Vaccines Cause Autism, Until You Look At The Data

According to a much-discussed new paper, vaccines may cause autism after all: A Positive Association found between Autism Prevalence and Childhood Vaccination uptake across the U.S. Population.

The author is Gayle DeLong, who "teaches international finance at Baruch College, City University of New York", according to her profile as a board member of anti-vaccine group SafeMinds. She correlated rates of coverage of the government recommended full set of vaccines in the 51 US states including Washington D.C., with registered rates of autism in those states six years later.

Uh-oh - there was a correlation between vaccination in two year kids, and the rate of autism in the state six years later, when those kids were eight. As the abstract says:

The higher the proportion of children receiving recommended vaccinations, the higher was the prevalence of AUT... The results suggest that although mercury has been removed from many vaccines, other culprits may link vaccines to autism. Further study into the relationship between vaccines and autism is warranted.

Sounds rather scary. Until you look at the data, helpfully provided in the paper. First up, here's the scatterplot of all of the vaccination rates and all of the autism-six-years-later rates:

There's more than 51 data points as you can see: there's actually 355 because each state had seven different datapoints (1995 vaccines vs 2001 autism though to 2001 vs 2007). This scatterplot shows no correlation. You can tell just from looking at it, but the correlation coefficient confirms this, as it's a tiny r 0.012 (from a possible range of 0 to 1).

To be fair, that's a very noisy measure, because each state has unique characteristics, so the effect of vaccines will be diluted. However, it's still a useful sanity check, and shows that there can't be a major effect, otherwise it would be too big to get diluted.

To get around this I next looked at the change in the rates of vaccination from one year to the next, and correlated that with the corresponding change in future rates of autism, within each state. A "change" of 1 means no change, 0.5 means it halved and 2 means it doubled, etc.

Zilch. Correlation coeffiencent r is 0.034.

Maybe the changes year-to-year were too small? So I checked the changes between the last year, and the first year.

This made the changes bigger, because more tends to change over six years than in just one. And, to be fair, this does produces a slightly stronger vaccine-autism effect... but it's still tiny. The correlation coefficient here, r, is 0.18 which means that vaccination changes accounts for 3% of the variability in autism changes (r^2 = 0.034.) The p value is 0.20, statistically insignificant.

My conclusion is that this dataset shows no evidence of any association. The author nonetheless found one. How? By doing some statistical wizardry.

The statistical model used took into consideration the unique characteristics of each state. For example, each state had a unique mixture of pollution, which may have affected the prevalence of autism, yet such an effect was not included in this study. A fixed-effects, within-group panel regression (Hall and Cummins 2005) controlled for these unique yet undefined characteristics by deriving a different starting point (intercept) for each state.

The 51 different intercepts - one for each state - reflected the base level of autism or speech disorders occurring in that state that were not explained by the other independent variables (vaccination rates, income, or ethnicity). The model then produced a single relationship between the independent variables and the prevalence of autism or speech disorders.

OK, that's all very fancy, but when the raw data shows zilch and you can only find a signal by "controlling for" stuff, alarm bells start ringing. Given sufficient statistical analysis you can make any data say anything you want.

If the author had given details of the methods, and explained why she chose to control for the variables she did, and not others, that might be different. But she didn't. Nor did she justify only looking at the effects six years later, when five or seven or ten would be just as sensible... and so on.

(Note: whenever I've said "autism", that's my shorthand for autism + SLI, which is what the paper looked at; autism alone data are not presented. Note also that by "vaccination %" I mean "% who got the full vaccine schedule"; the other kids may have got vaccines, just not all of them.)

Delong G (2011). A Positive Association found between Autism Prevalence and Childhood Vaccination uptake across the U.S. Population. Journal of toxicology and environmental health. Part A, 74 (14), 903-16 PMID: 21623535

Vaccines Cause Autism, Until You Look At The Data

According to a much-discussed new paper, vaccines may cause autism after all: A Positive Association found between Autism Prevalence and Childhood Vaccination uptake across the U.S. Population.

The author is Gayle DeLong, who "teaches international finance at Baruch College, City University of New York", according to her profile as a board member of anti-vaccine group SafeMinds. She correlated rates of coverage of the government recommended full set of vaccines in the 51 US states including Washington D.C., with registered rates of autism in those states six years later.

Uh-oh - there was a correlation between vaccination in two year kids, and the rate of autism in the state six years later, when those kids were eight. As the abstract says:

The higher the proportion of children receiving recommended vaccinations, the higher was the prevalence of AUT... The results suggest that although mercury has been removed from many vaccines, other culprits may link vaccines to autism. Further study into the relationship between vaccines and autism is warranted.

Sounds rather scary. Until you look at the data, helpfully provided in the paper. First up, here's the scatterplot of all of the vaccination rates and all of the autism-six-years-later rates:

There's more than 51 data points as you can see: there's actually 355 because each state had seven different datapoints (1995 vaccines vs 2001 autism though to 2001 vs 2007). This scatterplot shows no correlation. You can tell just from looking at it, but the correlation coefficient confirms this, as it's a tiny r 0.012 (from a possible range of 0 to 1).

To be fair, that's a very noisy measure, because each state has unique characteristics, so the effect of vaccines will be diluted. However, it's still a useful sanity check, and shows that there can't be a major effect, otherwise it would be too big to get diluted.

To get around this I next looked at the change in the rates of vaccination from one year to the next, and correlated that with the corresponding change in future rates of autism, within each state. A "change" of 1 means no change, 0.5 means it halved and 2 means it doubled, etc.

Zilch. Correlation coeffiencent r is 0.034.

Maybe the changes year-to-year were too small? So I checked the changes between the last year, and the first year.

This made the changes bigger, because more tends to change over six years than in just one. And, to be fair, this does produces a slightly stronger vaccine-autism effect... but it's still tiny. The correlation coefficient here, r, is 0.18 which means that vaccination changes accounts for 3% of the variability in autism changes (r^2 = 0.034.) The p value is 0.20, statistically insignificant.

My conclusion is that this dataset shows no evidence of any association. The author nonetheless found one. How? By doing some statistical wizardry.

The statistical model used took into consideration the unique characteristics of each state. For example, each state had a unique mixture of pollution, which may have affected the prevalence of autism, yet such an effect was not included in this study. A fixed-effects, within-group panel regression (Hall and Cummins 2005) controlled for these unique yet undefined characteristics by deriving a different starting point (intercept) for each state.

The 51 different intercepts - one for each state - reflected the base level of autism or speech disorders occurring in that state that were not explained by the other independent variables (vaccination rates, income, or ethnicity). The model then produced a single relationship between the independent variables and the prevalence of autism or speech disorders.

OK, that's all very fancy, but when the raw data shows zilch and you can only find a signal by "controlling for" stuff, alarm bells start ringing. Given sufficient statistical analysis you can make any data say anything you want.

If the author had given details of the methods, and explained why she chose to control for the variables she did, and not others, that might be different. But she didn't. Nor did she justify only looking at the effects six years later, when five or seven or ten would be just as sensible... and so on.

(Note: whenever I've said "autism", that's my shorthand for autism + SLI, which is what the paper looked at; autism alone data are not presented. Note also that by "vaccination %" I mean "% who got the full vaccine schedule"; the other kids may have got vaccines, just not all of them.)

Delong G (2011). A Positive Association found between Autism Prevalence and Childhood Vaccination uptake across the U.S. Population. Journal of toxicology and environmental health. Part A, 74 (14), 903-16 PMID: 21623535

My Hobby

Os ventos que as vezes tiram algo que amamos, são os mesmos que trazem algo que aprendemos a amar... Por isso não devemos chorar pelo que nos foi tirado e sim, aprender a amar o que nos foi dado. Pois tudo aquilo que é realmente nosso, nunca se vai pra sempre. (Bob Marley )

......eu estava aqui o tempo todo, só você não viu! ♪

Um milhão vezes zero é zero.

Ou seja: não coloque sua intensidade

onde não tem nada.

queria poder embrulhar a dor, e devolver ao remetente.

E hoje eu tenho a certeza que encerrei

uma etapa da minha vida na hora exata.

Mudei quando tinha de mudar!

Boa Semana!!!

♪♫É melhor ser alegre que ser triste,

alegria é a melhor coisa que existe....♪♫

Gostaria de aproveitar este post para agradecer a todos pelas visitas, pelos comentários e pelo carinho com o blog. 

Uma semana maravilhosa e cheia de alegria a todos!!!

Comer, Rezar e Amar

"Parece um ferimento precioso como um coração partido que você não larga porque dói demais....Todos queremos que as coisas continuem iguais David, queremos aceitar viver no sofrimento porque temos medo da mudança, que as coisas sumam totalmente."

...."tem que aprender a escolher seus pensamentos da mesma forma que escolhe suas roupas todos os dia, trabalhe sua mente é a única coisa que deve controlar porque se não dominar seus pensamentos terá problemas sempre."

"Mande luz e amor toda vez que pensar nele e depois esqueça."

*Depois que li o livro já assisti o filme várias vezes, gosto do que ele desperta em mim uma vontade de mudar...vejo a protagonista deixando uma vida aparentemente perfeita para ir atrás do verdadeiro sentido da vida, em busca do autoconhecimento....em busca de Deus...viajar foi a forma que ela encontrou e usou mas cada um pode encontrar o seu jeito, na maioria das vezes nem precisamos ir tão longe....engraçado tem gente que olha e acha que a nossa vida é perfeita e muitas vezes aparentemente até pareça ser mas não estamos felizes e mesmo assim escolhemos continuar, temos medo das mudanças e de quanto elas podem nos custar e por isso optamos em ficar na nossa zona de conforto porque achamos mais seguro mas como diz no filme "se quiser chegar no castelo terá que andar no fosso"

  

Pra quem ainda não assistiu fica a dica, o livro também é muito bom e bem mais detalhado que o filme.

Do Antidepressants Work? The Internet Says...

..."yes and no". A while back I blogged about some researchers who analysed internet discussions of antidepressants to work out what users thought about them. Now a new paper's just come out, doing much the same thing but focussed on a single comment thread: Miracle Drug, Poison, or Placebo.

Back in 2008, MSNBC ran this article, prompted by the recent publication of the famous Kirsch paper. The article itself was short but the ensuing discussion in the comments rapidly grew to epic proportions. By the end of it there were a total of 1,629 posts by a total of over 1,200 people.

In the new paper, author Michael Montagne presents an analysis of the thread. He read through all of the postings and focussed on the ones written by people who had personally taken antidepressants. After excluding obvious spammers and other undesirables (see the picture...), there were still 960 antidepressant users who wrote 1,231 posts.

He first looked to see how many people thought antidepressants were "miracle drugs, poisons, or placebos", which was the title of the original article. However, only a handful of people used those terms in their comments. Almost everyone agreed that antidepressants were not just placebos.

Users employed a range of metaphors to describe the experience. 45 people described them as "livesaving" and 8 said they were a "Godsend". But 21 accused them of turning them into "a zombie".

Down at the bottom of the list were some more unique phrases that only one person used such as "Unleashes a 100 blind monkeys in your brain with instructions to rewire", "Uberpositive girl" and "Robot-zombie wrapped in 4 inches of insulation". That last one could be quite a good horror movie actually.

While there were a small number of absolutely negative comments like "evil" and "Devil's drug", the most consistent theme in the metaphors was that of emotional numbing, with the idea that these drugs remove the symptoms by removing the ability to feel (see e.g. "zombie", "robot", "disconnected", "in a bubble", "band aid".) which seems rather ambivalent. However, only about 10% of the users used any metaphors at all, so take that with a pinch of salt.

Even more salt is required for this graph I made from the table showing the number of positive, negative and mixed judgements on each antidepressant. I've not shown the data from drugs like tricyclics where there were less than 20 total responses. It's interesting, though, that people tended to be more positive about specific drugs than they were when talking about "antidepressants" in general.

There were various other themes in the comments including an ongoing debate between people who said that depressed people ought to seek help from God (who tended to be non-users) vs those who disagreed (who tended to be users). Overall it's an interesting read, but I think it's one of those papers that's more interesting than it really deserves to be. At the end of the day, it's one comment thread on one article on one site.

Montagne M (2011). Miracle drug, poison, or placebo: patients' experiences with antidepressant medications as described in postings on an online message board. Substance use & misuse, 46 (7), 922-30 PMID: 21599508

Do Antidepressants Work? The Internet Says...

..."yes and no". A while back I blogged about some researchers who analysed internet discussions of antidepressants to work out what users thought about them. Now a new paper's just come out, doing much the same thing but focussed on a single comment thread: Miracle Drug, Poison, or Placebo.

Back in 2008, MSNBC ran this article, prompted by the recent publication of the famous Kirsch paper. The article itself was short but the ensuing discussion in the comments rapidly grew to epic proportions. By the end of it there were a total of 1,629 posts by a total of over 1,200 people.

In the new paper, author Michael Montagne presents an analysis of the thread. He read through all of the postings and focussed on the ones written by people who had personally taken antidepressants. After excluding obvious spammers and other undesirables (see the picture...), there were still 960 antidepressant users who wrote 1,231 posts.

He first looked to see how many people thought antidepressants were "miracle drugs, poisons, or placebos", which was the title of the original article. However, only a handful of people used those terms in their comments. Almost everyone agreed that antidepressants were not just placebos.

Users employed a range of metaphors to describe the experience. 45 people described them as "livesaving" and 8 said they were a "Godsend". But 21 accused them of turning them into "a zombie".

Down at the bottom of the list were some more unique phrases that only one person used such as "Unleashes a 100 blind monkeys in your brain with instructions to rewire", "Uberpositive girl" and "Robot-zombie wrapped in 4 inches of insulation". That last one could be quite a good horror movie actually.

While there were a small number of absolutely negative comments like "evil" and "Devil's drug", the most consistent theme in the metaphors was that of emotional numbing, with the idea that these drugs remove the symptoms by removing the ability to feel (see e.g. "zombie", "robot", "disconnected", "in a bubble", "band aid".) which seems rather ambivalent. However, only about 10% of the users used any metaphors at all, so take that with a pinch of salt.

Even more salt is required for this graph I made from the table showing the number of positive, negative and mixed judgements on each antidepressant. I've not shown the data from drugs like tricyclics where there were less than 20 total responses. It's interesting, though, that people tended to be more positive about specific drugs than they were when talking about "antidepressants" in general.

There were various other themes in the comments including an ongoing debate between people who said that depressed people ought to seek help from God (who tended to be non-users) vs those who disagreed (who tended to be users). Overall it's an interesting read, but I think it's one of those papers that's more interesting than it really deserves to be. At the end of the day, it's one comment thread on one article on one site.

Montagne M (2011). Miracle drug, poison, or placebo: patients' experiences with antidepressant medications as described in postings on an online message board. Substance use & misuse, 46 (7), 922-30 PMID: 21599508

Eu tenho os mesmos temores, eu tenho as mesmas cicatrizes que você, eu as mostrei pra você....mas eu acho que a única diferença entre nós é que você tem medo de amar de novo.....

(Comer, rezar e amar)

Não é disso que eu preciso que seja fácil....só não tem que ser tão difícil.

(Comer, rezar e amar)

Um brinde à todas as pessoas que amamos, aonde quer que estejam.

(Cartas para Julieta)

Não dá para ensinar ninguém a sentir.

(C.Azevedo)

Gi & Kim....

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ASSIM QUE VOLTAR PASSAREI EM SEUS BLOGS.

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VEJAM NA POSTAGEM ABAIXO O ROTEIRO DA VIAGEM..
UM GRANDE ABRAÇO NO CORAÇÃO DE TODOS.

Welcome to my Blog

This website ,100nadzmi.blogspot.com, contain some various contents. See my creativity through art ,
modelling, photo editor and more.

Autistic Brains 'Genes Differ'

The BBC say:

The brains of people with autism are chemically different to those without autism, according to researchers. A study, published in the journal Nature, showed the unique characters of the frontal and temporal lobes had disappeared.

It's not a bad summary, although it doesn't explain quite how interesting the new results are. Here's the paper, from a joint US/British team: Transcriptomic analysis of autistic brain reveals convergent molecular pathology

The authors took 19 brains from people with autism and 17 healthy ones. These came from people who donated their brains to science and then died. The study involved taking samples from three areas of the brain, the superior temporal gyrus, the prefrontal cortex, and the cerebellum. These are regions that have been implicated in autism, although to be honest, so has everywhere else in the brain.

They then looked at gene expression: mRNA levels. This measures the degree to which different genes are "activated" and being used to make proteins. Bear in mind that a gene itself could be completely normal, and yet be abnormally expressed: this was not a study of DNA mutations. So the BBC's headline is a bit misleading. The genes themselves were not the focus of this study.

Anyway, comparing the autistic and control brains, they found 444 genes that were statistically significantly either over- or under-expressed in the cerebral cortex samples from the autistic group. However, in the cerebellum, there were just 2 differences: so the cerebellum was ruled out from further analysis.

They then replicated the study in a different cortical area in 6 new cases and 5 new controls. They found extremely strong overlap with the original cohort, with the same genes being altered in the same direction in almost all cases. This makes me confident that there is something going on here. This scatterplot shows that almost all of the genes that were significantly different in the first batch were also different in same direction in the second one (although not always significantly, as you'd expect.)

However, the authors didn't stop there, and this is where it gets interesting. First, they used a pattern classification algorithm to try to distinguish patients and controls on the basis of gene expression. This is very much like the paper from last year showing that pattern classification could predict autism on the basis of brain structure.

Interestingly, the algorithm correctly " diagnosed" a case of autism who turned out to have a 15q duplication mutation. 15q duplication is a genetic disorder which causes autism, amongst other things, and it may explain up to 1% of cases of autism. This is only one case but it's important because it suggests that "15q autism" is not all that different to other kinds of autism on the neural level.

The authors then looked at what the over- and under- expressed genes actually were. They found that the "up" genes tended to be genes relating to immune and glial function, while the "down" genes tended to be involved in the formation and function of synapses between cells.

Very interestingly, one of the major clusters of genes , "M12", showed strong overlap with genes previously known to be expressed in a type of cell called PV+ GABA interneurons. In mouse models of autism, these are known to be deficient. M12 was underexpressed in autism, and it contains many genes which have previously been found to be mutated in some people with autism, such as CNTNAP2.

Another cluster, "M16", was overexpressed; it contains genes involved in immune and microglial function (microglia are specialized immune system cells inside the brain). However, M16 did not contain overrepresentation of suspected asd genes.

So this all points to something like this: autism is caused by disruption to the function of certain gene networks in the brain involved in synaptic function. This network is a delicate balance and it can be thrown off course by many different mutations and/or environmental factors.

There's no one gene for autism, but all of the genes for autism might be related, or rather, they might form a team that works together. If you want to look at it this way, you could say that autism is a bit like blindness. People can go blind for lots of different reasons: it could be damage to the surface of the eye, or the retina, or the optic nerve which carries information to the brain, or the brain itself. All of these parts depend on all the others to work, and if one of them goes wrong, the whole system suffers.

Also, whatever the abnormality in autism is, it seems to trigger a secondary change in the brain which is immune and/or glial related. By "secondary" I don't mean that it's less important. It might be what causes the symptoms of autism. But it's not the root cause (because if it were, mutations in this network would cause autism, and they don't seem to.)

This study raises many more questions than it answers, but in a good way. It certainly doesn't explain autism, but it's pointed the way towards more focussed research in the future - gene cluster M12.

Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, & Geschwind DH (2011). Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature PMID: 21614001

Autistic Brains 'Genes Differ'

The BBC say:

The brains of people with autism are chemically different to those without autism, according to researchers. A study, published in the journal Nature, showed the unique characters of the frontal and temporal lobes had disappeared.

It's not a bad summary, although it doesn't explain quite how interesting the new results are. Here's the paper, from a joint US/British team: Transcriptomic analysis of autistic brain reveals convergent molecular pathology

The authors took 19 brains from people with autism and 17 healthy ones. These came from people who donated their brains to science and then died. The study involved taking samples from three areas of the brain, the superior temporal gyrus, the prefrontal cortex, and the cerebellum. These are regions that have been implicated in autism, although to be honest, so has everywhere else in the brain.

They then looked at gene expression: mRNA levels. This measures the degree to which different genes are "activated" and being used to make proteins. Bear in mind that a gene itself could be completely normal, and yet be abnormally expressed: this was not a study of DNA mutations. So the BBC's headline is a bit misleading. The genes themselves were not the focus of this study.

Anyway, comparing the autistic and control brains, they found 444 genes that were statistically significantly either over- or under-expressed in the cerebral cortex samples from the autistic group. However, in the cerebellum, there were just 2 differences: so the cerebellum was ruled out from further analysis.

They then replicated the study in a different cortical area in 6 new cases and 5 new controls. They found extremely strong overlap with the original cohort, with the same genes being altered in the same direction in almost all cases. This makes me confident that there is something going on here. This scatterplot shows that almost all of the genes that were significantly different in the first batch were also different in same direction in the second one (although not always significantly, as you'd expect.)

However, the authors didn't stop there, and this is where it gets interesting. First, they used a pattern classification algorithm to try to distinguish patients and controls on the basis of gene expression. This is very much like the paper from last year showing that pattern classification could predict autism on the basis of brain structure.

Interestingly, the algorithm correctly " diagnosed" a case of autism who turned out to have a 15q duplication mutation. 15q duplication is a genetic disorder which causes autism, amongst other things, and it may explain up to 1% of cases of autism. This is only one case but it's important because it suggests that "15q autism" is not all that different to other kinds of autism on the neural level.

The authors then looked at what the over- and under- expressed genes actually were. They found that the "up" genes tended to be genes relating to immune and glial function, while the "down" genes tended to be involved in the formation and function of synapses between cells.

Very interestingly, one of the major clusters of genes , "M12", showed strong overlap with genes previously known to be expressed in a type of cell called PV+ GABA interneurons. In mouse models of autism, these are known to be deficient. M12 was underexpressed in autism, and it contains many genes which have previously been found to be mutated in some people with autism, such as CNTNAP2.

Another cluster, "M16", was overexpressed; it contains genes involved in immune and microglial function (microglia are specialized immune system cells inside the brain). However, M16 did not contain overrepresentation of suspected asd genes.

So this all points to something like this: autism is caused by disruption to the function of certain gene networks in the brain involved in synaptic function. This network is a delicate balance and it can be thrown off course by many different mutations and/or environmental factors.

There's no one gene for autism, but all of the genes for autism might be related, or rather, they might form a team that works together. If you want to look at it this way, you could say that autism is a bit like blindness. People can go blind for lots of different reasons: it could be damage to the surface of the eye, or the retina, or the optic nerve which carries information to the brain, or the brain itself. All of these parts depend on all the others to work, and if one of them goes wrong, the whole system suffers.

Also, whatever the abnormality in autism is, it seems to trigger a secondary change in the brain which is immune and/or glial related. By "secondary" I don't mean that it's less important. It might be what causes the symptoms of autism. But it's not the root cause (because if it were, mutations in this network would cause autism, and they don't seem to.)

This study raises many more questions than it answers, but in a good way. It certainly doesn't explain autism, but it's pointed the way towards more focussed research in the future - gene cluster M12.

Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, & Geschwind DH (2011). Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature PMID: 21614001

É difícil esperar por algo que talvez nunca aconteça, mas é ainda mais difícil desistir, principalmente quando é tudo que você quer.

(Pedro Bial)

Esquinas - Djavan

Só eu sei

As esquinas por que passei

Só eu sei só eu sei

Sabe lá o que é não ter e ter que ter pra dar...

Jogue pro alto, se voltar é seu.

(Caio F. Abreu)

VIAJANDO PARA A EUROPA

DO DIA 28 DE MAIO ATÉ DIA 12 DE JUNHO VOU REALIZAR UMA LINDA E GOSTOSA VIAGEM PELA EUROPA.

CONHECEREMOS:

ROMA-ITÁLIA

SUÍÇA.

ZURIQUE



FRANÇA


PARIS


ALEMANHA


BELGICA


HOLANDA


AMSTERDÃ


BERLIN


(todas as imagens aqui foram retiradas da net. para ilustrar. Mas logo postarei as minhas)

CONTO COM O CARINHO DE TODOS EM ESTAR VOTANDO NA CURIOSA. BASTA CLICAR NA IMAGEM E VOTAR. MUITO OBRIGADA

TOP BLOG 2011-CONTO COM O SEU VOTO!

AGRADEÇO A SUA COMPANHIA!!!

Blog Coletivo-Uma Interação de Amigos-

MEUS MIMOS/SEUS PRESENTES- VOU TE ESPERAR POR LÁ.
CANCRO DE MAMA....IMPORTANTE LER....

Poetas-Um Voo Livre-

Sinal de Liberdade-uma expressão de sentimento-