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Obstructive sleep apnea (OSA) is associated with adverse and interdependent cognitive and cardiovascular consequences. Increasing evidence suggests that nitric oxide synthase (NOS) and endothelin family (EDN) genes underlie mechanistic aspects of OSA-associated morbidities. We aimed to identify single nucleotide polymorphisms (SNPs) in the NOS family (3 isoforms), and EDN family (3 isoforms) to identify potential associations of these SNPs in children with OSA.
A pediatric community cohort (ages 5–10 years) enriched for snoring underwent overnight polysomnographic (NPSG) and a fasting morning blood draw. The diagnostic criteria for OSA were an obstructive apnea-hypopnea Index (AHI) >2/h total sleep time (TST), snoring during the night, and a nadir oxyhemoglobin saturation <92%. Control children were defined as non-snoring children with AHI <2/h TST (NOSA). Endothelial function was assessed using a modified post-occlusive hyperemic test. The time to peak reperfusion (Tmax) was considered as the indicator for normal endothelial function (NEF; Tmax<45 sec), or ED (Tmax≥45 sec). Genomic DNA from peripheral blood was extracted and allelic frequencies were assessed for, NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), endothelin receptor A, EDNRA, (27 SNPs), and endothelin receptor B, EDNRB (23 SNPs) using a custom SNPs array. The relative frequencies of NOS-1,-2, and −3, and EDN-1,-2,-3,-EDNRA, and-EDNRB genotypes were evaluated in 608 subjects [128 with OSA, and 480 without OSA (NOSA)]. Furthermore, subjects with OSA were divided into 2 subgroups: OSA with normal endothelial function (OSA-NEF), and OSA with endothelial dysfunction (OSA-ED). Linkage disequilibrium was analyzed using Haploview version 4.2 software.
For NOSA vs. OSA groups, 15 differentially distributed SNPs for NOS1 gene, and 1 SNP for NOS3 emerged, while 4 SNPs for EDN1 and 1 SNP for both EDN2 and EDN3 were identified. However, in the smaller sub-group for whom endothelial function was available, none of the significant SNPs was retained due to lack of statistical power.
Differences in the distribution of polymorphisms among NOS and EDN gene families suggest that these SNPs could play a contributory role in the pathophysiology and risk of OSA-induced cardiovascular morbidity. Thus, analysis of genotype-phenotype interactions in children with OSA may assist in the formulation of categorical risk estimates.
Keywords:Children; OSA; Nitric oxide synthase (NOS); Endothelin (EDN); SNP; Polymorphisms
Obstructive sleep apnea (OSA), is the most prevalent form of sleep disordered breathing both in adults and children [1-3] and has been associated with significant neurocognitive, metabolic, and cardiovascular morbidities [4-8]. OSA is characterized by episodes of total and/or partial collapse of the upper airway alternating with normal breathing during sleep, leading to chronic intermittent hypoxia and hypercapnia, sleep fragmentation and increased swings in intrathoracic pressures. This condition may affect 1– 3% of healthy school-aged children [2]. There is accumulating evidence that OSA is strongly linked to cardiovascular morbidity independent of obesity [9-11]. The presence of altered endothelial function is currently viewed as an early risk marker of cardiovascular disease, and is a relatively common occurrence in both adult and pediatric patients with OSA [12-14], and can precede the onset of hypertension [15]. However, not every child with OSA will develop ED, suggesting that genetic factors may play a role.
Nitric oxide synthase (NOS) is encoded by three distinct genes, namely neuronal NOS (nNOS, NOS1), inducible NOS (iNOS, NOS2), and endothelial NOS (eNOS, NOS3), which are located on chromosomes 12, 17 and 7, respectively. Studies have examined the possibility that SNPs in these genes may influence their expression and functional activity, and potentially alter the predisposition to cardiovascular disease [16-18]. Accordingly, single nucleotide polymorphisms (SNPs) have been identified in NOS genes, and their association with coronary artery disease, hypertension, and diabetes has been explored [19-22]. Considering the potential role of these enzymes in either OSA or its downstream adverse consequences, it is somewhat surprising that the potential associations between NOS polymorphisms and OSA remain thus far unexplored.
The endothelins (EDN) are a family of endothelium-derived peptides that possess vasoconstrictor properties, and are important mediators of both physiological and pathophysiologic processes [23]. The genes encoding for EDN-1,-2 and-3 are located on chromosomes 6, 1, and 20, respectively [24]. Several studies have been identified various SNPs on EDN genes and also in the genes encoding for their cognate receptors (EDNRA and EDNRB), and some of these gene variants have been associated with altered susceptibility and prognosis of diseases such as heart failure, dilated cardiomyopathy, diabetic retinopathy, and atherosclerosis [25-31]. Furthermore, genetic polymorphisms in the endothelin-receptor-subtype-A (EDNRA) gene have been identified as conferring increased susceptibility for OSA in adults [32].
Based on aforementioned considerations, we hypothesized that single nucleotide polymorphisms (SNPs) in NOS- and EDN-related genes in children may contribute to the risk of pediatric OSA or its downstream vascular consequences.
The study was approved by the University of Louisville Human Research Committee, and informed consent was obtained from the legal caretaker of each participant. Consecutive healthy pre-pubertal children (ages 5–10 years) were recruited from the community, and the cohort was enriched for the presence of habitual snoring. All children underwent a standard polysomnographic evaluation in the sleep laboratory at the University of Louisville Pediatric Sleep Laboratory, after which assessment of endothelial function (when possible) and a blood draw were performed between 7:00 to 8:00AM in fasting conditions.
Overnight polysomnography
A standard overnight multichannel polysomnographic evaluation was performed in the sleep laboratory as described previously [33]. Sleep architecture was assessed by standard techniques [34]. The proportion of time spent in each sleep stage was expressed as percentage of total sleep time (%TST). Obstructive apnea was defined as the absence of airflow with continued chest wall and abdominal movement for duration of at least two breaths [33]. Hypopneas were defined as a decrease in oronasal flow of ≥50% with a corresponding decrease in SpO2 of ≥4% and/or arousal [33]. The obstructive apnea/hypopnea index was defined as the number of apneas and hypopneas per hour of TST. Arousals were defined as recommended [35] and included respiratory-related (occurring immediately following an apnea, hypopnea, or snore), technician-induced, and spontaneous arousals. Arousals were expressed as the total number of arousals per hour of sleep time (arousal index). Control children required the presence of an AHI<2 in the absence of a history of snoring as well as no snoring detected during the sleep study. Habitually snoring children with AHI>2/hrTST and a nadir oxyhemoglobin saturation <92% were considered to have OSA [33].
Body mass index
Children were weighed using the InBody 320 scale (Biospace; Cerritos, CA), and height (to 0.1 cm) was measured using a stadiometer (Holtain, Crosswell, UK). The BMI was calculated and the BMI z-score was computed using US Centers for Disease Control and Prevention 2000 growth standards (http://www.cdc.gov/growthcharts/ webcite) and online software (http://wwwn.cdc.gov/epiinfo/ webcite). A BMI z-score > 1.65 (> 95th percentile) was considered as fulfilling obesity criteria.
All children had arterial blood pressure measured noninvasively using an automated mercury sphygmomanometer (Welch Allyn; Skaneateles Falls, New York) at the brachial artery, using the appropriate cuff size on the non-dominant arm.[36] Systolic BP and diastolic BP indices were calculated by dividing the average systolic and diastolic pressure by the respective 95th percentile for BP using National Heart, Lung and Blood Institute guidelines http://www.nhlbi.nih.gov/guidelines/hypertension/child_tbl.htm webcite), computed for age, sex, and height. Hypertension was defined when the SBPi or DBPi was > 1.
Endothelial function tests
Endothelial function was assessed upon awakening from the sleep study in the morning, using a modified hyperemic test after cuff-induced occlusion of the radial and ulnar arteries as previously described [14,15,37,38]. Briefly, a laser Doppler sensor (Periflux 5000 System, Perimed, Jarfalla, Sweden) was applied over the volar aspect of the hand at the 1st finger distal metacarpal surface and the hand was gently immobilized. Once cutaneous blood flow over the area became stable, the pressure within an inflatable cuff placed at the forearm and connected to a computer-controlled manometer was raised to 200 mmHg for 60 sec during which blood flow was reduced to undetectable levels. The cuff was rapidly deflated and the laser Doppler measured hyperemic responses. As previously shown, the time to peak regional blood flow after occlusion release (Tmax) is highly reproducible and is representative of the post-occlusion hyperemic response, an index of endothelial function [39]. A Tmax value ≥45 sec was considered as the criterion for abnormal endothelial function as previously described [9,10,14,15,37,38].
DNA extraction
Peripheral blood samples were collected in vacutainer tubes containing EDTA (Becton Dickinson, Franklin Lakes, NJ, USA). All DNA samples were extracted using QIAmp DNA blood kit (Qiagen, Valencia, CA) according the manufacturer's protocol. The concentration and quality of the DNA were determined using a ND-1000 Spectrophotometer (Nanodrop Technologies, Wilmington, DE, USA). The precise length of genomic DNA was determined by gel electrophoresis using 1% agarose gel. All the purified samples were stored at −80°C until further analyses.
Custom cardiovascular gene SNP array
The IBC array was developed using SNP and linkage disequilibrium information from the HapMap as well as data from Seattle SNPs, and National Institute of Environmental Health Sciences (NIEHS) SNPs [40]. Briefly, the IBC array contains about 50,000 SNPs from genetic diversity across approximately 2100 genes related to cardiovascular, inflammatory, hemostasis/coagulation, and metabolic phenotypes and pathways. Among those genes, we selected the NOS genes which include NOS1 (209 SNPs), NOS2 (122 SNPs) and NOS3 (50 SNPs). Furthermore, we selected the EDN and EDN receptor genes family which includes EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14SNPs), EDNRA (27 SNPs) and EDNRB (23 SNPs). SNPs were clustered into genotypes with the Illumina Beadstudio software and subjected to quality-control filters at the sample and SNP levels separately within each cohort. Samples were excluded for individual call rates <90%, gender mismatch, and duplicate discordance. SNPs were removed for call rates <95% or Hardy-Weinberg Equilibrium p <10−7 in controls from each cohort (regardless of ethnicity). Due to the low-frequency SNPs included in the design and the aim to capture low-frequency variants of large effect across the large dataset, we filtered only on minor allele frequency (MAF) < 0.005.
Total RNA isolation
Fasting peripheral blood samples were drawn from children within the first hour after awakening and collected in PAXgene Blood RNA tubes (Becton Dickinson, UK). Total RNA was isolated using PAXgene Blood RNA Kit and treated with DNase I (QIAGEN, CA), according to the manufacturer's protocol. The RNA quantity and integrity were determined using a Nanodrop Spectrophotometer and Agilent 2100 Bioanalyzer Nano 6000 LabChip assay (Agilent Technologies, Santa Clara, CA).
qPCR validation
Quantitative real-time PCR (QRT-PCR) were performed using the ABI 7500 instrument (Applied Biosystems, Foster City, CA). Complementary DNA was synthesized using a High-Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA). Five hundred nanograms (500 ng) of total RNA from NOSA and OSA samples were used to generate cDNA templates for RT-PCR with primer specific for EDN1 gene. The TaqMan® Master Mix Reagent Kit (Applied Biosystems, Foster City, CA) was in 25 μl reactions. Various negative controls were included in the PCR reaction to ensure specific amplification. Triplicate PCR reactions were performed in 96-well plates for each gene in parallel with the 18S rRNA. The steps involved in the reaction program included: the initial step of 2 minutes at 50°C; denaturation at 95°C for 10 min, followed by 45 thermal cycles of denaturation (15 seconds at 95°C) and elongation (1 min at 60°C). The expression values were obtained from the cycle number (Ct value) using the Biosystems analysis software. The threshold cycle (CT) values were averaged from each reaction, and each gene was normalized to the 18S rRNA level. These Ct values were averaged and the difference between the 18S Ct (Avg) and the gene of interest Ct (Avg) was calculated (Ct-diff). The relative expression of the gene of interest was analyzed using the 2-ΔΔCT method [41]. Quantitative results are expressed as the mean ±standard deviation (SD). Statistical significance was evaluated by the Student's t-test.
Statistical analysis
All analyses were conducted using SPSS software (version 19.0; SPPS Inc., Chicago, Ill.), and data are presented as mean ± SD. The association analysis was assessed by using Pearson's chi-square test implemented in SPSS. A P-value < 0.05 was considered statistically significant for all analyses. Odd ratio and 95% confidence interval were calculated for the minor allele of each SNP. The Haploview version 4.2 software (http://hppt://www.borad.mit.edu/mpg/haploview webcite) was used to analyze the linkage disequilibrium structure, calculating D' to define haplotype block [42] and to estimate haplotype frequencies. Additionally, pair-wise linkage disequilibrium (LD) among the SNPs was examined using Lewontin's standardized coefficient D' and LD coefficient r2 [43], and haplotype blocks were defined according to the method of Gabriel et al. [42] in Haploview 4.2 with default settings. Haplotypes within these blocks were estimated using the estimation of maximization algorithm [44]. The associations derived from the comparisons across OSA and NOSA were assessed in terms of odds ratios (OR) both unadjusted and adjusted for age, gender, ethnicity, and obesity with the corresponding 95% confidence interval (CI).
The recruitment process of children in this study is shown in Figure 1. As indicated in Figure 1, 970 subjects were recruited, and 362 were excluded from the study because they had chronic medical conditions, such as known genetic syndromes, severe asthma or allergies, or they were receiving chronic medications. A total of 608 children were therefore included, and divided into two groups based on their apnea-hypopnea index (AHI) results in the sleep study: 480 children were controls (NOSA) and 128 children fulfilled the criteria for OSA (OSA) based on AHI. The demographic characteristics and polysomnographic findings of children with OSA and NOSA groups are shown in Table 1, and show markedly similar age, gender, and ethnic distribution indicating that the 2 groups were overall matched for these characteristics. As would be expected based on category attribution criteria, the AHI, apnea index and arousal index were all significantly higher in the OSA group (P<0.0001). Furthermore, mean SpO2 levels in OSA were significantly lower than NOSA group (P<0.001). Notably, we did not find any significant differences in systemic blood pressure among the 2 groups.
Figure 1. Schema illustrating the recruitment process in this study. Children were matched for age, gender and ethnicity. Children were excluded from the study, if they had any chronic medical conditions such as known genetic syndromes, severe asthma or allergies, or if they were on any chronic medications.
Table 1. Demographic characteristics in children with and without OSA
From a total of 381 SNPs assayed for the 3 NOS-1,-2 and-3 genes, 15 SNPs in the NOS1 gene and 1 SNP for NOS3 gene exhibited statistically significant differences in their frequencies among children with OSA and their matched controls, even after correction for multiple comparisons (Table 2). Linkage disequilibrium (LD) analysis of the 15 SNPs in the NOS1 gene was assessed for both OSA and NOSA subjects. In NOSA subjects, two haplotype blocks emerged, and are outlined in black triangular regions in Figure 2 (Panel A). In OSA subjects, the haplotype showed the presence of 2 blocks as well (Figure 2, Panel B). The haplotype of these blocks and their frequencies in OSA and NOSA are shown in Figure 3, Panels A and B, respectively. Taken together, the patterns of LD and haplotype frequencies differed between OSA and NOSA, suggesting that some of these SNPs may contribute to OSA risk.
Table 2. Distributions of allele and genotype frequencies of NOS SNPs in children with and without OSA
Figure 2. Pairwise linkage disequilibrium (LD) structure and 15 SNPs of the NOS1 gene. Panel (A) represents children without OSA (NOSA), and Panel (B) represents children with OSA (OSA). The plot was generated using Haploview 4.2 with D' Color Scheme (D'=0, D'<1 and D'=1 shown by white, shades of pink and red (respectively) and pairwise r2 values shown in diamonds. The value within each diamond represents the pair-wise LD (correlation, measured as D') between the two SNPs defined by the top left and the top right of the diamond. Solid lines represent SNPs that were used in the haplotype analysis, and are part of the haplotype from SNP block whereas dashed lines represent SNPs that were used in the analysis, but were not part of the haplotype.
Figure 3. Haplotype frequencies in children with and without OSA. Panel (A) represents haplotype for children without OSA (NOSA), and Panel (B) represents haplotype for children with OSA (OSA).
From a total of 155 SNPs for the three EDN-1,-2 and-3 genes and their associated EDN receptors (EDNRA and EDNRB), there were 4 SNPs in EDN1, and 1 SNP in both of EDN2 and EDN3, in which allelic frequencies were significantly altered in children with OSA (Table 3). No differences emerged for EDN receptor (EDNRA, EDNRB) SNPs. The list and the summary of the significant SNPs in both NOS and EDN genes such as location of these SNPs, percentage of minor allele frequency (%MAF) are shown in Additional file 1: Table S1.
Table 3. Distributions of allele and genotype frequencies of EDN SNPs in children with and without OSA
Additional file 1: Table S1. List of single nucleotide polymorphisms (SNPs) of NOS and EDN genes.
Format: XLSX Size: 11KB Download file
Next, we divided OSA subjects into 2 subgroups based on their individual Tmax values, when such values were available: OSA with normal endothelial function (OSA-NEF), and OSA with endothelial dysfunction (OSA-ED). As shown in Figure 4, Tmax values were significantly higher in the 6 OSA-ED subjects compared to 17 subjects with OSA-NEF (P<0.002).
Figure 4. Individual Tmax values in children with OSA and normal endothelial function (OSA-NEF), and children with OSA with endothelial dysfunction (OSA-ED).
In addition, we quantified the mRNA expression of the EDN1 gene in 18 matched subjects, 9 with NOSA and 9 with OSA using qRT-PCR. As shown in Figure 5, EDN1 was significantly increased in children with OSA compared to NOSA (P-value 0.0005).
Figure 5. qRT-PCR analysis for EDN1 gene expression in children with OSA and controls (NOSA). Data are presented as relative mRNA expression levels normalized to 18s, and individual values and boxplots are shown (OSA vs. NOSA: P-value <0.0005).
In this study, we report on the allelic frequencies associations of NOS and EDN gene families in children with and without OSA. The frequency of specific NOS1 and EDN1 SNPs was significantly associated with the presence of OSA, while the frequencies of all other SNPs tested for the NOS and EDN genes did not show any significant differences between OSA and NOSA. In addition, a subset of the children with OSA showed evidence of endothelial dysfunction even though they were asymptomatic and identified through community-based systematic surveys, thereby confirming previous findings in clinical cohorts on the adverse effect of OSA on endothelial function. Furthermore, in a small subset of children for whom RNA samples were available from peripheral blood monocytes, EDN1 gene expression was elevated in children with OSA compared to controls.
Before we discuss the potential significance of our findings, some methodological issues deserve comment, in particular subject selection considerations and genetic variances. First, we excluded any child with known diabetes, hypertension, or any other chronic disease condition. This approach could therefore have artificially reduced the magnitude of the association of any given NOS of EDN allelic variant with OSA. Second, we narrowed the age range of the current cohort such as to minimize as much as possible any confounding factors that might be operational across a wide age range in OSA. Thirdly, closely matched control children are included which should minimize the effect of modifying factors that could be involved in the process of subject selection. In addition, the use of the laser Doppler technique for assessment of vascular responses following cuff-induced arterial occlusion not only permits reproducible determination of the kinetics of post-ischemic reperfusion, but also serves as an accurate reporter of nitric oxide-mediated physiological recruitment of the microvasculature [37,45]. In this context, we also excluded children with a variety of diagnoses that can be associated with endothelial dysfunction [46]. The two important limitations of this study include the relatively small size of the cohort of children studied which could hamper statistical power, and the absence of endothelin plasma level measurements in blood cells for the genes of interest. Although highly desirable, the latter were not possible due to limitations in the amount of blood samples. However, inclusion of the present preliminary findings on endothelial function are intent on further illustrating future directions that will need to encompass specific gene variants to not only the presence or absence of a disorder, i.e., OSA, but also to the presence or absence of a consequence of the disorder, i.e., endothelial dysfunction. We and others have previously shown significant associations between specific gene candidate variances and OSA-associated phenotypes, and this study adds incremental information to potentially significant contributions of EDN and NOS gene polymorphisms to this issue [8,47-51]. However, the overall modulatory effects of these polymorphisms to the clinical phenotype of pediatric OSA will have to await more extensive studies involving much larger cohorts. Accordingly, we opted not to implement additional valuable analytical methodologies to derive what we perceive as somewhat premature inferential conclusions from such methods [52,53].
OSA is a multi-factorial and highly prevalent disorder in which both genetic and environmental factors may be involved [54,55]. The role of specific genes that influence the development of OSA is unclear. A precise genetic foundation of OSA has been thus far difficult to identify, because it is still unknown whether some of the putative candidate genes for OSA are directly causal to the expression of the disorder or whether their role in OSA is mediated through other intermediate genes. Similarly, the phenotypic expression of OSA and its consequences is most likely determined by multiple genetic and environmental factors and their interactions. Some of the factors assumed to operate as intrinsic genetic determinants of susceptibility [56-58] have been shown to include inflammatory pathways, lipid membrane transport, and growth factors [58]. Additional external factors that have yet to be corroborated in clinical pediatric cohorts include lifestyle components, such as physical activity, and dietary habits. Previous studies have reported that several single nucleotide polymorphisms might be involved in the pathogenesis of OSA both in adult and children, such as serotonin transporter (5-HTT) [59], TNF-α [49,60], fatty acid binding protein 4 [48,61], macrophage migration inhibitory factor [47], NADPH oxidase p22 sub-unit [8,50], and angiotensin I converting enzyme (ACE) [62,63].
In this study, we used 536 SNPs from different genes and pathways to study the association of their allelic frequencies in children with OSA. Here, we show in a total of 209 SNPs assayed with NOS1 gene, we identified 15 significantly SNPs those allelic frequencies were associated in children with OSA. To the best of our knowledge, no studies were conducted on genetic variance of NOS genes in children with OSA. However, several studies have been reported in human using NOS SNPs. For example, several polymorphisms located in NOS1, NOS2, and NOS3 genes have been identified; some of these polymorphic sites could be responsible for variations in the genetic control of plasma NOS levels, which would be a useful tool for studying the relationship between NOS and diseases including asthma [64,65], depressive disorder [66], Parkinson's disease [67], diabetic nephropathy [68], and stroke [69].
The endothelin system consists of G protein–coupled endothelin receptors (EDNR) that are activated by endothelin (EDN) signaling peptides. Specific interactions between the three different endothelin-subtypes (EDN-1, -2, -3) and the two human endothelin receptors (EDNRA, EDNRB) are known [70]. Endothelin-1 (EDN 1), the most potent vasoconstrictor of the human organism, uses mainly the EDNRA as a signal transduction pathway. Our results show different allelic frequencies of EDN polymorphisms between OSA subjects and controls. For example, of 155 SNPs for the three EDN-1,-2 and-3 genes and their associated EDN receptors (EDNRA and EDNRB), there were 4 SNPs in EDN1, and 1 SNP in both of EDN2 and EDN3, in which allelic frequencies were significantly altered in children with OSA. We are only aware of a single published report on genetic polymorphisms in endothelin-receptor-subtype-a-gene as a susceptibility factor for adult OSA [32]. These investigators identified 4 candidate SNPs out of 100 in ENDRA in patients with OSA, but did not ascertain the significance of their findings by haplotype analysis. Endothelin-1(EDN1) is an intercellular signaling molecule expressed in many different organ systems and tissues. Although EDN1 is best known as a potent vasoconstrictor, EDN1 also plays important roles in the kidney, nervous system, and in the heart [71]. Furthermore, genetic polymorphisms in the EDN1 promoter region have been linked to an increased incidence of left ventricular hypertrophy [72], and asthma [73], a known consequence of OSA in children [74]. The increased expression of EDN1 among children with OSA in the present study would further suggest that genotype-phenotype interactions may indeed be present in pediatric OSA and its cardiovascular morbidities. Indeed, several lines of evidence derived from both clinical studies and animal models have shown that increases in circulating EDN1 in OSA [75-77].
In conclusion, our results suggest that the NOS1 and EDN1 genes may confer an increased risk for the presence of OSA or downstream morbidity. The susceptibility to OSA is a multifactorial process and may result from genetic variants in many genes on different chromosomes. Also, genetic epidemiological studies of biological phenotypes involved in the same pathway can provide relevant information, and can contribute to unravel the mechanisms underlying complex diseases such as OSA. More specifically, the changes in EDN1 gene expression particularly when combined with differences in the distribution of EDN1 polymorphisms, suggest these specific SNPs influence the genetic predisposition to OSA. Thus, analysis of the currently identified EDN1 polymorphism may be useful in the assessment of risk for OSA in a high risk population, such as those children who manifest snoring or have enlarged tonsils and adenoids. Further studies should be carried out to confirm the association reported herein in expanded pediatric cohorts, and tentatively include protein and gene expression levels to enable deciphering the importance and functionality of these genetic factors.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
SC performed data analysis, and qRT-PCR validation, DG provided the conceptual design of the project, participated in the data analysis and editing final version of the manuscript, L K-G participated in data analysis and sleep studies, RB participated in clinical data, AAK participated in data analysis and haploview, YW reviewed data, WS participated in general discussion and review data, and AK carried data analysis, overall the project and SNPs analysis, writing and editing manuscript. All authors read and approved the final manuscript.
Funding sources
DG is supported by National Institutes of Health grants HL-065270 and HL-086662. SC is the recipient of the Royal Golden Jubilee Ph. D. Program Award from the Thailand Research Fund (PHD/0138/2552).
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Pre-publication history
The pre-publication history for this paper can be accessed here:


text:
Talk to me, December.
Tell me where you hid the green.
What secrets do you hold inside your mittens,
under your hat?
You practice your seasonal math,
knowing the requirement for fourths.
Stick branches poke into the skies,
licorice or clarinet against the grayish-blue.
You hum your melodies composed of wind,
surprise us with the first fresh fall of snow.
December, culmination of the warming,
warmed, then cooled, now cold.

subset: commoncrawl


text:
Rated 4 out of 5 by 1 reviewer.
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text:
Optimizing Strategies to Improve STD Partner Services
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
This research tests the effectiveness of a social cognitive intervention (with option of patient-delivered medication) geared toward increasing patient referral of partners.
Chlamydia Trachomatis
Neisseria Gonorrhoeae
Behavioral: Social Cognitive Counseling
Phase 1
|Study Type:
|Study Design:
|Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Educational/Counseling/Training
|Official Title:
|Optimizing Strategies to Improve STD Partner Services
- Partner notification 1 month
- Repeat Infection 6 month
- Intent to notify partner baseline post-test
- Changes in relationship 1 month, 6 month
|Estimated Enrollment:
|Study Start Date:
|June 2001
|Estimated Study Completion Date:
|August 2005
This is a four-year study involving longitudinal data collection for 800 men and women recruited from four clinics in Brooklyn, NY. Participants were eligible for enrollment at any of the study sites if diagnosed as having C trachomatis or N gonorrhoeae genital infection or if they have an STD syndrome likely to be related to either of these pathogens (i.e., males with NGU). Consenting patients were randomly assigned to receive either standard-of-care patient referral for partner notification (N = 350), a social-cognitive intervention geared toward increasing patient referral (N = 350), or the social-cognitive intervention with an option of patient-delivered medication (N = 100). Evaluation activities include an interviewer administered measure provided at baseline, one month, and six months, a screen for N gonorrhoeae and C trachomatis using urine-based ligase chain reaction screening (Abbott LCx) at baseline and six months, and medical chart abstraction at one and six months.
|Ages Eligible for Study:
|18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- Any individual presenting at study sites with STD-related symptoms who receives a microbiologic diagnosis with N gonorrhoeae and/or C trachomatis will be eligible for study participation if they meet the following criteria: 1) are 18 years of age or older; 2) have been sexually active in the previous two months; 3) are able to understand English or Spanish; 4) have resided within the catchment area for at least one year prior to enrollment; 5) plan to remain in the area through the course of the study period. .
Exclusion Criteria:
- Any potential participant deemed by a provider or member of the study staff to have psychological impairment, brought on by drug use or some other illness, to an extent that it would affect the ability to understand or provide informed consent.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00207454
|United States, New York
|STD Clinic at Kings County Hospital Center (KCHC).
|Brooklyn, New York, United States, 11203
|Principal Investigator:
|Tracey Wilson, PhD
|State University of New York - Downstate Medical Center
No publications provided
|ClinicalTrials.gov Identifier:
|NCT00207454 History of Changes
|Other Study ID Numbers:
|Study First Received:
|September 13, 2005
|Last Updated:
|September 13, 2005
|Health Authority:
|United States: Federal Government
Keywords provided by Centers for Disease Control and Prevention:
Partner Referral
Social Cognitive Intervention
Partner Delivered Medication
ClinicalTrials.gov processed this record on October 09, 2015


text:
In part three of this series, phase one of a radio frequency identification (RFID) implementation was outlined and discussed in detail (please see Radio Frequency Identification Implementation: The First Steps. For more background on RFID, please see previous parts of this series: Are You Tuned into Radio Frequency Identification? and A How-to Guide for a Radio Frequency Identification Site Survey.
Phase Two: Test and Validation
Since RFID is uncharted territory for many organizations, deployment represents a long journey. Best practices indicate that organizations involve an experienced person who understands existing operations, systems, and processes. As a provisionary measure, someone with additional expertise in interpreting data, which provides value to the supply chain part of the business, should be also engaged. Usually a business analyst that can configure, interpret, and modify the system for ongoing and post-implementation support becomes necessary.
Organizations may not realize the intricacies of RFID technology and the need for a commitment to the project. Integration partners have recognized this trend and have adapted their business models toward a service integration model. Value-added resellers (VARs) and implementers have addressed this lack of expertise, and they are heavily leveraged as professional services organizations. The partner fills the business analysis expertise gap in order to evaluate business practices and the ability to create workflows, and to understand the current information infrastructure. Best practices dictate that Project Management Institute (PMI) methodology be followed: proper RFID expertise should be employed, workflows should be created, and realistic performance targets, milestones, and responsibilities should be followed.
Following are the steps in phase two of an RFID implementation:
Phase Three: Pilot Implementation
Best practices indicate that the objective of the pilot program is to develop predictability and scalability to accommodate as many scenarios as possible that affect the business on a day-to-day basis. In phase three, achievement of precision, placement, output, and performance will need to be verified and recorded. The recording of the findings will provide a useful troubleshooting and training tool, and can act as a knowledge transfer document for personnel. At this point, proper label placement should have been established, and reader interaction and flow of data among systems should have been dealt with in the previous phases.
The pilot implementation is actually a test of the complete system in the full working environment where the production system will exist. The difference is that the operation and use of the system will be scaled back to manageable portions. Load testing should expose any further flaws in business processes and anomalies within the system, and should allow the full operational scale that is required to run the business on a daily basis.
Best practices suggest completing a checklist of tasks during the pilot phase of the project. If a "yes" is checked for one item, then proceed to the next item. If the answer to an item is "no," then re-perform that task before advancing to the next one.
Table 1. Pilot implementation checklist.
If the automation process is causing delays in production, consider a manual operation. If time is running short, the organization should consider making the application of smart labels a post-production step rather than incorporating it into the manufacturing process. Deconsolidation and re-palletizing might be a short-term solution (slap and ship). This will allow a quicker deployment time if necessary.
Many slap and ship solutions contain the basic necessities to satisfy an RFID mandate (such as offering the option of tags to be applied), but they do not require the heavy investment that a full implementation does. The concept is this: the organization can apply the tags and verify the information without needing to buy extra features it does not require. Many WMS companies offer a slap and ship package that is usually added just before product leaves the warehouse. These kits usually include readers, tags, and encoders, and sometimes a light version of middleware to manage the data and hardware. For the supplier issuing the mandate, this usually satisfies the information requirement.
Best practices recommend a phased approach to an RFID implementation. Such an approach will allow for manageable tasks that can be controlled and rectified if necessary. Use of a vendor, a handful of product items, information flow between suppliers, and business procedures should all be validated. When a problem occurs, its magnitude and whether the number of resolutions is manageable will determine how easy it is to troubleshoot. When the organization completes the RFID transactions, a combination of system and manual verification should occur to validate that everything is correct. Data that is manually interpreted for validity (checking if product data is correct) and tracked throughout all the systems affected (interface validity) confirms that the end-to-end test is validated.
Once the end-to-end test is verified, the organization should add suppliers and products gradually so that should an issue arise, it will be easier to manage. In other words, troubleshooting will be more manageable in portions of data; application corrections can be made more easily (if necessary) and the resources can be allocated to handle the crisis. The concept of adding the suppliers and products one by one allows the users to see if a problem exists with a particular product or supplier. If a supplier has made an error, the steps to correct the error should be minimal, as the other customers and products have already been validated. Resolving the problem involves dealing with the issue internally as well as informing the trading partner in question if the problem exists on its side as well. Collaboration will allow a quicker resolution to the problem. Once all products are live, all suppliers are satisfied with the state of integration, and data integrity is tested, then it is safe to progress to the fourth step of the implementation process.
Stay tuned for the final phase and cutover of an RFID implementation, covered in the next part of the series Are You Tuned into Radio Frequency Identification?
For more information and to start your own custom solution comparison, please visit


text:
Scott Fly'Air £400
Best for: Nippy short turns
The front 35cm of the Fly'Airs is rockered, and their sidewall construction incorporates a paulownia wood core, reinforced with fibreglass. They're deemed best of this category for short turns, also scoring excellently for low speed, liveliness/responsiveness and moguls. These extremely light touring skis are super easy to manoeuvre, especially in bumps, and reasonably smooth on edge in long turns. They're better on piste than off, but can handle anything as long as you don't go too fast.
Pros: Short turns, low speed, liveliness/responsiveness, moguls
Cons: Straight-line stability, off piste
Lengths 155, 165, 175 Sidecut 118/78/108 (175) Radius 14m (175)


text:
To celebrate the new partnership with Arizona Youth Soccer, on Saturday, March 23rd all Arizona Chipotle locations are hosting "AYSA Jersey Day". This event will provide AYSA players (wearing their jersey's) and their families with a special "Buy One/Get One Free" promotion!
AYSA would like to thank Chipotle for their partnership and encourage all members to take advantage of this special promotion!
Note: Coupons are not required. To receive this offer, players must wear their jersey's into the location to take advantage of this promotion.


text:
Mac2Matt: Oregon opens Matthew Knight Arena
EUGENE, Ore. (AP) — Oregon is finally opening Matthew Knight Arena, the $227 million replacement for aged but beloved McArthur Court.
The debut of the Ducks' new court was originally supposed to happen at the start of the Pac-10 season, but it was delayed back in August just in case the school's football team went to a bowl game. Smart move, because it turns out that Oregon went to the BCS championship.
The Ducks played their last game at Mac Court, as it was known, on New Year's Day. Oregon fell 60-55 to Arizona State.
Now that the big football game — a 22-19 loss to Auburn on Monday night — is over, Oregon's focus turned to the gala opening Thursday night of the 12,500-seat facility, named after the late son of Nike co-founder and Ducks benefactor Phil Knight and his wife, Penny.
Nike made special "Mac2Matt" T-shirts to commemorate the opening.
GOING TO THE GAME? Parking information | Share your fan photos
Southern California (10-6, 2-1 Pac-10) is the first team to visit the Ducks (7-9, 0-4) in their new building, which features a distinctive floor painted to look as if it's shaded by a forest.
First-year head coach Dana Altman said the team just had its first practices on the intricately designed floor this week, which some have suggested may take players some getting used to.
"The floor is something I think they like, and I don't think they'll have problems with it at all," Altman said.
The Knights donated $100 million to the athletic department's Legacy Fund, which helped jump-start the new arena project. Their son Matthew died in a 2004 scuba diving accident in El Salvador, where he was working for an orphanage.
Mac Court was the second oldest active on-campus arena in Division I, just two years younger than Fordham's Rose Hill Gym. The first men's game was played there on Jan. 14, 1927, when Oregon defeated Willamette 38-10.
The building was later home to the Oregon's famed "Tall Firs" team, which beat Ohio State 46-33 to win the first NCAA basketball championship in 1939.
What Mac Court lacked in modern conveniences, it made up in character. Known as one of the more intimidating courts in the Pac-10, the raucous "Pit Crew" could shake the baskets just by stomping.
Altman said the new arena, with a state-of-the-art video scoreboard that has been dubbed "Knight Vision," should stand the test of time too, and will likely help with recruiting.
"Great venue," he said in a conference call with Pac-10 coaches earlier this week. "I think our fans will really enjoy it. I think our players definitely will — new locker rooms, the player's lounge, all those things will make it a great home for us."
Copyright 2011 The Associated Press.


text:
|Men's Basketball » Schedule » Roster » News » Statistics » Coaches » Camps » Archives
Lipscomb (12-13, 7-6 A-Sun)
Stetson (8-17, 5-9 A-Sun)
2/11/2012 | DeLand, Fla. (Edmunds Center) | Attendance: 1542
Saturday, February 11, 2012
DELAND, Fla. - The Lipscomb men's basketball team entered Saturday's Atlantic Sun Conference game against the Stetson Hatters with several question marks following the dismissal of all-conference guard Jordan Burgason.
The Bison (12-13, 7-6) overcame the adversity and question marks to win a gritty 99-91 overtime battle against Stetson (8-17, 5-9). Lipscomb won 104-103 in overtime in the first meeting between the two teams on Jan. 16 in Allen Arena.
With the loss of Burgason and his 16.4 points per game, three Bison stepped up and reached career scoring highs. Junior Deonte Alexander led Lipscomb with 27 points while freshman Marvin Williams had 16 points and freshman Damarius Smith posted 14 points.
"I'm really proud of our guys with all that has gone on this week," said Lipscomb head coach Scott Sanderson. "It's about 'team' and when something happens you have to rally around each other. I thought we had a really good team effort."
Marvin Williams scored 14 of his points in the opening period as the Bison led 43-37 at halftime.
Stetson utilized a 13-2 run to take a five-point lead with 3:47 to play in regulation. Alexander cut the game to 69-67 with a three on the next possession. Lipscomb scored its next two baskets on fastbreaks following Stetson turnovers.
With about ten seconds to play and the game tied, Alexander missed a running jumper and Stetson pushed the ball down the court on the break. Damarius fouled Stetson's Willie Green to prevent a layup. He made both free throws to put Stetson ahead with 6.4 seconds left.
Damarius took the inbounds and went coast-to-coast making a layup and picking up a foul with 1.6 ticks left. He missed the free throw and the game went into overtime tied at 74.
Lipscomb scored on its first six possessions in overtime and posted 25 points in the extra five minute period.
The Bison led 42-36 on the boards. Marvin Williams, Justin Glenn, and Malcolm Smith had six boards each.
Lipscomb shot 47.8 percent from the field and 3-of-15 (20 percent) from beyond the arc. Stetson shot 47.6 percent.
Lipscomb had 52 points in the paints and connected on a season-high 30-of-42 free throws.
Adam Pegg led four Hatters in double figures with 18 points. Green had 17 tallies.
Lipscomb continues its road trip Monday night against Florida Gulf Coast in Ft. Myers, Fla, at 6 p.m. central. The Lipscomb Sports Network presented by Jackson will carry the action on 102.5 The Game.
Men's Basketball Archives
2011-12 Men's Basketball


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Perspectives for Sustained Prosperity in AsiaMarch 5th, 2012
I recently met a distinguished historian who confidently told me that 'Asia' didn't exist until Europeans invented it.
Each of the many nations in the region, he explained, thought itself unique and apart from the others, a continent unto itself, until European traders came and gave the region a single unifying name.
An elaborate argument, but he was wrong. Asia has existed for millennia and the glue that holds this unique continent together is a set of core values that just about all Asians share – values that center on family, education and financial thrift.
While it is true that there is great cultural diversity across the continent, it is these core values, more than anything else, that define what it means to be Asian. They are at the heart of an identity that all Asians, from Turkey to Thailand, recognize and adhere to with pride.
Asia Is Big
Just about every aspect of Asia is impressive.
With about 30% of the planet's land area, Asia is the world's largest continent. Asia is also rich. It possesses vast mineral and agricultural resources. But, without a doubt, the continent's most valuable resource is its large and industrious population. Asia is home to just under 4 billion people, about 60% of the world's population.
Three of the four most populous countries in the world are located here. About 1.4 billion people live in China, about 1.1 billion live in India and about 230 million live in Indonesia.
Asia also supports a wide array of cultural diversity. More than 2,100 languages are spoken in its 48 independent nations and the world's four major religions were born here – Buddhism, Christianity, Hinduism and Islam.
While Asia can be proud of this rich heritage, history is still being made here today. Where once only wrenching poverty and fabulous wealth existed, a huge middle class is now rising up and flexing its economic and political muscle.
Asia's Economic Miracle
The success of Asian nations competing in the world economy is well known. Chinese electronics, Korean cars, Indian call centers, Japanese robots – the list of product categories that Asian nations dominate is almost endless, and it is continually growing longer.
Looking at Asia's gleaming cities and powerhouse economies, it is hard to imagine that only 60 years ago Japan, China and the East Asian 'Tigers' were just beginning to recover from the devastation of World War II. Cities were in ruin, refugees were abundant and food was in short supply.
With Asia's traditional values of family, education and financial thrift to guide them, millions of entrepreneurs and small businesses began the arduous task of rebuilding. They succeeded beyond everyone's wildest expectations. Today, many East and Southeast Asian countries can be counted among the most economically advanced nations in the world.
China and Japan have significant aerospace and satellite capabilities and are gearing up to produce commercial aircraft. Thailand is becoming one of the world's major automotive engineering and manufacturing centers. Indian firms are playing an increasingly dominant role in software and systems development. Korean firms have taken the lead in television and computer display technology.
Will Growth Continue?
The question is whether Asian economies can sustain the current furious pace of growth over the long term. The answer, I believe, is both yes and no.
Can the huge trade imbalances that currently fuel the growth of Asian economies be sustained over the next 50 years? In my opinion, they cannot.
Trade patterns between Asia and the rest of the world will eventually balance out. But that doesn't mean that the region's economies will slow down. In fact, I am sure they won't.
Gross Domestic Product is not purely a function of inbound or outbound trade, investment and domestic consumption are also important factors.
Countries like China, India, Korea, Thailand and Indonesia, are investing heavily in sophisticated infrastructure, education and industrial productivity. This, I am sure, is the beginning of an important transformation.
Asian nations are taking the funds gained though export-driven trade policies and redirecting them into the domestic sector. This redeployment of capital has many positive impacts, but most significantly, it is creating an affluent middle-class. In the last three years China has doubled the number of citizens earning US$12,500 a year to 500 million.
As more Asians become affluent, there will be more spending and more saving. Both these activities stimulate and sustain economic growth.
The only danger I can see is Asians abandoning their traditional emphasis on fiscal prudence. Consumption is needed to stimulate the economy, but if consumers over-consume, the economy can be damaged.
Striking the right balance won't be easy, but a proclivity towards traditional Asian thrift will help countries like China, India, Singapore and Korea to maintain growth without excessive debt.
Building Trust
Asia-based companies tend to keep logistics and supply chain operations in-house. This trend is driven by a lack of trust in outside service providers and by a lack of appreciation for how complex modern supply chain processes are becoming.
This is frustrating for us and, as the recent Japanese earthquake and tsunami demonstrated, it can create unexpected and costly problems for companies that manage their own logistics.
In the wake of the devastation in Japan, many companies experienced supply chain disruptions that sometimes took weeks to overcome. We have to demonstrate to Asian businesses that we have the world's best logistics resources and an unrivaled expertise in transport and inventory management, and that we are consistently reliable.
Given that Asian companies are notoriously conservative about outsourcing functions such as supply chain management, building this kind of trust is a challenge that is going to take some time.
What the Future Holds
Over the past 50 years, Asian businesses have learned from the West about the importance of nimbleness and innovation, and they applied what they learned extremely well.
But the world is now learning something from Asia. The deeply rooted values that put family, education and financial thrift at the center of every Asian's life are now resonating around the world.
I believe that this two-way exchange of values between East and West bodes well for everyone everywhere.
As my future grandchildren grow into productive adults, I don't want them to think of themselves as Asian or Western. I want them to think of themselves as international citizens who naturally combine the best values from both worlds.
I want them to cherish their family and value education as Asians do. But, I also want them to approach the tasks and problems they will encounter in their lives innovatively, like a Westerner, and to be able to react to opportunities with nimbleness.
In this sense, I believe that the future of Asia is the future of the world … and vice versa.
Leave a comment
William Katunda, Business Analyst, Congo (DRC), DHL Global Forwarding: "The future of logistics tends to silence an era of transport professionalism in a chaotic perfectionist endeavour. It might voice the consumer's hyper-saturated need for instant-delivery fancies, soon driving to immaterial cargo teleportation and/or instant delivery-appearances".
Hello, i believe that i saw you visited my weblog thus i got here to "return the favor".I'm attempting to in finding things to improve my web site!I guess its good enough to use a few of your ideas!!
With the amount of troubles worldwide right now, from political issues towards the overall economy, I don't know which one to be concerned a lot more. Most straining us out! Who in order to election with regard to, tips on how to secure my own cash, will i keep my own work, maybe there is war?


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Although I do not support the actions of the French military, by "enjoying the local tourist attractions" I assume you mean "illegally monitoring and hampering French nuclear tests". Still, the French were at fault for the death of Fernando Pereira.
It reminds of the flash mob pranks, but I`d say this is one of them.
Of course they do! What about the French government's joke on the innocent civilians on board the Greenpeace vessel Rainbow Warrior, docked in the neutral country of New Zealand and enjoying the local tourist attractions? That joke was a real blast!


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Ink and watercolour on paper, 5x7 inches. The original drawing is sold.
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Win Hall & Oates Tickets This Thursday!
September 25, 2013 9:01 AM
101.9 Lite FM welcomes Daryl Hall & John Oates to the Warner Theatre in DC next Wednesday, October 2, and we have tickets!
Listen to win yours throughout the day on Thursday– TICKET THURSDAY– beginning with Greg Carpenter and Mary Anne Perry at 8:55am.


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Your presentations don't happen in a vacuum. Whether it's an online meeting, a customer demo or sales presentation, you may need to switch presenters. Good news! The Zoho Meeting Team has revamped the Change Presenter feature to make it easier for you and your audience.
'Share My Screen' option for Participants
Previously, only the Presenter of the meeting can change the presenter role to a Participant. To make this easier, we have introduced a 'Share My Screen' option to let an attendee request to share his or her screen when desired. A light-weight application will be downloaded, and the Participant can share the screen once the Presenter approves the request. Further, to make it smoother, we have also introduced an easy launching set up in Google Chrome browser on Windows OS.


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Built to harness the power of next generation consoles NHL 15 allows you to experience the sights, sounds and feel of real hockey action like never before. The game features a new level of player likeness, intelligence and emotion, the most diverse and animated crowd of any sports game and an added level of control as you dangle opponents using the accessible Superstar Skill Stick.
There are currently no cheats available for NHL 15.
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In response to recent concerns voiced about vaccine rights, this is a case of the rights of the many vs. the rights of the few. Vaccines only work to preserve the general population if "herd immunity" is achieved, when vaccines are administered to a high percentage (85 percent).
With fewer parents vaccinating their children whether due to personal choice, safety concerns or greater awareness of the health risks to a susceptible child, this high percentage is not being met in some areas and outbreaks have occurred. Our medical community is rightly concerned and has tightened the circumstances under which a parent may refuse to vaccinate their children.
Is the information now required too onerous or private for our government to collect? Good point. Are so many parents now refusing to give vaccines that the rest of the population is at risk? And doesn't that majority have the right to health? Good point. Both groups have their rights infringed. Which group is larger? Which rights are more important?
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Hyper-V Program Manager
When you install the Virtual Machine Additions under Virtual PC you get a lot of benefits. You get faster performance, integrated mouse cursor support, folder sharing, clipboard integration, drag and drop integration and dynamic desktop resizing. There are times - however - when all this integration can be a problem. For instance, you may be working in an environment where you do not want to be able to easily transfer data between the host and the guest (for security or confidentiality reasons). It is possible, thought non-intuitive, to disable folder sharing,clipboard integration, drag and drop integration and dynamic desktop resizing while still having improved performance and mouse cursor integration.
To do this under Virtual PC 2007 (note - this will not work on earlier releases), you need to go into the guest OS and delete the following registry key:
[HKEY_LOCAL_MACHINE\SOFTWARE\Microsoft\Windows\CurrentVersion\Run]"VMUserServices"="C:\\Program Files\\Virtual Machine Additions\\vmusrvc.exe"
When you restart the virtual machine these services will now no longer be present (you may want to delete 'vmusrvc.exe' if you are worried about users starting it themselves).
I want to know how to disable audio! The darn hardware beep still works even when I turn off all sounds.
I really admire Virtual PC for keeping things as simple as possible. However, it's things like this that frustrate me.
Mostly Virtual PC just works the way I expect it to work. But there really should be an "Advanced" panel with a few extra options and tweaks.
(While I'm whining) It would also be really helpful if there were a few more tools provided. Virtual PC can read virtual floppy, hard, and compact disks, but it comes with no tools to allow access to these from the host (vhdmount finally arrived, but still not easy to get installed on VPC machines, and still no access to VFD or ISO files). A simple tool to make an ISO from a CD, to make a VFD from a floppy, and vice-versa would be great.
Another helpful tool would be a way to access the virtual serial ports. I only have so many real serial ports, and I run out quickly if I try to do a loopback. The named pipes are nice, but none of the tools I want to use (terminal emulators, etc.) support connecting over named pipes. A tool to expose the guest serial ports as virtual serial ports would be very helpful.
Ok, I'm done whining (for now).
If you're using Windows, you can disable the beep in Device Manager (in the VM). Click View-->show hidden devices, then expand Non-Plug and Play Drivers(Devices) and disable Beep. Reboot the Vm and you're done.
To make an ISO CD image from a CD, and vice-versa:
I don't remember if I tried using it to make a DVD image from a DVD. In XP it can't burn a DVD from a DVD image, but other tools can. The Windows 2003 Resource Kit has a tool DVDBURN which works in Windows 2003, and documentation suggests that it would work in XP but I didn't try it.
> I want to know how to disable audio! The darn hardware beep still works even when I turn off all sounds.
You can disable it using regedit in virtual machine:
[HKEY_CURRENT_USER\Control Panel\Sound]
It would be useful to more people to be able to restart the clipboard sync when it up and dies.
I'm guessing that killing and restarting the process would do that?
Or... you could use MS virtual server.
Gae -
For the beeping issue - try 'net stop beep'.
dcook -
Yes - I agree with you on this. In the Windows Server virtualization release we provide some very simple UI to allow you to turn integration features on and off from the host operating system.
In regards to tools for VFDs / CDs / etc... This is something that we have discussed internally a number of times - and at least for now we beleive that this is best left to third party tools (like www.winimage.com)
Xepol -
Restarting this executable is something to try - I do not know if it will help though.
Actually I was wonder how to ENABLE drag and drop integration. I am using Windows XP, Virtual PC 7.0.3 and OS 10.4.11.
I was using Windows 98 (i know--ancient,but it's all I had) under same setting above, but upgraded the Windows to XP. In Windows 98, the drag and drop between OS X and Windows worked fine.
But for the life of me, I can't get it to work now that I upgraded. Any ideas?!


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FEMA Floodplain Program
Unincorporated County Floodplain Program
Flooding Information
Flooding Information
90 percent of all natural disasters in California are flood related. All rivers and creeks have floodplains that flood on a regular basis. This flooding is natural and serves a beneficial function. Unfortunately, floodplains have also been a prime area for development. As a result, many homes and other structures are currently in danger of flooding.
Floods in this area often occur with little or no warning. However, by being aware of your flood risk, you can prepare ahead of time to save lives and property.
Flooding in our area are from many different sources:
Backed up creeks that overflow
Drainage inlets / pipes may become blocked
Heavy rainfall that overwhelms our storm drains or creeks
Levies that break as a result of high tides, heavy rainfall, or rapid snowmelt
Floodwaters can damage cover many blocks to a depth of several feet.
Notify Me
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Reducing Flood Damages


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Bollywood star denies Banderas affair, while he's linked to Sharon Stone
Mallika Sherawat denies rumors that she and the actor had an affair that brought his 18-year relationship with Melanie Griffith to an end.
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Albany NY (March 28, 2013) (CULRAV.ORG) –
According to Transparency Market Research (www.transparencymarketresearch.com)" Global Oleochemicals Market (Glycerine, Fatty Acids, Fatty Alcohols), Downstream Application Potential, 2010 – 2018", the global market for oleochemicals was estimated to be over 13 million tons in 2010 which is expected to reach 15 million tons by 2018, growing at a CAGR of around 6.0% from 2013 to 2018. Asia Pacific is the fastest growing market for oleochemicals, growing at a CAGR of 8.2% from 2013 to 2018.
Browse the full report at http://www.transparencymarketresearch.com/global-oleochemicals-market.html
The global market for Oleochemicals was led by Asia Pacific market sharing approximately 68% of the global market in 2011. Asia Pacific also accounted for over 60% of the global capacity for oleochemicals in 2011. Europe was the second largest market with 18% of the global market for the same year.
Oleochemicals are widely used in many industries including soaps and detergents, plastics, rubber, lubricants, paper, paints, coatings and personal care. Personal care and soap & detergents account for the largest segment, whereas food and beverages segment is the fastest growing segment, growing at a CAGR of 6.9% from 2013 to 2018.
Some of the major factors driving the global market of oleochemicals include the growing demand for environment friendly products and regulatory/government support for the production of oleochemicals. Some of the factors acting as barriers to the growth of global oleochemicals market include poor utilization rates practiced in the industry and rising feedstock cost, especially in the European market.
However huge opportunities lie in the Asia Pacific market owing to growing demand for oleochemicals in emerging countries like China and India. Malaysia and Indonesia are two countries where abundant raw material is available at cheap rates. Indonesia is also the largest producer of coconut oil, which is used as one of the major feedstock for producing oleochemicals.
Some of the major players in the oleochemicals market include Myriant, Genomatica, Gevo, Amyris, Solazyme, Codexis, Metabolix, Wilmar International, Emery Oleochemicals, Evonic, and Goldschmidt among some other companies
This research is specially designed to estimate and analyze the demand and performance of oleochemicals in global scenario. This research provides in-depth analysis of oleochemical manufacturers, trend analysis by segments and demand by geography. The report covers all the major segments of the global oleochemicals market and provides in-depth analysis, historical data and statistically refined forecast for the segments covered. The study presents a comprehensive assessment of the stakeholder strategies and winning imperatives for them by segmenting the global oleochemicals market as below:
- Oleochemicals Market, by Types:
-Fatty Acids
-Fatty Alcohols
- Oleochemicals Market, by Applications:
-Pharmaceuticals and Personal Care
-Food and Beverages
-Soaps and Detergents
The report provides a cross-sectional analysis of all the above segments with respect to following geographical markets:
- North America
- Europe
- Asia-Pacific
- Rest of the World (RoW)
Related Report:
Automotive Plastics Market By Product (ABS, PP, PU, PVC, PE, PC, PMMA, PA), By Application (Power Trains, Under the Hood, Electrical Components, Chassis, Furnishing), Bio-based Opportunity (PLA, PHA, PCL, PBS) – Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 – 2018
The global automotive plastics market is witnessing an upsurge in demand due to an increase in passenger cars production and increasing utilization of automotive plastics in designing of vehicles. Plastic helps in reducing the weight of vehicles, improves aesthetics, controls vibration and noise, and helps in cabin insulation. Plastic can be used in interior, exterior, and under bonnet components of automobiles. Properties of plastic like easy moldability, scratch resistance, recyclability, high volume to weight resistance, impact strength, thermal stability, and resistance to abrasion makes it suitable for use in automobiles and are the major reasons for its growing demand globally.
Reasons to Buy this Report
This report provides leading industry opinions that help you stay abreast of the latest news and trends
It provides a comprehensive overview of forces driving and restraining the market growth
It will help in making more informed decisions with in-depth analysis of market performance
It provides an outlook on different market issues affecting the industry
It provides a six-year forecast assessed on the basis of market projections
Automotive Plastics Market Segmentation
Segmentation of the automotive plastics market is as follows:
High Density Polyethylene
Polymethyl Methacrylate
Acrylonitrile Butadiene Styrene
The research study on automotive plastics market analyzes the global market size, current market trends, and market figures. It analyzes the overall market growth rate, recent advancements in the automotive plastics market along with Porter's five force analysis and detailed company profiles of top industry players. It also discusses micro and macro factors significant for the existing market players and newly emerging companies with value chain analysis.
Major regions analyzed under this research report are North America, Europe, Asia-Pacific, and the Rest of the World.
The key players dominating this market are Akzonobel N.V., Basf Se, Bayer Material Science Ag, Borealis Ag, Delphi Automotive PIc, The Dow Chemical Company, Evonik Industries, Faurecia S.A., Grupo Antolin-irausa S.A., Hanwha Azdel Inc., Johnson Controls Inc., Lear Corporation, Magna International Incorporated, Momentive Performance Materials Inc., Owens Corning, Quadrant Ag, Royale Dsm N.V., Saudi Basic Industries Corporation (Sabic), Teijin Ltd., Zoltec Company Inc., and others.
About Us
Transparency Market Research is a global market intelligence company, providing global business information reports and services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insight for thousands of decision makers. We are privileged with highly experienced team of Analysts, Researchers, and Consultants, who use proprietary data sources and various tools and techniques to gather, and analyze information.
Our data repository is continuously updated and revised by a team of research experts, so that it always reflects the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.
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Richard Blumenthal appears in the following:
Thursday, June 27, 2013
After yesterday's Supreme Court decision to strike down the Defense of Marriage Act (DOMA), married same-sex couples became entitled to recognition in the 12 states that currently allow gay marriages. But there was another issue the ruling did not touch—discrimination against gay individuals in the workplace. Senator Richard Blumenthal is on The Takeaway to explain why he sponsored this bill, and how the Supreme Court's decision on DOMA affects its future.
Newtown Shooting: The Monday After
Monday, December 17, 2012
We continue to cover the latest news from Newtown, CT, where 27 people were killed in a mass shooting. With:
- WNYC's Richard Hake, provides the latest news updates.
- Dr. Alex Afshar, head of Family Health Care Center of Newtown talks about trauma counseling after the shooting.
- Connecticut Senator Richard Blumenthal on what action the Senate will take and how his office is responding.
- Connecticut Congressman (CT-1) John Larson on what he is doing for his constituents.
- Evan Osnos, New Yorker China reporter, discusses a 36 year-old man's knife attack on an elementary school in China over the weekend in which all 22 victims survived.
Sen. Richard Blumenthal Calls for Investigation of Legality of Asking Job Applicants for Facebook Passwords
Monday, March 26, 2012
Senators Richard Blumenthal from Connecticut and Charles Schumer of New York wrote to the Department of Justice and U.S. Equal Employment Opportunity Commission on March 25 asking them to investigate whether requesting and using prospective employees' social network passwords violates current federal law. We're joined by Sen. Blumenthal (D-Conn.) to find out why he chose to take action on the issue.
Senator-Elect Blumenthal
Monday, November 08, 2010
Connecticut Senator-elect Richard Blumenthal discusses his win over Linda McMahon and his agenda as he heads to Washington D.C.


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Most young people who try drugs or alcohol do not develop substance use problems. For some, it can become a problem.
During your teenage and young adult years, you will likely be faced with decisions about drinking or using other drugs. Adolescence and young adulthood is a time for trying new things, and deciding whether to use alcohol and other drugs is a personal decision. The decisions that you make can have an impact not only on yourself, but on others in your life as well. Some young people will choose not to use substances, others will try them and decide not to use again, and a small percentage will continue to use.
Substances include
- alcohol
- illegal or street drugs (examples include marijuana, ecstasy, cocaine, heroin, or crystal meth)
- prescription drugs which are used in a non-medical way (in a way not prescribed by a doctor)
- over-the-counter medicines which are used for recreational rather than medical purposes
All substances have risks associated with them, and their use can negatively impact your current life and future dreams.
In this section you will find information and resources for dealing with substance use.
Our goal is to help you better understand how the use of alcohol and other drugs is impacting you, and to give you tips on how to reduce potential harms.


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|Found Dog
|Written by Noah Lockamy
|Monday, 29 August 2011 09:44
About 9 pm on Friday, August 26, a male, Golden Retriever, was found at the Moose Lodge and is still there. No identification, other than an invisible fence collar. It looks to be between 8 to 10 years old and is very friendly. Please call 828-264-3804 and ask for the bartender on duty.
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When you can't sleep, or wake up in the middle of the night and can't go back to sleep -- don't reach for sweet snacks! Have a half of a banana instead. I heard that bananas have something in them to make you sleep well, and it sure works for me without fail and guilt!! Our kitchen is never without bananas.
I sometimes get insomnia, so I've started having an herbal tea before bed
Even though you're not tired, make yourself get into bed by midnight and switch off all the lights, to break the cycle of insomnia.102
Hey everyone, was having a bit of insomnia last night and tried this free phone app called Rainmaker. You can find it in the App store as Rainmaker of if you search for insomnia. It's a sound program that creates all different kinds of soothing rain. It really helped me get back to sleep last night.