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This routine could be disrupted by road accidents where you may not even be at fault. Besides accidents, certain locations are naturally prone to calamities such as floods and landslides which cause damage to property, including your vehicle. To deal with the prospect of expenses due to this imminent damage, insurance companies in India provide policies in line with the Motor Vehicle Act. This law makes it compulsory for all car owners to have their vehicles insured and ensure the yearly renewal of their insurance policy.
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Ask An Alchemist – Is Alchemy Evil?
Eugene writes: Hello Mr. Forest, My name is Eugene and I am studying Physics at a University in New Hampshire. I have recently taken an interest in alchemy and I want to learn more about it to see if it is something I would be interested in. I have heard that Sir Isaac Newton, a […]Read more "Ask An Alchemist – Is Alchemy Evil?"

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Port Phillip Ecohouse
Architect Peter Ho
Blessington Gardens, St Kilda
Sustainable building concepts have been around for many years. The basic principle is that we build so as not to dissipate things. Buildings are made to last, so we don't damage the environment, and we don't waste energy.
Simple enough, one might think. If we can put a man on the moon, travel underwater and climb buildings in an elevator, surely we can build sensibly and sustainably.
But there are major issues to consider if a true sustainable result is to be met - from social and cultural suitability; energy usage and cost; how to generate energy (using solar power, tidal movement, wind, for example); recycling materials and water; waste management and green-house emissions.
Experimental buildings are scattered through out the world, some aggressively seeking a solution to all sustainable issues, others dealing with a few issues only, and the success rate for each is measurable. So we learn each time how to improve our designs.
But, so often, these experimental buildings show all the signs of mud-brickness, a kind of parsimonious earnestness, as if hand-wrought things are better than those made by a machine.
Often, the buildings are constructed of rough timbers, designed to mimic a normal house, but detailed for green credentials, replete with the machinery of sustainability, including solar panels, water tanks and huge, plastic, recycling and garden compost bins.
There is often a clumsiness and rugged character about these places, not much polish in the finish. It is possible to design beautiful, sustainable buildings, but few examples exist.
The City of Port Phillip has a genuine and positive program for encouraging sustainability. It sets guidelines, provides information, measures household waste, encourages rooftop gardens and generously supports the idea. Part of its program is Port Phillip EcoHouse, on a corner of Blessington Gardens in St Kilda, designed by Peter Ho.
The stated intention was to construct an ordinary house and garden as a model sustainable site, focusing on water, energy and waste management, building and garden design, and what the council calls, "personal wellbeing".
The building comprises recycled timbers, rugged brick walls, timber veranda frames. Inside, it is a standard plasterboard container. It is planned simply, with rooms flanking a corridor, and it is used for a variety of purposes as a community resource, meeting hall, offices and study resource.
The roof contains a solar heater and more solar panels and the gardens (by Martin Reeves) produce food and are planted with native vegetation to encourage wildlife.
Warming sun is captured in winter with window sizes and locations preventing heat build-up during summer. Water from the roof and from the sewerage system (black water) is recycled via tanks and sensible management of the resource is encouraged.
It all sounds wonderful: a clean, ambitious soft-technology that provides a glimpse into what could become normal building before we run out of natural resources.
Praise is due for the idea to mimic a normal-looking house so that people will understand the benefits sustainable design offers.
But this exercise becomes a kind of caricature of greenness when we touch the rough timbers, brush past the knotty posts and realise the lack of spatial invention inside.
This is a very ugly house.
The point is, a truly sustainable building would be best represented by good, inventive architecture. Such an approach would allow for greater experimentation with form, materials, glazing, shading and the mechanics of sustainability.
Historicism, a humble ordinariness, imitation and the banal expression of domestic architectural bliss result in a weak and meagre aesthetic for this otherwise exciting idea.
True sustainability would benefit most by good engineering (including environmental issues), good functionality and that "something else". Sustainable architecture should also enchant and nourish the imagination.
Norman Day is a practising architect, adjunct professor of architecture (RMIT) and architecture writer for The Age.


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Before you read ahead, ask yourself this question: "who am I" and write your answer down. You don't need to spend a lot of time. Just jot down what first comes to your mind.
Did you immediately jump to answers such as "I'm a mom", "I'm an athlete", I'm a student", "I'm a secretary"? Perhaps you leapt into a more descriptive stance: "I'm a hardworking, single female that desperately wants to be in a relationship." Like a personal ad of sorts. Regardless, you have attached labels to yourself that 1. describe who you believe you are and how you see yourself; and 2. serve as reinforcements for how you will behave and the manner in which you carry yourself. A self-fulfilling prophecy?
In her new book, Delusions of Gender, Cordelia Fine demonstrates how as humans, we do not just fall into categories. We create them for ourselves and think of ourselves as being these types of people. With each category comes assumptions, roles, behaviors, expectations, and personality traits. But each of us may define the category differently. My definition of "mom" might be very different than my best friend's. But it's this definition that governs how we behave within that category.
A study conducted at Northwestern University revealed that when participants were asked to imagine themselves as both a "cheerleader" and a "professor", profound differences came to light regarding the characterizations of themselves. "After the exercise…those individuals who had imaginatively adopted the perspective of the professor were more likely to describe themselves as clever than those who had been assigned the cheerleader persona. And those who had adopted the cheerleader perspective, were correspondingly more likely to describe themselves as gorgeous."
Taking this a step further, when participants were given a test of analytical intelligence, those who identified with the professor performed better than those who identified as the cheerleader. What does this mean?
It's more than biology and genetics that account for personality differences, behavior, and cognitions between men and women. This isn't big news– you've heard me repeat over and over again how crucial our thoughts are to the manner in which we feel and act. But what is most interesting is that without a point of reference….without a concept from which to classify yourself, you don't have any basis from which to decide who you are or who you want to be. In essence, you need the category to decide if you want to fall into it or construct a new identity altogether!
Now go back and reread your first answer. Are you who you want to be within your self-instituted categories? How is your category determining your performance and the way you see yourself?


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This A2B has a rather distinctive look. The motor pushes it very smoothly, but forcefully, up to 30 km/h, and there's the option of riding up to 20 km/h without pedaling at all.
Named after Thomas Alva Edison, American inventor and pioneer of DC electrical power.
An evolution of our ever-popular Alva (formerly known as Velociti), the Alva+ features both pedal assist and throttle power on demand. The model offers ease and style – and the unique flexibility to enjoy a range of journeys in your preferred way.


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The aim of Mendelian randomization is to provide a robust test of the association between low-density lipoprotein cholesterol (LDL-C) and aortic stenosis (association 3). Association 3 can be tested simply using standard epidemiologic methods, but these methods may be biased (eg, confounding, reverse causality, etc). To overcome this bias, Mendelian randomization indirectly tests association 3 by first establishing via linear regression that LDL-C–related single-nucleotide polymorphisms (SNPs) increase LDL-C (association 1). These LDL-C SNPs are then tested for an association with aortic stenosis (association 2). Under the assumption that the entire effect of the LDL-C SNPs on aortic stenosis (association 2) is mediated by their effect on increasing LDL-C (association 1), an unconfounded assessment of association 3 can be obtained (ie, instrumental variable estimate).
Each dot represents a single low-density lipoprotein cholesterol (LDL-C) single-nucleotide polymorphism (SNP). Across all 57 LDL-C–associated SNPs, a given genetic increase in LDL-C is correlated with a concomitant increase in the odds of aortic valve calcium (AVC). The solid line represents the best line of fit, and the dashed lines represent the 95% CI for this relationship. P value reported is for the linear association.
eTable 1. Components of the Genetic Score for LDL-C in CHARGE
eTable 2. Components of the Genetic Score for HDL-C in CHARGE
eTable 3. Components of the Genetic Score for TG in CHARGE
eTable 4. Components of the Genetic Score for LDL-C in the MDCS
eTable 5. Components of the Genetic Score for HDL-C in the MDCS
eTable 6. Components of the Genetic Score for TG in the MDCS
eTable 7. Genetic proxies in the MDCS
eTable 8. Association of genetic lipid scores with plasma lipids in the MDCS
eTable 9. Association of LDL GRS with lipoprotein (a)
eTable 10. Mean and median Lp(a) by tertile of the LDL-C GRS
eTable 11. Regression analyses of ßAVC on ßLDL-C, ßHDL-C and ßTRIGLYCERIDES
eFigure. ßLDL-C vs ßAVC across 1000 simulated LDL-C GRS subsets by random exclusion of 30% of the LDL SNPs per subset
Customize your JAMA Network experience by selecting one or more topics from the list below.
Smith JG, Luk K, Schulz C, et al. Association of Low-Density Lipoprotein Cholesterol–Related Genetic Variants With Aortic Valve Calcium and Incident Aortic Stenosis. JAMA. 2014;312(17):1764–1771. doi:10.1001/jama.2014.13959
© 2019
Copyright 2014 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
Plasma low-density lipoprotein cholesterol (LDL-C) has been associated with aortic stenosis in observational studies; however, randomized trials with cholesterol-lowering therapies in individuals with established valve disease have failed to demonstrate reduced disease progression.
To evaluate whether genetic data are consistent with an association between LDL-C, high-density lipoprotein cholesterol (HDL-C), or triglycerides (TG) and aortic valve disease.
Design, Setting, and Participants
Using a Mendelian randomization study design, we evaluated whether weighted genetic risk scores (GRSs), a measure of the genetic predisposition to elevations in plasma lipids, constructed using single-nucleotide polymorphisms identified in genome-wide association studies for plasma lipids, were associated with aortic valve disease. We included community-based cohorts participating in the CHARGE consortium (n = 6942), including the Framingham Heart Study (cohort inception to last follow-up: 1971-2013; n = 1295), Multi-Ethnic Study of Atherosclerosis (2000-2012; n = 2527), Age Gene/Environment Study–Reykjavik (2000-2012; n = 3120), and the Malmö Diet and Cancer Study (MDCS, 1991-2010; n = 28 461).
Main Outcomes and Measures
Aortic valve calcium quantified by computed tomography in CHARGE and incident aortic stenosis in the MDCS.
The prevalence of aortic valve calcium across the 3 CHARGE cohorts was 32% (n = 2245). In the MDCS, over a median follow-up time of 16.1 years, aortic stenosis developed in 17 per 1000 participants (n = 473) and aortic valve replacement for aortic stenosis occurred in 7 per 1000 (n = 205). Plasma LDL-C, but not HDL-C or TG, was significantly associated with incident aortic stenosis (hazard ratio [HR] per mmol/L, 1.28; 95% CI, 1.04-1.57; P = .02; aortic stenosis incidence: 1.3% and 2.4% in lowest and highest LDL-C quartiles, respectively). The LDL-C GRS, but not HDL-C or TG GRS, was significantly associated with presence of aortic valve calcium in CHARGE (odds ratio [OR] per GRS increment, 1.38; 95% CI, 1.09-1.74; P = .007) and with incident aortic stenosis in MDCS (HR per GRS increment, 2.78; 95% CI, 1.22-6.37; P = .02; aortic stenosis incidence: 1.9% and 2.6% in lowest and highest GRS quartiles, respectively). In sensitivity analyses excluding variants weakly associated with HDL-C or TG, the LDL-C GRS remained associated with aortic valve calcium (P = .03) and aortic stenosis (P = .009). In instrumental variable analysis, LDL-C was associated with an increase in the risk of incident aortic stenosis (HR per mmol/L, 1.51; 95% CI, 1.07-2.14; P = .02).
Conclusions and Relevance
Genetic predisposition to elevated LDL-C was associated with presence of aortic valve calcium and incidence of aortic stenosis, providing evidence supportive of a causal association between LDL-C and aortic valve disease. Whether earlier intervention to reduce LDL-C could prevent aortic valve disease merits further investigation.
Aortic valve disease remains the most common form of heart valve disease in Europe and North America and is the most common cause of valve replacement.1,2 Despite the heavy disease burden, no medical treatments are known to stop or retard disease progression. Although aortic valve disease shares several risk factors with vascular disease,3 it remains largely unknown which factors are causal and should be targeted to reduce valve disease. Our group recently described evidence for a causal association between a common variant in the LPA gene, via elevated plasma lipoprotein(a) (Lp[a]), and aortic valve disease.4 Whether other plasma lipids are causally associated with the development of aortic valve disease remains unclear.
Low-density lipoprotein cholesterol (LDL-C) is an important risk factor for aortic valve disease in epidemiologic studies3; however, large randomized trials of LDL-C–lowering therapy in patients with advanced aortic stenosis have failed to demonstrate effectiveness in reducing disease progression.5-7 Nonetheless, if LDL-C plays a causal role in the earlier stages of aortic valve disease, this could have important implications for prevention.
Because of the random allocation of genetic information that occurs at conception, genetic variation can be used as an effective tool to distinguish potentially causal from noncausal biomarkers. Termed "Mendelian randomization," this approach has been successfully applied to assess for causality of several biomarkers with various clinical end points.4,8 Genetic risk scores (GRSs) for lipids, incorporating multiple genetic variants, have been shown to be strongly associated with their corresponding lipid levels in both children9 and adults,10 providing strong support for the contention that a higher GRS confers life-long exposure to higher lipid levels. Here, we used a Mendelian randomization approach to determine whether genetic contributions to elevations in LDL-C and other lipids were associated with early subclinical aortic valve disease and incident clinical aortic stenosis.
Associations of GRSs with aortic valve calcium were evaluated in the 3 CHARGE cohorts where data from computed tomographic (CT) imaging were available; associations with incident aortic stenosis were estimated in the population-based Malmö Diet and Cancer Study (MDCS).
The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium is an ongoing collaboration among several large, well-phenotyped, prospective, longitudinal cohort studies from the United States and Europe.11 This analysis included white European participants with aortic valve calcium data and genome-wide association study (GWAS) data from the Multi-Ethnic Study of Atherosclerosis (MESA, n = 2527; cohort inception to last follow-up: 2000-2012), the Age, Gene/Environment Susceptibility–Reykjavik Study (AGES-RS, n = 3120; from 2000-2012), and the Framingham Heart Study (FHS, n = 1295, from 1971-2013). Details of the CHARGE consortium and each of these cohorts have been previously described.4,11 The studies were approved by relevant regulatory bodies and participants provided informed consent.
The MDCS is a prospective, population-based cohort study from the city of Malmö in southern Sweden. Data collection, sample characteristics, and clinical definitions for MDCS have been described previously.12 Briefly, 30 447 randomly selected men born between 1923 and 1945 and women born between 1923 and 1950 attended a baseline examination between 1991 and 1996. Follow-up for events was completed on December 31, 2010. For the present study, DNA was available for 28 461 participants. Participants underwent sampling of peripheral venous blood and measurement of blood pressure and anthropometric measures and filled out a questionnaire. Measurements of cholesterol (high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], total cholesterol) were performed in a random subset of 5269 participants, on fresh blood samples according to standard procedures at the Department of Clinical Chemistry, Skåne University Hospital, Malmö.12 Levels of LDL-C were calculated according to the Friedewald formula, with exclusion of individuals where TG exceeded 4.52 mmol/L (to convert TG to mg/dL, divide by 0.0113). Informed consent was obtained from all participants and the study was approved by the ethics committee of Lund University, Sweden.
Details of the genotyping and HapMap imputation methods used in the FHS, AGES-RS, and MESA have previously been described.4,11 To construct each lipid GRS, we included previously reported, linkage disequilibrium-pruned (ie, uncorrelated) single-nucleotide polymorphisms (SNPs) from large-scale lipid GWAS13,14 that were associated with the primary lipid traits (LDL-C, HDL-C, and TG) at P value <5.0 × 10−8 and were available in the aortic valve calcium GWAS data set. We constructed separate weighted genetic scores for LDL-C (57 SNPs), HDL-C (70 SNPs), and TG (39 SNPs) weighted by the β coefficients of each individual SNP from large-scale lipid GWASs.13,14 The possible range of the GRS was from 0 to 5.17, 0 to 6.94, and 0 to 3.66 for LDL-C, HDL-C, and TG, respectively. Because of the known association of aortic valve calcium and aortic stenosis with Lp(a), we specifically excluded the rs10455872 SNP, which is strongly associated with Lp(a).4 We also calculated secondary SNP scores that were specific for each single lipid trait by excluding SNPs that were associated with a secondary lipid trait (P value <5.0 × 10−8). The SNPs included in each score are summarized in eTables 1 through 3 in the Supplement.
Genotyping and genotype quality control for the 116 SNPs associated with plasma concentrations of LDL-C, HDL-C, or TG in the Global Lipid Genetics consortium (GLGC) study13 in the MDCS are described in detail in the eMethods in the Supplement. The final SNPs included in the genetic scores for LDL-C (31 SNPs), HDL-C (41 SNPs), and TG (26 SNPs) are summarized in eTables 4-7 in the Supplement. Weighted GRSs were calculated using PLINK version 1.0715 as the sum of the number of alleles associated with increased LDL-C or TG or decreased HDL-C weighted by the β coefficients (expressed in mmol/L) of each individual SNP from the GLGC study. The possible range of the GRS was from 0 to 3.61, 0 to 1.70, and 0 to 2.84 for LDL-C, HDL-C, and TG, respectively. The secondary SNP scores specific for each lipid trait are described in eTables 4-6 in the Supplement.
To assess aortic valve calcium, standard CT scanning was performed on all participants and images were analyzed for the presence of aortic valve calcium using offline digital software. Using standard Agatston methods, the presence of calcium was defined as 3 or more contiguous pixels with a brightness of at least 130 Hounsfield units.4 Aortic valve calcium was defined as calcium residing within the aortic-valve leaflets or commissures, excluding aortic annulus, proximal aorta, and coronary arteries.
Prevalent and incident diagnoses of aortic stenosis and aortic valve replacement were identified by record linkage with nationwide registers on hospitalizations and causes of death as described previously.4 Incident aortic stenosis includes all cases of aortic stenosis identified in the MDCS whereas the aortic valve replacement outcome includes all aortic stenosis cases that underwent aortic valve replacement in the MDCS. High diagnostic validity of aortic stenosis in national Swedish registers has previously been confirmed, and most patients with an aortic stenosis diagnosis in national registers had moderate to severe aortic stenosis.4 A summary of case ascertainment procedures is provided in the eMethods in the Supplement.
To test the hypothesis of a possible causal association between each lipid trait and aortic valve calcium, we used GWAS summary-level data from the 3 CHARGE participating cohorts with aortic valve calcium data.4 The CHARGE aortic valve calcium GWAS has been previously described4 and was performed using an age- and sex-adjusted additive model. To estimate the association for each lipid GRS (LDL-C, HDL-C, and TG) with aortic valve calcium presence, we extracted summary-level SNP data from the CHARGE aortic valve calcium GWAS for all lipid SNPs in each GRS and used the Genetics ToolboX (gtx) R package version 0.0816 to generate GRS effect sizes (βGRS) expressed as odds ratios (ORGRS = eβGRS) with 95% confidence intervals for presence of aortic valve calcium. This method has been shown to provide GRS estimates that are equivalent to using individual participant data for GRS association studies.17,18 Details of the statistical methods can be found in the eMethods in the Supplement.
We also performed 3 sensitivity analyses to address the issue of genetic pleiotropy, in which a given lipid SNP may have several biological effects other than their known effects on plasma lipid levels. First, using the same approach outlined above, we reanalyzed the association between each lipid GRS and aortic valve calcium using a secondary "specific" GRS in which SNPs associated with more than 1 lipid were excluded. Second, we also addressed pleiotropy using a recently developed regression method called multivariable Mendelian randomization,10 which uses a linear regression model to adjust for any possible known pleiotropic effects of the included SNPs by other lipids traits. The details of this method are available in the eMethods in the Supplement. Third, as a final sensitivity analysis, we simulated 1000 LDL-C GRS randomly excluding 30% of the available LDL-C SNPs in each set. Each LDL-C GRS was then tested against aortic valve calcium and the β coefficient for the GRS association was plotted against the LDL-C effect for each of these LDL-C GRS. We also report the mean GRS association and the upper and lower 95% confidence intervals for the effect estimate across all 1000 simulated GRS.
In contrast to the summary-level data used in the CHARGE cohorts, direct genotype-phenotype data were used in the MDCS. The association of each linear GRS with incident clinical aortic stenosis was examined using Cox proportional hazards regression with censoring at death from other causes, emigration, or aortic valve replacement from other causes, adjusting for age, sex, height, weight, diabetes, hypertension, and current smoking at baseline. Age was used as the time scale, and both prevalent and incident diagnoses at the first study examination were included. Wald tests were used for significance testing of the hazard ratios (HRs). A sensitivity analysis was also performed, restricted to participants who underwent aortic valve replacement due to aortic stenosis. Cumulative incidence by GRS quartiles was calculated using cumulative incidence functions (CIF macro in SAS).
To estimate the possible causal association of LDL-C on aortic stenosis risk, an instrumental variable analysis was performed in the MDCS that considered both the GRS association with aortic stenosis and the GRS association with LDL-C and provided an estimate for the increased risk of aortic stenosis per unit change in LDL-C. We used a 2-stage regression approach in which (1) the association between the LDL GRS and LDL-C was estimated in the subset of MDCS with cholesterol measurements (n = 5269) and (2) the association between the predicted LDL-C levels (from the first level regression) and incident aortic stenosis was estimated in the entire MDCS cohort (n = 28 461). Analyses were adjusted for age and sex. To account for error terms across both stages, we used the delta method to estimate standard errors of the instrumental variable ratio estimates.19 Analyses in the MDCS were performed using IBM SPSS version 21.0 (IBM Corporation), Stata version 12.0 (StataCorp), and SAS version 9.4 (SAS Institute). For all analyses, we considered a 2-tailed P value of <.05 to be statistically significant.
Baseline characteristics of CHARGE and MDCS participants are detailed in Table 1 and Table 2. The numbers of individuals who qualified for analysis were as follows: FHS, n = 1295; AGES-RS, n = 3120; MESA, n = 2527; MDCS, n = 28 461. The prevalence of aortic valve calcium across the 3 CHARGE cohorts was 32% (n = 2245). In the MDCS, over a median follow-up time of 16.1 years (interquartile range, 14.8-17.7 years), aortic stenosis developed in 17 per 1000 participants (n = 473) and aortic valve replacement for aortic stenosis occurred in 7 per 1000 (n = 205). In the MDCS, we confirmed that each lipid GRS was associated with the corresponding lipid level as shown in eTable 8 in the Supplement. Each GRS explained 7.1%, 5.7%, and 4.3% of the variance of LDL-C, HDL-C, and TG, respectively. Pleiotropic associations with other lipid traits were also noted for all scores. However, the specific LDL-C GRS that excluded variants with associations with lipid fractions in the GLGC study (at P < 5.0 × 10−8) other than LDL-C was only significantly associated with LDL-C and total cholesterol (eTable 8 in the Supplement). The LDL-C GRS was also not associated with Lp(a) levels in the CHARGE cohorts with available Lp(a) data. As expected, Lp(a) levels were appropriately randomized across LDL-C GRS tertiles (eTables 9-10 in the Supplement).
In the subcohort of the MDCS where lipid fractions were measured (n = 5269), baseline LDL-C was significantly associated with incident aortic stenosis (HR per mmol/L, 1.28; 95% CI, 1.04-1.57; P = .02; incidence of aortic stenosis: 1.3% and 2.4% in lowest and highest LDL-C quartiles, respectively). Baseline HDL-C or TG levels were not significantly associated with incident aortic stenosis (Table 3).
In CHARGE participants, the LDL-C GRS, but not the HDL-C or the TG GRS, was significantly associated with presence of aortic valve calcium (OR per GRS increment, 1.38; 95% CI, 1.09-1.74; P = .007) (Table 4). After exclusion of pleiotropic SNPs that were associated with more than 1 lipid trait, a "specific" LDL-C GRS remained associated with presence of aortic valve calcium (OR per GRS increment, 1.39; 95% CI, 1.04-1.86; P = .03).
In the MDCS, the LDL-C GRS was strongly associated with LDL-C (+2.4 mmol/L per GRS increment; P = 4 × 10−93). Only the LDL-C GRS, but not the HDL-C or TG GRS, was significantly associated with increased aortic stenosis incidence (HR per GRS increment in LDL-C, 2.78; 95% CI, 1.22-6.37; P = .02; aortic stenosis incidence: 1.9% and 2.6% in lowest and highest GRS quartiles, respectively) (Table 4). For aortic stenosis requiring aortic valve replacement, the increased risk was not statistically significant (HR per GRS increment, 3.15; 95% CI, 0.90-11.03; P = .06; aortic valve replacement incidence: 0.8% and 1.4% in lowest and highest GRS quartiles, respectively). After exclusion of pleiotropic SNPs that were associated with more than 1 lipid trait, a "specific" LDL-C GRS remained associated with incident aortic stenosis (HR per GRS increment, 3.85; 95% CI, 1.37-10.79; P = .009; aortic stenosis incidence: 1.6% and 2.7% in lowest and highest GRS quartiles, respectively).
In formal instrumental variable analysis, which may provide a more robust causal association estimate between change in LDL-C and risk of aortic stenosis, genetic increases in LDL-C were significantly associated with an increased risk of aortic stenosis (HR per mmol/L, 1.51; 95% CI, 1.07-2.14; P = .02) (Figure 1).
In CHARGE participants, we also used multivariable Mendelian randomization, a regression-based method, to assess the association between βLDL and βaortic valve calcium and observed a strong linear association (P for linear trend 7 × 10−13) indicating a significant relation between the magnitude of change in LDL-C and the increase in aortic valve calcium presence (Figure 2). Adjustments for βHDL and βTG did not materially change the observed relation between βLDL and βaortic valve calcium (P for linear trend 3 × 10−13) (eTable 11 in the Supplement). Finally, the results after simulating 1000 LDL-C GRS by random SNP exclusion were largely in keeping with the main analysis, demonstrating no major dependencies of the LDL-C GRS association with aortic valve calcium on any set of specific SNPs (eFigure 1 in the Supplement).
In this study of 6942 participants with subclinical data on aortic valve calcium and more than 28 000 participants with more than 15 years of follow-up for aortic stenosis, we demonstrate that genetic elevation in LDL-C, as determined by a GRS, is associated with both presence of aortic valve calcium and incident aortic stenosis. We also found no evidence of association between genetically elevated HDL-C or TG with presence of valve calcium or aortic stenosis, indicating that a mechanism specifically attributable to LDL-C is likely responsible for the association with aortic valve disease. Our findings link a genetically mediated increase in plasma LDL-C with early subclinical valve disease, as measured by aortic valve calcium,20,21 and incident clinical aortic stenosis, providing supportive evidence for a causal role of LDL-C in the development of aortic stenosis. Our results are in keeping with prior observations of a higher risk of aortic stenosis in patients with familial hypercholesterolemia,22 due to marked elevations in LDL-C, caused by rare mutations in the LDL receptor gene (and other related genes), and extend these findings to individuals with common variants that modestly increase LDL-C in the general population. These data suggest that, in addition to the established risks for myocardial infarction and other vascular diseases, increases in LDL-C are also associated with increased risk for aortic stenosis.
Epidemiological studies have previously demonstrated that higher LDL-C is a risk factor for aortic valve calcium and aortic stenosis.3,23,24 Although observational studies have also reported a reduction in the incidence and progression of aortic stenosis in statin users,25 this was not observed in subsequent large randomized trials.5-7 The disappointing results of these trials have cast doubt on the LDL hypothesis in aortic valve disease and dampened enthusiasm for LDL-C lowering in the prevention of valve disease. So how do we reconcile our Mendelian randomization data supporting an association between LDL-C and the development of aortic valve disease with the failure of LDL-C lowering in randomized trials of aortic stenosis?
All trials of LDL-C lowering for aortic stenosis enrolled older participants with established valve disease (in most cases, moderate or severe aortic stenosis),5-7 in which LDL-C may no longer be an important mediator of progressive disease. Once valve calcification and remodeling are well established, factors other than LDL-C, including hemodynamic forces and other procalcifying mediators, may become more important for progression. We have previously shown that higher total cholesterol in early adulthood, prior to any valve disease, was strongly associated with presence of valve calcification 25 years later.23 Similarly, in MESA, the association between LDL-C and aortic valve calcium was strongest among younger, rather than older, participants.24 It also remains to be seen whether part of the failure of prior randomized clinical trials may be related to the use of statins for lipid lowering, which may promote calcification in advanced valve disease.26
Lipoprotein deposition is a seminal process in both valve disease and vascular atherosclerosis. In early valve lesions, apolipoprotein B (the carrier molecule of LDL-C) has been demonstrated to co-localize to regions of early leaflet remodeling and calcification.27 Although LDL-C may play a common role in both vascular and valvular disease, LDL-C may play a more important role in the early calcification and mineralization phase that is strongly characteristic of early valve lesions, as opposed to vascular lesions.28 Low-density lipoprotein cholesterol may promote calcification in these early lesions, via the formation of cholesterol microcrystals that act as nidi for initial calcification,29 and also via oxidized LDL, a potent proinflammatory and pro-oxidant mediator that is known to strongly induce an osteogenic phenotype in valvular cells.30 The importance of LDL-C in the early stages of aortic valve disease is also well supported by transgenic animal data demonstrating that the genetic induction of hypercholesterolemia leads to an early procalcific phenotype at the aortic valve that can be arrested, but not reversed, with reversion to normal cholesterol levels.31 Based on the known biology of valve calcification and the failure of prior randomized trials targeting advanced disease, our results suggest that early lipid lowering, prior to the development of even mild forms of aortic stenosis, may be required to prevent aortic valve disease; this hypothesis remains to be tested in a randomized trial.
Our study has limitations that deserve mention. First, the use of summary-level data from the CHARGE consortium precluded adjustment for additional covariates. However, large Mendelian randomization studies are unlikely to be confounded because of the inherent randomization in these analyses. Indeed, adjusting for several potential confounders in the MDCS did not materially change our findings. Second, although we performed several sensitivity analyses to exclude potential pleiotropic effects of the included SNPs, a non–LDL-C–related mechanism for the observed associations cannot be entirely excluded: an important caveat of all Mendelian randomization studies. In addition, our estimates from instrumental variable analysis may be biased due to time-varying LDL-C and other considerations; therefore, the magnitude of these estimates must be interpreted cautiously.32 Third, we used diagnostic codes to identify incident aortic stenosis in the MDCS. However, these codes have been validated and shown to have a predictive value greater than 90% when compared with echocardiography.4 Fourth, the LDL-C GRS in the CHARGE and MDCS analyses differed because of the lack of GWAS data and fewer SNPs available in the MDCS; however, results in CHARGE were not materially different when we used the same LDL-C GRS used in the MDCS. Finally, our study was performed only in individuals of European descent; whether our results apply to other ethnicities will require further study.
Genetic predisposition to elevated LDL-C was associated with presence of aortic valve calcium and incidence of aortic stenosis, providing evidence supportive of a causal association between LDL-C and aortic valve disease. Whether earlier intervention to reduce LDL-C could prevent aortic valve disease merits further investigation.
Corresponding Author: George Thanassoulis, MD, Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, 687 Pine Ave W, H4.55, Montreal QC H3A 1A1, Canada (email@example.com).
Published Online: October 26, 2014. doi:10.1001/jama.2014.13959.
Author Contributions: Drs J. G. Smith and Thanassoulis had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: J. G. Smith, Thanassoulis.
Acquisition, analysis, or interpretation of data: J. G. Smith, Luk, Schultz, Engert, Do, Hindy, Rukh, Dufresne, Almgren, Owens, Harris, Peloso, Kerr, Wong, A. V. Smith, Budoff, Rotter, Cupples, Rich, Kathiresan, Orho-Melander, Gudnason, Post, Thanassoulis.
Drafting of the manuscript: J. G. Smith, Luk, Thanassoulis.
Critical revision of the manuscript for important intellectual content: J. G. Smith, Schultz, Engert, Do, Hindy, Rukh, Dufresne, Almgren, Owens, Harris, Peloso, Kerr, Wong, A. V. Smith, Budoff, Rotter, Cupples, Rich, Kathiresan, Orho-Melander, Gudnason, O'Donnell, Post, Thanassoulis.
Statistical analysis: J. G. Smith, Luk, Schultz, Engert, Do, Dufresne, Almgren, Peloso, Kerr, A. V. Smith, Cupples, Kathiresan, Thanassoulis.
Obtained funding: J. G. Smith, Harris, Budoff, Rotter, Orho-Melander, Gudnason, O'Donnell, Thanassoulis.
Administrative, technical, or material support: J. G. Smith, Luk, Owens, Harris, Rotter, Rich, Kathiresan, Orho-Melander, Gudnason, Thanassoulis.
Study supervision: J. G. Smith, Thanassoulis.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Cupples reported having received funding from Boston Heart Diagnostics. Dr Thanassoulis reported having received speaker fees from Servier Canada. No other disclosures were reported.
Funding/Support: The Malmö Diet and Cancer study was supported by the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, the Albert Påhlsson and Gunnar Nilsson Foundations, and the Malmö city council. Dr J. G. Smith was supported by the Swedish Heart-Lung Foundation, governmental funding of clinical research within the Swedish National Health Service, the Crafoord Foundation, Skåne University Hospital, and the Thorsten Westerström Foundation. The Age, Gene/Environment Susceptibility–Reykjavik Study was supported by a grant from the National Institute on Aging (N01-AG-12100) and by the National Eye Institute, the National Institute on Deafness and Other Communication Disorders, the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (Icelandic parliament). The MESA, MESA CARe, and the MESA SHARe project were supported by contracts N01-HC-95159 through 95169, N01-HC-65226, and N02-HL-64278 and grants from the NHLBI (UL1 RR024156, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259). Computed tomographic measures in MESA were supported by a grant to Dr Budoff (R01 HL071739). The Framingham Heart Study was supported by contracts from the NHLBI (N01-HC-25195, N02-HL-64278) with Affymetrix for genotyping services. Dr Kathiresan was supported by the American College of Cardiology Foundation/Merck Adult Cardiology Research Fellowship Award and the GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease Young Investigator Award. Dr Thanassoulis was supported by a Clinician-Scientist Salary Award from the Fonds de la Recherche du Québec–Santé and operating grants from the RI-MUHC/Merck Research Competition and the Canadian Institutes of Health Research (MOP-119380 and MOP-126033).
Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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KPMG in India
Pradip has more than 20 years of technology consulting experience and has personally led technology transformational engagements across the government & public sector clientele. He has also been responsible for setting up and operating the technology delivery units for a number of global clients including one of the world's largest insurance companies, a global beverage giant and multiple government departments in Asia Pac, SAARC, Caribbean and the Middle East. Pradip has been heavily involved in transformations in the Government sector, enterprise architecture, and independent verification and valiudation of banking systems and technologies.
BE, Electronics & Tele-Communication, Bengal Engineering College, West Bengal


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I worked at the Lodge for 6 months (April to September 2010) as a volunteer when I got back to Melbourne from my PDC. I've no idea how I found out about them needing people but as the universe has it, it found me, and it's bee a great thing. Not only have I learned a lot through workshops, interacted with like minded people, helped the residents get into the garden and eat more healthily, but I managed to design and implement my first irrigation design. So great!
Matt from CERES was employed to run workshops every alternate Saturday on all sorts of topics from seed saving to irrigation to companion planting to seasons to water management. I attended most of them, assisting the residents in their learning, and gaining a good deal of knowledge myself.
After the irrigation workshop where we laid pipe in one of the veggie beds, Matt asked if someone could design the rest, which I jumped at the chance of. Then, we waited until spring to put the plan into action. The funding comes from Merri Community Health, to pay for materials and 2 part-time Permies to help out each week. The result is fantastic - it's a Pc garden that gets a LOT of love from lots of people. A good way to see what you can get for your efforts. I'll post up photos of it soon.
So yeah, volunteering rocks, as does a smart irrigation design =:o)


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Sharing in Faith: I had to trust God's word
In my early years, I lived a life that had the appearance of discipleship, and yet my life was devoid of true contrition, repentance and godliness.
I attended church every Sunday and could be counted on to participate in myriad ministries and church activities.
I was absolutely certain that Jesus loved me, but I had multiple areas of my life that were not in line with the word and will of God.
I rationalized my behavior, by saying, "That no longer applies to me; God's grace is enough." Or I fell back on my favorite, "God knows my heart."
Among the demons with which I struggled was the misuse of my sexuality and the distortion of this sacred and good gift from God.
I grew up in a community where participating in promiscuous activities was a badge of honor to be celebrated among my peers.
The church accepted my behavior by practicing "don't ask, don't tell."
Everything was going fine except there was a war raging in my heart, and my soul was dying. I was living a life that asked God to conform to my sense of morality.
I finally asked myself, "Who am I? Is my relationship with Jesus truly genuine; am I committed to following him and denying anything and anyone starting with me?"
I then came to a place in my life where I understood I had to absolutely trust that God knows what's best for me. I could no longer rely on opinion polls or media-driven outcomes to determine what I believe or how I was to behave. The word of God alone was to be trusted.
I finally understood that when my mind, experiences and even my traditions are contrary to the clear, consistent witness of Scripture, I had to choose the witness of Scripture and trust the Holy Spirit to give me the capacity to live into God's will.
I served for 30 years as a local preacher in rural, urban, suburban, and multicultural settings. During that time, I preached to, prayed with and wept with members and nonmembers of just about every sexual persuasion imaginable.
I loved them and extended to them not just my time and presence, but more importantly, I shared the assurance of Jesus' love for them –– a love that will never let them go.
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I also told them that God's unshakeable love is not a pass to do whatever we want.
In cases where single heterosexual adults were engaged in sexual relationships outside of marriage, I invited them to consider whether their walk was in harmony with the word and will of God.
Many continued the same conduct, but not a single one ever said, "I believe God is pleased with my conduct."
When people who struggle with same-sex attractions and conduct came to me, I invited them to consider questions about what is pleasing to God. I can't imagine the torment and the pain they went through as they honestly tried to answer the questions.
I seek to be the best pastor I can be, without compromising the clear word that God's design for living out our sexuality is within the bond of marriage between a man and a woman.
At the heart of our struggle is whether the Bible is authoritative for our lives. Are we a people of the Book only when it says what we want to hear?
I am so grateful that Jesus would not leave me where he found me. I believe there is no struggle, no attraction or orientation or cultural shift that is stronger than God's determination to reconcile the world to God's self.
In my own life I am reminded daily of Romans 12:1-2: "Therefore, I urge you, brothers and sisters, in view of God's mercy, to offer your bodies as a living sacrifice, holy and pleasing to God; this is true worship. Do not conform to the pattern of this world, but be transformed by the renewing of your mind. Then you will be able to test and approve what God's will is — his good, pleasing and perfect will."
The Rev. Kenneth Levingston
Houston, Texas
Posted August 21, 2014


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Bone cancer is a malignant (cancerous) tumor of the bone that ruins normal bone tissue. Harmless. The truth is, benign (noncancerous) bone tumors tend to be more common than malignant ones. Both benign and malignant bone tumors may grow and compress healthy bone tissue, but benign tumors don't spread, don't ruin bone tissue, and are seldom a danger to life.
Various kinds of cancer may start in the bones. The most typical kinds, Ewing tumors and osteosarcoma, appear most frequently in adolescents and kids. Here we'll concentrate on different kinds of bone tumors.
Whether you are worried about making choices about treatment, growing bone cancer, or attempting to remain well after treatment, there are certain things you need to know.
Malignant tumors that start in bone tissue are called primary bone cancer. Cancer that metastasizes (spreads) to the bones from the rest of the body, including the breast, lung, or prostate, is called metastatic cancer, and is named after the organ or tissue where it started. Primary bone cancer is much less common.
Standard bone marrow and blood
Various kinds of leukemia are formed from various kinds of cells. To comprehend the various kinds of leukemia, it is helpful to possess some fundamental understanding of the lymph and blood systems. The advice which follows is not rather simple. It might prove helpful, but you do not need to comprehend it all to learn more.
Bone marrow is the soft inner part of some bones such as backs, shoulder blades, ribs, pelvis, and the skull. Bone marrow consists of a few blood stem cells mature blood-forming cells, fat cells, and supporting tissues which help cells develop.
In the bone marrow, blood stem cells grow into blood cells that are new. In this method, the cells become either lymphocytes (a type of white blood cell) or other blood-forming cells. These blood-forming cells can grow red blood cells, white blood cells (other than lymphocytes), or platelets.
Red blood cells carry oxygen from your lungs to other tissues within the body, and take carbon dioxide back to the lungs to be eliminated. Having too few red blood cells in the body (anemia) can cause you to feel exhausted, poor, and short of breath because your body tissues will not be receiving sufficient oxygen.
Platelets are actually cell fragments made with a form of bone marrow cell called the megakaryocyte. Platelets are essential in plugging up holes in blood vessels due to wounds or bruises. Having too few platelets (thrombocytopenia) may cause one to bleed or bruise easily.
White blood cells help the body fight diseases. Having too few white blood cells (neutropenia) lowers your defense mechanisms and will allow you to be prone to get an illness.
Lymphocytes are not immature, disease-fighting cells that grow from lymphoblasts, a kind of blood stem cell in the bone marrow. Lymphocytes are the primary cells which make up an important portion of the immune system, lymphoid tissue. Lymphoid tissue can be found in the thymus gland, lymph nodes, the spleen, the tonsils and adenoids, and is scattered throughout the bone marrow as well as the respiratory and digestive systems. The 2 major kinds of lymphocytes are known as B lymphocytes (B cells) and T lymphocytes (T cells). Lymphocytes help shield the body. Some kinds of lymphocytes help control the immune system.
Granulocytes are mature, disease-fighting cells that grow from myeloblasts, a kind of blood. Granulocytes have granules that show up as spots underneath the microscope. These granules contain other materials that could destroy germs, including bacteria and enzymes. The 3 kinds of granulocytes -- basophils, neutrophils, and eosinophils -- are recognized under the microscope by color as well as the size of the granules. Neutrophils are the most frequent form of granulocyte in the blood. They may be in destroying bacteria which have invaded the blood, crucial.
Monocytes grow from blood-forming monoblasts and therefore are related to granulocytes. After circulating in the bloodstream for around a day, monocytes enter body tissues to become macrophages, which can ruin some germs by digesting and smothering them. Macrophages help germs are recognized by lymphocytes and begin making antibodies to fight them.
Are there many types of primary bone cancer?
Yes. Cancer can start in almost any bone tissue. Bones comprise of osteoid (hard or streamlined), cartilaginous (tough, flexible), and fibrous (threadlike) tissue, along with components of bone marrow (soft, spongy tissue in the middle of the majority of bones).
Common forms of primary bone cancer contain the following:
Osteosarcoma, which originates from osteoid tissue in the bone. This tumor occurs frequently in upper arm and the knee.
Chondrosarcoma, which starts in cartilaginous tissue. Cartilage pads the ends of lines and bones the joints. Chondrosarcoma appears frequently in the pelvis (found between the hip bones), upper leg, and shoulder. Occasionally a chondrosarcoma includes bone cells that are cancerous. If so, the tumor is classified by physicians as an osteosarcoma.
The Ewing Sarcoma Family of Tumors (ESFTs), which will appear in bone but might also appear in soft tissue (muscle, fat, fibrous tissue, arteries, or other supporting tissue). Scientists believe that ESFTs originate from components of archaic nerve tissue in the bone or soft tissue. ESFTs happen most commonly over pelvis and the spinal column and in arms and the legs.
Other forms of cancer that originate in soft tissue are called soft tissue sarcomas. They're not bone cancer and will not be described in this resource.
Do you know the potential factors behind bone cancer?
Scientists have identified several variables that raise the chance of developing these tumors although bone cancer doesn't possess a clearly defined cause. Osteosarcoma happens more often in individuals who have had high- dose external radiation therapy or treatment with anticancer drugs that are certain; kids appear to be especially susceptible. A few bone cancers are due to heredity. For instance, kids who've had hereditary retinoblastoma (an unusual cancer of the eye) are at an increased danger of developing osteosarcoma, especially if they have been treated with radiation. Also, individuals who have hereditary defects of people and bones with alloy implants, which physicians occasionally use to fix breaks, tend to be prone to come up with osteosarcoma. Ewing sarcoma isn't firmly correlated with congenital childhood diseases any heredity cancer syndromes, or previous radiation exposure.
How frequently does bone cancer happen?
Primary bone cancer is uncommon. It accounts for much less than 1 percent of cancers. About 2,300 new cases of primary bone cancer are diagnosed in the United States each year. Various kinds of bone cancer are far prone to happen in people that are some specific
Osteosarcoma occurs between ages 10 and 19. Nevertheless, individuals over age 40 who have other illnesses, including Paget disease (a benign condition characterized by abnormal growth of new bone cells), are at increased danger of developing this cancer.
Chondrosarcoma happens mostly in elderly adults (over age 40). With advancing age the danger increases. This disease rarely occurs in teens and kids.
ESFTs happen most frequently in teens and kids under 19 years old. Boys are affected more frequently than girls. These tumors are very uncommon in African American kids.
What are the indications of bone cancer?
Pain is the most frequent symptom of bone cancer, although not all bone cancers cause pain. Unusual pain or constant or swelling in or near a bone may result from cancer or by other illnesses. It is necessary to see a physician to find out the reason.
In the beginning, the pain isn't continuous. It could be worse at night or when the bone is used (for instance, leg pain when walking). The pain is going to be there all the time as the cancer grows. The pain increases with the individual as well as task might limp if your leg is called for.
Swelling in the region of the pain might not occur until weeks afterwards. It may not be impossible to sense a lump or mass with respect to the location of the tumor.
Cancers in the bones of the neck may create a lump in the trunk of the throat which make it difficult to breathe or could bring about trouble consuming.
Bone cancer can weaken the bone it grows in, but all the time the bones tend not to fracture (break). People who have a break next to or by way of a bone cancer generally describe unexpected intense pain in a limb that had been raw for some months.
Cancer in the bones of the spinal column can press on nerves, resulting in numbness and tingling as well as weakness.
Cancer may cause tiredness and weight loss. It can cause other symptoms, also, in the event the cancer spreads to internal organs. For instance, in the event the cancer spreads to the lung, you could have trouble breathing.
These symptoms are commonly due to conditions besides cancer, including arthritis or injuries. However, if these issues go on for quite a while with no reason that is known, you need to see your physician.
How is bone cancer diagnosed?
The physician asks about the individual's individual and family medical history, to help diagnose bone cancer. The physician also performs a physical examination and can order other diagnostic tests and lab. These evaluations can contain the following
X rays, which may reveal the place, size, and shape of a bone tumor. If x-rays indicate that the unusual region could be cancer, the physician will probably advocate imaging evaluations that are specific. If x-rays indicate that the abnormal area is not malignant, a doctor might want to do additional evaluations, particularly when the individual is experiencing pain that is constant or unusual.
A bone scan, which will be a test in a little bit of radioactive material is injected into a blood vessel and travels throughout the bloodstream, which it subsequently accumulates in the bones and is detected with a scanner.
A computed tomography (CT or CAT) scan, which will be some detailed pictures of areas within the body, shot from different angles, which are made with a computer linked to an x-ray machine.
A magnetic resonance imaging (MRI) process, which runs on the strong magnet linked to a pc to produce detailed images of areas in the body without using x rays.
A positron emission tomography (PET) scan, by which a little bit of radioactive glucose (sugar) is injected right into a vein, and also a scanner can be used to create detailed, computerized pictures of areas in the body where the glucose can be used. The images may be used to find cancer cells in the entire body, because cancer cells often use more glucose than normal cells.
An angiogram, which is an x ray of blood vessels.
How can bone cancer be treated?
Treatment choices are determined by the kind, size, place, and phase of the cancer, in addition to his or her age and general well-being. Treatment alternatives for bone cancer include chemotherapy, surgery, radiation therapy, and cryosurgery.
Operation is the common treatment for bone cancer. The surgeon removes the whole tumor with negative margins (no cancer cells are observed in the edge or border of the tissue removed during operation). The surgeon could also use specific surgical methods to minimize the number of healthy tissue removed with all the tumor.
Dramatic advancements in surgical techniques and preoperative tumor treatment have made it easy for many patients with bone cancer in an arm or leg to avoid revolutionary surgical procedures (removal of the whole limb). Nevertheless, most patients who experience limb-sparing operation want reconstructive surgery to increase limb function.
Chemotherapy is using anticancer drugs to kill cancer cells. Patients that have bone cancer generally get a variety of anticancer drugs. Nevertheless, chemotherapy isn't presently used to deal with chondrosarcoma.
Radiation therapy, also called radiotherapy, involves using high energy x-rays to kill cancer cells. This treatment can be utilized together with operation. It's used to deal with ESFTs, along with chondrosarcoma, which can't be treated with chemotherapy. It can also be useful for patients who refuse surgery.
Cryosurgery is using liquid nitrogen. This technique will often be utilized instead of traditional operation to destroy the tumor.
Peripheral blood or bone marrow stem cell transplant for acute myeloid leukemia
The injury to the bone marrow may be deadly, although quite high doses of chemo drugs might work to kill cancer cells. A stem cell transplant (SCT) offers a means for physicians to make use of high doses of chemo. The drugs ruin the individuals bone marrow, but it is restored by the transplanted stem cells.
Stem cells for a transplant come from the bone marrow or from the blood. Bone marrow transplants were more common before, but now peripheral blood stem cell transplant (PBSCT) is a lot more common.
There are 2 primary kinds of stem cell transplants: autologous and allogeneic. The difference is the source of the blood-forming stem cells.
There's an excellent motive to make use of stem cells. These cells appear to aid fight with any remaining leukemia cells through an immune reaction. That is known as a graft-versus-leukemia response and is described below. In addition, some leukemia cells may be contained by the individuals own stem cells, when the leukemia is in remission, even though they can be gathered.
The procedure works like this: stem cells are collected in the bloodstream in a procedure called apheresis. The cells are frozen and kept. Patients are given high doses of chemo to kill the cancer cells. In addition they may get whole body radiation. After treatment, the stored stem cells get to the individual as a blood transfusion. The stem cells begin to develop and make new blood cells and settle to the individuals bone marrow during the following several days.
Those who get a donor's stem cells are given drugs to avoid some other medications together with rejection as needed to prevent diseases. Generally, stem cells begin making white blood cells that are new within several weeks as soon as they have been given. They start making eventually, and platelets, red blood cells.
Patients must be kept away from germs as much as you can until their white blood cell count is at an amount that is secure. They remain in the hospital before a specific amount is reached by the white cell count, generally around 1,000. As soon as they go home, they'll be viewed for many weeks nearly every day in the outpatient clinic.
Most patients that are elderly cannot have a routine transplant that uses high doses of chemo. Some may have the ability to have what's known as a mini-transplant (also called a non-myeloablative transplant or reduced-intensity transplant), where they get lower doses of chemo and radiation that don't ruin the all cells inside their bone marrow. They are given stem cells to the donor. These cells enter the body and form a fresh immune system, which finds the leukemia cells as foreign and attacks them (a graft-versus-leukemia effect). That is not the typical kind of transplant plus some physicians think of the strategy as experimental in this disorder.
Stem cell transplantation (SCT) is a complicated treatment. In the event the physicians believe this treatment might help the person suffering from leukemia, it is necessary that it be done in a hospital where the staff has expertise.
SCT a long hospital stay can be more expensive than $100,000 and might Because insurance providers may see as experimental specific sorts of SCT, they may well not pay because of it. You need to learn everything you may need to pay before choosing a transplant and what your insurance will cover.
Common unwanted effects are substantially exactly the same as those caused by another form of chemo and may be serious. Included in these are vomiting and nausea, mouth sores, and acute low blood counts. Among the very frequent and serious short term effects is the greater danger of; disease due to low blood cell counts that are white. Antibiotics in many cases are given to try and keep this from happening. Other negative effects, like low red blood cell and platelet counts, frequently mean transfusions will be needed; by the patient.
Graft-versus-host disease (GVHD) is the key issue of a donor stem cell (allogeneic) transplant. It occurs when that of the donor takes over the immune system of the individual. The donor immune system begins to attack the individuals other tissues and organs. In serious instances, GVHD can be life threatening.
Symptoms may include skin rashes that are poor with itching and acute diarrhea. Lungs and the liver are often damaged. The individual also have aching muscles and might also be really exhausted. GVHD may be deadly if awful enough. Drugs that weaken the immune system could possibly be given to try and command it. The plus side of graft-versus-host disease is that any remaining leukemia cells are normally killed by the donor bone marrow. That is known as the graft-versus-leukemia effect.
Donor matching for allogeneic transplant
The immune system usually keeps us healthy by destroying anything for example viruses or bacteria. Cells are recognized by a working immune system from others as foreign, also. This becomes crucial in a allogeneic stem cell transplant.
In case the tissue type match between donor and receiver isn't close, the newest stem cells may be seen by the individuals defense mechanisms and destroy them. That is known as graft rejection, also it may cause graft failure. When the donor and receiver are matched, that is uncommon.
A widespread issue is the fact that when the donor stem cells make their particular immune cells, the cells that are brand new turn against their new house and may find the individuals cells as foreign. This kind of assault is known as graft-versus-host disease. The grafted stem cells attack the body of the one who got the transplant. This is an alternative reason it is essential to seek out the closest match possible.
Many variables play a role in the way the immune system understands the difference between self and non-self, but the most essential for transplants is the human leukocyte antigen (HLA) system. Human leukocyte antigens are proteins found on the surface of the majority of cells. They make up a person's tissue type, which differs from an individuals blood type.
Each individual has several pairs of HLA antigens. We inherit one of all the pairs from every one of our parents (and pass one of each pair on to every one of our kids). When finding a donor to get a man obtaining a stem cell transplant doctors attempt to match these antigens.
How nicely recipient's as well as the donor's HLA tissue types match plays with a big part in if the transplant will work. A match is better when all 6 of the known important HLA antigens are the same 6 out of 6 match. Individuals with one of these matches have a lesser potential for graft-versus-host disease, graft rejection, receiving serious diseases, and having a poor immune apparatus. For bone marrow and peripheral blood stem cell transplants, occasionally a donor using one mismatched antigen is used. For cord blood transplants a perfect HLA match does not appear to be critical for success, and a sample with a couple of proteins that are mismatched may be OK.
Doctors keep learning more about better methods to match donors. Fewer evaluations might be required, for sibs since their cells change less than an unrelated donor now. But more in relation to the fundamental 6 HLA antigens in many cases are analyzed on unrelated donors to decrease the hazards of mismatched types. Occasionally physicians may wish to look at 5 pairs of antigens, for instance, to get a 10 out of 10 match. Transplant facilities that are specific now need high resolution fitting, which seems more deeply into tissue types. Clinical trials are being done by other facilities with associated half- matched donors and chemotherapy programs that are differing. That is an active part of research because it is generally difficult to locate a HLA match that is great.
You'll find a large number of distinct combinations of HLA tissue types that are potential. This can allow it to be difficult to chance upon a precise match. HLA antigens are inherited from both parents. When possible, the hunt to get a donor typically begins using the patient's brothers and sisters (siblings), who possess the exact same parents as the individual. The opportunity that any one sib would have been an ideal match (that's, that you both received the identical set of HLA antigens from every one of your parents) is 1 out of 4.
If your sibling isn't an excellent fit, the search could then go forward to relatives that are not as likely to be an excellent match for parents, half sibs, and extended family, including aunts, uncles, or cousins. (Partners are no more prone to be great fits than other individuals who will not be linked.) If no relatives are observed to be a close match, the search will be widened by the transplant team to the public.
As improbable as it looks, it is not impossible to locate a great fit having a stranger. To help with this particular procedure, transplant registries will be used by the team. Registries function as matchmakers between volunteer donors and patients. They are able to hunt for and access thousands of cord blood units and millions of potential donors. The biggest registry in America is Be the Match (previously known as the National Marrow Donor Program) which has recently merged with a different bureau, the Caitlin Raymond International Registry. They have matched thousands of donors and receivers, and have access to millions of international records.
The odds of finding an unrelated donor match as more volunteers sign up, enhance each year. Now, about half of white people who want a stem cell transplant may uncover an ideal match among donors that are unrelated. This drops out of 10 folks in other ethnic groups, mainly because their HLA types tend to be more varied plus they appear to be more unlikely to be a part of donor registries. Depending on an individuals tissue typing, several other international registries also are accessible. Occasionally the most effective matches are discovered in people who have a similar racial or ethnic heritage. Though cord blood could be a little quicker locating an unrelated donor can take months. One match can demand going through numerous records.
Since transplant centers are more frequently using high resolution tests, fitting has become more sophisticated. At that level are considerably more difficult to locate, perfect 10 out of 10 matches. But transplant teams will also be becoming better at figuring out what sorts of mismatches they are able to get away with in which scenarios that's, and mismatched sites are more unlikely to change transplant success and survival.
Remember there are phases to the procedure there could be several matches that seem promising however do not work out as expected. Registry and the team will keep trying to find perfect match for you personally. In case your team locates an adult donor by means of a transplant registry, the registry will contact the donor to set up contribution and the last testing. The registry is going to have the cord blood sent to your own transplant center in case your team finds fitting cord blood.
Is follow-up treatment required? What exactly does it include?
Yes. Bone cancer occasionally metastasizes, especially to the lungs, or can recur (come back), either in exactly the same place or in other bones within the body. Individuals who experienced bone cancer should report any unusual symptoms immediately and should see their physician frequently. Follow-up changes for different kinds and phases of bone cancer. Typically, patients are assessed often by their physician and have routine blood tests and x-rays. Individuals who experienced bone cancer, especially teenagers and kids, have a heightened chance of developing another form of cancer, including leukemia, after in life. Routine follow-up attention helps to ensure that issues are treated when you can and that changes in health are discussed.
Are clinical trials (research studies) available if you have bone cancer?
Yes. Involvement in clinical trials is an essential treatment alternative for a lot of people who have bone cancer. To develop new treatments and better methods to utilize current treatments, organizations are sponsoring clinical trials in several hospitals and cancer centers across the United States. Clinical trials are an essential part of the evolution of new types of treatment. Before any new treatment may be recommended for general use, doctors conduct clinical trials to learn if the treatment is safe for patients and effective against the disorder.
Can bone metastases be prevented?
Doctors do not understand how to prevent all bone metastases. But it might be possible to prevent many instances of bone metastasis before they experienced an opportunity to propagate if cancers are found and treated efficiently. That is particularly true for cancers that often spread to the bones, including prostate and breast cancers.
Some cancers, including breast cancer, can often be discovered with; screening evaluations, before they've an opportunity to propagate. But a lot of cancers cannot faithfully be found by the evaluations we've now, before they can be found, plus some cancers may have previously spread.
There are methods to lower your own risk of having cancer in the very first place, such as not smoking, remaining in a healthier weight, getting regular physical activity, and eating a healthier diet (including restricting alcohol).
Researchers are examining methods to stop metastasis in those who have cancer, but only at that time the most effective means to do that is to treat the cancer before it spreads.
Bone cancer surgery
Operation is the principal (main) treatment for many bone cancers. Operation are often required to have a biopsy of the cancer. The biopsy as well as the surgical treatment are different procedures, but it is extremely significant that both are planned by the physician jointly. Ideally, exactly the same surgeon should do the primary operation as well as the biopsy. When the surgeon does the surgery to take away the cancer, a biopsy taken in the incorrect spot can cause difficulties. Occasionally a biopsy that is poor placed may also allow it to be impossible to get rid of the cancer without cutting the limb off.
The primary aim of surgery would be to remove the cancer all. They are able to grow and multiply to make a fresh tumor if even several cancer cells are left behind. To strive to make sure that this does not occur, surgeons remove the tumor plus some of the ordinary-appearing tissue that surrounds it. This is referred to as broad-excision. Removing some ordinary-appearing tissue helps ensure that all of the cancer is removed. After operation, a pathologist can look in the tissue that has been removed beneath the microscope to find out whether the borders (outer edges) have cancer cells. The borders are called positive, if cancer cells were seen in the borders of the tissue. Positive borders can mean that some cancer was left behind. When no cancer is observed in the borders of the tissue, the borders are considered clear, tidy, or negative. A broad-excision with margins that are clean minimizes the danger the cancer will grow back where it began.
Occasionally the whole limb must be eliminated in order to do a great broad-excision (and remove all the cancer). This procedure is called an amputation. But all the time the surgeon can take away the cancer. That is called limb-salvage or limb-sparing operation. It is necessary to understand there are benefits and disadvantages with either kind of operation in going over treatment choices. As an example, although for many individuals limb-salvage appears less unacceptable than amputation, it's less simple and can have significantly more complications. Both procedures possess exactly the same overall survival rates when done by skilled surgeons. Studies have revealed little difference in how individuals respond to the final result of the processes that were different. Probably the largest concern was found in adolescents who worry regarding the societal effects of the surgery. Psychological problems may be extremely significant and encouragement and support are needed for the majority of patients.
Whichever kind of operation is performed, rehabilitation will likely be needed later. This may be the most difficult section of treatment. When possible, the individual should meet before operation with a specialist in rehabilitation to realize what is going to be entailed.
Amputation: Amputation is operation to eliminate part or all of a limb (an arm or leg). When used to take care of cancer, amputation removes some healthy tissue above it, the limb part together with the tumor, and everything below it. Before, amputation was the primary strategy to deal with bone cancers discovered in legs or the arms. Currently, this procedure is selected when there is a reason to not do limb-salvage surgery. By way of example, an amputation might be needed if removing all the cancer needs removing arteries vital nerves, or muscles that will make the limb without great function.
MRI scans and evaluation of the tissue by the pathologist during the period of operation will help the surgeon determine just how much of leg or the arm must be eliminated. Operation is planned so that the skin as well as muscles is going to form a cuff across the amputated bone. This cuff fits to the end of an artificial limb (or prosthesis). After operation, an individual must find out the best way to make use of the prosthesis. With physical therapy that is appropriate they're frequently walking after leg amputation.
Limb-salvage operation: The purpose of limb-salvage operation will be to remove all the cancer but still make a functioning leg (or arm). Over 90% of patients with bone cancer in a limb really are able to have their limb saved. This kind of operation is extremely complicated and needs surgeons with expertise and specific abilities. While saving the nearby tendons, nerves, and vessels, the challenge for the surgeon would be to eliminate the whole tumor. That is necessarily impossible. They are going to have to be eliminated together with the tumor if your cancer has exploded into these constructions. This will often lead to a limb which is not painless or cannot be used. If so, amputation could be the most effective choice.
In this kind of operation, a broad-excision is carried out to eliminate the tumor. An endoprosthesis or a bone graft can be used to replace the bone that's lost. Endoprostheses are made from metal as well as other substances and may be quite complex. Some can be made more without any additional operation as the little one grows since they can be utilized in growing kids.
Additional operation may be needed in the event the bone graft or endoprosthesis becomes broken, loose, or contaminated. Limb-salvage surgery patients and some may need more operation and an amputation, respectively.
Rehabilitation is a lot more extreme after limb-salvage operation than it is after amputation. It will take a typical time of a year for patients -salvage of a leg. The salvaged arm or leg can become worthless, in the event the patient will not take part in the rehabilitation program.
Reconstructive surgery: In the event the leg has to be amputated mid-thigh, foot and the lower leg may be rotated and attached to the thigh bone. The ankle joint that is old becomes the newest knee joint. This operation is named rotationplasty. A prosthesis can be used to create the brand new leg the same span as the other (healthy) leg.
The tumor could be removed and then the lower arm attached in case the bone tumor can be found in the top arm. This leaves the patient with the arm that works but is not considerably longer.
Bone cancer in the pelvis is treated using a broad-excision when potential. Bone grafts may be used to reconstruct the pelvic bones if necessary.
To get a tumor in the lower jaw bone, the whole lower half the jaw could be removed and replaced with bones from the rest of the body.
For tumors in places such as the skull or the back, it might impossible to do a broad-excision. Cancers in these bones may need a variety of treatments including cryosurgery, curettage, and radiation.
Curettage: In this process, the physician scoops the tumor from your bone out without removing a segment of the bone. This makes a hole in the bone. Sometimes, after all the tumor was removed, the surgeon will treat the bone tissue that is nearby to kill any remaining tumor cells. This is finished with cryosurgery or by using bone cement.
Cryosurgery: Because of this treatment, liquid nitrogen is poured to the hole that's made in the bone following the tumor was removed. This substance that is exceptionally chilly kills tumor cells. This treatment is also called. After cryosurgery, bone grafts or by bone cement can fill the hole in the bone.
Bone cement: The bone cement PMMA (polymethylmethyacrylate) starts out as a liquid and hardens over time. It could be put in a hole in the bone in liquid form. As PMMA hardens, it gives plenty of heat off. Heat helps kill any remaining tumor cells. This enables PMMA to be utilized without cryosurgery for a number of kinds of bone tumors.
In order to treat a bone cancer, any present metastases and it have to be taken away with surgery. The lungs would be the most frequent site of distant spread for bone cancer. Operation to get rid of bone cancer metastases has to be planned. Prior to the surgery, the surgeon will look at how many tumors, their place (one lung or both lungs), their size, as well as the individuals general state.
The chest CT scan might not demonstrate all of the tumors that actually exist. Than may be observed in the chest CT scan, the surgeon is going to have treatment strategy in case more tumors are observed through the procedure.
Removing each of the lung metastases might be the sole opportunity to get a remedy. Yet, not all lung metastases may be taken off. Some tumors are excessively huge or are too close to significant structures in the chest (for example large blood vessels) to be removed safely. Individuals whose general state isn't great (due to poor nutritional status or issues with all the heart, liver, or kidneys) might not have the capacity to resist the strain of anesthesia and operation to eliminate metastases.
The risk factors of bone cancer
A risk factor is whatever changes your possibility of having a disease like cancer. Different cancers have different risk factors. By way of example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, mouth, larynx, bladder, kidney, and other organs. But having a risk factor, or even several, doesn't imply you will get the disorder. Many people who have bone cancers would not have some risk factors that are apparent.
A tiny amount of bone cancers (particularly osteosarcomas) seem to be hereditary and therefore are due to defects (mutations) in particular genes.
Kids with particular rare familial syndromes have a higher danger of developing osteosarcoma.
Eventually, there are families with several members that have grown osteosarcoma without familial changes in the genes that are known. The gene defects which could cause cancers have not been found yet.
Multiple exostoses (occasionally called multiple osteochondromas) syndrome is an inherited condition that causes many lumps on someones bones. These lumps are created largely of cartilage. They could be deform and debilitating or fracture bones. A mutation in any one of the 3 genes causes this illness EXT1, EXT2, or EXT3. Patients with this specific condition have a heightened danger of chondrosarcoma.
An enchondroma is a benign cartilage tumor that develops to the bone. Those who get several tumors have a condition. They've a higher danger of growing chondrosarcomas.
Chordomas appear to run in certain families. Genetic chordoma was associated with changes on chromosome 7, although the genes responsible haven't yet been discovered.
Patients together with the familial syndrome tuberous sclerosis, which is often due to defects (mutations) in both of the genes TSC1 and TSC2, appear to really have a high risk of chordomas during youth.
Paget disease is a benign (non-cancerous) but precancerous condition which affects one or more bones. It is mainly a disorder of individuals older than 50 and ends in formation of abnormal bone tissue. Affected bones are fragile, thick, and heavy. They may be poorer than normal bones and prone to fracture (break). All the time Paget disease isn't life-threatening. Bone cancer (generally osteosarcoma) grows in about 1% of those with Paget disease, typically when many bones are changed.
Bones which were exposed to ionizing radiation could even have an increased danger of developing bone cancer. A typical x ray of a bone is safe, but exposure to substantial doses of radiation does present a threat. For instance, radiation therapy to treat cancer may lead to a cancer that is new to grow in among the bones in the procedure region. Being treated when you're younger and/or being treated with higher doses of radiation (typically over 60 Gy) raises the chance of developing bone cancer.
Exposure to radioactive materials like strontium and radium also can cause bone cancer because these minerals develop in bones.
Non-ionizing radiation, like microwaves, electromagnetic fields from power lines, cellular phones, and household appliances, will not raise bone cancer hazard.
Osteosarcoma was reported in several patients that have undergone bone marrow (stem cell) transplantation.
Folks have wondered whether cancer can be caused by harm to your bone, but this hasn't been established. A lot of people with bone cancer recall having damage that element of the bone. Most physicians consider that the cancer was not caused by this, but instead the cancer caused them to recall the event or that their attention was drawn by the harm to that particular bone and caused a difficulty that had been present for a while to be noticed by them.
What is new in treatment and bone cancer research?
Analysis on bone cancer is currently being done at other associations, university hospitals, as well as many medical centers throughout the country. There are lots of on-going clinical trials.
Some clinical trials are looking into methods to join operation radiation therapy, and chemotherapy (chemo), and drugs known as targeted therapy. One study discovered the blend of the chemo drug cyclophosphamide (Cytoxan) as well as the targeted drug sirolimus can help prevent chondrosarcomas from growing to get a period.
New chemo drugs are being tested by some.
Targeted therapy drugs work differently from conventional chemo. These drugs target proteins and specific genes.
One case of targeted therapy is the drug imatinib (Gleevec), which targets specific proteins made by the cancer cells in chordomas. Adding another drug to imatinib, including the targeted therapy drug sirolimus (Rapamune) or the chemo drug cisplatin helps prevent the development of chordomas when imatinib quits working. Panobinostat, another drug, is being examined to treat chordoma.
Lapatinib is another targeted drug which may be helpful in treating chordoma. In a single study of patients with tumors that had protein too many duplicates of the EGFR gene or too much EGFR, it helped prevent them from growing to get a period and shrink tumors.
Some chordomas reveal powerful reflection of parts of an insulin-like growth factor. It's led to examining antibodies from the insulin-like growth factor receptor 1 (IGF1R) in chordoma patients.
Studies of other targeted drugs are going on right now, including nilotinib (Tasigna) and dasatinib (Sprycel) in chordoma, and pazopanib (Votrient) everolimus (Afinitor), and vismodegib (GDC-0449) in chondrosarcoma.
The most frequent form of radiation used to treat cancer uses columns of x rays. Proton beam radiation uses particles made up of protons (protons are little positively charged particles which are part of atoms). Another less common type of particle radiation which can be utilized to deal with chordomas and chondrosarcomas is carbon ion radiation. This is useful in treating tumors of the skull base, but is just obtainable in several centers globally.
In learning regarding what causes bone tumors as well as clinical trials, researchers are making progress. As an example, changes into a particular section of chromosome 6 have now been discovered in chordomas. Alters the COL2A1 gene, which codes to get an important type of collagen found in cartilage, happen to be discovered in several chondrosarcomas. Hopefully additional information in regards to the DNA changes that cause bone cancers will finally result in treatments.


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Tom Haines
Tom trained as a classical composer at the Guildhall School of music and Drama, where he graduated in 2000. Since then he has been composing scores for Film, TV and theatre. He has always had an intense passion for film scores and sound. Tom's extensive library of film soundtracks, scores and unusual records have formed a primary focus in his musical studies over the years. Tom's live work often collides live instrumental performance with the use of narrative, and extended studio and film sound techniques. Tom is fanatical about studio music technique and is just as familiar with making music with modular synthesis and max/msp as he is writing an Orchestral Score. Tom is also an artistic associate of Filter theatre, with Whom he has been developing critically acclaimed music and sound based theatre projects for over 10 years.


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- The award is for bloggers with less than 300 followers
- The nominees must link back to the blogger who awarded them
- If you are nominated write 11 random facts about yourself and answer the 11 questions written by the blogger who nominated you
- Make up 11 new questions to be answered and nominate 11 other bloggers!
11 random facts
- I love british television (monty python's flying circus, doctor who, the mighty boosh, sherlock, luxury comedy, peep show, etc.)
- i play the drums and the ukelele and try to sing
- music means a lot to me, and my ultimate dream is to be a professional musician
- if i don't become a pro-musician i want to be a screenwriter, actress, model, vintage shop owner, or crazy bag lady
- i watch a lot of movies (and older television shows) and my two favorite directors are quentin tarantino and wes anderson
- i'm allergic to cats, grass, dust, gluten, dust mites, and a million other things
- i started this blog because i was bored (and i'm really happy i did!)
- i enjoy reading rookiemag(.com)
- i like drooling over keith moon, ryan gosling, mick jagger, brian jones, tom hughes, noel fielding, and a million other people
- i hoard vinyl records
- and apparently i am very dramatic and funny (according to the folks i surround myself with and the occasional stranger)
questions from essine!
my 11 questions
- who is your favorite musician/band and how did you get into them?
- what is your life goal(s)?
- do you like school, and why(or why not)?
- oh no, you're given a five minutes notice that you are going to be stranded on an island! what three are you going to bring with you? (someone better say WILSON)
- what's your favorite monty python movie/skit? (and if you don't know who they are please educate yourself right away)
- who do you look up to? explain
- if you had all the money in the world what would be the first thing you'd buy?
- what is your views on racism/equality issues?
- where is your favorite place to shop (clothing, music, anything)?
- who is your favorite artist?
- who are you favorite blogs?
people i tag
that's not 11 but whateva~
bye for now,


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Zaiqa Food Recipes
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EYESHADOW PRIMER: the Advanced Eye Fix Primer by Elizabeth Arden.
I dont know much makeup brand. I am not into it.
Your eyes look beautiful. I am loving those purple lashes ;)
Hi dear, thanks a lot for yr comment! If you have the occasion try Wet n Wild products, the quality is good.Delete
wow stupendo! le prime due e l'ultima foto mi hanno incantata! il tuo occhio è valorizzatissimo e ancora più bello del solito perchè lasciato libero e si vede quanto è chiaro e luminoso! adoro il mascara viola, che su di te risalta, anche per via dell'ombretto rosa dietro. voto per altri mille look come questo e perchè tu viva costantemente col mascara viola addosso! :)ReplyDelete
Ah ah grazie mille Ghila!!! Tra l'altro non secca nemmeno sto mascara, nonostante l'alta pigmentazione! Un abbraccione!Delete
This is so... flowery :D Lovely.ReplyDelete
Thanks a lot dear Aneta! Smuack!Delete
It is very unique - would take a little getting used to on me hahahahaReplyDelete
Ahh ah you absolutely have to try violet mascara dear Maria!!! All considered, the effect is natural! A big kiss!Delete
Wow, so wonderful on your eyelashes :)))
I love violet! kisses
Thanks a lot dear Amira!♡Delete
absolutely stunning Marghe! I love purple mascara :)ReplyDelete
Yes,sometimes I like to wear it, but I have to be in the right mood! A big kiss dear Edyta!Delete
very pretty looks! I love the effect on that purple mascara!ReplyDelete
Ciao Natalia! Grazie mille per essere passata! ♡Delete
Ficou ótima a mistura de cores.
Gostei demais.
Bjim ...
blog Usei Hoje
Muchas gracias por tu comentario! Un abrazo!Delete
Wow...This one is very interesting look of yours! I love it! :-)ReplyDelete
Thanks a lot my dear! Smuack!Delete
Gorgeous mascara! <3ReplyDelete
Yes it is dear Irina! ♡Delete
I never tried violet mascara but looks great with your eye color:)ReplyDelete
Hey my dear! You have to try a violet mascara, I think it would suit your eyes too! A big kiss!Delete
WOW !!! I love the purple mascara. I have blue and black...you are inspiring me to buy purple as well :)ReplyDelete
That looks amazing! What a great look, I love it! <3ReplyDelete
Wow! Muy juvenil y llamativo, me encanta!ReplyDelete
This is one of my absolute favorite looks that you´ve done!
I love the purple mascara and the soft shades on your lid :)
LOVE that pop of pink on your top lash liner as well :)
so so so pretty :)
This look is absolutely stunning! I'm going to keep an eye out for that mascara!ReplyDelete