ratio and product of Normal means problems outside Normality, while explicitly

  20. Theory of normal metals

    International Nuclear Information System (INIS)

    Mahan, G.D.

    1992-01-01

    The organizers requested that I give eight lectures on the theory of normal metals, ''with an eye on superconductivity.'' My job was to cover the general properties of metals. The topics were selected according to what the students would need to known for the following lectures on superconductivity. My role was to prepare the ground work for the later lectures. The problem is that there is not yet a widely accepted theory for the mechanism which pairs the electrons. Many mechanisms have been proposed, with those of phonons and spin fluctuations having the most followers. So I tried to discuss both topics. I also introduced the tight-binding model for metals, which forms the basis for most of the work on the cuprate superconductors

  1. Large Aspect Ratio Tokamak Study

    International Nuclear Information System (INIS)

    Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Wiseman, G.W.

    1980-06-01

    The Large Aspect Ratio Tokamak Study (LARTS) at Oak Ridge National Laboratory (ORNL) investigated the potential for producing a viable longburn tokamak reactor by enhancing the volt-second capability of the ohmic heating transformer through the use of high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were assessed in the context of extended burn operation. Using a one-dimensional transport code plasma startup and burn parameters were addressed. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the startup and shutdown portions of the tokamak cycle. A representative large aspect ratio tokamak with an aspect ratio of 8 was found to achieve a burn time of 3.5 h at capital cost only approx. 25% greater than that of a moderate aspect ratio design tokamak

  2. Sex Ratio Elasticity Influences the Selection of Sex Ratio Strategy

    Science.gov (United States)

    Wang, Yaqiang; Wang, Ruiwu; Li, Yaotang; (Sam) Ma, Zhanshan

    2016-12-01

    There are three sex ratio strategies (SRS) in nature—male-biased sex ratio, female-biased sex ratio and, equal sex ratio. It was R. A. Fisher who first explained why most species in nature display a sex ratio of ½. Consequent SRS theories such as Hamilton’s local mate competition (LMC) and Clark’s local resource competition (LRC) separately explained the observed deviations from the seemingly universal 1:1 ratio. However, to the best of our knowledge, there is not yet a unified theory that accounts for the mechanisms of the three SRS. Here, we introduce the price elasticity theory in economics to define sex ratio elasticity (SRE), and present an analytical model that derives three SRSs based on the following assumption: simultaneously existing competitions for both resources A and resources B influence the level of SRE in both sexes differently. Consequently, it is the difference (between two sexes) in the level of their sex ratio elasticity that leads to three different SRS. Our analytical results demonstrate that the elasticity-based model not only reveals a highly plausible mechanism that explains the evolution of SRS in nature, but also offers a novel framework for unifying two major classical theories (i.e., LMC & LRC) in the field of SRS research.

  3. Genes that bias Mendelian segregation.

    Science.gov (United States)

    Grognet, Pierre; Lalucque, Hervé; Malagnac, Fabienne; Silar, Philippe

    2014-01-01

    Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

  4. Genes that bias Mendelian segregation.

    Directory of Open Access Journals (Sweden)

    Pierre Grognet

    Full Text Available Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs, complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

  5. Holes at High Blowing Ratios

    Directory of Open Access Journals (Sweden)

    Phillip M. Ligrani

    1996-01-01

    Full Text Available Experimental results are presented which describe the development and structure of flow downstream of a single row of holes with compound angle orientations producing film cooling at high blowing ratios. This film cooling configuration is important because similar arrangements are frequently employed on the first stage of rotating blades of operating gas turbine engines. With this configuration, holes are spaced 6d apart in the spanwise direction, with inclination angles of 24 degrees, and angles of orientation of 50.5 degrees. Blowing ratios range from 1.5 to 4.0 and the ratio of injectant to freestream density is near 1.0. Results show that spanwise averaged adiabatic effectiveness, spanwise-averaged iso-energetic Stanton number ratios, surveys of streamwise mean velocity, and surveys of injectant distributions change by important amounts as the blowing ratio increases. This is due to injectant lift-off from the test surface just downstream of the holes.

  6. Deriving aerosol scattering ratio using range-resolved lidar ratio

    Indian Academy of Sciences (India)

    2014-02-13

    Feb 13, 2014 ... ratio (LDR) are used to suggest the type of aerosols. The altitude-dependent ... to the station and the experimentally measured lidar data. The 'model ... The integrated aerosol extinction profile with altitude-dependent S and k.

  7. RATIO_TOOL - SOFTWARE FOR COMPUTING IMAGE RATIOS

    Science.gov (United States)

    Yates, G. L.

    1994-01-01

    Geological studies analyze spectral data in order to gain information on surface materials. RATIO_TOOL is an interactive program for viewing and analyzing large multispectral image data sets that have been created by an imaging spectrometer. While the standard approach to classification of multispectral data is to match the spectrum for each input pixel against a library of known mineral spectra, RATIO_TOOL uses ratios of spectral bands in order to spot significant areas of interest within a multispectral image. Each image band can be viewed iteratively, or a selected image band of the data set can be requested and displayed. When the image ratios are computed, the result is displayed as a gray scale image. At this point a histogram option helps in viewing the distribution of values. A thresholding option can then be used to segment the ratio image result into two to four classes. The segmented image is then color coded to indicate threshold classes and displayed alongside the gray scale image. RATIO_TOOL is written in C language for Sun series computers running SunOS 4.0 and later. It requires the XView toolkit and the OpenWindows window manager (version 2.0 or 3.0). The XView toolkit is distributed with Open Windows. A color monitor is also required. The standard distribution medium for RATIO_TOOL is a .25 inch streaming magnetic tape cartridge in UNIX tar format. An electronic copy of the documentation is included on the program media. RATIO_TOOL was developed in 1992 and is a copyrighted work with all copyright vested in NASA. Sun, SunOS, and OpenWindows are trademarks of Sun Microsystems, Inc. UNIX is a registered trademark of AT&T Bell Laboratories.

  8. Rotator Cuff Strength Ratio and Injury in Glovebox Workers

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, Amelia M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-01-30

    Rotator cuff integrity is critical to shoulder health. Due to the high workload imposed upon the shoulder while working in an industrial glovebox, this study investigated the strength ratio of the rotator cuff muscles in glovebox workers and compared this ratio to the healthy norm. Descriptive statistics were collected using a short questionnaire. Handheld dynamometry was used to quantify the ratio of forces produced in the motions of shoulder internal and external rotation. Results showed this population to have shoulder strength ratios that were significantly different from the healthy norm. The deviation from the normal ratio demonstrates the need for solutions designed to reduce the workload on the rotator cuff musculature of glovebox workers in order to improve health and safety. Assessment of strength ratios can be used to screen for risk of symptom development.

  9. Short proofs of strong normalization

    OpenAIRE

    Wojdyga, Aleksander

    2008-01-01

    This paper presents simple, syntactic strong normalization proofs for the simply-typed lambda-calculus and the polymorphic lambda-calculus (system F) with the full set of logical connectives, and all the permutative reductions. The normalization proofs use translations of terms and types to systems, for which strong normalization property is known.

  10. High ratio recirculating gas compressor

    Science.gov (United States)

    Weinbrecht, J.F.

    1989-08-22

    A high ratio positive displacement recirculating rotary compressor is disclosed. The compressor includes an integral heat exchanger and recirculation conduits for returning cooled, high pressure discharge gas to the compressor housing to reducing heating of the compressor and enable higher pressure ratios to be sustained. The compressor features a recirculation system which results in continuous and uninterrupted flow of recirculation gas to the compressor with no direct leakage to either the discharge port or the intake port of the compressor, resulting in a capability of higher sustained pressure ratios without overheating of the compressor. 10 figs.

  11. Output factors and scatter ratios

    Energy Technology Data Exchange (ETDEWEB)

    Shrivastava, P N; Summers, R E; Samulski, T V; Baird, L C [Allegheny General Hospital, Pittsburgh, PA (USA); Ahuja, A S; Dubuque, G L; Hendee, W R; Chhabra, A S

    1979-07-01

    Reference is made to a previous publication on output factors and scatter ratios for radiotherapy units in which it was suggested that the output factor should be included in the definitions of scatter-air ratio and tissue-maximum ratio. In the present correspondence from other authors and from the authors of the previous publication, the original definitions and the proposed changes are discussed. Radiation scatter from source and collimator degradation of beam energy and calculation of dose in tissue are considered in relation to the objective of accurate dosimetry.

  12. Cerebral perfusion in homogeneity in normal volunteers

    International Nuclear Information System (INIS)

    Gruenwald, S.M.; Larcos, G.

    1998-01-01

    Full text: In the interpretation of cerebral perfusion scans, it is important to know the normal variation in perfusion which may occur between the cerebral hemispheres. For this reason 24 normal volunteers with no neurological or psychiatric history, and who were on no medications, had 99m Tc-HMPAO brain SPECT studies using a single headed gamma camera computer system. Oblique, coronal and sagittal images were reviewed separately by two experienced observers and any differences were resolved by consensus. Semi-quantitation was performed by summing two adjacent oblique slices and drawing right and left mirror image ROIs corresponding to the mid section level of anterior and posterior frontal lobes, anterior and posterior parietal lobes, temporal lobes and cerebellum. From the mean counts per pixel, right: left ROI ratios and ROI: cerebellar ratios were calculated. On qualitative review 6/24 subjects had mild asymmetry in tracer distribution between right and left cerebral lobes. Semi-quantitation revealed a 5-10% difference in counts between right and left ROIs in 12/24 subjects and an additional three subjects had 10-20% difference in counts between right and left temporal lobes. This study demonstrates the presence of mild asymmetry of cerebral perfusion in a significant minority of normal subjects

  13. Large aspect ratio tokamak study

    International Nuclear Information System (INIS)

    Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Sardella, C.; Wiseman, G.W.

    1979-01-01

    The Large Aspect Ratio Tokamak Study (LARTS) investigated the potential for producing a viable long burn tokamak reactor through enhanced volt-second capability of the ohmic heating transformer by employing high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were accessed in the context of extended burn operation. Plasma startup and burn parameters were addressed using a one-dimensional transport code. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the field in the ohmic heating coil and the wave shape of the ohmic heating discharge. A high aspect ratio reference reactor was chosen and configured

  14. Estimate of the therapeutic ratio for charged particle beams

    International Nuclear Information System (INIS)

    Phillips, T.S.; Goldstein, L.S.

    1980-01-01

    To establish the RBE in normal and tumor tissue of heavy ion beams, the dose response for normal tissues, tumors and hypoxic and euoxic cells in vitro to single fraction irradiation and their ability to recover has been studied. The data demonstrate that the therapeutic ratio (RBE in tumor/RBE in normal tissue) of the murine systems increases with increasing LET up to the LET of the peak of the modulated neon beam. Although the argon beam has some features which make it attractive for therapy, its application may be limited because of its unfavorable biological depth-dose distribution

  15. Arcjet nozzle area ratio effects

    Science.gov (United States)

    Curran, Francis M.; Sarmiento, Charles J.; Birkner, Bjorn W.; Kwasny, James

    1990-01-01

    An experimental investigation was conducted to determine the effect of nozzle area ratio on the operating characteristics and performance of a low power dc arcjet thruster. Conical thoriated tungsten nozzle inserts were tested in a modular laboratory arcjet thruster run on hydrogen/nitrogen mixtures simulating the decomposition products of hydrazine. The converging and diverging sides of the inserts had half angles of 30 and 20 degrees, respectively, similar to a flight type unit currently under development. The length of the diverging side was varied to change the area ratio. The nozzle inserts were run over a wide range of specific power. Current, voltage, mass flow rate, and thrust were monitored to provide accurate comparisons between tests. While small differences in performance were observed between the two nozzle inserts, it was determined that for each nozzle insert, arcjet performance improved with increasing nozzle area ratio to the highest area ratio tested and that the losses become very pronounced for area ratios below 50. These trends are somewhat different than those obtained in previous experimental and analytical studies of low Re number nozzles. It appears that arcjet performance can be enhanced via area ratio optimization.

  16. Arcjet Nozzle Area Ratio Effects

    Science.gov (United States)

    Curran, Francis M.; Sarmiento, Charles J.; Birkner, Bjorn W.; Kwasny, James

    1990-01-01

    An experimental investigation was conducted to determine the effect of nozzle area ratio on the operating characteristics and performance of a low power dc arcjet thruster. Conical thoriated tungsten nozzle inserts were tested in a modular laboratory arcjet thruster run on hydrogen/nitrogen mixtures simulating the decomposition products of hydrazine. The converging and diverging sides of the inserts had half angles of 30 and 20 degrees, respectively, similar to a flight type unit currently under development. The length of the diverging side was varied to change the area ratio. The nozzle inserts were run over a wide range of specific power. Current, voltage, mass flow rate, and thrust were monitored to provide accurate comparisons between tests. While small differences in performance were observed between the two nozzle inserts, it was determined that for each nozzle insert, arcjet performance improved with increasing nozzle area ratio to the highest area ratio tested and that the losses become very pronounced for area ratios below 50. These trends are somewhat different than those obtained in previous experimental and analytical studies of low Re number nozzles. It appears that arcjet performance can be enhanced via area ratio optimization.

  17. Association between Risk Factors and Overnight Albumin/Creatinine Ratio - even in its Normal Range

    DEFF Research Database (Denmark)

    Olivarius, Niels de Fine; Andreasen, A.H.; Mogensen, C.E.

    1994-01-01

    I denne lille artikel påvises det, at selv en ganske let forøget udskillelse af albumin i urinen forekommer hyppigere hos aldersdiabetikere med (andre) risikofaktorer såsom hypertension, hyperlipidæmi, hyperglykæmi etc. Udgivelsesdato: 1994...

  18. Person fit for test speededness: normal curvatures, likelihood ratio tests and empirical Bayes estimates

    NARCIS (Netherlands)

    Goegebeur, Y.; de Boeck, P.; Molenberghs, G.

    2010-01-01

    The local influence diagnostics, proposed by Cook (1986), provide a flexible way to assess the impact of minor model perturbations on key model parameters’ estimates. In this paper, we apply the local influence idea to the detection of test speededness in a model describing nonresponse in test data,

  19. Normal bone mineral content but unfavourable muscle/fat ratio in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Aksglaede, L.; Mølgaard, Christian; Skakkebaek, N.E.

    2008-01-01

    OBJECTIVE: To evaluate body composition and bone mineral content (BMC) in children and adolescents with Klinefelter syndrome (KS). DESIGN: Retrospective cross-sectional study. SETTING: Tertiary endocrine clinic at the University Hospital, Copenhagen. PATIENTS: Eighteen untreated boys with KS...

  20. Restrictions on the Ratio of Normal to Tangential Field Components in Magnetic Rubber Testing

    National Research Council Canada - National Science Library

    Burke, S. K; Ibrahim, M. E

    2007-01-01

    Magnetic Rubber Testing (MRT) is an extremely sensitive method for deteckng surface-breaking cracks in ferromagnetic materials, and is used extensively in critical inspections for D6ac steel components of the F-111 aircraft...

  1. Normalizing the causality between time series

    Science.gov (United States)

    Liang, X. San

    2015-08-01

    Recently, a rigorous yet concise formula was derived to evaluate information flow, and hence the causality in a quantitative sense, between time series. To assess the importance of a resulting causality, it needs to be normalized. The normalization is achieved through distinguishing a Lyapunov exponent-like, one-dimensional phase-space stretching rate and a noise-to-signal ratio from the rate of information flow in the balance of the marginal entropy evolution of the flow recipient. It is verified with autoregressive models and applied to a real financial analysis problem. An unusually strong one-way causality is identified from IBM (International Business Machines Corporation) to GE (General Electric Company) in their early era, revealing to us an old story, which has almost faded into oblivion, about "Seven Dwarfs" competing with a giant for the mainframe computer market.

  2. Robust Confidence Interval for a Ratio of Standard Deviations

    Science.gov (United States)

    Bonett, Douglas G.

    2006-01-01

    Comparing variability of test scores across alternate forms, test conditions, or subpopulations is a fundamental problem in psychometrics. A confidence interval for a ratio of standard deviations is proposed that performs as well as the classic method with normal distributions and performs dramatically better with nonnormal distributions. A simple…

  3. Albumin: Creatinine Ratio during long term Diabetes Mellitus in the ...

    African Journals Online (AJOL)

    Albumin: Creatinine Ratio during long term Diabetes Mellitus in the Assessment of early Nephropathy in Sudanese Population. ... Further studies with 24 hour urine sample are recommended for assessment of Microalbuminuria in long term Diabetic patients, provided that the patients are on a normal diet with regular ...

  4. Bicervical normal uterus with normal vagina | Okeke | Annals of ...

    African Journals Online (AJOL)

    To the best of our knowledge, only few cases of bicervical normal uterus with normal vagina exist in the literature; one of the cases had an anterior‑posterior disposition. This form of uterine abnormality is not explicable by the existing classical theory of mullerian anomalies and suggests that a complex interplay of events ...

  5. Incentive Ratios of Fisher Markets

    DEFF Research Database (Denmark)

    Chen, Ning; Deng, Xuaitue; Zhang, Hongyang

    2012-01-01

    In a Fisher market, a market maker sells m items to n potential buyers. The buyers submit their utility functions and money endowments to the market maker, who, upon receiving submitted information, derives market equilibrium prices and allocations of its items. While agents may benefit...... by misreporting their private information, we show that the percentage of improvement by a unilateral strategic play, called incentive ratio, is rather limited—it is less than 2 for linear markets and at most $e^{1/e}\\thickapprox 1.445$ for Cobb-Douglas markets. We further prove that both ratios are tight....

  6. Group normalization for genomic data.

    Science.gov (United States)

    Ghandi, Mahmoud; Beer, Michael A

    2012-01-01

    Data normalization is a crucial preliminary step in analyzing genomic datasets. The goal of normalization is to remove global variation to make readings across different experiments comparable. In addition, most genomic loci have non-uniform sensitivity to any given assay because of variation in local sequence properties. In microarray experiments, this non-uniform sensitivity is due to different DNA hybridization and cross-hybridization efficiencies, known as the probe effect. In this paper we introduce a new scheme, called Group Normalization (GN), to remove both global and local biases in one integrated step, whereby we determine the normalized probe signal by finding a set of reference probes with similar responses. Compared to conventional normalization methods such as Quantile normalization and physically motivated probe effect models, our proposed method is general in the sense that it does not require the assumption that the underlying signal distribution be identical for the treatment and control, and is flexible enough to correct for nonlinear and higher order probe effects. The Group Normalization algorithm is computationally efficient and easy to implement. We also describe a variant of the Group Normalization algorithm, called Cross Normalization, which efficiently amplifies biologically relevant differences between any two genomic datasets.

  7. Group normalization for genomic data.

    Directory of Open Access Journals (Sweden)

    Mahmoud Ghandi

    Full Text Available Data normalization is a crucial preliminary step in analyzing genomic datasets. The goal of normalization is to remove global variation to make readings across different experiments comparable. In addition, most genomic loci have non-uniform sensitivity to any given assay because of variation in local sequence properties. In microarray experiments, this non-uniform sensitivity is due to different DNA hybridization and cross-hybridization efficiencies, known as the probe effect. In this paper we introduce a new scheme, called Group Normalization (GN, to remove both global and local biases in one integrated step, whereby we determine the normalized probe signal by finding a set of reference probes with similar responses. Compared to conventional normalization methods such as Quantile normalization and physically motivated probe effect models, our proposed method is general in the sense that it does not require the assumption that the underlying signal distribution be identical for the treatment and control, and is flexible enough to correct for nonlinear and higher order probe effects. The Group Normalization algorithm is computationally efficient and easy to implement. We also describe a variant of the Group Normalization algorithm, called Cross Normalization, which efficiently amplifies biologically relevant differences between any two genomic datasets.

  8. Ventilation and ventilation/perfusion ratios

    International Nuclear Information System (INIS)

    Valind, S.O.

    1989-01-01

    The thesis is based on five different papers. The labelling of specific tracer compounds with positron emitting radionuclides enables a range of structural, physiological and biochemical parameters in the lung to be measured non-invasively, using positron emission tomography. This concept affords a unique opportunity for in vivo studies of different expressions of pulmonary pathophysiology at the regional level. The present thesis describes the application of positron emission tomography to the measurements of ventilation and ventilation/perfusion ratios using inert gas tracers, neon-19 and nitrogen-13 respectively. The validity of the methods applied was investigated with respect to the transport of inert gas tracers in the human lung. Both ventilation and the ventilation/perfusion ratio may be obtained with errors less than 10 % in the normal lung. In disease, however, errors may increase in those instances where the regional ventilation is very low or the intra-regional gas flow distribution is markedly nonuniform. A 2-3 fold increase in ventilation was demonstrated in normal nonsmoking subjects going from ventral to dorsal regions in the supine posture. These large regional differences could be well explained by the intrinsic elastic properties of lung tissue, considering the gravitational gradient in transpulmonary pressure. In asymptomatic smokers substantial regional ventilatroy abnormalities were found whilst the regional gas volume was similar in smokers and nonsmokers. The uncoupling between ventilation and gas volume probably reflects inflammatory changes in the airways. The regional differences in dV/dt/dQ/dt were relatively small and blood flow was largely matched to ventilation in the supine posture. However, small regions of lung with very low ventilation, unmatched by blood flow commonly exists in the most dependent parts of the lung in both smokers and nonsmokers. (29 illustrations, 7 tables, 113 references)

  9. Comparison of spectrum normalization techniques for univariate ...

    Indian Academy of Sciences (India)

    Laser-induced breakdown spectroscopy; univariate study; normalization models; stainless steel; standard error of prediction. Abstract. Analytical performance of six different spectrum normalization techniques, namelyinternal normalization, normalization with total light, normalization with background along with their ...

  10. Ratio Bias and Policy Preferences

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2016-01-01

    Numbers permeate modern political communication. While current scholarship on framing effects has focused on the persuasive effects of words and arguments, this article shows that framing of numbers can also substantially affect policy preferences. Such effects are caused by ratio bias, which...

  11. Global Carbon Reservoir Oxidative Ratios

    Science.gov (United States)

    Masiello, C. A.; Gallagher, M. E.; Hockaday, W. C.

    2010-12-01

    Photosynthesis and respiration move carbon and oxygen between the atmosphere and the biosphere at a ratio that is characteristic of the biogeochemical processes involved. This ratio is called the oxidative ratio (OR) of photosynthesis and respiration, and is defined as the ratio of moles of O2 per moles of CO2. This O2/CO2 ratio is a characteristic of biosphere-atmosphere gas fluxes, much like the 13C signature of CO2 transferred between the biosphere and the atmosphere has a characteristic signature. OR values vary on a scale of 0 (CO2) to 2 (CH4), with most ecosystem values clustered between 0.9 and 1.2. Just as 13C can be measured for both carbon fluxes and carbon pools, OR can also be measured for fluxes and pools and can provide information about the processes involved in carbon and oxygen cycling. OR values also provide information about reservoir organic geochemistry because pool OR values are proportional to the oxidation state of carbon (Cox) in the reservoir. OR may prove to be a particularly valuable biogeochemical tracer because of its ability to couple information about ecosystem gas fluxes with ecosystem organic geochemistry. We have developed 3 methods to measure the OR of ecosystem carbon reservoirs and intercalibrated them to assure that they yield accurate, intercomparable data. Using these tools we have built a large enough database of biomass and soil OR values that it is now possible to consider the implications of global patterns in ecosystem OR values. Here we present a map of the natural range in ecosystem OR values and begin to consider its implications. One striking pattern is an apparent offset between soil and biospheric OR values: soil OR values are frequently higher than that of their source biomass. We discuss this trend in the context of soil organic geochemistry and gas fluxes.

  12. Normal matter storage of antiprotons

    International Nuclear Information System (INIS)

    Campbell, L.J.

    1987-01-01

    Various simple issues connected with the possible storage of anti p in relative proximity to normal matter are discussed. Although equilibrium storage looks to be impossible, condensed matter systems are sufficiently rich and controllable that nonequilibrium storage is well worth pursuing. Experiments to elucidate the anti p interactions with normal matter are suggested. 32 refs

  13. The N'ormal Distribution

    Indian Academy of Sciences (India)

    An optimal way of choosing sample size in an opinion poll is indicated using the normal distribution. Introduction. In this article, the ubiquitous normal distribution is intro- duced as a convenient approximation for computing bino- mial probabilities for large values of n. Stirling's formula. • and DeMoivre-Laplace theorem ...

  14. Stopping-power ratios for dosimetry

    International Nuclear Information System (INIS)

    Andreo, P.

    1988-01-01

    The determination of the absorbed dose at a specified location in a medium irradiated with an electron or photon beam normally consists of two steps: (1) the determination of the mean absorbed dose to a detector by using a calibration factor or performing an absolute measurement, (2) the determination of the absorbed dose to the medium at the point of interest by calculations based on the knowledge of the absorbed dose to the detector and the different stopping and scattering properties of the medium and the detector material. When the influence of the detector is so small that the electron fluence in the medium is not modified, the ratio of the mass collision stopping power of the two materials accounts for the differences in energy deposition, and provides a conversion factor to relate the absorbed dose in both materials. Today, all national and international dosimetry protocols and codes of practice are based on such procedures, and the user easily can carry out these steps using tabulated data to convert a measured quantity to absorbed dose in the irradiated medium at the location of interest. Effects due to the spatial extension of the detector are taken into account using perturbation correction factors. The Monte Carlo method has become the most common and powerful calculational technique for determining the electron fluence (energy spectra) under different irradiation conditions. Cavity theory is then used to calculate stopping-power ratios. In this chapter, the different steps needed to evaluate s-ratios will be considered, emphasizing the different types of cavity-theory integrals and the Monte Carlo techniques used to derive the necessary electron spectra in the range of energies commonly used in radiation dosimetry, i.e., photon and electron beams with energies up to 50 MeV

  15. Internal combustion engine cylinder-to-cylinder balancing with balanced air-fuel ratios

    Science.gov (United States)

    Harris, Ralph E.; Bourn, Gary D.; Smalley, Anthony J.

    2006-01-03

    A method of balancing combustion among cylinders of an internal combustion engine. For each cylinder, a normalized peak firing pressure is calculated as the ratio of its peak firing pressure to its combustion pressure. Each cylinder's normalized peak firing pressure is compared to a target value for normalized peak firing pressure. The fuel flow is adjusted to any cylinder whose normalized peak firing pressure is not substantially equal to the target value.

  16. The human heart: application of the golden ratio and angle.

    Science.gov (United States)

    Henein, Michael Y; Zhao, Ying; Nicoll, Rachel; Sun, Lin; Khir, Ashraf W; Franklin, Karl; Lindqvist, Per

    2011-08-04

    The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. GUT Scale Fermion Mass Ratios

    International Nuclear Information System (INIS)

    Spinrath, Martin

    2014-01-01

    We present a series of recent works related to group theoretical factors from GUT symmetry breaking which lead to predictions for the ratios of quark and lepton Yukawa couplings at the unification scale. New predictions for the GUT scale ratios y μ /y s , y τ /y b and y t /y b in particular are shown and compared to experimental data. For this comparison it is important to include possibly large supersymmetric threshold corrections. Due to this reason the structure of the fermion masses at the GUT scale depends on TeV scale physics and makes GUT scale physics testable at the LHC. We also discuss how this new predictions might lead to predictions for mixing angles by discussing the example of the recently measured last missing leptonic mixing angle θ 13 making this new class of GUT models also testable in neutrino experiments

  18. Ratio Bias and Policy Preferences

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2017-01-01

    Numbers permeate modern political communication. While current scholarship on framing effects has focused on the persuasive effects of words and arguments, this article shows that framing of numbers can also substantially affect policy preferences. Such effects are caused by ratio bias, which...... is a general tendency to focus on numerators and pay insufficient attention to denominators in ratios. Using a population-based survey experiment, I demonstrate how differently framed but logically equivalent representations of the exact same numerical value can have large effects on citizens’ preferences...... regarding salient political issues such as education and taxes. Furthermore, the effects of numerical framing are found across most groups of the population, largely regardless of their political predisposition and their general ability to understand and use numerical information. These findings have...

  19. High aspect ratio spheromak experiments

    International Nuclear Information System (INIS)

    Robertson, S.; Schmid, P.

    1987-05-01

    The Reversatron RFP (R/a = 50cm/8cm) has been operated as an ohmically heated spheromak of high aspect ratio. We find that the dynamo can drive the toroidal field upward at rates as high as 10 6 G/sec. Discharges can be initiated and ramped upward from seed fields as low as 50 G. Small toroidal bias fields of either polarity (-0.2 < F < 0.2) do not significantly affect operation. 5 refs., 3 figs

  20. Determination of Optimum Compression Ratio: A Tribological Aspect

    Directory of Open Access Journals (Sweden)

    L. Yüksek

    2013-12-01

    Full Text Available Internal combustion engines are the primary energy conversion machines both in industry and transportation. Modern technologies are being implemented to engines to fulfill today's low fuel consumption demand. Friction energy consumed by the rubbing parts of the engines are becoming an important parameter for higher fuel efficiency. Rate of friction loss is primarily affected by sliding speed and the load acting upon rubbing surfaces. Compression ratio is the main parameter that increases the peak cylinder pressure and hence normal load on components. Aim of this study is to investigate the effect of compression ratio on total friction loss of a diesel engine. A variable compression ratio diesel engine was operated at four different compression ratios which were "12.96", "15:59", "18:03", "20:17". Brake power and speed was kept constant at predefined value while measuring the in- cylinder pressure. Friction mean effective pressure ( FMEP data were obtained from the in cylinder pressure curves for each compression ratio. Ratio of friction power to indicated power of the engine was increased from 22.83% to 37.06% with varying compression ratio from 12.96 to 20:17. Considering the thermal efficiency , FMEP and maximum in- cylinder pressure optimum compression ratio interval of the test engine was determined as 18.8 ÷ 19.6.

  1. Envera Variable Compression Ratio Engine

    Energy Technology Data Exchange (ETDEWEB)

    Charles Mendler

    2011-03-15

    Aggressive engine downsizing, variable compression ratio and use of the Atkinson cycle are being combined to improve fuel economy by up to 40 percent relative to port fuel injected gasoline engines, while maintaining full engine power. Approach Engine downsizing is viewed by US and foreign automobile manufacturers as one of the best options for improving fuel economy. While this strategy has already demonstrated a degree of success, downsizing and fuel economy gains are currently limited. With new variable compression ratio technology however, the degree of engine downsizing and fuel economy improvement can be greatly increased. A small variable compression ratio (VCR) engine has the potential to return significantly higher vehicle fuel economy while also providing high power. Affordability and potential for near term commercialization are key attributes of the Envera VCR engine. VCR Technology To meet torque and power requirements, a smaller engine needs to do more work per stroke. This is typically accomplished by boosting the incoming charge with either a turbo or supercharger so that more energy is present in the cylinder per stroke to do the work. With current production engines the degree of engine boosting (which correlates to downsizing) is limited by detonation (combustion knock) at high boost levels. Additionally, the turbo or supercharger needs to be responsive and efficient while providing the needed boost. VCR technology eliminates the limitation of engine knock at high load levels by reducing compression ratio to {approx}9:1 (or whatever level is appropriate) when high boost pressures are needed. By reducing the compression ratio during high load demand periods there is increased volume in the cylinder at top dead center (TDC) which allows more charge (or energy) to be present in the cylinder without increasing the peak pressure. Cylinder pressure is thus kept below the level at which the engine would begin to knock. When loads on the engine are low

  2. Quantitative structure activity relationships (QSAR) for binary mixtures at non-equitoxic ratios based on toxic ratios-effects curves.

    Science.gov (United States)

    Tian, Dayong; Lin, Zhifen; Yin, Daqiang

    2013-01-01

    The present study proposed a QSAR model to predict joint effects at non-equitoxic ratios for binary mixtures containing reactive toxicants, cyanogenic compounds and aldehydes. Toxicity of single and binary mixtures was measured by quantifying the decrease in light emission from the Photobacterium phosphoreum for 15 min. The joint effects of binary mixtures (TU sum) can thus be obtained. The results showed that the relationships between toxic ratios of the individual chemicals and their joint effects can be described by normal distribution function. Based on normal distribution equations, the joint effects of binary mixtures at non-equitoxic ratios ( [Formula: see text]) can be predicted quantitatively using the joint effects at equitoxic ratios ( [Formula: see text]). Combined with a QSAR model of [Formula: see text]in our previous work, a novel QSAR model can be proposed to predict the joint effects of mixtures at non-equitoxic ratios ( [Formula: see text]). The proposed model has been validated using additional mixtures other than the one used for the development of the model. Predicted and observed results were similar (p>0.05). This study provides an approach to the prediction of joint effects for binary mixtures at non-equitoxic ratios.

  3. Is this the right normalization? A diagnostic tool for ChIP-seq normalization.

    Science.gov (United States)

    Angelini, Claudia; Heller, Ruth; Volkinshtein, Rita; Yekutieli, Daniel

    2015-05-09

    Chip-seq experiments are becoming a standard approach for genome-wide profiling protein-DNA interactions, such as detecting transcription factor binding sites, histone modification marks and RNA Polymerase II occupancy. However, when comparing a ChIP sample versus a control sample, such as Input DNA, normalization procedures have to be applied in order to remove experimental source of biases. Despite the substantial impact that the choice of the normalization method can have on the results of a ChIP-seq data analysis, their assessment is not fully explored in the literature. In particular, there are no diagnostic tools that show whether the applied normalization is indeed appropriate for the data being analyzed. In this work we propose a novel diagnostic tool to examine the appropriateness of the estimated normalization procedure. By plotting the empirical densities of log relative risks in bins of equal read count, along with the estimated normalization constant, after logarithmic transformation, the researcher is able to assess the appropriateness of the estimated normalization constant. We use the diagnostic plot to evaluate the appropriateness of the estimates obtained by CisGenome, NCIS and CCAT on several real data examples. Moreover, we show the impact that the choice of the normalization constant can have on standard tools for peak calling such as MACS or SICER. Finally, we propose a novel procedure for controlling the FDR using sample swapping. This procedure makes use of the estimated normalization constant in order to gain power over the naive choice of constant (used in MACS and SICER), which is the ratio of the total number of reads in the ChIP and Input samples. Linear normalization approaches aim to estimate a scale factor, r, to adjust for different sequencing depths when comparing ChIP versus Input samples. The estimated scaling factor can easily be incorporated in many peak caller algorithms to improve the accuracy of the peak identification. The

  4. An experimental study on the normal stress of magnetorheological fluids

    International Nuclear Information System (INIS)

    Jiang, Jile; Tian, Yu; Ren, Dongxue; Meng, Yonggang

    2011-01-01

    The dependence of the normal stress on the shear rate and magnetic field strength in the shear flow of magnetorheological (MR) fluids has been studied experimentally. An obvious normal stress could be observed when the applied magnetic field was higher than a critical value. The normal stress increases considerably with increase of the shear rate and magnetic field, and decreases suddenly and significantly upon the onset of shear thickening in MR fluids. The ratio of shear stress to normal stress, an analogue of the friction coefficient, increases with increase of the shear rate, but decreases with increase of the applied magnetic field. Along with the shear stress, the normal stress in MR fluids could provide a more comprehensive understanding of the MR effect, and the evolution of the particle structure in shear flow, and may have important implications for preparing high performance magnetostrictive elastomers with high force output along the magnetic field direction

  5. Complete Normal Ordering 1: Foundations

    CERN Document Server

    Ellis, John; Skliros, Dimitri P.

    2016-01-01

    We introduce a new prescription for quantising scalar field theories perturbatively around a true minimum of the full quantum effective action, which is to `complete normal order' the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all `cephalopod' Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of `complete normal ordering' (which is an extension of the standard field theory definition of normal ordering) reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative i...

  6. The normal and pathological language

    OpenAIRE

    Espejo, Luis D.

    2014-01-01

    The extraordinary development of normal and pathological psychology has achieved in recent decades, thanks to the dual method of objective observation and oral survey enabled the researcher spirit of neuro-psychiatrist penetrate the intimate mechanism of the nervous system whose supreme manifestation is thought. It is normal psychology explaining the complicated game of perceptions: their methods of transmission, their centers of projection, its transformations and its synthesis to construct ...

  7. DPOAE generation dependence on primary frequencies ratio

    Science.gov (United States)

    Botti, Teresa; Sisto, Renata; Moleti, Arturo; D'Amato, Luisa; Sanjust, Filippo

    2015-12-01

    Two different mechanisms are responsible for the DPOAE generation. The nonlinear distortion wave-fixed mechanism generates the DPOAE Zero-Latency (ZL) component, as a backward traveling wave from the "overlap" region. Linear reflection of the forward DP wave (IDP) generates the DPOAE Long-Latency (LL) component through a place-fixed mechanism. ZL and LL components add up vectorially to generate the DPOAE recorded in the ear canal. The 2f1 - f2 and 2f2 - f1 DPOAE intensity depends on the stimulus level and on the primary frequency ratio r = f2/f1, where f1 and f2 are the primary stimuli frequencies. Here we study the behavior of the ZL and LL DPOAE components as a function of r by both numerical and laboratory experiments, measuring DPAOEs with an equal primary levels (L1 = L2) paradigm in the range [35, 75] dB SPL, with r ranging in [1.1, 1.45]. Numerical simulations of a nonlocal nonlinear model have been performed without cochlear roughness, to suppress the linear reflection mechanism. In this way the model solution at the base represents the DPOAE ZL component, and the solution at the corresponding DPOAE tonotopic place corresponds to the IDP. This technique has been not effectual to study the 2f2 - f1 DPOAE, as a consequence of its generation mechanism. While the 2f1 - f2 generation place is known to be the tonotopic place x(f2), the 2f2 - f1 DPOAE one has to be assumed basal to its corresponding reflection place. That is because ZL components generated in x(f2) cannot significantly pass through their resonant place. Moreover increasing the ratio r, 2f2 - f1 ZL and LL generation place approach each other, because the overlap region of primary tones decreases. Consequently, the distinction between the two places becomes complicated. DPOAEs have been measured in six young normal-hearing subjects. DPOAE ZL and LL components have been separated by a time-frequency filtering method based on the wavelet transform 1. due to their different phase gradient delay

  8. Is normal science good science?

    Directory of Open Access Journals (Sweden)

    Adrianna Kępińska

    2015-09-01

    Full Text Available “Normal science” is a concept introduced by Thomas Kuhn in The Structure of Scientific Revolutions (1962. In Kuhn’s view, normal science means “puzzle solving”, solving problems within the paradigm—framework most successful in solving current major scientific problems—rather than producing major novelties. This paper examines Kuhnian and Popperian accounts of normal science and their criticisms to assess if normal science is good. The advantage of normal science according to Kuhn was “psychological”: subjective satisfaction from successful “puzzle solving”. Popper argues for an “intellectual” science, one that consistently refutes conjectures (hypotheses and offers new ideas rather than focus on personal advantages. His account is criticized as too impersonal and idealistic. Feyerabend’s perspective seems more balanced; he argues for a community that would introduce new ideas, defend old ones, and enable scientists to develop in line with their subjective preferences. The paper concludes that normal science has no one clear-cut set of criteria encompassing its meaning and enabling clear assessment.

  9. nth roots of normal contractions

    International Nuclear Information System (INIS)

    Duggal, B.P.

    1992-07-01

    Given a complex separable Hilbert space H and a contraction A on H such that A n , n≥2 some integer, is normal it is shown that if the defect operator D A = (1 - A * A) 1/2 is of the Hilbert-Schmidt class, then A is similar to a normal contraction, either A or A 2 is normal, and if A 2 is normal (but A is not) then there is a normal contraction N and a positive definite contraction P of trace class such that parallel to A - N parallel to 1 = 1/2 parallel to P + P parallel to 1 (where parallel to · parallel to 1 denotes the trace norm). If T is a compact contraction such that its characteristics function admits a scalar factor, if T = A n for some integer n≥2 and contraction A with simple eigen-values, and if both T and A satisfy a ''reductive property'', then A is a compact normal contraction. (author). 16 refs

  10. Reproducibility of isotope ratio measurements

    International Nuclear Information System (INIS)

    Elmore, D.

    1981-01-01

    The use of an accelerator as part of a mass spectrometer has improved the sensitivity for measuring low levels of long-lived radionuclides by several orders of magnitude. However, the complexity of a large tandem accelerator and beam transport system has made it difficult to match the precision of low energy mass spectrometry. Although uncertainties for accelerator measured isotope ratios as low as 1% have been obtained under favorable conditions, most errors quoted in the literature for natural samples are in the 5 to 20% range. These errors are dominated by statistics and generally the reproducibility is unknown since the samples are only measured once

  11. GOLD and the fixed ratio

    Directory of Open Access Journals (Sweden)

    Vestbo J

    2012-09-01

    Full Text Available Jørgen VestboUniversity of Manchester, Manchester, UKI read with interest the paper entitled "Diagnosis of airway obstruction in the elderly: contribution of the SARA study" by Sorino et al in a recent issue of this journal.1 Being involved in the Global Initiative for Obstructive Lung Diseases (GOLD, it is nice to see the interest sparked by the GOLD strategy document. However, in the paper by Sorino et al, there are a few misunderstandings around GOLD and the fixed ratio (forced expiratory volume in 1 second/forced volume vital capacity < 0.70 that need clarification.View original paper by Sorino and colleagues.

  12. A likelihood ratio-based method to predict exact pedigrees for complex families from next-generation sequencing data.

    Science.gov (United States)

    Heinrich, Verena; Kamphans, Tom; Mundlos, Stefan; Robinson, Peter N; Krawitz, Peter M

    2017-01-01

    Next generation sequencing technology considerably changed the way we screen for pathogenic mutations in rare Mendelian disorders. However, the identification of the disease-causing mutation amongst thousands of variants of partly unknown relevance is still challenging and efficient techniques that reduce the genomic search space play a decisive role. Often segregation- or linkage analysis are used to prioritize candidates, however, these approaches require correct information about the degree of relationship among the sequenced samples. For quality assurance an automated control of pedigree structures and sample assignment is therefore highly desirable in order to detect label mix-ups that might otherwise corrupt downstream analysis. We developed an algorithm based on likelihood ratios that discriminates between different classes of relationship for an arbitrary number of genotyped samples. By identifying the most likely class we are able to reconstruct entire pedigrees iteratively, even for highly consanguineous families. We tested our approach on exome data of different sequencing studies and achieved high precision for all pedigree predictions. By analyzing the precision for varying degrees of relatedness or inbreeding we could show that a prediction is robust down to magnitudes of a few hundred loci. A java standalone application that computes the relationships between multiple samples as well as a Rscript that visualizes the pedigree information is available for download as well as a web service at www.gene-talk.de CONTACT: heinrich@molgen.mpg.deSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  13. Using Ratio Analysis to Evaluate Financial Performance.

    Science.gov (United States)

    Minter, John; And Others

    1982-01-01

    The ways in which ratio analysis can help in long-range planning, budgeting, and asset management to strengthen financial performance and help avoid financial difficulties are explained. Types of ratios considered include balance sheet ratios, net operating ratios, and contribution and demand ratios. (MSE)

  14. Normal Aging and Decision Making: The Role of Motivation

    Science.gov (United States)

    Depping, Miriam K.; Freund, Alexandra M.

    2011-01-01

    The main argument of this review is that motivational development associated with normal aging affects decision making. With increasing age, the ratio of gains to losses becomes more and more unfavorable. Reflecting the increasing losses in resources, goal orientation changes from a predominant orientation towards gains in young adulthood to an…

  15. Cereal Production Ratio and NDVI in Spain

    Science.gov (United States)

    Saa-Requejo, Antonio; Recuero, Laura; Palacios, Alicia; Díaz-Ambrona, Carlos G. H.; Tarquis, Ana M.

    2014-05-01

    Droughts are long-term phenomena affecting large regions causing significant damages both in human lives and economic losses. The use of remote sensing has proved to be very important in monitoring the growth of agricultural crops and trying to asses weather impact on crop loss. Several indices has been developed based in remote sensing data being one of them the normalized difference vegetation index (NDVI). In this study we have focus to know the correlation between NDVI data and the looses of rain fed cereal in the Spanish area where this crop is majority. For this propose data from drought damage in cereal come from the pool of agricultural insurance in Spain (AGROSEGURO) including 2007/2008 to 2011/2012 (five agricultural campaigns). This data is given as a ratio between drought party claims against the insured value of production aggregated at the agrarian region level. Medium resolution (500x500 m2) MODIS images were used during the same campaigns to estimate the eight-day composites NDVI at these locations. The NDVI values are accumulated following the normal cycle of the cereal taking in account the sowing date at different sites. At the same time, CORINE Land Cover (2006) was used to classify the pixels belonging to rain fed cereal use including a set of conditions such as pixels showing dry during summer, area in which there has been no change of use. Fallow presence is studied with particular attention as it imposes an inter annual variation between crop and bare soil and causes decreases in greenness in a pixel and mix both situations. This is more complex in the situation in which the avoid fallow and a continuous monoculture is performed. The results shown that around 40% of the area is subject to the regime of fallow while 60% have growing every year. In addition, another variation is detected if the year is humid (decrease of fallow) or dry (increase of fallow). The level of correlation between the drought damage ratios and cumulative NDVI for the

  16. Nearly Efficient Likelihood Ratio Tests of the Unit Root Hypothesis

    DEFF Research Database (Denmark)

    Jansson, Michael; Nielsen, Morten Ørregaard

    Seemingly absent from the arsenal of currently available "nearly efficient" testing procedures for the unit root hypothesis, i.e. tests whose local asymptotic power functions are indistinguishable from the Gaussian power envelope, is a test admitting a (quasi-)likelihood ratio interpretation. We...... show that the likelihood ratio unit root test derived in a Gaussian AR(1) model with standard normal innovations is nearly efficient in that model. Moreover, these desirable properties carry over to more complicated models allowing for serially correlated and/or non-Gaussian innovations....

  17. Precaval retropancreatic space: Normal anatomy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yeon Hee; Kim, Ki Whang; Kim, Myung Jin; Yoo, Hyung Sik; Lee, Jong Tae [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1992-07-15

    The authors defined precaval retropancreatic space as the space between pancreatic head with portal vein and IVC and analyzed the CT findings of this space to know the normal structures and size in this space. We evaluated 100 cases of normal abdominal CT scan to find out normal anatomic structures of precaval retropancreatic space retrospectively. We also measured the distance between these structures and calculated the minimum, maximum and mean values. At the splenoportal confluence level, normal structures between portal vein and IVC were vessel (21%), lymph node (19%), and caudate lobe of liver (2%) in order of frequency. The maximum AP diameter of portocaval lymph node was 4 mm. Common bile duct (CBD) was seen in 44% and the diameter was mean 3 mm and maximum 11 mm. CBD was located in extrapancreatic (75%) and lateral (60.6%) to pancreatic head. At IVC-left renal vein level, the maximum distance between CBD and IVC was 5 mm and the structure between posterior pancreatic surface and IVC was only fat tissue. Knowledge of these normal structures and measurement will be helpful in differentiating pancreatic mass with retropancreatic mass such as lymphadenopathy.

  18. Normal probability plots with confidence.

    Science.gov (United States)

    Chantarangsi, Wanpen; Liu, Wei; Bretz, Frank; Kiatsupaibul, Seksan; Hayter, Anthony J; Wan, Fang

    2015-01-01

    Normal probability plots are widely used as a statistical tool for assessing whether an observed simple random sample is drawn from a normally distributed population. The users, however, have to judge subjectively, if no objective rule is provided, whether the plotted points fall close to a straight line. In this paper, we focus on how a normal probability plot can be augmented by intervals for all the points so that, if the population distribution is normal, then all the points should fall into the corresponding intervals simultaneously with probability 1-α. These simultaneous 1-α probability intervals provide therefore an objective mean to judge whether the plotted points fall close to the straight line: the plotted points fall close to the straight line if and only if all the points fall into the corresponding intervals. The powers of several normal probability plot based (graphical) tests and the most popular nongraphical Anderson-Darling and Shapiro-Wilk tests are compared by simulation. Based on this comparison, recommendations are given in Section 3 on which graphical tests should be used in what circumstances. An example is provided to illustrate the methods. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. 3j Symbols: To Normalize or Not to Normalize?

    Science.gov (United States)

    van Veenendaal, Michel

    2011-01-01

    The systematic use of alternative normalization constants for 3j symbols can lead to a more natural expression of quantities, such as vector products and spherical tensor operators. The redefined coupling constants directly equate tensor products to the inner and outer products without any additional square roots. The approach is extended to…

  20. CT and MRI normal findings

    International Nuclear Information System (INIS)

    Moeller, T.B.; Reif, E.

    1998-01-01

    This book gives answers to questions frequently heard especially from trainees and doctors not specialising in the field of radiology: Is that a normal finding? How do I decide? What are the objective criteria? The information presented is three-fold. The normal findings of the usual CT and MRI examinations are shown with high-quality pictures serving as a reference, with inscribed important additional information on measures, angles and other criteria describing the normal conditions. These criteria are further explained and evaluated in accompanying texts which also teach the systematic approach for individual picture analysis, and include a check list of major aspects, as a didactic guide for learning. The book is primarily intended for students, radiographers, radiology trainees and doctors from other medical fields, but radiology specialists will also find useful details of help in special cases. (orig./CB) [de

  1. Marrow transfusions into normal recipients

    International Nuclear Information System (INIS)

    Brecher, G.

    1983-01-01

    During the past several years we have explored the transfusion of bone marrow into normal nonirradiated mice. While transfused marrow proliferates readily in irradiated animals, only minimal proliferation takes place in nonirradiated recipients. It has generally been assumed that this was due to the lack of available proliferative sites in recipients with normal marrow. Last year we were able to report that the transfusion of 200 million bone marrow cells (about 2/3 of the total complement of marrow cells of a normal mouse) resulted in 20% to 25% of the recipient's marrow being replaced by donor marrow. Thus we can now study the behavior of animals that have been transfused (donor) and endogenous (recipient) marrow cells, although none of the tissues of either donor or recipient have been irradiated. With these animals we hope to investigate the nature of the peculiar phenomenon of serial exhaustion of marrow, also referred to as the limited self-replicability of stem cells

  2. The construction of normal expectations

    DEFF Research Database (Denmark)

    Quitzau, Maj-Britt; Røpke, Inge

    2008-01-01

    The gradual upward changes of standards in normal everyday life have significant environmental implications, and it is therefore important to study how these changes come about. The intention of the article is to analyze the social construction of normal expectations through a case study. The case...... concerns the present boom in bathroom renovations in Denmark, which offers an excellent opportunity to study the interplay between a wide variety of consumption drivers and social changes pointing toward long-term changes of normal expectations regarding bathroom standards. The study is problemoriented...... and transdisciplinary and draws on a wide range of sociological, anthropological, and economic theories. The empirical basis comprises a combination of statistics, a review of magazine and media coverage, visits to exhibitions, and qualitative interviews. A variety of consumption drivers are identified. Among...

  3. Normalized cDNA libraries

    Science.gov (United States)

    Soares, Marcelo B.; Efstratiadis, Argiris

    1997-01-01

    This invention provides a method to normalize a directional cDNA library constructed in a vector that allows propagation in single-stranded circle form comprising: (a) propagating the directional cDNA library in single-stranded circles; (b) generating fragments complementary to the 3' noncoding sequence of the single-stranded circles in the library to produce partial duplexes; (c) purifying the partial duplexes; (d) melting and reassociating the purified partial duplexes to moderate Cot; and (e) purifying the unassociated single-stranded circles, thereby generating a normalized cDNA library.

  4. Random Generators and Normal Numbers

    OpenAIRE

    Bailey, David H.; Crandall, Richard E.

    2002-01-01

    Pursuant to the authors' previous chaotic-dynamical model for random digits of fundamental constants, we investigate a complementary, statistical picture in which pseudorandom number generators (PRNGs) are central. Some rigorous results are achieved: We establish b-normality for constants of the form $\\sum_i 1/(b^{m_i} c^{n_i})$ for certain sequences $(m_i), (n_i)$ of integers. This work unifies and extends previously known classes of explicit normals. We prove that for coprime $b,c>1$ the...

  5. Corticocortical feedback increases the spatial extent of normalization.

    Science.gov (United States)

    Nassi, Jonathan J; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T

    2014-01-01

    Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a "normalization pool." Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing.

  6. Corticocortical feedback increases the spatial extent of normalization

    Science.gov (United States)

    Nassi, Jonathan J.; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T.

    2014-01-01

    Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a “normalization pool.” Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing. PMID:24910596

  7. Aspect Ratio Scaling of Ideal No-wall Stability Limits in High Bootstrap Fraction Tokamak Plasmas

    International Nuclear Information System (INIS)

    Menard, J.E.; Bell, M.G.; Bell, R.E.; Gates, D.A.; Kaye, S.M.; LeBlanc, B.P.; Maingi, R.; Sabbagh, S.A.; Soukhanovskii, V.; Stutman, D.

    2003-01-01

    Recent experiments in the low aspect ratio National Spherical Torus Experiment (NSTX) [M. Ono et al., Nucl. Fusion 40 (2000) 557] have achieved normalized beta values twice the conventional tokamak limit at low internal inductance and with significant bootstrap current. These experimental results have motivated a computational re-examination of the plasma aspect ratio dependence of ideal no-wall magnetohydrodynamic stability limits. These calculations find that the profile-optimized no-wall stability limit in high bootstrap fraction regimes is well described by a nearly aspect ratio invariant normalized beta parameter utilizing the total magnetic field energy density inside the plasma. However, the scaling of normalized beta with internal inductance is found to be strongly aspect ratio dependent at sufficiently low aspect ratio. These calculations and detailed stability analyses of experimental equilibria indicate that the nonrotating plasma no-wall stability limit has been exceeded by as much as 30% in NSTX in a high bootstrap fraction regime

  8. Complete normal ordering 1: Foundations

    Directory of Open Access Journals (Sweden)

    John Ellis

    2016-08-01

    Full Text Available We introduce a new prescription for quantising scalar field theories (in generic spacetime dimension and background perturbatively around a true minimum of the full quantum effective action, which is to ‘complete normal order’ the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all ‘cephalopod’ Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of ‘complete normal ordering’ (which is an extension of the standard field theory definition of normal ordering reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative interactions, and by using a point splitting ‘trick’ we extend this result to theories with derivative interactions, such as those appearing as non-linear σ-models in the world-sheet formulation of string theory. We focus here on theories with trivial vacua, generalising the discussion to non-trivial vacua in a follow-up paper.

  9. Normal forms in Poisson geometry

    NARCIS (Netherlands)

    Marcut, I.T.

    2013-01-01

    The structure of Poisson manifolds is highly nontrivial even locally. The first important result in this direction is Conn's linearization theorem around fixed points. One of the main results of this thesis (Theorem 2) is a normal form theorem in Poisson geometry, which is the Poisson-geometric

  10. Mixed normal inference on multicointegration

    NARCIS (Netherlands)

    Boswijk, H.P.

    2009-01-01

    Asymptotic likelihood analysis of cointegration in I(2) models, see Johansen (1997, 2006), Boswijk (2000) and Paruolo (2000), has shown that inference on most parameters is mixed normal, implying hypothesis test statistics with an asymptotic 2 null distribution. The asymptotic distribution of the

  11. Is My Child's Appetite Normal?

    Science.gov (United States)

    Is My Child’s Appetite Normal? Cayla, who is 4 years old, did not finish her lunch. But she is ready to play. Her ... snack for later. That is okay! Your child’s appetite changes. Children do not grow as fast in ...

  12. Transforming Normal Programs by Replacement

    NARCIS (Netherlands)

    Bossi, Annalisa; Pettorossi, A.; Cocco, Nicoletta; Etalle, Sandro

    1992-01-01

    The replacement transformation operation, already defined in [28], is studied wrt normal programs. We give applicability conditions able to ensure the correctness of the operation wrt Fitting's and Kunen's semantics. We show how replacement can mimic other transformation operations such as thinning,

  13. Semigroups of data normalization functions

    NARCIS (Netherlands)

    Warrens, Matthijs J.

    2016-01-01

    Variable centering and scaling are functions that are typically used in data normalization. Various properties of centering and scaling functions are presented. It is shown that if we use two centering functions (or scaling functions) successively, the result depends on the order in which the

  14. Normalizing Catastrophe: Sustainability and Scientism

    Science.gov (United States)

    Bonnett, Michael

    2013-01-01

    Making an adequate response to our deteriorating environmental situation is a matter of ever increasing urgency. It is argued that a central obstacle to achieving this is the way that scientism has become normalized in our thinking about environmental issues. This is taken to reflect on an underlying "metaphysics of mastery" that vitiates proper…

  15. Neutron RBE for normal tissues

    International Nuclear Information System (INIS)

    Field, S.B.; Hornsey, S.

    1979-01-01

    RBE for various normal tissues is considered as a function of neutron dose per fraction. Results from a variety of centres are reviewed. It is shown that RBE is dependent on neutron energy and is tissue dependent, but is not specially high for the more critical tissues or for damage occurring late after irradiation. (author)

  16. Normal and abnormal growth plate

    International Nuclear Information System (INIS)

    Kumar, R.; Madewell, J.E.; Swischuk, L.E.

    1987-01-01

    Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities

  17. Log-Normality and Multifractal Analysis of Flame Surface Statistics

    Science.gov (United States)

    Saha, Abhishek; Chaudhuri, Swetaprovo; Law, Chung K.

    2013-11-01

    The turbulent flame surface is typically highly wrinkled and folded at a multitude of scales controlled by various flame properties. It is useful if the information contained in this complex geometry can be projected onto a simpler regular geometry for the use of spectral, wavelet or multifractal analyses. Here we investigate local flame surface statistics of turbulent flame expanding under constant pressure. First the statistics of local length ratio is experimentally obtained from high-speed Mie scattering images. For spherically expanding flame, length ratio on the measurement plane, at predefined equiangular sectors is defined as the ratio of the actual flame length to the length of a circular-arc of radius equal to the average radius of the flame. Assuming isotropic distribution of such flame segments we convolute suitable forms of the length-ratio probability distribution functions (pdfs) to arrive at corresponding area-ratio pdfs. Both the pdfs are found to be near log-normally distributed and shows self-similar behavior with increasing radius. Near log-normality and rather intermittent behavior of the flame-length ratio suggests similarity with dissipation rate quantities which stimulates multifractal analysis. Currently at Indian Institute of Science, India.

  18. Correspondence normalized ghost imaging on compressive sensing

    International Nuclear Information System (INIS)

    Zhao Sheng-Mei; Zhuang Peng

    2014-01-01

    Ghost imaging (GI) offers great potential with respect to conventional imaging techniques. It is an open problem in GI systems that a long acquisition time is be required for reconstructing images with good visibility and signal-to-noise ratios (SNRs). In this paper, we propose a new scheme to get good performance with a shorter construction time. We call it correspondence normalized ghost imaging based on compressive sensing (CCNGI). In the scheme, we enhance the signal-to-noise performance by normalizing the reference beam intensity to eliminate the noise caused by laser power fluctuations, and reduce the reconstruction time by using both compressive sensing (CS) and time-correspondence imaging (CI) techniques. It is shown that the qualities of the images have been improved and the reconstruction time has been reduced using CCNGI scheme. For the two-grayscale ''double-slit'' image, the mean square error (MSE) by GI and the normalized GI (NGI) schemes with the measurement number of 5000 are 0.237 and 0.164, respectively, and that is 0.021 by CCNGI scheme with 2500 measurements. For the eight-grayscale ''lena'' object, the peak signal-to-noise rates (PSNRs) are 10.506 and 13.098, respectively using GI and NGI schemes while the value turns to 16.198 using CCNGI scheme. The results also show that a high-fidelity GI reconstruction has been achieved using only 44% of the number of measurements corresponding to the Nyquist limit for the two-grayscale “double-slit'' object. The qualities of the reconstructed images using CCNGI are almost the same as those from GI via sparsity constraints (GISC) with a shorter reconstruction time. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  19. Chest Pain with Normal Thallium-201 Myocardial Perfusion Image – Is It Really Normal?

    Science.gov (United States)

    Liu, Pang-Yen; Lin, Wen-Yu; Lin, Li-Fan; Lin, Chin-Sheng; Lin, Wei-Shiang; Cheng, Shu-Meng; Yang, Shih-Ping; Liou, Jun-Ting

    2016-01-01

    Background Thallium-201 myocardial perfusion image (MPI) is commonly used to detect coronary artery disease in patients with chest pain. Although a normal thallium-201 MPI result is generally considered to be a good prognosis and further coronary angiogram is not recommended, there are still a few patients who suffer from unexpected acute coronary events. The aim of this study was to investigate the clinical prognosis in patients with normal thallium-201 MPI. Methods From January 2006 to August 2012, a total 22,003 patients undergoing thallium-201 MPI in one tertiary center were screened. Of these, 8092 patients had normal results and were investigated retrospectively. During follow-up, 54 patients underwent coronary angiogram because of refractory typical angina pectoris or unexpected acute coronary events. These 54 patients were divided into 2 groups: group I consisted of 26 (48.1%) patients with angiography-proven significant coronary artery stenosis, and group II consisted of 28 (51.9%) patients without significant stenosis. Results Patients in group I had a higher prevalence of prior coronary stenting and electrocardiographic features of ST depression compared with patients in group II. The multivariate analysis demonstrated that both prior coronary stenting and ST depression were risk predictors of unexpected acute coronary events in the patients with normal thallium-201 MPI [odds ratio (OR), 5.93; 95% confidence interval (CI): 1.03-34.06, p = 0.05 and OR, 7.10; 95% CI: 1.28-39.51, p = 0.03,respectively]. Conclusions Although there is a low incidence of unexpected acute coronary events in patients with chest pain and normal thallium-201 MPI, physicians should be aware of the potentials risk in certain patients in this specific population. PMID:27274174

  20. Isokinetic Hamstrings: Quadriceps Ratios in Intercollegiate Athletes.

    Science.gov (United States)

    Rosene, John M.; Fogarty, Tracey D.; Mahaffey, Brian L.

    2001-01-01

    Compared the differences in the concentric hamstrings to quadriceps (H:Q) ratio among athletes in different sports at three velocities. Measurement of H:Q ratio of both knees among male and female college athletes indicated that the H:Q ratio increased as velocity increased. No differences existed for the H:Q ratio for sport or side of body. (SM)

  1. RECENT TRENDS IN GENDER RATIO AT BIRTH IN HANGZHOU, CHINA.

    Science.gov (United States)

    Tang, L; Qiu, L Q; Yau, Kkw; Hui, Y V; Binns, C W; Lee, A H

    2015-12-01

    Higher than normal sex ratios at birth in China have been reported since the early 1980's. This study aimed to investigate recent trends in sex ratio at birth in Hangzhou, capital of Zhejiang Province in southeast China. Information on selected maternal and birth-related characteristics was extracted from the Hangzhou Birth Information Database for all pregnant women who delivered live births during 2005-2014. The sex ratios at birth were calculated after excluding infants with missing data on gender and those born with ambiguous genitalia. A total of 478,192 male births and 430,852 female births were recorded giving an overall ratio of 111.0. The sex ratio at birth was almost constant at around 110.7 during the period 2005-2008, followed by an increase to the peak at 113.1 in 2010 and then declined back to 109.6 in 2014. The gender ratio at birth in Hangzhou remained unbalanced for the past decade.

  2. Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults

    DEFF Research Database (Denmark)

    Bergholdt, Helle K M; Nordestgaard, Børge G; Varbo, Anette

    2015-01-01

    of Danish descent, aged 20-100 years, from three studies of the general population. Information on IHD (N = 10,372) and MI (N = 4188) were obtained from national Danish registries. First, we investigated observational associations between milk intake and incident IHD and MI. Second, we confirmed...... of 5.4 years, the observational hazard ratio for a 1 glass/week higher milk intake was 1.00 [95% confidence interval (CI): 1.00,1.01] for both IHD and MI. Median milk intake was 3 glasses/week (interquartile range: 0-7) in lactase CC non-persistent individuals compared with 5 glasses/week (0...

  3. Sacroiliac Joint/Sacrum Uptake Ratio Measured by Quantitative Sacroiliac Joint Scintigraphy

    International Nuclear Information System (INIS)

    Lee, Young Yiul; Park, Seon Yang; Lee, Myung Chul; Choi, Sang Jae; Cho, Bo Youn; Choe, Kang Won; Koh, Chang Soon

    1982-01-01

    To evaluate the diagnostic usefulness and significance of quantitative sacroiliac joint scintigraphy in the assessment of sacroiliitis, we measured Sacroiliac Joint/Sacrum Uptake Ratio (SIS Ratio) by region of interest (ROI) method using 99m Tc-methylene diphosphonate. The observed results were as follows:1) Using ROI method, the SIS ratios for the control group of 65 persons were 1.05±0.08 (left) and 1.06±0.07 (right) which were narrower in range than those of slice method (mean±S.D.) 2) The effects of age, gender and laterality on SIS ratio were not significant. 3) In left side, one of 6 patients with rheumatoid arthritis had SIS ratio in excess of 2 standard deviation of normal control group, and remainder had SIS ratios within normal limit. In right side, 3 patients had SIS ratios in excess of 2 standard deviation of normal control group, and remainder, within normal limit. 4) In both sacroiliac joint, 2 of 3 patients having sacroiliitis clinically with Reiter's syndrome whose pelvis A-P X-ray findings showed normal had high SIS ratios (left/right; 1.31/1.69, 1.90/1.80), but SIS ratio of one patient who bad no evidence of sacroiliitis clinically was within normal limit. 5) In 6 patients with ankylosing spondylitis in both sacroiliac joints, q whose pelvis A-P X-ray findings showed severe sclerotic change of sacroiliac pints had SIS ratio within normal limit or below that of normal control group, and SIS ratios of 2 patients whose pelvis A-P X-ray findings showed were increased. 6) 4 of 5 patients with low back pain of which cause could not be evaluated clinically and radiologically had SIS ratios in excess of that of normal control group. It would be concluded the quantitative sacroiliac joint scintigraphy is useful and sensitive screening method in the diagnosis as well as in the assessment clinical activity of sacroiliitis.

  4. Monocular and binocular development in children with albinism, infantile nystagmus syndrome, and normal vision.

    Science.gov (United States)

    Huurneman, Bianca; Boonstra, F Nienke

    2013-12-01

    To compare interocular acuity differences, crowding ratios, and binocular summation ratios in 4- to 8-year-old children with albinism (n = 16), children with infantile nystagmus syndrome (n = 10), and children with normal vision (n = 72). Interocular acuity differences and binocular summation ratios were compared between groups. Crowding ratios were calculated by dividing the single Landolt C decimal acuity with the crowded Landolt C decimal acuity mono- and binocularly. A linear regression analysis was conducted to investigate the contribution of 5 predictors to the monocular and binocular crowding ratio: nystagmus amplitude, nystagmus frequency, strabismus, astigmatism, and anisometropia. Crowding ratios were higher under mono- and binocular viewing conditions for children with infantile nystagmus syndrome than for children with normal vision. Children with albinism showed higher crowding ratios in their poorer eye and under binocular viewing conditions than children with normal vision. Children with albinism and children with infantile nystagmus syndrome showed larger interocular acuity differences than children with normal vision (0.1 logMAR in our clinical groups and 0.0 logMAR in children with normal vision). Binocular summation ratios did not differ between groups. Strabismus and nystagmus amplitude predicted the crowding ratio in the poorer eye (p = 0.015 and p = 0.005, respectively). The crowding ratio in the better eye showed a marginally significant relation with nystagmus frequency and depth of anisometropia (p = 0.082 and p = 0.070, respectively). The binocular crowding ratio was not predicted by any of the variables. Children with albinism and children with infantile nystagmus syndrome show larger interocular acuity differences than children with normal vision. Strabismus and nystagmus amplitude are significant predictors of the crowding ratio in the poorer eye.

  5. Superconducting versus normal conducting cavities

    CERN Document Server

    Podlech, Holger

    2013-01-01

    One of the most important issues of high-power hadron linacs is the choice of technology with respect to superconducting or room-temperature operation. The favour for a specific technology depends on several parameters such as the beam energy, beam current, beam power and duty factor. This contribution gives an overview of the comparison between superconducting and normal conducting cavities. This includes basic radiofrequency (RF) parameters, design criteria, limitations, required RF and plug power as well as case studies.

  6. Normal Movement Selectivity in Autism

    OpenAIRE

    Dinstein, Ilan; Thomas, Cibu; Humphreys, Kate; Minshew, Nancy; Behrmann, Marlene; Heeger, David J.

    2010-01-01

    It has been proposed that individuals with autism have difficulties understanding the goals and intentions of others because of a fundamental dysfunction in the mirror neuron system. Here, however, we show that individuals with autism exhibited not only normal fMRI responses in mirror system areas during observation and execution of hand movements, but also exhibited typical movement-selective adaptation (repetition suppression) when observing or executing the same movement repeatedly. Moveme...

  7. Normalization reduces intersubject variability in cervical vestibular evoked myogenic potentials.

    Science.gov (United States)

    van Tilburg, Mark J; Herrmann, Barbara S; Guinan, John J; Rauch, Steven D

    2014-09-01

    Cervical vestibular evoked myogenic potentials are used to assess saccular and inferior vestibular nerve function. Normalization of the VEMP waveform has been proposed to reduce the variability in vestibular evoked myogenic potentials by correcting for muscle activation. In this study, we test the hypothesis that normalization of the raw cervical VEMP waveform causes a significant decrease in the intersubject variability. Prospective cohort study. Large specialty hospital, department of otolaryngology. Twenty healthy subjects were used in this study. All subjects underwent cervical vestibular evoked myogenic potential testing using short tone bursts at 250, 500, 750, and 1,000 Hz. Both intersubject and intrasubject variability was assessed. Variability between raw and normalized peak-to-peak amplitudes was compared using the coefficient of variation. Intrasubject variability was assessed using the intraclass correlation coefficient and interaural asymmetry ratio. cVEMPs were present in most ears. Highest peak-to-peak amplitudes were recorded at 750 Hz. Normalization did not alter cVEMP tuning characteristics. Normalization of the cVEMP response caused a significant reduction in intersubject variability of the peak-to-peak amplitude. No significant change was seen in the intrasubject variability. Normalization significantly reduces cVEMP intersubject variability in healthy subjects without altering cVEMP characteristics. By reducing cVEMP amplitude variation due to nonsaccular, muscle-related factors, cVEMP normalization is expected to improve the ability to distinguish between healthy and pathologic responses in the clinical application of cVEMP testing.

  8. Correlates of lung/heart ratio of thallium-201 in coronary artery disease

    International Nuclear Information System (INIS)

    Homma, S.; Kaul, S.; Boucher, C.A.

    1987-01-01

    We studied 306 patients with chest pain (262 with coronary artery disease and 44 with no coronary artery disease) to determine which of 23 clinical, exercise, thallium, and angiographic variables best discriminate between patients with increased lung/heart ratios of thallium versus those with normal ratios. Normal lung/heart ratio values were defined using an additional 45 subjects with less than 1% probability of coronary artery disease. The number of diseased vessels was the best discriminator between patients with increased ratios versus those with normal ratios. Double product at peak exercise, number of segments with abnormal wall motion, patient gender, and duration of exercise were also significant discriminators. Using discriminant function analysis these variables could correctly identify 81% of cases with increased lung/heart ratios and 72% of cases with normal ratios. These results indicate that an increased lung/heart ratio of thallium reflects exercise-induced left ventricular dysfunction and affords a better understanding of why this thallium parameter is a powerful prognostic indicator in patients with chest pain

  9. Lithium control during normal operation

    International Nuclear Information System (INIS)

    Suryanarayan, S.; Jain, D.

    2010-01-01

    Periodic increases in lithium (Li) concentrations in the primary heat transport (PHT) system during normal operation are a generic problem at CANDU® stations. Lithiated mixed bed ion exchange resins are used at stations for pH control in the PHT system. Typically tight chemistry controls including Li concentrations are maintained in the PHT water. The reason for the Li increases during normal operation at CANDU stations such as Pickering was not fully understood. In order to address this issue a two pronged approach was employed. Firstly, PNGS-A data and information from other available sources was reviewed in an effort to identify possible factors that may contribute to the observed Li variations. Secondly, experimental studies were carried out to assess the importance of these factors in order to establish reasons for Li increases during normal operation. Based on the results of these studies, plausible mechanisms/reasons for Li increases have been identified and recommendations made for proactive control of Li concentrations in the PHT system. (author)

  10. Normalization of Gravitational Acceleration Models

    Science.gov (United States)

    Eckman, Randy A.; Brown, Aaron J.; Adamo, Daniel R.

    2011-01-01

    Unlike the uniform density spherical shell approximations of Newton, the con- sequence of spaceflight in the real universe is that gravitational fields are sensitive to the nonsphericity of their generating central bodies. The gravitational potential of a nonspherical central body is typically resolved using spherical harmonic approximations. However, attempting to directly calculate the spherical harmonic approximations results in at least two singularities which must be removed in order to generalize the method and solve for any possible orbit, including polar orbits. Three unique algorithms have been developed to eliminate these singularities by Samuel Pines [1], Bill Lear [2], and Robert Gottlieb [3]. This paper documents the methodical normalization of two1 of the three known formulations for singularity-free gravitational acceleration (namely, the Lear [2] and Gottlieb [3] algorithms) and formulates a general method for defining normalization parameters used to generate normalized Legendre Polynomials and ALFs for any algorithm. A treatment of the conventional formulation of the gravitational potential and acceleration is also provided, in addition to a brief overview of the philosophical differences between the three known singularity-free algorithms.

  11. "Ser diferente é normal?"/"Being different: is it normal?"

    Directory of Open Access Journals (Sweden)

    Viviane Veras

    2007-01-01

    Full Text Available A pergunta título deste trabalho retoma o slogan “Ser diferente é normal”, que é parte da campanha criada para uma organização não-governamental que atende portadores de Síndrome de Down. O objetivo é a inclusão social da pessoa com deficiência e o primeiro passo foi propor a inclusão de um grupo de diferentes no grupo dito normal. No vídeo de lançamento da campanha, o diferente, identificado como normal, é mostrado por meio de exemplos – um negro com cabelo black-power, um skin-head, um corpo tatuado, um corpo feminino halterofílico, uma família hippie, uma garota com síndrome de Down. A visão da adolescente dançando reduz, de certo modo, o efeito imaginário que vai além da síndrome, uma vez que apenas o corpo com seus olhinhos puxados se destacam, e não se interrogam questões cognitivas. Minha proposta é refletir sobre o estatuto paradoxal do exemplo, tal como é trabalhado nesse vídeo: se, por definição, um exemplo mostra de fato seu pertencimento a uma classe, pode-se concluir que é exatamente por ser exemplar que ele se encontra fora dela, no exato momento em que a exibe e define. The question in the title of this paper refers to the slogan "ser diferente é normal" ("It´s normal to be different", which is part of a campaign created for a NGO that supports people with Down syndrome. The objective of the campaign is to promote the social inclusion of individuals with Down syndrome, and the first step was to propose the inclusion of a group of "differents" in the so-called normal group. The film launching the campaign shows the different identified as normal by means of examples: a black man exhibiting blackpower haircut, a skin-head, a tattooed body, an over-athletic female body, a hippie family and a girl with Down syndrome. The vision of the dancing teenager lessens the imaginary effect that surpasses the syndrome, since only her body and her little oriental eyes stand out and no cognitive issues are

  12. Concentration ratio of radon progeny in air

    International Nuclear Information System (INIS)

    Kobayashi, Tsuneo

    2000-01-01

    Investigations have been made on the concentration ratio of radon progeny in air. Data have been acquired intermittently since 1988 using alpha spectroscopic method around the author's office that is located in the northeastern part of Japan. Clarifying the behavior of radon progeny is an issue of wide importance to radiation protection, predicting earthquakes, etc. Let Rabc=ECRn(RaA)/{ECRn(RaB) + ECRn(RaC)}; the concentration ratio, Rabc, is relevant to the stability of the air. Statistical and time series analyses indicated several interesting results. To examine the log-normal distribution, Lilliefors test was made for logarithm of outdoor data every one year. Rabc passed the test 6 times for 9 years, while Radon progeny passed 8 times. Outdoor data indicated that the value of Rabc was lower in the morning, in other world, the air was more stable in the morning than in the afternoon. To see the seasonal variation, one-way layout analysis was made for four groups of data, i.e., spring (March to May), summer (June to August), autumn (September to November), and winter (December to February). Rabc indicated significantly higher level in spring and winter, in other word, air was stable in summer and autumn. Time series analysis was made for various variables; power spectra were estimated with autoregressive model that is equivalent to maximum entropy method. Power spectrum for Rabc was most similar to that of wind speed. One-year period, that is always remarkable for radon progeny, was not significant for Rabc. Three- to nine-day periods were often seen for Rabc, radon progeny, wind speed, and atmospheric pressure. These several-day periods are probably attributed to the passage of air masses. Twenty-day to thirty-day peak may be attributed to meteorological phenomena corresponding to the rotation period of the sun. Temperature indicated no significant periodicity except overwhelming one-year period. Wind speed is well known to affect the radon progeny concentration

  13. Understanding a Normal Distribution of Data.

    Science.gov (United States)

    Maltenfort, Mitchell G

    2015-12-01

    Assuming data follow a normal distribution is essential for many common statistical tests. However, what are normal data and when can we assume that a data set follows this distribution? What can be done to analyze non-normal data?

  14. Quantiles for Finite Mixtures of Normal Distributions

    Science.gov (United States)

    Rahman, Mezbahur; Rahman, Rumanur; Pearson, Larry M.

    2006-01-01

    Quantiles for finite mixtures of normal distributions are computed. The difference between a linear combination of independent normal random variables and a linear combination of independent normal densities is emphasized. (Contains 3 tables and 1 figure.)

  15. [Ratio of erythrocyte and plasma in massive blood transfusion].

    Science.gov (United States)

    Wen, Xian-Hui; Liu, Feng-Xia; Zhang, Jun-Hua; Gui, Rong

    2014-06-01

    This study was purposed to explore the suitable ratio between fresh frozen plasma and erythrocyte by retrospective analysis of coagulation in patients with massive blood transfusion. The clinical data of 151 cases with massive blood transfusion from January 2011 to January 2013 were analyzed retrospectively. According to coagulation, patients were divided into coagulation normal group (138 cases) and coagulation dysfunction group (13 cases). Based on the ratio of 1:1 of fresh frozen plasma and erythrocyte, the patients were divided into high plasma group(2:1), medium plasma group (1:1) and low plasma (blood transfusion. The results showed that prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) were prolonged, fibrinogen (FIB) level decreased significantly (all P blood transfusion 24 h; the high plasma and the medium plasma group of coagulation normal group had no significant changes in coagulation (P > 0.05); prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen level in the medium plasma and low plasma subgroup of coagulation dysfunction group after massive transfusion was still in abnormal levels (P > 0.05), coagulation function in high plasma subgroup was improved significantly (P blood transfusion, the ratio between fresh frozen plasma and erythrocyte is recommended to be 2:1 in patients of coagulation dysfunction in order to improve the patient's coagulation function and to reduce the incidence of adverse event, the ratio of fresh frozen plasma to erythrocyte is recommended to be 1:1 in patients with normal coagulation so as to reduce the dilutional coagulopathy and hypervolemia of blood.

  16. Maternal serum ratio of ghrelin to obestatin decreased in preeclampsia.

    Science.gov (United States)

    Wu, Weiguang; Fan, Xiaobin; Yu, Yuecheng; Wang, Yingchun

    2015-10-01

    Ghrelin, an endogenous for the growth hormone secretagogue receptor, has been shown to participate in blood pressure regulation. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. We hypothesized that ghrelin/obestatin imbalance played a role in the pathogenesis. This study was designed to determine the alterations of ghrelin and obestatin concentrations and ghrelin/obestatin ratio in maternal serum in preeclampsia. This retrospective case-control study included 31 preeclampsia and 31 gestational week-matched normal pregnancies. Ghrelin and obestatin concentrations in maternal serum were determined by radioimmunoassay, and the ghrelin/obestatin ratio was calculated. The ghrelin concentration and ghrelin/obestatin ratio in maternal serum were significantly lower in preeclampsia than in normal pregnancies (214.34±14.27pg/mL vs 251.49±16.15pg/mL, P=0.041, 1.07±0.09 vs 0.82±0.08, P=0.023). The obestatin concentration in maternal serum was significantly higher in preeclampsia than in normal pregnancies (276.35±15.38pg/mL vs 223.53±18.61pg/mL, P=0.019). The systolic blood pressure in preeclampsia was negatively correlated with ghrelin concentration and ghrelin/obestatin ratio (r=-0.549, P=0.003; r=-0.491, P=0.004) and was positively correlated with obestatin concentrations in preeclampsia (r=0.388, P=0.013). The findings of this study suggested disturbance of ghrelin and obestatin in maternal serum in preeclampsia, and ghrelin/obestatin imbalance might play a role in the pathogenesis of preeclampsia. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  17. Plutonium isotope ratios in polychaete worms

    International Nuclear Information System (INIS)

    Beasley, T.M.; Fowler, S.W.

    1976-01-01

    Reference is made to recent reports that suggest that terrestrial and aquatic organisms may preferentially take up 238 Pu compared with sup(239+240)Pu. It is stated that although kinetic isotope effects are known to occur in biological systems for low mass number elements, such as H, C and N, such effects are generally discounted with higher mass numbers, and differences in the biological 'uptake' of isotopes of high mass number elements, such as those of Pu, are normally attributable to differences in the chemical or physical forms of the isotopes or to different quantities of isotopes available to organisms. This has been applied to explain differential Pu isotope behaviour in animals under controlled laboratory conditions, but it is not certain that it can be applied to explain anomalies of Pu isotope behaviour in organisms contaminated by nuclear test debris or by wastes from nuclear fuel reprocessing plants. Geochemical weathering may also have an effect. Described here are experiments in which it was found that deposit feeding marine worms living in sediments contaminated in different ways with Pu isotopes did not show preferential accumulation of 238 Pu. The worms had been exposed to different chemical and physical forms of the isotopes, including exposure to laboratory-labelled sediment, sediment collected from a former weapons test site, and sediment contaminated by wastes from a nuclear fuel reprocessing plant. The worms were allowed to accumulate Pu for times of 5 to 40 days. Isotope ratios were determined by α-spectrometric techniques. It is considered that the results are important for environmental samples where Pu activity levels are low. (U.K.)

  18. Measurement of normal auditory ossicles by high-resolusion CT with application of normal criteria to disease cases

    International Nuclear Information System (INIS)

    Hara, Jyoko

    1988-01-01

    The purposes of this study were to define criteria for the normal position of ossicles and to apply them in patients with rhinolaryngologically or pathologically confirmed diseases. Ossicles were measured on high-resolution CT images of 300 middle ears, including 241 normal ears and 59 diseased ears, in a total of 203 subjects. Angles A, B, and C to the baseline between the most lateral margins of bilateral internal auditory canals, and distance ratio b/a were defined as measurement items. Normal angles A, B, and C and distance ratio b/a ranged from 19 deg to 59 deg, 101 deg to 145 deg, 51 deg to 89 deg, and 0.49 to 0.51, respectively. Based on these criteria, all of these items were within the normal range in 30/34 (88.2 %) ears for otitis media and mastoiditis. One or more items showed far abnormal values (standard deviation; more than 3) in 5/7 (71.4 %) ears for cholesteatoma and 4/4 (100 %) ears for external ear anomaly. These normal measurements may aid in evaluating the position of auditory ossicles especially in the case of cholesteatoma and auditory ossicle abnormality. (Namekawa, K.)

  19. Measurement of normal auditory ossicles by high-resolusion CT with application of normal criteria to disease cases

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Jyoko

    1988-09-01

    The purposes of this study were to define criteria for the normal position of ossicles and to apply them in patients with rhinolaryngologically or pathologically confirmed diseases. Ossicles were measured on high-resolution CT images of 300 middle ears, including 241 normal ears and 59 diseased ears, in a total of 203 subjects. Angles A, B, and C to the baseline between the most lateral margins of bilateral internal auditory canals, and distance ratio b/a were defined as measurement items. Normal angles A, B, and C and distance ratio b/a ranged from 19 deg to 59 deg, 101 deg to 145 deg, 51 deg to 89 deg, and 0.49 to 0.51, respectively. Based on these criteria, all of these items were within the normal range in 30/34 (88.2 %) ears for otitis media and mastoiditis. One or more items showed far abnormal values (standard deviation; more than 3) in 5/7 (71.4 %) ears for cholesteatoma and 4/4 (100 %) ears for external ear anomaly. These normal measurements may aid in evaluating the position of auditory ossicles especially in the case of cholesteatoma and auditory ossicle abnormality. (Namekawa, K.).

  20. Confidence bounds and hypothesis tests for normal distribution coefficients of variation

    Science.gov (United States)

    Steve Verrill; Richard A. Johnson

    2007-01-01

    For normally distributed populations, we obtain confidence bounds on a ratio of two coefficients of variation, provide a test for the equality of k coefficients of variation, and provide confidence bounds on a coefficient of variation shared by k populations.

  1. Illumination normalization based on simplified local binary patterns for a face verification system

    NARCIS (Netherlands)

    Tao, Q.; Veldhuis, Raymond N.J.

    2007-01-01

    Illumination normalization is a very important step in face recognition. In this paper we propose a simple implementation of Local Binary Patterns, which effectively reduces the variability caused by illumination changes. In combination with a likelihood ratio classifier, this illumination

  2. Bowman Capsule Volume and Related Factors in Adults With Normal Renal Function

    Directory of Open Access Journals (Sweden)

    Takaya Sasaki

    2018-03-01

    Conclusion: In the normal adult kidney, there may be an optimal BV to GV ratio for maintaining effective filtration in a variety of clinical situations, including advanced age, obesity, and hypertension.

  3. A locally adaptive normal distribution

    DEFF Research Database (Denmark)

    Arvanitidis, Georgios; Hansen, Lars Kai; Hauberg, Søren

    2016-01-01

    entropy distribution under the given metric. The underlying metric is, however, non-parametric. We develop a maximum likelihood algorithm to infer the distribution parameters that relies on a combination of gradient descent and Monte Carlo integration. We further extend the LAND to mixture models......The multivariate normal density is a monotonic function of the distance to the mean, and its ellipsoidal shape is due to the underlying Euclidean metric. We suggest to replace this metric with a locally adaptive, smoothly changing (Riemannian) metric that favors regions of high local density...

  4. Normal pediatric postmortem CT appearances

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Willemijn M.; Bosboom, Dennis G.H.; Koopmanschap, Desiree H.J.L.M. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Nievelstein, Rutger A.J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Nikkels, Peter G.J. [University Medical Center Utrecht, Department of Pathology, Utrecht (Netherlands); Rijn, Rick R. van [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands)

    2015-04-01

    Postmortem radiology is a rapidly developing specialty that is increasingly used as an adjunct to or substitute for conventional autopsy. The goal is to find patterns of disease and possibly the cause of death. Postmortem CT images bring to light processes of decomposition most radiologists are unfamiliar with. These postmortem changes, such as the formation of gas and edema, should not be mistaken for pathological processes that occur in living persons. In this review we discuss the normal postmortem thoraco-abdominal changes and how these appear on CT images, as well as how to differentiate these findings from those of pathological processes. (orig.)

  5. Multispectral histogram normalization contrast enhancement

    Science.gov (United States)

    Soha, J. M.; Schwartz, A. A.

    1979-01-01

    A multispectral histogram normalization or decorrelation enhancement which achieves effective color composites by removing interband correlation is described. The enhancement procedure employs either linear or nonlinear transformations to equalize principal component variances. An additional rotation to any set of orthogonal coordinates is thus possible, while full histogram utilization is maintained by avoiding the reintroduction of correlation. For the three-dimensional case, the enhancement procedure may be implemented with a lookup table. An application of the enhancement to Landsat multispectral scanning imagery is presented.

  6. Normal modes and continuous spectra

    International Nuclear Information System (INIS)

    Balmforth, N.J.; Morrison, P.J.

    1994-12-01

    The authors consider stability problems arising in fluids, plasmas and stellar systems that contain singularities resulting from wave-mean flow or wave-particle resonances. Such resonances lead to singularities in the differential equations determining the normal modes at the so-called critical points or layers. The locations of the singularities are determined by the eigenvalue of the problem, and as a result, the spectrum of eigenvalues forms a continuum. They outline a method to construct the singular eigenfunctions comprising the continuum for a variety of problems

  7. Normal movement selectivity in autism.

    Science.gov (United States)

    Dinstein, Ilan; Thomas, Cibu; Humphreys, Kate; Minshew, Nancy; Behrmann, Marlene; Heeger, David J

    2010-05-13

    It has been proposed that individuals with autism have difficulties understanding the goals and intentions of others because of a fundamental dysfunction in the mirror neuron system. Here, however, we show that individuals with autism exhibited not only normal fMRI responses in mirror system areas during observation and execution of hand movements but also exhibited typical movement-selective adaptation (repetition suppression) when observing or executing the same movement repeatedly. Movement selectivity is a defining characteristic of neurons involved in movement perception, including mirror neurons, and, as such, these findings argue against a mirror system dysfunction in autism. Copyright 2010 Elsevier Inc. All rights reserved.

  8. A Librarian's Primer on Financial Ratios.

    Science.gov (United States)

    Kerbel, Sandra Sandor

    1982-01-01

    Explains in simple terms the nature and function of a number of basic types of business and industrial financial ratios. An annotated list of five basic sources for ratios is included and a reference list and bibliography are attached. (JL)

  9. Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals.

    Science.gov (United States)

    Nordestgaard, Ask Tybjærg; Nordestgaard, Børge Grønne

    2016-12-01

    Coffee has been associated with modestly lower risk of cardiovascular disease and all-cause mortality in meta-analyses; however, it is unclear whether these are causal associations. We tested first whether coffee intake is associated with cardiovascular disease and all-cause mortality observationally; second, whether genetic variations previously associated with caffeine intake are associated with coffee intake; and third, whether the genetic variations are associated with cardiovascular disease and all-cause mortality. First, we used multivariable adjusted Cox proportional hazard regression models evaluated with restricted cubic splines to examine observational associations in 95 366 White Danes. Second, we estimated mean coffee intake according to five genetic variations near the AHR (rs4410790; rs6968865) and CYP1A1/2 genes (rs2470893; rs2472297; rs2472299). Third, we used sex- and age adjusted Cox proportional hazard regression models to examine genetic associations with cardiovascular disease and all-cause mortality in 112 509 Danes. Finally, we used sex and age-adjusted logistic regression models to examine genetic associations with ischaemic heart disease including the Cardiogram and C4D consortia in a total of up to 223 414 individuals. We applied similar analyses to ApoE genotypes associated with plasma cholesterol levels, as a positive control. In observational analyses, we observed U-shaped associations between coffee intake and cardiovascular disease and all-cause mortality; lowest risks were observed in individuals with medium coffee intake. Caffeine intake allele score (rs4410790 + rs2470893) was associated with a 42% higher coffee intake. Hazard ratios per caffeine intake allele were 1.02 (95% confidence interval: 1.00-1.03) for ischaemic heart disease, 1.02 (0.99-1.02) for ischaemic stroke, 1.02 (1.00-1.03) for ischaemic vascular disease, 1.02 (0.99-1.06) for cardiovascular mortality and 1.01 (0.99-1.03) for all-cause mortality. Including

  10. Stable isotope ratios in hair and teeth reflect biologic rhythms.

    Directory of Open Access Journals (Sweden)

    Otto Appenzeller

    Full Text Available Biologic rhythms give insight into normal physiology and disease. They can be used as biomarkers for neuronal degenerations. We present a diverse data set to show that hair and teeth contain an extended record of biologic rhythms, and that analysis of these tissues could yield signals of neurodegenerations. We examined hair from mummified humans from South America, extinct mammals and modern animals and people, both healthy and diseased, and teeth of hominins. We also monitored heart-rate variability, a measure of a biologic rhythm, in some living subjects and analyzed it using power spectra. The samples were examined to determine variations in stable isotope ratios along the length of the hair and across growth-lines of the enamel in teeth. We found recurring circa-annual periods of slow and fast rhythms in hydrogen isotope ratios in hair and carbon and oxygen isotope ratios in teeth. The power spectra contained slow and fast frequency power, matching, in terms of normalized frequency, the spectra of heart rate variability found in our living subjects. Analysis of the power spectra of hydrogen isotope ratios in hair from a patient with neurodegeneration revealed the same spectral features seen in the patient's heart-rate variability. Our study shows that spectral analysis of stable isotope ratios in readily available tissues such as hair could become a powerful diagnostic tool when effective treatments and neuroprotective drugs for neurodegenerative diseases become available. It also suggests that similar analyses of archaeological specimens could give insight into the physiology of ancient people and animals.

  11. Update on normal tension glaucoma

    Directory of Open Access Journals (Sweden)

    Jyotiranjan Mallick

    2016-01-01

    Full Text Available Normal tension glaucoma (NTG is labelled when typical glaucomatous disc changes, visual field defects and open anterior chamber angles are associated with intraocular pressure (IOP constantly below 21 mmHg. Chronic low vascular perfusion, Raynaud's phenomenon, migraine, nocturnal systemic hypotension and over-treated systemic hypertension are the main causes of normal tension glaucoma. Goldmann applanation tonometry, gonioscopy, slit lamp biomicroscopy, optical coherence tomography and visual field analysis are the main tools of investigation for the diagnosis of NTG. Management follows the same principles of treatment for other chronic glaucomas: To reduce IOP by a substantial amount, sufficient to prevent disabling visual loss. Treatment is generally aimed to lower IOP by 30% from pre-existing levels to 12-14 mmHg. Betaxolol, brimonidine, prostaglandin analogues, trabeculectomy (in refractory cases, systemic calcium channel blockers (such as nifedipine and 24-hour monitoring of blood pressure are considered in the management of NTG. The present review summarises risk factors, causes, pathogenesis, diagnosis and management of NTG.

  12. Normal variation of hepatic artery

    International Nuclear Information System (INIS)

    Kim, Inn; Nam, Myung Hyun; Rhim, Hyun Chul; Koh, Byung Hee; Seo, Heung Suk; Kim, Soon Yong

    1987-01-01

    This study was an analyses of blood supply of the liver in 125 patients who received hepatic arteriography and abdominal aortography from Jan. 1984 to Dec. 1986 at the Department of Radiology of Hanyang University Hospital. A. Variations in extrahepatic arteries: 1. The normal extrahepatic artery pattern occurred in 106 of 125 cases (84.8%) ; Right hepatic and left hepatic arteries arising from the hepatic artery proper and hepatic artery proper arising from the common hepatic artery. 2. The most common type of variation of extrahepatic artery was replaced right hepatic artery from superior mesenteric artery: 6 of 125 cases (4.8%). B. Variations in intrahepatic arteries: 1. The normal intrahepatic artery pattern occurred in 83 of 125 cases (66.4%). Right hepatic and left hepatic arteries arising from the hepatic artery proper and middle hepatic artery arising from lower portion of the umbilical point of left hepatic artery. 2. The most common variation of intrahepatic arteries was middle hepatic artery. 3. Among the variation of middle hepatic artery; Right, middle and left hepatic arteries arising from the same location at the hepatic artery proper was the most common type; 17 of 125 cases (13.6%)

  13. Consumption of 125I labelled fibrinogen in normal subjects

    International Nuclear Information System (INIS)

    Langer, B.; Camargo, E.E.; Reis, J.M.M. dos; Carvalho, N.; Leao, L.E.P.

    1978-01-01

    The metabolism of iodine- 125 labeled human fibrinogen is studied by using three different sets of the radiopharmaceutical (0.9, 1.3 and 1.84 iodine atoms/fibrinogen molecule ratios) in 19 normal subjects. An aliquot of 40 μCi of fibrinogem- 125 I is injected in each subject, on normal dietary conditions and blood samples are withdrawn at 30, 60, 180, 36 and 720 minutes after the injection and, thereafter, one daily sample during 10 days. The compartmental distribution of the tracer is defined by plotting plasma and serum sample counts on a semilogarithmic graph paper. A rapid phase and 3 compartments are obtained. A 'rapid' consumption half-life and a 'real' consumption half-life are defined. The fibrinogen clottability is followed up to the last blood sample by checking the ratios of serum and plasma radioactivities [pt

  14. Contribution to the problem of liquidity ratios

    OpenAIRE

    Dvoøáèek Jaroslav

    1997-01-01

    The article is based on the importance of the financial analysis in mining industry. The author pays attention to liquidity ratios given in literature from the standpoint of their number, content, units and recommended quantity value of single ratios. For the application in practice two liquidity ratios are suggested and the methodology of their recommended values determination is given.

  15. Relationships between breath ratios, spirituality and health ...

    African Journals Online (AJOL)

    The aim of this retrospective, quantitative study was to investigate relationships between breath ratios, spirituality perceptions and health perceptions, with special reference to breath ratios that best predict optimal health and spirituality. Significant negative correlations were found between breath ratios and spirituality ...

  16. Contribution to the problem of liquidity ratios

    Directory of Open Access Journals (Sweden)

    Dvoøáèek Jaroslav

    1997-03-01

    Full Text Available The article is based on the importance of the financial analysis in mining industry. The author pays attention to liquidity ratios given in literature from the standpoint of their number, content, units and recommended quantity value of single ratios. For the application in practice two liquidity ratios are suggested and the methodology of their recommended values determination is given.

  17. Ventilation-perfusion distribution in normal subjects.

    Science.gov (United States)

    Beck, Kenneth C; Johnson, Bruce D; Olson, Thomas P; Wilson, Theodore A

    2012-09-01

    Functional values of LogSD of the ventilation distribution (σ(V)) have been reported previously, but functional values of LogSD of the perfusion distribution (σ(q)) and the coefficient of correlation between ventilation and perfusion (ρ) have not been measured in humans. Here, we report values for σ(V), σ(q), and ρ obtained from wash-in data for three gases, helium and two soluble gases, acetylene and dimethyl ether. Normal subjects inspired gas containing the test gases, and the concentrations of the gases at end-expiration during the first 10 breaths were measured with the subjects at rest and at increasing levels of exercise. The regional distribution of ventilation and perfusion was described by a bivariate log-normal distribution with parameters σ(V), σ(q), and ρ, and these parameters were evaluated by matching the values of expired gas concentrations calculated for this distribution to the measured values. Values of cardiac output and LogSD ventilation/perfusion (Va/Q) were obtained. At rest, σ(q) is high (1.08 ± 0.12). With the onset of ventilation, σ(q) decreases to 0.85 ± 0.09 but remains higher than σ(V) (0.43 ± 0.09) at all exercise levels. Rho increases to 0.87 ± 0.07, and the value of LogSD Va/Q for light and moderate exercise is primarily the result of the difference between the magnitudes of σ(q) and σ(V). With known values for the parameters, the bivariate distribution describes the comprehensive distribution of ventilation and perfusion that underlies the distribution of the Va/Q ratio.

  18. Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

    Science.gov (United States)

    Chen, Juanjuan; Khalil, Raouf A.

    2017-01-01

    Normal pregnancy is associated with marked hemodynamic and uterine changes that allow adequate uteroplacental blood flow and uterine expansion for the growing fetus. These pregnancy-associated changes involve significant uteroplacental and vascular remodeling. Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. Increases in MMP-2 and MMP-9 have been implicated in vasodilation, placentation and uterine expansion during normal pregnancy. The increases in MMPs could be induced by the increased production of estrogen and progesterone during pregnancy. MMP expression/activity may be altered during complications of pregnancy. Decreased vascular MMP-2 and MMP-9 may lead to decreased vasodilation, increased vasoconstriction, hypertensive pregnancy and preeclampsia. Abnormal expression of uteroplacental integrins, cytokines and MMPs may lead to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate remodeling of spiral arteries, and reduced uterine perfusion pressure (RUPP). RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, or stimulate the release of inflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could target MMPs in the extracellular matrix as well as endothelial and vascular smooth muscle cells, causing generalized vascular dysfunction, increased vasoconstriction and hypertension in pregnancy. MMP activity can also be altered by endogenous tissue inhibitors of metalloproteinases (TIMPs) and changes in the MMP/TIMP ratio. In addition to their vascular effects, decreases in expression/activity of MMP-2 and MMP-9 in the uterus could impede uterine growth and expansion and lead to premature labor. Understanding the role of MMPs in uteroplacental and

  19. On a radioimmunoassay ratio making the diagnosis of dysthyroidism easier

    International Nuclear Information System (INIS)

    Bresson, Y.; Marty, D.; Moullart, V.

    1982-01-01

    The offered ratio is a dimensionless number, independant of kits, or units and usually fluctuates around one. We obtain it by [TBGsub(m)/Tsub(4m)].[T 4 ]/[TBG] and, divided by a constant, it represents the first term of the development in series of the free thyroxin index mathematical expression from which it gives a nearly perfect value. Using this ratio the discrimination between eu- and hyperthyroidism is very apparent as well as the distinction between hypo and euthyroidism. The children from two to fifteen years of age and the women under hormonal contraception treatment show normal value. These results have been confirmed by a statistical investigation including 184 normal subjects, 76 hyperthyroid subjects without treatment, 18 euthyroid women under hormonal contraception treatment and 32 children from birth to fifteen years of age. It is conclued from this statistical investigation that the offered ratio is more accurate and more reliable as a mean of diagnosis than the free thyroxin index when calculated from the T3 uptake test [fr

  20. Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis.

    Science.gov (United States)

    Hartwig, Fernando Pires; Horta, Bernardo Lessa; Smith, George Davey; de Mola, Christian Loret; Victora, Cesar Gomes

    2016-10-01

    Milk intake has been associated with lower blood pressure (BP) in observational studies, and randomized controlled trials suggested that milk-derived tripeptides have BP-lowering effects. Milk intake has also been associated with body mass index (BMI). Nevertheless, it is unclear whether increasing milk consumption would reduce BP in the general population. We investigated the association of milk intake with obesity and BP using genetically-defined lactase persistence (LP) based on the rs4988235 polymorphism in a Mendelian randomization design in the 1982 Pelotas (Southern Brazil) Birth Cohort. These results were combined with published reports identified through a systematic review using meta-analysis. In the 1982 Pelotas Birth Cohort, milk intake was 42 [95% confidence interval (CI): 18; 67) ml/day higher in LP individuals. In conventional observational analysis, each 1-dl/day increase in milk intake was associated with -0.26 (95% CI: -0.33; -0.19) kg/m 2 in BMI and -0.31 (95% CI: -0.46; -0.16) and -0.35 (95% CI: -0.46; -0.23) mmHg in systolic and diastolic BP, respectively. These results were not corroborated when analysing LP status, but confidence intervals were large. In random effects meta-analysis, LP individuals presented higher BMI [0.17 (95% CI: 0.07; 0.27) kg/m 2 ] and higher odds of overweight-obesity [1.09 (95% CI: 1.02; 1.17)]. There were no reliable associations for BP. Our study supports that LP is positively associated with obesity, suggesting that the negative association of milk intake with obesity is likely due to limitations of conventional observational studies. Our findings also do not support that increased milk intake leads to lower BP. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  1. Normal aging and decision making: The role of motivation

    OpenAIRE

    Depping, Miriam K; Freund, Alexandra M

    2011-01-01

    The main argument of this review is that motivational development associated with normal aging affects decision making. With increasing age, the ratio of gains to losses becomes more and more unfavorable. Reflecting the increasing losses in resources, goal orientation changes from a predominant orientation towards gains in young adulthood to an increasingly stronger orientation towards the prevention of loss in older adulthood. As goals serve as reference points for the evaluation of decision...

  2. Is My Penis Normal? (For Teens)

    Science.gov (United States)

    ... Videos for Educators Search English Español Is My Penis Normal? KidsHealth / For Teens / Is My Penis Normal? Print en español ¿Es normal mi pene? ... any guy who's ever worried about whether his penis is a normal size. There's a fairly wide ...

  3. Normal vibrations in gallium arsenide

    International Nuclear Information System (INIS)

    Dolling, G.; Waugh, J.L.T.

    1964-01-01

    The triple axis crystal spectrometer at Chalk River has been used to observe coherent slow neutron scattering from a single crystal of pure gallium arsenide at 296 o K. The frequencies of normal modes of vibration propagating in the [ζ00], (ζζζ], and (0ζζ] crystal directions have been determined with a precision of between 1 and 2·5 per cent. A limited number of normal modes have also been studied at 95 and 184 o K. Considerable difficulty was experienced in obtaining welt resolved neutron peaks corresponding to the two non-degenerate optic modes for very small wave-vector, particularly at 296 o K. However, from a comparison of results obtained under various experimental conditions at several different points in reciprocal space, frequencies (units 10 12 c/s) for these modes (at 296 o K) have been assigned: T 8·02±0·08 and L 8·55±02. Other specific normal modes, with their measured frequencies are (a) (1,0,0): TO 7·56 ± 008, TA 2·36 ± 0·015, LO 7·22 ± 0·15, LA 6·80 ± 0·06; (b) (0·5, 0·5, 0·5): TO 7·84 ± 0·12, TA 1·86 ± 0·02, LO 7·15 ± 0·07, LA 6·26 ± 0·10; (c) (0, 0·65, 0·65): optic 8·08 ±0·13, 7·54 ± 0·12 and 6·57 ± 0·11, acoustic 5·58 ± 0·08, 3·42 · 0·06 and 2·36 ± 004. These results are generally slightly lower than the corresponding frequencies for germanium. An analysis in terms of various modifications of the dipole approximation model has been carried out. A feature of this analysis is that the charge on the gallium atom appears to be very small, about +0·04 e. The frequency distribution function has been derived from one of the force models. (author)

  4. Normal vibrations in gallium arsenide

    Energy Technology Data Exchange (ETDEWEB)

    Dolling, G; Waugh, J L T

    1964-07-01

    The triple axis crystal spectrometer at Chalk River has been used to observe coherent slow neutron scattering from a single crystal of pure gallium arsenide at 296{sup o}K. The frequencies of normal modes of vibration propagating in the [{zeta}00], ({zeta}{zeta}{zeta}], and (0{zeta}{zeta}] crystal directions have been determined with a precision of between 1 and 2{center_dot}5 per cent. A limited number of normal modes have also been studied at 95 and 184{sup o}K. Considerable difficulty was experienced in obtaining welt resolved neutron peaks corresponding to the two non-degenerate optic modes for very small wave-vector, particularly at 296{sup o}K. However, from a comparison of results obtained under various experimental conditions at several different points in reciprocal space, frequencies (units 10{sup 12} c/s) for these modes (at 296{sup o}K) have been assigned: T 8{center_dot}02{+-}0{center_dot}08 and L 8{center_dot}55{+-}02. Other specific normal modes, with their measured frequencies are (a) (1,0,0): TO 7{center_dot}56 {+-} 008, TA 2{center_dot}36 {+-} 0{center_dot}015, LO 7{center_dot}22 {+-} 0{center_dot}15, LA 6{center_dot}80 {+-} 0{center_dot}06; (b) (0{center_dot}5, 0{center_dot}5, 0{center_dot}5): TO 7{center_dot}84 {+-} 0{center_dot}12, TA 1{center_dot}86 {+-} 0{center_dot}02, LO 7{center_dot}15 {+-} 0{center_dot}07, LA 6{center_dot}26 {+-} 0{center_dot}10; (c) (0, 0{center_dot}65, 0{center_dot}65): optic 8{center_dot}08 {+-}0{center_dot}13, 7{center_dot}54 {+-} 0{center_dot}12 and 6{center_dot}57 {+-} 0{center_dot}11, acoustic 5{center_dot}58 {+-} 0{center_dot}08, 3{center_dot}42 {center_dot} 0{center_dot}06 and 2{center_dot}36 {+-} 004. These results are generally slightly lower than the corresponding frequencies for germanium. An analysis in terms of various modifications of the dipole approximation model has been carried out. A feature of this analysis is that the charge on the gallium atom appears to be very small, about +0{center_dot}04 e. The

  5. The impact of tissue Doppler index E/e' ratio on instantaneous wave-free ratio.

    Science.gov (United States)

    Arashi, Hiroyuki; Yamaguchi, Junichi; Ri, Tonre; Otsuki, Hisao; Nakao, Masashi; Kamishima, Kazuho; Jujo, Kentaro; Minami, Yuichiro; Ogawa, Hiroshi; Hagiwara, Nobuhisa

    2018-03-01

    The instantaneous wave-free ratio (iFR) is a vasodilator-free, invasive pressure wire index of the functional severity of coronary stenosis and is calculated under resting conditions. In a recent study, iFR was found to be more closely linked to coronary flow reserve (CFR) than fractional flow reserve (FFR). E/e' is a surrogate marker of left ventricular (LV) filling pressure and LV diastolic dysfunction. Coronary resting flow was found to be increased in patients with elevated E/e', and higher coronary resting flow was associated with lower CFR. Higher baseline coronary flow induces a greater loss of translesional pressure and may affect iFR. However, no reports have examined the impact of E/e' on iFR. The purpose of this study was to assess the relationship between iFR and E/e' compared with FFR. We retrospectively examined 103 consecutive patients (142 with stenosis) whose iFR, FFR, and E/e' were measured simultaneously. The mean age, LV mass index, and systolic blood pressure of patients with elevated E/e' were higher than those of patients with normal E/e'. Although no significant differences were observed in mean FFR values and % diameter stenosis, the mean iFR value in patients with elevated E/e' was significantly lower than that in patients with normal E/e'. The iFR was negatively correlated with E/e', while there was no correlation between FFR and E/e'. Multivariate analysis showed that E/e' and % diameter stenosis were independent determinants of iFR. E/e' ratio affects iFR values. Our results suggest that FFR mainly reflects the functional severity of the epicardial stenosis whereas iFR could potentially be influenced by not only epicardial stenosis but also other factors related to LV filling pressure or LV diastolic dysfunction. Further research is needed to understand the underlying mechanisms that influence the evaluation of iFR in patients with elevated E/e'. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights

  6. Application of Performance Ratios in Portfolio Optimization

    Directory of Open Access Journals (Sweden)

    Aleš Kresta

    2015-01-01

    Full Text Available The cornerstone of modern portfolio theory was established by pioneer work of Harry Markowitz. Based on his mean-variance framework, Sharpe formulated his well-known Sharpe ratio aiming to measure the performance of mutual funds. The contemporary development in computer’s computational power allowed to apply more complex performance ratios, which take into account also higher moments of return probability distribution. Although these ratios were proposed to help the investors to improve the results of portfolio optimization, we empirically demonstrated in our paper that this may not necessarily be true. On the historical dataset of DJIA components we empirically showed that both Sharpe ratio and MAD ratio outperformed Rachev ratio. However, for Rachev ratio we assumed only one level of parameters value. Different set-ups of parameters may provide different results and thus further analysis is certainly required.

  7. Poisson's ratio of fiber-reinforced composites

    Science.gov (United States)

    Christiansson, Henrik; Helsing, Johan

    1996-05-01

    Poisson's ratio flow diagrams, that is, the Poisson's ratio versus the fiber fraction, are obtained numerically for hexagonal arrays of elastic circular fibers in an elastic matrix. High numerical accuracy is achieved through the use of an interface integral equation method. Questions concerning fixed point theorems and the validity of existing asymptotic relations are investigated and partially resolved. Our findings for the transverse effective Poisson's ratio, together with earlier results for random systems by other authors, make it possible to formulate a general statement for Poisson's ratio flow diagrams: For composites with circular fibers and where the phase Poisson's ratios are equal to 1/3, the system with the lowest stiffness ratio has the highest Poisson's ratio. For other choices of the elastic moduli for the phases, no simple statement can be made.

  8. Striving for the unknown normal

    DEFF Research Database (Denmark)

    Nielsen, Mikka

    During the last decade, more and more people have received prescriptions for ADHD drug treatment, and simultaneously the legitimacy of the ADHD diagnosis has been heavily debated among both professionals and laymen. Based on an anthropological fieldwork among adults with ADHD, I illustrate how...... the ADHD diagnosis both answers and produces existential questions on what counts as normal behaviour and emotions. The diagnosis helps the diagnosed to identify, accept and handle problems by offering concrete explanations and solutions to diffuse experienced problems. But the diagnostic process...... is not only a clarifying procedure with a straight plan for treatment and direct effects. It is also a messy affair. In a process of experimenting with drugs and attempting to determine how or whether the medication eliminates the correct symptoms the diagnosed is put in an introspective, self...

  9. IIH with normal CSF pressures?

    Directory of Open Access Journals (Sweden)

    Soh Youn Suh

    2013-01-01

    Full Text Available Idiopathic intracranial hypertension (IIH is a condition of raised intracranial pressure (ICP in the absence of space occupying lesions. ICP is usually measured by lumbar puncture and a cerebrospinal fluid (CSF pressure above 250 mm H 2 O is one of the diagnostic criteria of IIH. Recently, we have encountered two patients who complained of headaches and exhibited disc swelling without an increased ICP. We prescribed acetazolamide and followed both patients frequently; because of the definite disc swelling with IIH related symptoms. Symptoms and signs resolved in both patients after they started taking acetazolamide. It is generally known that an elevated ICP, as measured by lumbar puncture, is the most important diagnostic sign of IIH. However, these cases caution even when CSF pressure is within the normal range, that suspicion should be raised when a patient has papilledema with related symptoms, since untreated papilledema may cause progressive and irreversible visual loss.

  10. Generating a normalized geometric liver model with warping

    International Nuclear Information System (INIS)

    Boes, J.L.; Weymouth, T.E.; Meyer, C.R.; Quint, L.E.; Bland, P.H.; Bookstein, F.L.

    1990-01-01

    This paper reports on the automated determination of the liver surface in abdominal CT scans for radiation treatment, surgery planning, and anatomic visualization. The normalized geometric model of the liver is generated by averaging registered outlines from a set of 15 studies of normal liver. The outlines have been registered with the use of thin-plate spline warping based on a set of five homologous landmarks. Thus, the model consists of an average of the surface and a set of five anatomic landmarks. The accuracy of the model is measured against both the set of studies used in model generation and an alternate set of 15 normal studies with use of, as an error measure, the ratio of nonoverlapping model and study volume to total model volume

  11. CT in normal pressure hydrocephalus

    International Nuclear Information System (INIS)

    Fujita, Katsuzo; Nogaki, Hidekazu; Noda, Masaya; Kusunoki, Tadaki; Tamaki, Norihiko

    1981-01-01

    CT scans were obtained on 33 patients (age 73y. to 31y.) with the diagnosis of normal pressure hydrocephalus. In each case, the diagnosis was made on the basis of the symptoms, CT and cisternographic findings. Underlying diseases of normal pressure hydrocephalus are ruptured aneurysms (21 cases), arteriovenous malformations (2 cases), head trauma (1 case), cerebrovascular accidents (1 case) and idiopathie (8 cases). Sixteen of 33 patients showed marked improvement, five, moderate or minimal improvement, and twelve, no change. The results were compared with CT findings and clinical response to shunting. CT findings were classified into five types, bases on the degree of periventricular hypodensity (P.V.H.), the extent of brain damage by underlying diseases, and the degree of cortical atrophy. In 17 cases of type (I), CT shows the presence of P.V.H. with or without minimal frontal lobe damage and no cortical atrophy. The good surgical improvements were achieved in all cases of type (I) by shunting. In 4 cases of type (II), CT shows the presence of P.V.H. and severe brain damage without cortical atrophy. The fair clinical improvements were achieved in 2 cases (50%) by shunting. In one case of type (III), CT shows the absence of P.V.H. without brain damage nor cortical atrophy. No clinical improvement was obtained by shunting in this type. In 9 cases of type (IV) with mild cortical atrophy, the fair clinical improvement was achieved in two cases (22%) and no improvement in 7 cases. In 2 cases of type (V) with moderate or marked cortical atrophy, no clinical improvement was obtained by shunting. In conclusion, it appeared from the present study that there was a good correlation between the result of shunting and the type of CT, and clinical response to shunting operation might be predicted by classification of CT findings. (author)

  12. PENGARUH PERUBAHAN RETURN ON ASSETS, PERUBAHAN DEBT TO EQUITY RATIO DAN PERUBAHAN CASH RATIO TERHADAP PERUBAHAN DIVIDEND PAYOUT RATIO

    Directory of Open Access Journals (Sweden)

    Yuli Soesetio

    2008-02-01

    Full Text Available Dividend Payout Ratio used to calculate all of revenue that will be accepted by stockholders as cash dividend, usually explained as percentage. This research was conducted to know several factors that affected change of Dividend Payout Ratio and to know the significance level and the correlation between dependent and independent variable. Analysis instrument used was parametric statistic. Based on the result of statistic test,  The Change of Return on Asset (X1, The Change of Debt to Equity Ratio (X2,  were able to explain dependent variable of the change Dividend Payout Ratio, and The Change of CashRatio can’t explain dependent variable of the change Dividend Payout Ratio

  13. Cerebrospinal fluid lactate and pyruvate concentrations and their ratio.

    Science.gov (United States)

    Zhang, Wan-Ming; Natowicz, Marvin R

    2013-05-01

    Determinations of cerebrospinal fluid (CSF) lactate and pyruvate concentrations and CSF lactate:pyruvate (L/P) ratios are important in several clinical settings, yet published normative data have significant limitations. We sought to determine a large dataset of stringently-defined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios. We evaluated data from 627 patients who had determinations of CSF lactate and/or CSF pyruvate from 2001 to 2011 at the Cleveland Clinic. Inclusion in the normal reference population required normal CSF cell counts, glucose and protein and routine serum chemistries and absence of progressive brain disorder, epilepsy, or seizure within 24h. Brain MRI, if done, showed no evidence of tumor, acute changes or basal ganglia abnormality. CSF cytology, CSF alanine and immunoglobulin levels, and oligoclonal band analysis were required to be normal, if done. Various inclusion/exclusion criteria were compared. 92 patients fulfilled inclusion/exclusion criteria for a reference population. The 95% central intervals (2.5%-97.5%) for CSF lactate and pyruvate levels were 1.01-2.09mM and 0.03-0.15mM, respectively, and 9.05-26.37 for CSF L/P. There were no significant gender-related differences of CSF lactate or pyruvate concentrations or of CSF L/P. Weak positive correlations between the concentration of CSF lactate or pyruvate and age were noted. Using stringent inclusion/exclusion criteria, we determined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios in a large, well-characterized reference population. Normalcy of routine CSF and blood analytes are the most important parameters in determining reference intervals for CSF lactate and pyruvate. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  14. Magnetic resonance imaging of the normal placenta

    International Nuclear Information System (INIS)

    Blaicher, Wibke; Brugger, Peter C.; Mittermayer, Christoph; Schwindt, Jens; Deutinger, Josef; Bernaschek, Gerhard; Prayer, Daniela

    2006-01-01

    The goal of this study was to provide a representative description of the normal placenta with contrast medium-free magnetic resonance imaging (MRI) in order to determine a standard of reference. One hundred consecutive singleton pregnancies were investigated by MRI without application of a contrast medium. The mean gestational age (GA) at the time of investigation was 29.5 weeks (range 19-40). Patients with suspected utero-placental insufficiency (UPI) or placental anomalies were excluded. Signal intensities were assessed and correlated with the respective GA. Antenatal MRI without contrast medium was able to depict placental status and morphological changes during gestation. A regular homogeneous structure was found in weeks 19-23. Subsequently, sporadic, slightly marked lobules appeared, which increased in number and markedness with ongoing gestation. Stratification of the lobules was observed after 36 weeks. The ratio of placental and amniotic fluid signal intensities decreased significantly with higher GA and with placental grading. MRI is well suited as an imaging method for the placenta. Our data may be used as a reference in the assessment of the placenta on MRI, and may have further clinical impact with respect to the determination of UPI

  15. Magnetic resonance imaging of the normal placenta

    Energy Technology Data Exchange (ETDEWEB)

    Blaicher, Wibke [Department of Gynecology and Obstetrics, University Hospital Vienna (Austria)]. E-mail: wibke.blaicher@meduniwien.ac.at; Brugger, Peter C. [Center of Anatomy and Cell Biology, University Hospital of Vienna (Austria); Mittermayer, Christoph [Department of Pediatrics, Division of Neonatology and Intensive Care, University Hospital of Vienna (Austria); Schwindt, Jens [Department of Pediatrics, Division of Neonatology and Intensive Care, University Hospital of Vienna (Austria); Deutinger, Josef [Department of Gynecology and Obstetrics, University Hospital Vienna (Austria); Bernaschek, Gerhard [Department of Gynecology and Obstetrics, University Hospital Vienna (Austria); Prayer, Daniela [Department of Radiology, Division of Neuroradiology, University Hospital of Vienna (Austria)

    2006-02-15

    The goal of this study was to provide a representative description of the normal placenta with contrast medium-free magnetic resonance imaging (MRI) in order to determine a standard of reference. One hundred consecutive singleton pregnancies were investigated by MRI without application of a contrast medium. The mean gestational age (GA) at the time of investigation was 29.5 weeks (range 19-40). Patients with suspected utero-placental insufficiency (UPI) or placental anomalies were excluded. Signal intensities were assessed and correlated with the respective GA. Antenatal MRI without contrast medium was able to depict placental status and morphological changes during gestation. A regular homogeneous structure was found in weeks 19-23. Subsequently, sporadic, slightly marked lobules appeared, which increased in number and markedness with ongoing gestation. Stratification of the lobules was observed after 36 weeks. The ratio of placental and amniotic fluid signal intensities decreased significantly with higher GA and with placental grading. MRI is well suited as an imaging method for the placenta. Our data may be used as a reference in the assessment of the placenta on MRI, and may have further clinical impact with respect to the determination of UPI.

  16. Normalized GNSS Interference Pattern Technique for Altimetry

    Directory of Open Access Journals (Sweden)

    Miguel Angel Ribot

    2014-06-01

    Full Text Available It is well known that reflected signals from Global Navigation Satellite Systems (GNSS can be used for altimetry applications, such as monitoring of water levels and determining snow height. Due to the interference of these reflected signals and the motion of satellites in space, the signal-to-noise ratio (SNR measured at the receiver slowly oscillates. The oscillation rate is proportional to the change in the propagation path difference between the direct and reflected signals, which depends on the satellite elevation angle. Assuming a known receiver position, it is possible to compute the distance between the antenna and the surface of reflection from the measured oscillation rate. This technique is usually known as the interference pattern technique (IPT. In this paper, we propose to normalize the measurements in order to derive an alternative model of the SNR variations. From this model, we define a maximum likelihood estimate of the antenna height that reduces the estimation time to a fraction of one period of the SNR variation. We also derive the Cramér–Rao lower bound for the IPT and use it to assess the sensitivity of different parameters to the estimation of the antenna height. Finally, we propose an experimental framework, and we use it to assess our approach with real GPS L1 C/A signals.

  17. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

    Science.gov (United States)

    Lotta, Luca A; Scott, Robert A; Sharp, Stephen J; Burgess, Stephen; Luan, Jian'an; Tillin, Therese; Schmidt, Amand F; Imamura, Fumiaki; Stewart, Isobel D; Perry, John R B; Marney, Luke; Koulman, Albert; Karoly, Edward D; Forouhi, Nita G; Sjögren, Rasmus J O; Näslund, Erik; Zierath, Juleen R; Krook, Anna; Savage, David B; Griffin, Julian L; Chaturvedi, Nishi; Hingorani, Aroon D; Khaw, Kay-Tee; Barroso, Inês; McCarthy, Mark I; O'Rahilly, Stephen; Wareham, Nicholas J; Langenberg, Claudia

    2016-11-01

    Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes.

  18. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis

    Science.gov (United States)

    Lotta, Luca A.; Scott, Robert A.; Luan, Jian’an; Tillin, Therese; Stewart, Isobel D.; Perry, John R. B.; Karoly, Edward D.; Forouhi, Nita G.; Zierath, Juleen R.; Savage, David B.; Griffin, Julian L.; Hingorani, Aroon D.; Khaw, Kay-Tee; O’Rahilly, Stephen; Langenberg, Claudia

    2016-01-01

    Background Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Methods and Findings Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26–1.65, p = 9.5 × 10−8) for isoleucine, 1.85 (95% CI 1.41–2.42, p = 7.3 × 10−6) for leucine, and 1.54 (95% CI 1.28–1.84, p = 4.2 × 10−6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. Conclusions Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the

  19. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

    Directory of Open Access Journals (Sweden)

    Luca A Lotta

    2016-11-01

    Full Text Available Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question.Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8. The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25, encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8 for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6 for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6 for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are

  20. Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals.

    Science.gov (United States)

    Bergholdt, Helle K M; Nordestgaard, Børge G; Ellervik, Christina

    2015-08-01

    High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown. We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically. In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence. Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight-obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally. High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification

  1. Monocular and binocular development in children with albinism, infantile nystagmus syndrome and normal vision

    NARCIS (Netherlands)

    Huurneman, B.; Boonstra, F.N.

    2013-01-01

    Background/aims: To compare interocular acuity differences, crowding ratios, and binocular summation ratios in 4- to 8-year-old children with albinism (n = 16), children with infantile nystagmus syndrome (n = 10), and children with normal vision (n = 72). Methods: Interocular acuity differences and

  2. Monocular and binocular development in children with albinism, infantile nystagmus syndrome, and normal vision

    NARCIS (Netherlands)

    Huurneman, B.; Boonstra, F.N.

    2013-01-01

    Abstract Background/aims: To compare interocular acuity differences, crowding ratios, and binocular summation ratios in 4- to 8-year-old children with albinism (n = 16), children with infantile nystagmus syndrome (n = 10), and children with normal vision (n = 72). Methods: Interocular acuity

  3. NCBI disease corpus: a resource for disease name recognition and concept normalization.

    Science.gov (United States)

    Doğan, Rezarta Islamaj; Leaman, Robert; Lu, Zhiyong

    2014-02-01

    Information encoded in natural language in biomedical literature publications is only useful if efficient and reliable ways of accessing and analyzing that information are available. Natural language processing and text mining tools are therefore essential for extracting valuable information, however, the development of powerful, highly effective tools to automatically detect central biomedical concepts such as diseases is conditional on the availability of annotated corpora. This paper presents the disease name and concept annotations of the NCBI disease corpus, a collection of 793 PubMed abstracts fully annotated at the mention and concept level to serve as a research resource for the biomedical natural language processing community. Each PubMed abstract was manually annotated by two annotators with disease mentions and their corresponding concepts in Medical Subject Headings (MeSH®) or Online Mendelian Inheritance in Man (OMIM®). Manual curation was performed using PubTator, which allowed the use of pre-annotations as a pre-step to manual annotations. Fourteen annotators were randomly paired and differing annotations were discussed for reaching a consensus in two annotation phases. In this setting, a high inter-annotator agreement was observed. Finally, all results were checked against annotations of the rest of the corpus to assure corpus-wide consistency. The public release of the NCBI disease corpus contains 6892 disease mentions, which are mapped to 790 unique disease concepts. Of these, 88% link to a MeSH identifier, while the rest contain an OMIM identifier. We were able to link 91% of the mentions to a single disease concept, while the rest are described as a combination of concepts. In order to help researchers use the corpus to design and test disease identification methods, we have prepared the corpus as training, testing and development sets. To demonstrate its utility, we conducted a benchmarking experiment where we compared three different

  4. An Intersection–Union Test for the Sharpe Ratio

    Directory of Open Access Journals (Sweden)

    Gabriel Frahm

    2018-04-01

    Full Text Available An intersection–union test for supporting the hypothesis that a given investment strategy is optimal among a set of alternatives is presented. It compares the Sharpe ratio of the benchmark with that of each other strategy. The intersection–union test takes serial dependence into account and does not presume that asset returns are multivariate normally distributed. An empirical study based on the G–7 countries demonstrates that it is hard to find significant results due to the lack of data, which confirms a general observation in empirical finance.

  5. Superconducting spin-triplet-MRAM with infinite magnetoresistance ratio

    Energy Technology Data Exchange (ETDEWEB)

    Lenk, Daniel; Ullrich, Aladin; Obermeier, Guenter; Mueller, Claus; Krug von Nidda, Hans-Albrecht; Horn, Siegfried; Tidecks, Reinhard [Institut fuer Physik, Universitaet Augsburg, D-86159 Augsburg (Germany); Morari, Roman [Institut fuer Physik, Universitaet Augsburg, D-86159 Augsburg (Germany); D. Ghitsu Institute of Electronic Engineering and Nanotechnologies ASM, Academiei Str. 3/3, MD2028 Kishinev (Moldova, Republic of); Solid State Physics Department, Kazan Federal University, 420008 Kazan (Russian Federation); Zdravkov, Vladimir I. [Institut fuer Physik, Universitaet Augsburg, D-86159 Augsburg (Germany); D. Ghitsu Institute of Electronic Engineering and Nanotechnologies ASM, Academiei Str. 3/3, MD2028 Kishinev (Moldova, Republic of); Institute of Applied Physics and Interdisciplinary Nanoscience Center, Universitaet Hamburg, Jungiusstrasse 9A, D-20355 Hamburg (Germany); Sidorenko, Anatoli S. [D. Ghitsu Institute of Electronic Engineering and Nanotechnologies ASM, Academiei Str. 3/3, MD2028 Kishinev (Moldova, Republic of); Tagirov, Lenar R. [Institut fuer Physik, Universitaet Augsburg, D-86159 Augsburg (Germany); Solid State Physics Department, Kazan Federal University, 420008 Kazan (Russian Federation)

    2016-07-01

    We fabricated a nanolayered hybrid superconductor-ferromagnet spin-valve structure, i.e. the superconducting transition temperature of this structure depends on its magnetic history. The observed spin-valve effect is based on the generation of the long range odd in frequency triplet component, arising from a non-collinear relative orientation of the constituent ferromagnetic layers. We investigated the effect both as a function of the sweep amplitude of the magnetic field, determining the magnetic history, and the applied transport current. Moreover, we demonstrate the possibility of switching the system from the normal o the superconducting state by applying field pulses, yielding an infinite magnetoresistance ratio.

  6. Sequential probability ratio controllers for safeguards radiation monitors

    International Nuclear Information System (INIS)

    Fehlau, P.E.; Coop, K.L.; Nixon, K.V.

    1984-01-01

    Sequential hypothesis tests applied to nuclear safeguards accounting methods make the methods more sensitive to detecting diversion. The sequential tests also improve transient signal detection in safeguards radiation monitors. This paper describes three microprocessor control units with sequential probability-ratio tests for detecting transient increases in radiation intensity. The control units are designed for three specific applications: low-intensity monitoring with Poisson probability ratios, higher intensity gamma-ray monitoring where fixed counting intervals are shortened by sequential testing, and monitoring moving traffic where the sequential technique responds to variable-duration signals. The fixed-interval controller shortens a customary 50-s monitoring time to an average of 18 s, making the monitoring delay less bothersome. The controller for monitoring moving vehicles benefits from the sequential technique by maintaining more than half its sensitivity when the normal passage speed doubles

  7. Deriving Light Interception and Biomass from Spectral Reflectance Ratio

    DEFF Research Database (Denmark)

    Christensen, Svend; Goudriaan, J.

    1993-01-01

    was calculated as the ratio between infrared (790–810 nm) and red (640–660 nm) reflectance. The cultivars form a different canopy structure. However, a regression analysis did not show any cultivar effect on the relation between RVI and fPAR The predicted fPAR from frequently measured RVI was used to calculate...... the product of daily fPAR and incoming PAR (cumulative PAR interception) in all spring barley cultivars grown in monoculture and in mixture with oil seed rape (Brassica napus). A regression analysis showed that the relation between cumulative intercepted PAR and total above ground biomass was the same in all...... monocultures and mixtures. The ratio α of incremental dry matter and intercepted PAR was normally 2.4 g MJ−1, but it declined below this value when temperatures fell below 12°C....

  8. Strain ratio measurement of femoral cartilage by real-time elastosonography: preliminary results

    International Nuclear Information System (INIS)

    Ipek, Ali; Unal, Ozlem; Kartal, Merve Gulbiz; Arslan, Halil; Isik, Cetin; Bozkurt, Murat

    2015-01-01

    The purpose of this study was to evaluate strain ratio measurement of femoral cartilage using real-time elastosonography. Twenty-five patients with femoral cartilage pathology on MRI (study group) were prospectively compared with 25 subjects with normal findings on MRI (control group) using real-time elastosonography. Strain ratio measurements of pathologic and normal cartilage were performed and compared, both within the study group and between the two groups. Elastosonography colour-scale coding showed a colour change from blue to red in pathologic cartilage and only blue colour-coding in normal cartilage. In the study group, the median strain ratio was higher in pathologic cartilage areas compared to normal areas (median, 1.49 [interquartile range, 0.80-2.53] vs. median, 0.01 [interquartile range, 0.01-0.01], p < 0.001, respectively). The median strain ratio of the control group was 0.01 (interquartile range, 0.01-0.01), and there was no significant difference compared to normal areas of the study group. There was, however, a significant difference between the control group cartilage and pathologic cartilage of the study group (p < 0.001). Elastosonography may be an effective, easily accessible, and relatively simple tool to demonstrate pathologic cartilage and to differentiate it from normal cartilage in the absence of advanced imaging facility such as MRI. (orig.)

  9. Urinary oxalate to creatinine ratios in healthy Turkish schoolchildren.

    Science.gov (United States)

    Dursun, Ismail; Çelik, İlknur; Poyrazoglu, Hakan M; Köse, Kader; Tanrıkulu, Esen; Sahin, Habibe; Yılmaz, Kenan; Öztürk, Ahmet; Yel, Sibel; Gündüz, Zübeyde; Düşünsel, Ruhan

    2017-11-01

    we aimed to establish reference values for urinary oxalate to creatinine ratios in healthy children aged 6-15 years and to investigate the relationship between their nutritional habits and oxalate excretion. Random urine specimens from 953 healthy children aged 6-15 years were obtained and analyzed for oxalate and creatinine. Additionally, a 24-h dietary recall form was prepared and given to them. The ingredient composition of the diet was calculated. The children were divided into three groups according to age: Group I (69 years, n = 353), Group II (10-12 years, n = 335), and Group III (13-15 years, n = 265). The 95th percentile of the oxalate to creatinine ratio for subjects aged 6-9, 10-12, and 13-15 years were 0.048, 0.042, and 0.042 mg/mg, respectively. The oxalate to creatinine ratio was significantly higher in Group 1 than in Group 2 and Group 3. Urinary oxalate excretion was positively correlated with increased protein intake and negatively correlated with age. A significant positive correlation was determined between urinary oxalate excretion and the proline, serine, protein, and glycine content of diet. Dietary proline intake showed a positive correlation with the urine oxalate to creatinine ratio and was found to be an independent predictor for urinary oxalate. These data lend support to the idea that every country should have its own normal reference values to determine the underlying metabolic risk factor for kidney stone disease since regional variation in the dietary intake of proteins and other nutrients can affect normal urinary excretion of oxalate.

  10. Discrimination of periodontal diseases using diffuse reflectance spectral intensity ratios

    Science.gov (United States)

    Chandra Sekhar, Prasanth; Betsy, Joseph; Presanthila, Janam; Subhash, Narayanan

    2012-02-01

    This clinical study was to demonstrate the applicability of diffuse reflectance (DR) intensity ratio R620/R575 in the quantification and discrimination of periodontitis and gingivitis from healthy gingiva. DR spectral measurements were carried out with white-light illumination from 70 healthy sites in 30 healthy volunteers, and 63 gingivitis- and 58 periodontitis-infected sites in 60 patients. Clinical parameters such as probing pocket depth, clinical attachment level, and gingival index were recorded in patient population. Diagnostic accuracies for discrimination of gingivitis and periodontitis from healthy gingiva were determined by comparison of spectral signatures with clinical parameters. Divergence of average DR spectral intensity ratio between control and test groups was studied using analysis of variance. The mean DR spectrum on normalization at 620 nm showed marked differences between healthy tissue, gingivitis, and periodontitis. Hemoglobin concentration and apparent SO2 (oxygen saturation) were also calculated for healthy, gingivitis, and periodontitis sites. DR spectral intensities at 545 and 575 nm showed a decreasing trend with progression of disease. Among the various DR intensity ratios studied, the R620/R575 ratio provided a sensitivity of 90% and specificity of 94% for discrimination of healthy tissues from gingivitis and a sensitivity of 91% and specificity of 100% for discrimination of gingivitis from periodontitis.

  11. What is ''normal aging brain for his/her age'' ? The first report

    International Nuclear Information System (INIS)

    Taki, Yasuyuki; Kinomura, Shigeo; Goto, Ryoi

    2005-01-01

    We evaluated the correlations between the gray matter volume, white matter volume and age, and determined normal aging brain for his/her age in every decade. We analyzed magnetic resonance images of the brain from 828 normal Japanese subjects. Significant negative correlation between the gray matter ratio (ratio of the gray matter volume in intracranial volume) and age was shown. From these results, we determined ''normal aging brain for his/her age'' and ''atrophied brain for his/her age'' in every decade. (author)

  12. Hubungan Analisis Ratio Keuangan dengan Kesehatan Perusahaan

    Directory of Open Access Journals (Sweden)

    Soekarso Soekarso

    2009-09-01

    Full Text Available In the business world, companies develop a vision and mission to improve welfare in the future. The work program the company is to achieve productivity and profitability. Finance in the company is one of the strategic functions that includes wealth management and transformation of added value (added value and also the control of corporate health. The financial statements such as balance sheet (balance sheet, profit and loss statement (income statement, and financial ratio (financial ratios, reflects the company's performance and health. Financial ratio analysis relates to the health of the company through a ratio of effectiveness, efficiency, productivity, profitability, liquidity, and solvability. Analysis shows that whenever actual value of financial ratios is above standard it means the company is healthy, and when the actual value of financial ratios is below the standard, it reversely means that companies are not healthy.

  13. Combining Ratio Estimation for Low Density Parity Check (LDPC) Coding

    Science.gov (United States)

    Mahmoud, Saad; Hi, Jianjun

    2012-01-01

    The Low Density Parity Check (LDPC) Code decoding algorithm make use of a scaled receive signal derived from maximizing the log-likelihood ratio of the received signal. The scaling factor (often called the combining ratio) in an AWGN channel is a ratio between signal amplitude and noise variance. Accurately estimating this ratio has shown as much as 0.6 dB decoding performance gain. This presentation briefly describes three methods for estimating the combining ratio: a Pilot-Guided estimation method, a Blind estimation method, and a Simulation-Based Look-Up table. The Pilot Guided Estimation method has shown that the maximum likelihood estimates of signal amplitude is the mean inner product of the received sequence and the known sequence, the attached synchronization marker (ASM) , and signal variance is the difference of the mean of the squared received sequence and the square of the signal amplitude. This method has the advantage of simplicity at the expense of latency since several frames worth of ASMs. The Blind estimation method s maximum likelihood estimator is the average of the product of the received signal with the hyperbolic tangent of the product combining ratio and the received signal. The root of this equation can be determined by an iterative binary search between 0 and 1 after normalizing the received sequence. This method has the benefit of requiring one frame of data to estimate the combining ratio which is good for faster changing channels compared to the previous method, however it is computationally expensive. The final method uses a look-up table based on prior simulated results to determine signal amplitude and noise variance. In this method the received mean signal strength is controlled to a constant soft decision value. The magnitude of the deviation is averaged over a predetermined number of samples. This value is referenced in a look up table to determine the combining ratio that prior simulation associated with the average magnitude of

  14. Normalization of emotion control scale

    Directory of Open Access Journals (Sweden)

    Hojatoolah Tahmasebian

    2014-09-01

    Full Text Available Background: Emotion control skill teaches the individuals how to identify their emotions and how to express and control them in various situations. The aim of this study was to normalize and measure the internal and external validity and reliability of emotion control test. Methods: This standardization study was carried out on a statistical society, including all pupils, students, teachers, nurses and university professors in Kermanshah in 2012, using Williams’ emotion control scale. The subjects included 1,500 (810 females and 690 males people who were selected by stratified random sampling. Williams (1997 emotion control scale, was used to collect the required data. Emotional Control Scale is a tool for measuring the degree of control people have over their emotions. This scale has four subscales, including anger, depressed mood, anxiety and positive affect. The collected data were analyzed by SPSS software using correlation and Cronbach's alpha tests. Results: The results of internal consistency of the questionnaire reported by Cronbach's alpha indicated an acceptable internal consistency for emotional control scale, and the correlation between the subscales of the test and between the items of the questionnaire was significant at 0.01 confidence level. Conclusion: The validity of emotion control scale among the pupils, students, teachers, nurses and teachers in Iran has an acceptable range, and the test itemswere correlated with each other, thereby making them appropriate for measuring emotion control.

  15. Digital Pupillometry in Normal Subjects

    Science.gov (United States)

    Rickmann, Annekatrin; Waizel, Maria; Kazerounian, Sara; Szurman, Peter; Wilhelm, Helmut; Boden, Karl T.

    2017-01-01

    ABSTRACT The aim of this study was to evaluate the pupil size of normal subjects at different illumination levels with a novel pupillometer. The pupil size of healthy study participants was measured with an infrared-video PupilX pupillometer (MEye Tech GmbH, Alsdorf, Germany) at five different illumination levels (0, 0.5, 4, 32, and 250 lux). Measurements were performed by the same investigator. Ninety images were executed during a measurement period of 3 seconds. The absolute linear camera resolution was approximately 20 pixels per mm. This cross-sectional study analysed 490 eyes of 245 subjects (mean age: 51.9 ± 18.3 years, range: 6–87 years). On average, pupil diameter decreased with increasing light intensities for both eyes, with a mean pupil diameter of 5.39 ± 1.04 mm at 0 lux, 5.20 ± 1.00 mm at 0.5 lux, 4.70 ± 0.97 mm at 4 lux, 3.74 ± 0.78 mm at 32 lux, and 2.84 ± 0.50 mm at 250 lux illumination. Furthermore, it was found that anisocoria increased by 0.03 mm per life decade for all illumination levels (R2 = 0.43). Anisocoria was higher under scotopic and mesopic conditions. This study provides additional information to the current knowledge concerning age- and light-related pupil size and anisocoria as a baseline for future patient studies. PMID:28228832

  16. Normal modes of Bardeen discs

    International Nuclear Information System (INIS)

    Verdaguer, E.

    1983-01-01

    The short wavelength normal modes of self-gravitating rotating polytropic discs in the Bardeen approximation are studied. The discs' oscillations can be seen in terms of two types of modes: the p-modes whose driving forces are pressure forces and the r-modes driven by Coriolis forces. As a consequence of differential rotation coupling between the two takes place and some mixed modes appear, their properties can be studied under the assumption of weak coupling and it is seen that they avoid the crossing of the p- and r-modes. The short wavelength analysis provides a basis for the classification of the modes, which can be made by using the properties of their phase diagrams. The classification is applied to the large wavelength modes of differentially rotating discs with strong coupling and to a uniformly rotating sequence with no coupling, which have been calculated in previous papers. Many of the physical properties and qualitative features of these modes are revealed by the analysis. (author)

  17. Eccentric crank variable compression ratio mechanism

    Science.gov (United States)

    Lawrence, Keith Edward [Kobe, JP; Moser, William Elliott [Peoria, IL; Roozenboom, Stephan Donald [Washington, IL; Knox, Kevin Jay [Peoria, IL

    2008-05-13

    A variable compression ratio mechanism for an internal combustion engine that has an engine block and a crankshaft is disclosed. The variable compression ratio mechanism has a plurality of eccentric disks configured to support the crankshaft. Each of the plurality of eccentric disks has at least one cylindrical portion annularly surrounded by the engine block. The variable compression ratio mechanism also has at least one actuator configured to rotate the plurality of eccentric disks.

  18. Cy5 total protein normalization in Western blot analysis.

    Science.gov (United States)

    Hagner-McWhirter, Åsa; Laurin, Ylva; Larsson, Anita; Bjerneld, Erik J; Rönn, Ola

    2015-10-01

    Western blotting is a widely used method for analyzing specific target proteins in complex protein samples. Housekeeping proteins are often used for normalization to correct for uneven sample loads, but these require careful validation since expression levels may vary with cell type and treatment. We present a new, more reliable method for normalization using Cy5-prelabeled total protein as a loading control. We used a prelabeling protocol based on Cy5 N-hydroxysuccinimide ester labeling that produces a linear signal response. We obtained a low coefficient of variation (CV) of 7% between the ratio of extracellular signal-regulated kinase (ERK1/2) target to Cy5 total protein control signals over the whole loading range from 2.5 to 20.0μg of Chinese hamster ovary cell lysate protein. Corresponding experiments using actin or tubulin as controls for normalization resulted in CVs of 13 and 18%, respectively. Glyceraldehyde-3-phosphate dehydrogenase did not produce a proportional signal and was not suitable for normalization in these cells. A comparison of ERK1/2 signals from labeled and unlabeled samples showed that Cy5 prelabeling did not affect antibody binding. By using total protein normalization we analyzed PP2A and Smad2/3 levels with high confidence. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Defining the "normal" postejaculate urinalysis.

    Science.gov (United States)

    Mehta, Akanksha; Jarow, Jonathan P; Maples, Pat; Sigman, Mark

    2012-01-01

    Although sperm have been shown to be present in the postejaculate urinalysis (PEU) of both fertile and infertile men, the number of sperm present in the PEU of the general population has never been well defined. The objective of this study was to describe the semen and PEU findings in both the general and infertile population, in order to develop a better appreciation for "normal." Infertile men (n = 77) and control subjects (n = 71) were prospectively recruited. Exclusion criteria included azoospermia and medications known to affect ejaculation. All men underwent a history, physical examination, semen analysis, and PEU. The urine was split into 2 containers: PEU1, the initial voided urine, and PEU2, the remaining voided urine. Parametric statistical methods were applied for data analysis to compare sperm concentrations in each sample of semen and urine between the 2 groups of men. Controls had higher average semen volume (3.3 ± 1.6 vs 2.0 ± 1.4 mL, P sperm concentrations (112 million vs 56.2 million, P = .011), compared with infertile men. The presence of sperm in urine was common in both groups, but more prevalent among infertile men (98.7% vs 88.7%, P = .012), in whom it comprised a greater proportion of the total sperm count (46% vs 24%, P = .022). The majority of sperm present in PEU were seen in PEU1 of both controls (69%) and infertile men (88%). An association was noted between severe oligospermia (sperm counts in PEU (sperm in the urine compared with control, there is a large degree of overlap between the 2 populations, making it difficult to identify a specific threshold to define a positive test. Interpretation of a PEU should be directed by whether the number of sperm in the urine could affect subsequent management.

  20. Turbocharging Normalization in Highland Conditions

    Directory of Open Access Journals (Sweden)

    I. V. Filippov

    2017-01-01

    Full Text Available To ensure many production processes are used compressors of various types, including turbochargers, which produce compressed air. The actual performance values of turbochargers used in highlands are significantly different from the certified values, and parameters of compressed air do not always guarantee the smooth and efficient functioning for consumers.The paper presents research results of the turbochargers of 4CI 425MX4 type, a series of "CENTAC", manufactured by INGERSOL – RAND Company. The research has been conducted in industrial highland conditions in difficult climatic environment. There were almost no investigations of turbochargers running in highland conditions. The combination of low atmospheric pressure with high temperature of the intake air causes the abnormal operating conditions of a turbocharger. Only N. M. Barannikov in his paper shows the results of theoretical studies of such operating conditions, but as to the practical research, there is no information at all.To normalize the turbocharger operation an option of the mechanical pressurization in the suction pipe is adopted. As a result of theoretical research, a TurboMAX blower MAX500 was chosen as a supercharger. The next stage of theoretical research was to construct characteristics of the turbocharger 4CI 425MX4 with a mechanical supercharger in the suction pipe. The boost reduces to the minimum the time of using additional compressors when parameters of the intake air are changed and ensures the smooth and efficient functioning for consumers.To verify the results of theoretical studies, namely, the technique for recalculation of the turbocharger characteristics under the real conditions of suction, were carried out the experimental researches. The average error between experimental and theoretical data is 2,9783 %, which confirms the validity of the technique used for reduction of the turbocharger characteristics to those under the real conditions of suction.

  1. Effect of anesthesia, positioning, time, and feeding on the proventriculus: keel ratio of clinically healthy parrots.

    Science.gov (United States)

    Dennison, Sophie E; Paul-Murphy, Joanne R; Yandell, Brian S; Adams, William M

    2010-01-01

    Healthy, adult Hispaniolan Amazon parrots (Amazona ventralis) were imaged on three occasions to determine the effects of anesthesia, patient rotation, feeding, and short/long-term temporal factors on the proventriculus:keel ratio. Increasing rotation up to 15 degrees from right lateral resulted in increased inability to measure the proventriculus in up to 44% of birds, meaning that the proventriculus:keel ratio could not be calculated from those radiographs. There was a significant difference between the proventriculus:keel ratio for individual parrots when quantified 3 weeks apart. Despite this difference, all ratios remained within normal limits. No significant effect was identified due to anesthesia, feeding, fasting, or repeated imaging through an 8-h period. Interobserver agreement for measurability and correlation for the proventriculus:keel ratio values was high. It is recommended that the proventriculus:keel ratio be calculated from anesthetized parrots to attain images in true lateral recumbency. Ratio fluctuations within the normal range between radiographs obtained on different dates may be observed in normal parrots.

  2. Vaginal Discharge: What's Normal, What's Not

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Vaginal Discharge: What's Normal, What's Not KidsHealth / For Teens / ... Discharge: What's Normal, What's Not Print What Is Vaginal Discharge? Vaginal discharge is fluid that comes from ...

  3. Should Japan Become a Normal Country

    National Research Council Canada - National Science Library

    Yildiz, Ahmet

    2005-01-01

    This thesis evaluates Japanese geopolitical change in the post-Cold War era. It does so by analyzing Japan's history, its foreign policy since 1945, its reasons for becoming a normal country, and the impact of its normalization...

  4. Corporate prediction models, ratios or regression analysis?

    NARCIS (Netherlands)

    Bijnen, E.J.; Wijn, M.F.C.M.

    1994-01-01

    The models developed in the literature with respect to the prediction of a company s failure are based on ratios. It has been shown before that these models should be rejected on theoretical grounds. Our study of industrial companies in the Netherlands shows that the ratios which are used in

  5. Maternal preconception diet and the sex ratio

    NARCIS (Netherlands)

    Cramer, J.S.; Lumey, L.H.

    2009-01-01

    Temporal variations in the sex ratio or the ratio of boys over girls at birth have been widely studied and variously attributed to social changes, conditions of war, and environmental changes. Recently, Mathews, Johnson and Neil (2008) studied the direct evidence of individual pregnancies and

  6. The Golden Ratio--A Contrary Viewpoint

    Science.gov (United States)

    Falbo, Clement

    2005-01-01

    Many assertions about the occurrence of the golden ratio phi in art, architecture, and nature have been shown to be false, unsupported, or misleading. For instance, we show that the spirals found in sea shells, in particular the "Nautilus pompilius," are not in the shape of the golden ratio, as is often claimed. Some of the most interesting…

  7. Osmosis and Surface Area to Volume Ratio.

    Science.gov (United States)

    Barrett, D. R. B.

    1984-01-01

    Describes an experiment designed to help students understand the concepts of osmosis and surface area to volume ratio (SA:VOL). The task for students is to compare water uptake in different sizes of potato cubes and relate differences to their SA:VOL ratios. (JN)

  8. Key financial ratios can foretell hospital closures.

    Science.gov (United States)

    Lynn, M L; Wertheim, P

    1993-11-01

    An analysis of various financial ratios sampled from open and closed hospitals shows that certain leverage, liquidity, capital efficiency, and resource availability ratios can predict hospital closure up to two years in advance of the closure with an accuracy of nearly 75 percent.

  9. Charge ratio of muons from atmospheric neutrinos

    Energy Technology Data Exchange (ETDEWEB)

    Gaisser, T.K.; Stanev, Todor

    2003-05-22

    We calculate the intensities and angular distributions of positive and negative muons produced by atmospheric neutrinos. We comment on some sources of uncertainty in the charge ratio. We also draw attention to a potentially interesting signature of neutrino oscillations in the muon charge ratio, and we discuss the prospects for its observation (which are not quite within the reach of currently planned magnetized detectors)

  10. Maternal preconception diet and the sex ratio

    NARCIS (Netherlands)

    Cramer, J.S.; Lumey, L.H.

    2010-01-01

    Temporal variations in the sex ratio, or the ratio of boys to girls at birth, have been widely studied and variously attributed to social changes, conditions of war, and environmental changes. Recently, Mathews et al. ["You are what your mother eats: Evidence for maternal preconception diet

  11. Financial Ratio Analysis Comes to Nonprofits.

    Science.gov (United States)

    Chabotar, Kent John

    1989-01-01

    To evaluate their financial health, a growing number of colleges, universities, and other nonprofit organizations are using financial ratio analysis, a technique used in business. The strengths and weaknesses of ratio analysis are assessed and suggestions are made on how nonprofits can use it most effectively. (Author/MLW)

  12. Curious Sex Ratios and Cytoplasmic Genes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 6. Curious Sex Ratios and Cytoplasmic Genes Microbes Can Distort the Sex Ratio of Populations. Stephen J Freeland Laurence D Hurst. General Article Volume 2 Issue 6 June 1997 pp 68-78 ...

  13. Vascular corrosion casting of normal and pre-eclamptic placentas.

    Science.gov (United States)

    Yin, Geping; Chen, Ming; Li, Juan; Zhao, Xiaoli; Yang, Shujun; Li, Xiuyun; Yuan, Zheng; Wu, Aifang

    2017-12-01

    Pre-eclampsia is an important cause of maternal and fetal morbidity and mortality that is associated with decreased placental perfusion. In the present study, vascular corrosion casting was used to investigate the differences in structural changes of the fetoplacental vasculature between normal and pre-eclamptic placentas. An improved epoxy resin vascular casting technique was used in the present study. Casting media were infused into 40 normal and 40 pre-eclamptic placentas through umbilical arteries and veins in order to construct three dimensional fetoplacental vasculatures. The number of branches, diameter, morphology and peripheral artery-to-vein ratio were measured for each specimen. The results indicated that the venous system of normal placentas was divided into 5-7 grades of branches and the volume of the vascular bed was 155.5±45.3 ml. In severe pre-eclamptic placentas, the volume was 106.4±36.1 ml, which was significantly lower compared with normal placentas (P<0.01). The venous system of pre-eclamptic placentas was divided into 4-5 grades of branches, which was much more sparse compared with normal placentas. In additions, the diameters of grade 1-3 veins and grade 2-3 arteries were significantly smaller in severe pre-eclampsia (P<0.05). In conclusion, pre-eclamptic placentas displayed a decreased volume of vascular bed, smaller diameters of grade 1-3 veins and grade 2-3 arteries, and an increased peripheral artery-to-vein ratio, which may be a cause of the placental dysfunction during severe pre-eclampsia.

  14. Bone/soft-tissue enrichment ratio in skeletal scintiscanning

    International Nuclear Information System (INIS)

    Reuschel, W.

    1982-01-01

    The thesis aimed at establishing normal values for the enrichment intensity of sup(99m)Tc-MDP above the sacrum (S) as reference point for spongy bones in relation to soft-tissue (ST) enrichment (S/St ratio). A normal range for S/ST was determined for five age groups which was given separately for males and females. In addition, the question was examined what causes there could be for S/ST exceeding, the norm or an increased F/ST ratio (F=femur centre) between bone and soft tissue. The question was studied whether or not beniguity or malignancy of a base disease has an important influence on F/ST values. Dependence of F/ST values from primary tumour localization and the tendency of metastatic spread in bones were investigated in malignoma patients. In addition, an assessment was made of what correlation existed, between the laboratory parameters measured, particularly alkaline phosphatase, and the F/ST values. The questions were examined what correlation existed between the F/ST values established and scintiscan findings; whether or not solitary radionuclide enrichments or multiple foci were found in the scintiscan; and what influence the number of foci had on the F/ST values. In tumour patients, the question examined what correlation existed between a tumour-specific treatment and the F/ST values. (orig./MG) [de

  15. Urinary pregnandiol-3-glucuronide and estrone conjugates to creatinine ratios in early pregnancies complicated by vaginal bleeding.

    Science.gov (United States)

    Davidson, B J

    1986-10-01

    There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.

  16. Geometrical scaling in charm structure function ratios

    International Nuclear Information System (INIS)

    Boroun, G.R.; Rezaei, B.

    2014-01-01

    By using a Laplace-transform technique, we solve the next-to-leading-order master equation for charm production and derive a compact formula for the ratio R c =F L cc ¯ /F 2 cc ¯ , which is useful for extracting the charm structure function from the reduced charm cross section, in particular, at DESY HERA, at small x. Our results show that this ratio is independent of x at small x. In this method of determining the ratios, we apply geometrical scaling in charm production in deep inelastic scattering (DIS). Our analysis shows that the renormalization scales have a sizable impact on the ratio R c at high Q 2 . Our results for the ratio of the charm structure functions are in a good agreement with some phenomenological models

  17. Equity Theory Ratios as Causal Schemas

    Directory of Open Access Journals (Sweden)

    Alexios Arvanitis

    2016-08-01

    Full Text Available Equity theory approaches justice evaluations based on ratios of exchange inputs to exchange outcomes. Situations are evaluated as just if ratios are equal and unjust if unequal. We suggest that equity ratios serve a more fundamental cognitive function than the evaluation of justice. More particularly, we propose that they serve as causal schemas for exchange outcomes, that is, they assist in determining whether certain outcomes are caused by inputs of other people in the context of an exchange process. Equality or inequality of ratios in this sense points to an exchange process. Indeed, Study 1 shows that different exchange situations, such as disproportional or balanced proportional situations, create perceptions of give-and-take on the basis of equity ratios. Study 2 shows that perceptions of justice are based more on communicatively accepted rules of interaction than equity-based evaluations, thereby offering a distinction between an attribution and an evaluation cognitive process for exchange outcomes.

  18. Equity Theory Ratios as Causal Schemas.

    Science.gov (United States)

    Arvanitis, Alexios; Hantzi, Alexandra

    2016-01-01

    Equity theory approaches justice evaluations based on ratios of exchange inputs to exchange outcomes. Situations are evaluated as just if ratios are equal and unjust if unequal. We suggest that equity ratios serve a more fundamental cognitive function than the evaluation of justice. More particularly, we propose that they serve as causal schemas for exchange outcomes, that is, they assist in determining whether certain outcomes are caused by inputs of other people in the context of an exchange process. Equality or inequality of ratios in this sense points to an exchange process. Indeed, Study 1 shows that different exchange situations, such as disproportional or balanced proportional situations, create perceptions of give-and-take on the basis of equity ratios. Study 2 shows that perceptions of justice are based more on communicatively accepted rules of interaction than equity-based evaluations, thereby offering a distinction between an attribution and an evaluation cognitive process for exchange outcomes.

  19. Independent isomer yield ratio of 90Rb

    International Nuclear Information System (INIS)

    Reeder, P.L.; Warner, R.A.; Ford, G.P.; Willmes, H.

    1985-05-01

    The independent isomer yield ratio for 90 Rb from thermal neutron fission of 235 U has been measured by use of a new technique involving a pulsed reactor and an on-line mass spectrometer facility. The apparent isomer yield ratio was measured for different ion collection time intervals and extrapolated to zero collection time to eliminate interference from 90 Kr decay. The observed isomer yield ratio of 8.7 +- 1.0 is one of the largest ratios measured for a low energy fission process. However, a statistical model analysis shows that the average angular momentum ( = 4.5) deduced from this isomer yield ratio is consistent with average angular momentum for other products from low energy fission. 7 refs

  20. Comparison of CSF Distribution between Idiopathic Normal Pressure Hydrocephalus and Alzheimer Disease.

    Science.gov (United States)

    Yamada, S; Ishikawa, M; Yamamoto, K

    2016-07-01

    CSF volumes in the basal cistern and Sylvian fissure are increased in both idiopathic normal pressure hydrocephalus and Alzheimer disease, though the differences in these volumes in idiopathic normal pressure hydrocephalus and Alzheimer disease have not been well-described. Using CSF segmentation and volume quantification, we compared the distribution of CSF in idiopathic normal pressure hydrocephalus and Alzheimer disease. CSF volumes were extracted from T2-weighted 3D spin-echo sequences on 3T MR imaging and quantified semi-automatically. We compared the volumes and ratios of the ventricles and subarachnoid spaces after classification in 30 patients diagnosed with idiopathic normal pressure hydrocephalus, 10 with concurrent idiopathic normal pressure hydrocephalus and Alzheimer disease, 18 with Alzheimer disease, and 26 control subjects 60 years of age or older. Brain to ventricle ratios at the anterior and posterior commissure levels and 3D volumetric convexity cistern to ventricle ratios were useful indices for the differential diagnosis of idiopathic normal pressure hydrocephalus or idiopathic normal pressure hydrocephalus with Alzheimer disease from Alzheimer disease, similar to the z-Evans index and callosal angle. The most distinctive characteristics of the CSF distribution in idiopathic normal pressure hydrocephalus were small convexity subarachnoid spaces and the large volume of the basal cistern and Sylvian fissure. The distribution of the subarachnoid spaces in the idiopathic normal pressure hydrocephalus with Alzheimer disease group was the most deformed among these 3 groups, though the mean ventricular volume of the idiopathic normal pressure hydrocephalus with Alzheimer disease group was intermediate between that of the idiopathic normal pressure hydrocephalus and Alzheimer disease groups. The z-axial expansion of the lateral ventricle and compression of the brain just above the ventricle were the common findings in the parameters for differentiating

  1. A note on totally normal spaces

    International Nuclear Information System (INIS)

    Zougdani, H.K.

    1990-10-01

    In this note we give the necessary and sufficient condition for a topological space X such that the product space X x Y is totally normal for any (non discrete) metric space Y, and we show that a totally normal p-space need not be a perfectly normal in general, which makes Theorem 2 doubtful. (author). 6 refs

  2. Manufacturing technology for practical Josephson voltage normals

    International Nuclear Information System (INIS)

    Kohlmann, Johannes; Kieler, Oliver

    2016-01-01

    In this contribution we present the manufacturing technology for the fabrication of integrated superconducting Josephson serial circuits for voltage normals. First we summarize some foundations for Josephson voltage normals and sketch the concept and the setup of the circuits, before we describe the manufacturing technology form modern practical Josephson voltage normals.

  3. Energy ratios in Finnish agricultural production

    Directory of Open Access Journals (Sweden)

    H. J. MIKKOLA

    2008-12-01

    Full Text Available The objective of this study was to assess energy ratios and net energy in plant production and energy ratios in animal production in Finland. Energy ratios and net energy were determined on the basis of plant- and animal-specific energy analyses. In plant production, energy ratios and net energy were assessed as a function of nitrogen fertilization, because indirect energy input in the form of agrochemicals was 54—73% from the total energy input and nitrogen was responsible for the major part of this. The highest energy ratio was 18.6 for reed canary grass. As a whole reed canary grass was superior to the other crops, which were barley, spring wheat, spring turnip rape, ley for silage, potato and sugar beet. Reed canary grass and sugar beet gained the highest net energy yields of 111–115 GJ ha-1. The optimum energy ratio was gained in general with less nitrogen fertilization intensity than farmers use. The energy ratios in pork production varied between 0.14–1.28 depending on what was included or excluded in the analysis and for milk production between 0.15–1.85. Ratios of 1.28 in pork production and 1.85 in milk production are unrealistic as they do not give any shelter to the animals, although they can be approached in very low-input production systems. If the ratio is calculated with feed energy content then the ratio is low, 0.14–0.22 for pork and 0.15 for milk. This shows that animals can convert 14–22 percent of the input energy to usable products. In pork production, the largest portion of the energy input was the ventilation of the building. In milk production milking and cooling consumes a lot of energy and for this reason the electricity consumption is high.;

  4. Neutron scattering by normal liquids

    Energy Technology Data Exchange (ETDEWEB)

    Gennes, P.G. de [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1961-07-01

    Neutron data on motions in normal liquids well below critical point are reviewed and classified according to the order of magnitude of momentum transfers {Dirac_h}q and energy transfers {Dirac_h}w. For large momentum transfers a perfect gas model is valid. For smaller q and incoherent scattering, the major effects are related to the existence of two characteristic times: the period of oscillation of an atom in its cell, and the average lifetime of the atom in a definite cell. Various interpolation schemes covering both time scales are discussed. For coherent scattering and intermediate q, the energy spread is expected to show a minimum whenever q corresponds to a diffraction peak. For very small q the standard macroscopic description of density fluctuations is applicable. The limits of the various (q) and (w) domains and the validity of various approximations are discussed by a method of moments. The possibility of observing discrete transitions due to internal degrees of freedom in polyatomic molecules, in spite of the 'Doppler width' caused by translational motions, is also examined. (author) [French] L'auteur examine les donnees neutroniques sur les mouvements dans les liquides normaux, bien au-dessous du point critique, et les classe d'apres l'ordre de grandeur des transferts de quantite de mouvement {Dirac_h}q et des transferts d'energie {Dirac_h}w. Pour les grands transferts de, quantite de mouvement, un modele de gaz parfait est valable. En ce qui concerne les faibles valeurs de q et la diffussion incoherente, les principaux effets sont lies a l'existence de deux temps caracteristiques: la periode d'oscillation d'un atome dans sa cellule et la duree moyenne de vie de l'atome dans une cellule determinee. L'auteur etudie divers systemes d'interpolation se rapportant aux deux echelles de temps. Pour la diffusion coherente et les valeurs intermediaires de q, on presume que le spectre d'energie accuse un minimum chaque fois que q correspond a un pic de

  5. Normal distal pulmonary vein anatomy

    Directory of Open Access Journals (Sweden)

    Wiesława Klimek-Piotrowska

    2016-01-01

    Full Text Available Background. It is well known that the pulmonary veins (PVs, especially their myocardial sleeves play a critical role in the initiation and maintenance of atrial fibrillation. Understanding the PV anatomy is crucial for the safety and efficacy of all procedures performed on PVs. The aim of this study was to present normal distal PV anatomy and to create a juxtaposition of all PV ostium variants.Methods. A total of 130 randomly selected autopsied adult human hearts (Caucasian were examined. The number of PVs ostia was evaluated and their diameter was measured. The ostium-to-last-tributary distance and macroscopic presence of myocardial sleeves were also evaluated.Results. Five hundred forty-one PV ostia were identified. Four classical PV ostia patterns (two left and two right PVs were observed in 70.8% of all cases. The most common variant was the classical pattern with additional middle right PV (19.2%, followed by the common ostium for the left superior and the inferior PVs (4.44%. Mean diameters of PV ostia (for the classical pattern were: left superior = 13.8 ± 2.9 mm; left inferior = 13.3 ± 3.4 mm; right superior = 14.3 ± 2.9 mm; right inferior = 13.7 ± 3.3 mm. When present, the additional middle right PV ostium had the smallest PV ostium diameter in the heart (8.2 ± 4.1 mm. The mean ostium-to-last-tributary (closest to the atrium distances were: left superior = 15.1 ± 4.6 mm; left inferior = 13.5 ± 4.0 mm; right superior = 11.8 ± 4.0 mm; right inferior = 11.0 ± 3.7 mm. There were no statistically significant differences between sexes in ostia diameters and ostium-to-last-tributary distances.Conclusion. Only 71% of the cases have four standard pulmonary veins. The middle right pulmonary vein is present in almost 20% of patients. Presented data can provide useful information for the clinicians during interventional procedures or radiologic examinations of PVs.

  6. Normal SPECT thallium-201 bull's-eye display: gender differences

    International Nuclear Information System (INIS)

    Eisner, R.L.; Tamas, M.J.; Cloninger, K.

    1988-01-01

    The bull's-eye technique synthesizes three-dimensional information from single photon emission computed tomographic 201 TI images into two dimensions so that a patient's data can be compared quantitatively against a normal file. To characterize the normal database and to clarify differences between males and females, clinical data and exercise electrocardiography were used to identify 50 males and 50 females with less than 5% probability of coronary artery disease. Results show inhomogeneity of the 201 TI distributions at stress and delay: septal to lateral wall count ratios are less than 1.0 in both females and males; anterior to inferior wall count ratios are greater than 1.0 in males but are approximately equal to 1.0 in females. Washout rate is faster in females than males at the same peak exercise heart rate and systolic blood pressure, despite lower exercise time. These important differences suggest that quantitative analysis of single photon emission computed tomographic 201 TI images requires gender-matched normal files

  7. Approach to normalization of the secondary circuit water chemistry of NPP with WWER-1000

    International Nuclear Information System (INIS)

    Mamet, V.A.; Erpyleva, S.F.; Banyuk, G.F.

    1998-01-01

    The approach to normalization if indices of water-chemical regime of the secondary circuit of the NPP with WWER-1000 reactor, based on pH calculational values at the coolant working temperature in dependence on the normalized admixtures concentration is considered. The possibility for conducting the water regime of steam generators by the ratio of sodium concentration and electrical conductivity of H-cation sample of blow-through water is shown. The limitations (os action level) by deviation of normalized indices from recommended ones for normal operational conditions are described

  8. Computer tomography (CT) finding of normal pancreas

    International Nuclear Information System (INIS)

    Cho, Chi Ja; Kim, Byung Tae; Lee, Jeung Suk

    1983-01-01

    Conventional radiology of the pancreas are too often unsatisfactory. It is well known that the whole body CT is very useful in identifying retroperitoneal pathology. The authors intended to present normal pancreatic morphology and data for preparation of basis for interpretation of abnormalities. We results were as follows; 1. There were 36 male and 24 female patients, and their ages ranged from 7 to 78 years. 2. 1) The organs adjacent pancreas were stomach, inferior vena cava, duodenum, caudate lobe of the liver left kidney, left adrenal gland, superior mesenteric vessels, spleen. 2) In 19 patients, pancreatic tail at the level of left kidney in the transverse plane, it was either ventral in 13 (68%), ventromedial in 2 (19%), ventrolateral in 4 (21%) to left kidney, in the other 41 patients, it was cranial to the upper pole of left kidney, ventral in 25 (61%), ventromedial in 1 (2%), ventrolateral in 15 (37%). 3) Pancreatic tail was cranial to the pancreatic body, 3 cm cranial in 2 (4%), 2-3 cm in 5 (8%), 1-2 cm in 6 (10%), less than 1 cm in 11 (18%). In the other, caudal in 3 (5%). 4) Pancreatic tail was cranial to the level of the splenic hilum in 36 (60%), 0-2 cm caudal in 24 (40%). 3. Pancreatic shape was uniform tapering form in 37 (62%), lobulated form in 23 (38%). 4. Pancreatic orientation was horizontal in 13 (22%), vertical 56 (76%), S-shaped in 1 (2%). 5. Pancreatic margin was smooth in 22 (37%), lobulated in 38 (63%). 6. In most patients, pancreas was uniform in density. 7. Pancreatic size was 0.5 ± 0.1 in measurement ratio of the head in 48 (80%), 0.4 ± 0.1 of the body in 49 (88%), 0.5 ± 0.1 of the tail in 47 (78%)

  9. Platelet cyclooxygenase expression in normal dogs.

    Science.gov (United States)

    Thomason, J; Lunsford, K; Mullins, K; Stokes, J; Pinchuk, L; Wills, R; McLaughlin, R; Langston, C; Pruett, S; Mackin, A

    2011-01-01

    Human platelets express both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Variation in COX-2 expression could be a mechanism for variable response to aspirin. The hypotheses were that circulating canine platelets express COX-1 and COX-2, and that aspirin alters COX expression. The objective was to identify changes in platelet COX expression and in platelet function caused by aspirin administration to dogs. Eight female, intact hounds. A single population, repeated measures design was used to evaluate platelet COX-1 and COX-2 expression by flow cytometry before and after aspirin (10 mg/kg Q12h for 10 days). Platelet function was analyzed via PFA-100(®) (collagen/epinephrine), and urine 11-dehydro-thromboxane B(2) (11-dTXB(2)) was measured and normalized to urinary creatinine. Differences in COX expression, PFA-100(®) closure times, and urine 11-dTXB(2 ): creatinine ratio were analyzed before and after aspirin administration. Both COX-1 and COX-2 were expressed in canine platelets. COX-1 mean fluorescent intensity (MFI) increased in all dogs, by 250% (range 63-476%), while COX-2 expression did not change significantly (P = 0.124) after aspirin exposure, with large interindividual variation. PFA-100(®) closure times were prolonged and urine 11-dTXB(2) concentration decreased in all dogs after aspirin administration. Canine platelets express both COX isoforms. After aspirin exposure, COX-1 expression increased despite impairment of platelet function, while COX-2 expression varied markedly among dogs. Variability in platelet COX-2 expression should be explored as a potential mechanism for, or marker of, variable aspirin responsiveness. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  10. Vascular factors in suspected normal pressure hydrocephalus

    Science.gov (United States)

    Agerskov, Simon; Rabiei, Katrin; Marlow, Thomas; Jensen, Christer; Guo, Xinxin; Kern, Silke; Wikkelsø, Carsten; Skoog, Ingmar

    2016-01-01

    Objective: We examined clinical and imaging findings of suspected idiopathic normal pressure hydrocephalus (iNPH) in relation to vascular risk factors and white matter lesions (WMLs), using a nested case-control design in a representative, population-based sample. Methods: From a population-based sample, 1,235 persons aged 70 years or older were examined with CT of the brain between 1986 and 2000. We identified 55 persons with hydrocephalic ventricular enlargement, i.e., radiologic findings consistent with iNPH. Among these, 26 had clinical signs that fulfilled international guideline criteria for probable iNPH. These cases were labeled suspected iNPH. Each case was matched to 5 controls from the same sample, based on age, sex, and study cohort. Data on risk factors were obtained from clinical examinations and the Swedish Hospital Discharge Register. History of hypertension, diabetes mellitus (DM), smoking, overweight, history of coronary artery disease, stroke/TIA, and WMLs on CT were examined. Risk factors associated with iNPH with a p value <0.1 in χ2 tests were included in conditional logistic regression models. Results: In the regression analyses, suspected iNPH was related to moderate to severe WMLs (odds ratio [OR] 5.2; 95% confidence interval [CI]: 1.5–17.6), while hydrocephalic ventricular enlargement was related to hypertension (OR 2.7; 95% CI: 1.1–6.8), moderate to severe WMLs (OR 6.5; 95% CI: 2.1–20.3), and DM (OR 4.3; 95% CI: 1.1–16.3). Conclusions: Hypertension, WMLs, and DM were related to clinical and imaging features of iNPH, suggesting that vascular mechanisms are involved in the pathophysiology. These findings might have implications for understanding disease mechanisms in iNPH and possibly prevention. PMID:26773072

  11. The "normal" elongation of river basins

    Science.gov (United States)

    Castelltort, Sebastien

    2013-04-01

    The spacing between major transverse rivers at the front of Earth's linear mountain belts consistently scales with about half of the mountain half-width [1], despite strong differences in climate and rock uplift rates. Like other empirical measures describing drainage network geometry this result seems to indicate that the form of river basins, among other properties of landscapes, is invariant. Paradoxically, in many current landscape evolution models, the patterns of drainage network organization, as seen for example in drainage density and channel spacing, seem to depend on both climate [2-4] and tectonics [5]. Hovius' observation [1] is one of several unexplained "laws" in geomorphology that still sheds mystery on how water, and rivers in particular, shape the Earth's landscapes. This narrow range of drainage network shapes found in the Earth's orogens is classicaly regarded as an optimal catchment geometry that embodies a "most probable state" in the uplift-erosion system of a linear mountain belt. River basins currently having an aspect away from this geometry are usually considered unstable and expected to re-equilibrate over geological time-scales. Here I show that the Length/Width~2 aspect ratio of drainage basins in linear mountain belts is the natural expectation of sampling a uniform or normal distribution of basin shapes, and bears no information on the geomorphic processes responsible for landscape development. This finding also applies to Hack's [6] law of river basins areas and lengths, a close parent of Hovius' law. [1]Hovius, N. Basin Res. 8, 29-44 (1996) [2]Simpson, G. & Schlunegger, F. J. Geophys. Res. 108, 2300 (2003) [3]Tucker, G. & Bras, R. Water Resour. Res. 34, 2751-2764 (1998) [4]Tucker, G. & Slingerland, R. Water Resour. Res. 33, 2031-2047 (1997) [5]Tucker, G. E. & Whipple, K. X. J. Geophys. Res. 107, 1-1 (2002) [6]Hack, J. US Geol. Surv. Prof. Pap. 294-B (1957)

  12. Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

    International Nuclear Information System (INIS)

    Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

    1984-01-01

    Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient

  13. MR guided spatial normalization of SPECT scans

    International Nuclear Information System (INIS)

    Crouch, B.; Barnden, L.R.; Kwiatek, R.

    2010-01-01

    Full text: In SPECT population studies where magnetic resonance (MR) scans are also available, the higher resolution of the MR scans allows for an improved spatial normalization of the SPECT scans. In this approach, the SPECT images are first coregistered to their corresponding MR images by a linear (affine) transformation which is calculated using SPM's mutual information maximization algorithm. Non-linear spatial normalization maps are then computed either directly from the MR scans using SPM's built in spatial normalization algorithm, or, from segmented TI MR images using DARTEL, an advanced diffeomorphism based spatial normalization algorithm. We compare these MR based methods to standard SPECT based spatial normalization for a population of 27 fibromyalgia patients and 25 healthy controls with spin echo T 1 scans. We identify significant perfusion deficits in prefrontal white matter in FM patients, with the DARTEL based spatial normalization procedure yielding stronger statistics than the standard SPECT based spatial normalization. (author)

  14. Anomalous normal mode oscillations in semiconductor microcavities

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H. [Univ. of Oregon, Eugene, OR (United States). Dept. of Physics; Hou, H.Q.; Hammons, B.E. [Sandia National Labs., Albuquerque, NM (United States)

    1997-04-01

    Semiconductor microcavities as a composite exciton-cavity system can be characterized by two normal modes. Under an impulsive excitation by a short laser pulse, optical polarizations associated with the two normal modes have a {pi} phase difference. The total induced optical polarization is then expected to exhibit a sin{sup 2}({Omega}t)-like oscillation where 2{Omega} is the normal mode splitting, reflecting a coherent energy exchange between the exciton and cavity. In this paper the authors present experimental studies of normal mode oscillations using three-pulse transient four wave mixing (FWM). The result reveals surprisingly that when the cavity is tuned far below the exciton resonance, normal mode oscillation in the polarization is cos{sup 2}({Omega}t)-like, in contrast to what is expected form the simple normal mode model. This anomalous normal mode oscillation reflects the important role of virtual excitation of electronic states in semiconductor microcavities.

  15. Introducing optional reserve ratios in Hungary

    OpenAIRE

    Lóránt Varga

    2010-01-01

    As of the reserve maintenance period commencing in November 2010, Hungarian credit institutions will be free to decide whether to apply the previously valid 2% reserve ratio, or to apply a higher mandatory reserve ratio. Credit institutions required to hold reserves may select from reserve ratios of 2, 3, 4 and 5%, and may change their decision on a semi-annual basis. In line with the international best practice, the purpose of the MNB’s reserve requirement system is to support credit institu...

  16. Transcription and the aspect ratio of DNA

    DEFF Research Database (Denmark)

    Olsen, Kasper Wibeck; Bohr, Jakob

    2013-01-01

    analysis of transcription. It is shown that under certain reasonable assumptions transcription is only possible if the aspect ratio is in the regime corresponding to further twisting. We find this constraint to be in agreement with long-established crystallographic studies of DNA.......Two separate regimes exist for the aspect ratio of DNA. A low aspect regime where DNA will twist further under strain and a high aspect regime where DNA will untwist under strain. The question of the overall geometry, i.e. the aspect ratio, of DNA is revisited from the perspective of a geometrical...

  17. Financial Ratios and Perceived Household Financial Satisfaction

    Directory of Open Access Journals (Sweden)

    Scott Garrett

    2013-08-01

    Full Text Available This paper tests the relative strength of three objective measures of financial health (using the solvency, liquidity, and investment asset ratio in predicting a household’s subjective feeling of current financial satisfaction. Using a sample of 6,923 respondents in the 2008 Health and Retirement Study this paper presents evidence of two main findings: 1 the solvency ratio is most strongly associated with financial satisfaction levels based on a cross-sectional design and 2 changes in the investment asset ratio are most strongly associated with changes in financial satisfaction over time.

  18. Evaluation for moments of a ratio with application to regression estimation

    OpenAIRE

    Doukhan, Paul; Lang, Gabriel

    2008-01-01

    Ratios of random variables often appear in probability and statistical applications. We aim to approximate the moments of such ratios under several dependence assumptions. Extending the ideas in Collomb [C. R. Acad. Sci. Paris 285 (1977) 289–292], we propose sharper bounds for the moments of randomly weighted sums and for the Lp-deviations from the asymptotic normal law when the central limit theorem holds. We indicate suitable applications in finance and censored data analysis and focus on t...

  19. Tests and Confidence Intervals for an Extended Variance Component Using the Modified Likelihood Ratio Statistic

    DEFF Research Database (Denmark)

    Christensen, Ole Fredslund; Frydenberg, Morten; Jensen, Jens Ledet

    2005-01-01

    The large deviation modified likelihood ratio statistic is studied for testing a variance component equal to a specified value. Formulas are presented in the general balanced case, whereas in the unbalanced case only the one-way random effects model is studied. Simulation studies are presented......, showing that the normal approximation to the large deviation modified likelihood ratio statistic gives confidence intervals for variance components with coverage probabilities very close to the nominal confidence coefficient....

  20. Serum Thyroxine to Thyroxine-Binding Globulin Ratio in Pregnancy and Newborn

    International Nuclear Information System (INIS)

    Kim, Ji Yeul

    1982-01-01

    To evaluate the diagnostic value of the ratio of serum thyroxine(T 4 ) /thyroxine-binding globulin (TBG) for the thyroid status in pregnancy and newborn serum thyroxine, TBG, triiodothyronine, and free thyroxine levels were radioimmunoassayed in normal pregnant women at each of the trimesters, and the calculated serum T 4 /TBG ratios were compared with other parameters such as T 3 /TBG ratio and free T 4 /TBG ratio and free T 4 /TBG