First, the self-referred cohort did not include control subjects, which precluded the authors from determining whether the occurrence of autism following receipt of MMR vaccine was causal or coincidental. Second, endoscopic or neuropsychological assessments were not blind, and data were not collected systematically or completely. Third, gastrointestinal symptoms did not predate autism in several children, which is inconsistent with the notion that intestinal inflammation facilitated bloodstream invasion of encephalopathic peptides.
Fourth, measles, mumps, or rubella vaccine viruses have not been found to cause chronic intestinal inflammation or loss of intestinal barrier function. Indeed, a recent study by Hornig et al. Fifth, putative encephalopathic peptides traveling from the intestine to the brain have never been identified.
In contrast, the genes that have been associated with autism spectrum disorder to date have been found to code for endogenous proteins that influence neuronal synapse function, neuronal cell adhesion, neuronal activity regulation, or endosomal trafficking [ 4 ]. Although no data supporting an association between MMR vaccine and autism existed and a plausible biological mechanism was lacking, several epidemiologic studies were performed to address parental fears created by the publication by Wakefield et al.
Fortunately, several features of large-scale vaccination programs allowed for excellent descriptive and observational studies—specifically, large numbers of subjects, which generated substantial statistical power; high-quality vaccination records, which provided reliable historical data; multinational use of similar vaccine constituents and schedules; electronic medical records, which facilitated accurate analysis of outcome data; and the relatively recent introduction of MMR vaccine in some countries, which allowed for before and after comparisons.
Researchers in several countries performed ecological studies that addressed the question of whether MMR vaccine causes autism. Such analyses employ large databases that compare vaccination rates with autism diagnoses at the population level. In the United Kingdom, researchers evaluated autistic children born from through who were identified by computerized health records from 8 health districts [ 5 ].
Although a trend toward increasing autism diagnoses by year of birth was confirmed, no change in the rates of autism diagnoses after the introduction of MMR vaccine was observed. Further, MMR vaccination rates of autistic children were similar to those of the entire study population. Also, investigators did not observe a clustering of autism diagnoses relative to the time that children received MMR vaccine, nor did they observe a difference in age at autism diagnosis between those vaccinated and not vaccinated or between those vaccinated before or after 18 months of age.
These authors also found no differences in autism rates among vaccinated and unvaccinated children when they extended their analysis to include a longer time after MMR exposure or a second dose of MMR [ 6 ]. Also in the United Kingdom, researchers performed a time-trend analysis using the General Practice Research Database—a high-quality, extensively validated electronic medical record with virtually complete vaccination data [ 7 ].
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More than 3 million person-years of observation during — confirmed an increase in autism diagnoses despite stable MMR vaccination rates. In California, researchers compared year-specific MMR vaccination rates of kindergarten students with the yearly autism case load of the California Department of Developmental Services during — [ 8 ].
As was observed in the United Kingdom, the increase in the number of autism diagnoses did not correlate with MMR vaccination rates. In Canada, researchers estimated the prevalence of pervasive developmental disorder with respect to MMR vaccination in 27, children from 55 schools in Quebec [ 9 ].
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Autism rates increased coincident with a decrease in MMR vaccination rates. The results were unchanged when both exposure and outcome definitions varied, including a strict diagnosis of autism. Although it is difficult to analyze such a phenomenon when it is unclear that one exists which complicates the formulation of a case definition , conclusions may be gleaned from the data with respect to developmental regression alone i. In England, researchers performed a cross-sectional study of autistic children and demonstrated no difference in age of first parental concerns or rate of developmental regression by exposure to MMR vaccine [ 10 ].
No association between developmental regression and gastrointestinal symptoms was observed. In London, an analysis of autistic children used the introduction of MMR to compare vaccinated and unvaccinated cohorts [ 11 ]. The incidence of developmental regression did not differ between cohorts, and the authors observed no difference in the prevalence of gastrointestinal symptoms between vaccinated and unvaccinated autistic children.
Two conclusions are evident from these data. First, the explicit consideration of developmental regression among autistic children does not alter the consistent independence of MMR vaccine and autism. Second, these data argue against the existence of a new variant form of autism. Retrospective, observational studies. Four retrospective, observational studies addressed the relationship between MMR vaccine and autism.
In the United Kingdom, 71 MMR-vaccinated autistic children were compared with MMR-vaccinated matched control children through use of the Doctor's Independent Network, a general practice database [ 12 ]. The authors observed no differences between case and control children in practitioner consultation rates—a surrogate for parental concerns about their child's development—within 6 months after MMR vaccination, which suggests that the diagnosis of autism was not temporally related to MMR vaccination. In Finland, using national registers, researchers linked hospitalization records to vaccination records in , children vaccinated during — [ 13 ].
Of children hospitalized for autistic disorders, no clustering occurred relative to the time of MMR vaccination. In Denmark, again using a national registry, researchers determined vaccination status and autism diagnosis in , children born during — [ 14 ]. The authors observed no differences in the relative risk of autism between those who did and those who did not receive MMR vaccine. Among autistic children, no relationship between date of vaccination and development of autism was observed.
In metropolitan Atlanta, using a developmental surveillance program, researchers compared autistic children with matched control children [ 15 ]. Vaccination records were obtained from state immunization forms. The authors observed no differences in age at vaccination between autistic and nonautistic children, which suggests that early age of MMR vaccine exposure was not a risk factor for autism. Prospective observational studies. Capitalizing on a long-term vaccination project maintained by the National Board of Health, investigators in Finland performed 2 prospective cohort studies.
Researchers prospectively recorded adverse events associated with MMR-vaccinated children during — and identified 31 with gastrointestinal symptoms; none of the children developed autism [ 16 ]. A further analysis of this cohort revealed no vaccine-associated cases of autism among 1. Although this cohort was analyzed using a passive surveillance system, the complete absence of an association between gastrointestinal disease and autism after MMR vaccination was compelling.
In , the US Food and Drug Administration Modernization Act mandated identification and quantification of mercury in all food and drugs; 2 years later, the US Food and Drug Administration found that children might be receiving as much as Despite the absence of data suggesting harm from quantities of ethylmercury contained in vaccines, in , the American Academy of Pediatrics and the Public Health Service recommended the immediate removal of mercury from all vaccines given to young infants [ 19 ].
Widespread and predictable misinterpretation of this conservative, precautionary directive, coupled with a public already concerned by a proposed but unsubstantiated link between vaccination and autism, understandably provoked concern among parents, which led to the birth of several antimercury advocacy groups. However, because the signs and symptoms of autism are clearly distinct from those of mercury poisoning, concerns about mercury as a cause of autism were—similar to those with MMR vaccine—biologically implausible [ 20 ]; children with mercury poisoning show characteristic motor, speech, sensory, psychiatric, visual, and head circumference changes that are either fundamentally different from those of or absent in children with autism.
Consistent with this, a study performed by scientists at the Centers for Disease Control and Prevention years later showed that mercury in vaccines did not cause even subtle signs or symptoms of mercury poisoning [ 21 ]. Despite the biological implausibility of the contention that thimerosal in vaccines caused autism, 7 studies—again descriptive or observational—were performed table 2.
Four other studies have been reviewed in detail elsewhere [ 28 ] but are not discussed here because their methodology is incomplete and unclear and, thus, cause difficulty in drawing meaningful conclusions. Three ecological studies performed in 3 different countries compared the incidence of autism with thimerosal exposure from vaccines. In each case, the nationwide removal of thimerosal—which occurred in in Europe and in in the United States—allowed robust comparisons of vaccination with thimerosal-containing and thimerosal-free products, as follows:.
However, in , a steady increase in the incidence of autism began in both countries and continued through the end of the study period in , despite the removal of thimerosal from vaccines in In Quebec, researchers grouped 27, children from 55 schools by date of birth and estimated thimerosal exposure on the basis of the corresponding Ministry of Health vaccine schedules.
School records were obtained to determine age-specific rates of pervasive developmental disorder [ 9 ]. Thimerosal exposure and pervasive developmental disorder diagnosis were found to be independent variables.
Similar to previous analyses, the highest rates of pervasive developmental disorder were found in cohorts exposed to thimerosal-free vaccines. The results were unchanged when both exposure and outcome definitions varied.
The revealed second token? So dang close it isn't even funny how tight they have designed this game. Time to Draw to the Flame! Lola struggled to get set up - no magnifying glass, no Milan, no weapon. Sanity tracks flooded and health started going down.
This was it. Damage on Hastur was at 16 of the required 14 - we just needed to learn the secret - which could only be happen at the last remaining location - The Palace. Sef's Encounter resolution was bittersweet - she drew The King's Edict and watched the final clue on the location move to a Fanatic at the Palace, just before watching Lola resolve her card - Rotting Remains.
Lola had 11 Sanity and a Possession card killing her at 12 Sanity. She drew a -3 and was killed! Sef screamed out in anguish! On the next turn Sef begrudgingly moved into The Palace, and using a FAST action, flipped the final location, learning the secret and defeating Hastur. All four victories to date were with only one of the two investigators surviving Salt to the wound was the Possession Sef had, forcing her to intently pursue the revival of The King in Yellow for an encore performance, all in the memory of her late actress friend, Lola - who would have loved to see the show one more time, naturally.
Calvin in particular was on the edge of death - sporting 4 physical damage from the start and using the "Hastur" name to ramp up to 11 of 12 sanity - he needed the bonuses that badly. His floor was at 12 because of a Secret weakness in this hand - killing him if his sanity damage equaled his starting sanity! This became particularly nerve-wracking during the Encounter card draws - as any Horror would take him out. During that initial face off, Calvin Evaded Hastur so that Ursula could clear that Palace location - ready to flip in the endgame when the secret was needed.
Unfortunately, an Encounter card wiped away all the cards he had in play and in hand - but at least his Intellect and Willpower were at "11"! The pinnacle of this challenge - keeping Calvin around - came when he drew Lost Soul. He lives. Once nearly all the locations that could be flipped were with the exception of the location farthest from the starting location , Hastur had two health remaining Calvin used all his actions to learn the secret and evade the Beast at the Palace. It was now up to Ursula. And she had just top decked Strange Solution - Acidic Ichor. That was amazing.
Emotional, Climactic, Suspenseful, and just plain well -freaking- done. Well Done. Jan 01, Katherine Addison rated it really liked it Shelves: kill-me-twice-shame-on-me , 20th-century , true-crime , essays. Despite the phenomenal amount of arsenic Deborah Pignataro's doctors found in her system, some twenty times the naturally-occurring rate of arsenic in the human body, she survived. Pignataro pled guilty and was paroled in Sentenced to life without possibility of parole, he was nevertheless paroled in He violated his parole in and was sent back to prison, then was paroled again in Got an accounting degree; got a job as a state auditor, traveling around Washington state; got married.
Got divorced in Murdered another woman in And as Rule points out, there are plenty of unsolved murders between and that might be his work as well. As of , he was 74 and still imprisoned. He was paroled and reincarcerated, paroled and reincarcerated, paroled for the last time in and murdered again in He said there was something evil in him that he couldn't control.
He refused to allow his defense attorney to argue against the death penalty and refused to allow him to file appeals.
Elledge died by lethal injection in He was caught partially because of the knots he used to tie their hands, which were exactly the same as the knots he'd used eight years previously when he kidnapped several young boys, tied them to trees, and threatened to castrate them. He was sent to Western Washington State Hospital's sexual psychopath program and "released shortly thereafter. Psychiatrists argued about whether he was psychotic, schizophrenic, sociopathic, and whether he was or was not legally sane. He was found sane and guilty and sentenced to death in The death sentence was commuted to life, and the "life" sentence, as per usual, fell a fair ways short.